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The addition of olanzapine to a neurokinin receptor blocker, a serotonin receptor blocker, and dexamethasone markedly improved the control of nausea and vomiting in previously untreated patients receiving highly emetogenic chemotherapy. Chemotherapy-induced nausea and vomiting are associated with a significant deterioration in quality of life and are perceived by patients as major adverse effects of cancer treatment. 1 The use of 5-hydroxytryptamine type 3 (5-HT 3 ) receptor antagonists, 2 dexamethasone, 2 and neurokinin-1 (NK 1 ) receptor antagonists 3 – 9 has significantly improved the control of this troublesome side effect. International guidelines 10 – 12 recommend combinations of these agents to prevent chemotherapy-induced nausea and vomiting in patients receiving moderately or highly emetogenic chemotherapy. Nonetheless, nausea remains a major problem for many patients. 1 , 2 Olanzapine is approved by the Food and Drug Administration (FDA) as an . . .

Background Immune checkpoint inhibitors (ICI) and Tyrosine kinase inhibitors (TKI) are effective for several types of cancers, but they can have several cardiotoxicity sides effects. We present a case of TKI-ICI toxicity resulting in multiorgan inflammatory syndrome with myocarditis and thrombotic STEMI that were successfully treated with high-dose steroids and PCI. Case presentation Seventy-two year-old man patient treated with on pembrolizumab 200 mg IV every 3 weeks and Axitinib 5 mg PO q12h for the past 5 months complained of acute shortness of breath, altered mental status, and chronic diarrhea. Coronary angiography demonstrated a thrombotic lesion in the right coronary artery (RCA) that was treated successfully with percutaneous coronary intervention (PCI). Despite PCI he continued to complain of shortness of breath further workup with Cardiac MRI (CMR) was obtained showed an ejection fraction of 38%, small pericardial effusion, and delayed gadolinium enhancement (DGE) in the inferior wall suggestive of myocarditis. An empirical trial of high-dose steroids improved all patient symptoms and ejection fraction; therefore, the chemotherapy regimen was changed. Conclusion This case report highlights the potential vasculogenic effects of Axitinib and immune-related myocarditis of pembrolizumab. Cardiologists and oncologists should be vigilant for the cardiotoxic effects of Axitinib and pembrolizumab.

Immune checkpoint inhibitors (ICI) and Tyrosine kinase inhibitors (TKI) are effective for several types of cancers, but they can have several cardiotoxicity sides effects. We present a case of TKI-ICI toxicity resulting in multiorgan inflammatory syndrome with myocarditis and thrombotic STEMI that were successfully treated with high-dose steroids and PCI. Seventy-two year-old man patient treated with on pembrolizumab 200 mg IV every 3 weeks and Axitinib 5 mg PO q12h for the past 5 months complained of acute shortness of breath, altered mental status, and chronic diarrhea. Coronary angiography demonstrated a thrombotic lesion in the right coronary artery (RCA) that was treated successfully with percutaneous coronary intervention (PCI). Despite PCI he continued to complain of shortness of breath further workup with Cardiac MRI (CMR) was obtained showed an ejection fraction of 38%, small pericardial effusion, and delayed gadolinium enhancement (DGE) in the inferior wall suggestive of myocarditis. An empirical trial of high-dose steroids improved all patient symptoms and ejection fraction; therefore, the chemotherapy regimen was changed. This case report highlights the potential vasculogenic effects of Axitinib and immune-related myocarditis of pembrolizumab. Cardiologists and oncologists should be vigilant for the cardiotoxic effects of Axitinib and pembrolizumab.

Oral submucous fibrosis (OSMF) is a chronic progressive, scarring disease affecting oral, oropharyngeal, and sometimes the esophageal mucosa. It is characterized by the progressive fibrosis of the submucosal tissue. The pathogenesis of OSMF has been directly related to the habit of chewing areca nut and its commercial preparation, which is widespread in Indian subcontinent and Southeast Asia. The areca nut has been classified as a \"group one human carcinogen.\" Oral squamous cell carcinoma in the background of OSMF is one of the most common malignancies in South and Southeast Asian countries. Malignant transformation has been reported in 7%-12% cases of OSMF. Histopathological spectrum of OSMF includes the apparent alterations observed in the epithelium and connective tissue. Epithelial atrophy and sometimes epithelial hyperplasia with or without dysplasia are the peculiar alterations seen in the epithelium. In the connective tissue, there is extracellular matrix remodeling which results in excessive collagenization. Further cross-linking of collagen leads to hyalinization which makes the collagen resistant to proteolysis. Owing to fibrosis in the connective tissue, there is narrowing of blood vessels which further results in compromised blood supply to the local tissue milieu, that is, hypoxia. This tissue hypoxia elicits angiogenesis which may result in the malignant transformation of OSMF. Perpetual irritation of areca nut and its constituents to the oral mucosa leads to upregulation of pro-inflammatory cytokines and further juxtaepithelial inflammation. Thus, these coordinated reactions in epithelium and connective tissue leads the OSMF toward malignant transformation.

Atypical Parkinson syndromes (APSs) often have symptoms that overlap with those of Parkinson's disease (PD), especially early in the disease, making these disorders difficult to diagnose. Previous studies have demonstrated an association of oligomeric α-synuclein (α-Syn), a key element in the pathogenesis of PD, with Sirtuin (SIRT)2 proteins for modulating PD. We aimed to evaluate SIRT protein expression in serum of PD patients and compare it with APSs and normal elderly control (GC) and to correlate this with α-Syn. SIRT protein expression was evaluated in sera of 68 PD; 34 APS and 68 GC without any neuro-psychiatric illness as controls by surface plasmon resonance (SPR). SIRT2 expression was correlated with α-Syn in PD and GC. Significant ( < 0.0001) differences were observed between serum SIRT2 concentration in PD and APS and GC as well as between APS and GC. Receiver operating characteristic (ROC) analysis revealed the strong cut-off value to differentiate PD from APS and GC and also APS from GC. Significant correlation was observed among SIRT2 levels in early PD patients with Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr (H & Y) and increased duration of disease. In addition, a strong positive correlation of SIRT2 with α-Syn ( < 0.0001) was observed. However, no such difference was detected for serum SIRT1 in cases of PD and APS or for GC. The present study is the first to report elevated serum SIRT2 in PD. The study also provided a simple test to distinguish PD from APS and may have translational utility for diagnosis.

Both COVID-19 mRNA or recombinant Adenovirus vector (rAdVV) based vaccines have shown a great efficacy in generating humoral and cellular immune responses. Two doses of the COVID-19 vaccines generate enough antibodies and generate spike-specific T cell responses. However, after 6-8 months there is a decline in antibody production and T cell responses. Due to the rise of new SARS-CoV-2 variants of concern, a third or even fourth dose of vaccine was recommended for the elderly, immune comprised and frontline medical health care workers. However, despite additional booster doses given, those who were infected with either delta or omicron (during December 2021 – March 2022) had symptoms of illness. By what means these COVID-19 vaccines provide immunity against the SARS-CoV-2 virus at the molecular level is not explored extensively yet and, it is an emerging research field as to how the SARS-CoV-2 virus is able to evade the host immunity. Most of the infected people had mild symptoms whilst some were asymptomatic. Many of the people had developed nucleocapsid antibodies against the SARS-CoV-2 delta/omicron variants confirming a humoral immune response against viral infection. Furthermore, cellular analysis shows that post-vaccinated recovered COVID-19 individuals have significantly reduced NK cells and increased T naïve CD4+, TEM CD8+ and B cells. This decrease in cellular immunity corresponds to individuals who recovered from alpha variants infection and had mild symptoms. Our results highlight that booster doses clearly reduce the severity of infection against delta/omicron infection. Furthermore, our cellular and humoral immune system is trained by vaccines and ready to deal with breakthrough infections in the future.

COVID-19 vaccines based on a range of expression platforms have shown considerable protective efficacy, generating antibody and T cell immune responses. However, molecular pathways underpinning COVID-19 vaccine priming of immunity against the SARS-CoV-2 virus have not yet been explored extensively. This analysis is critical to optimization of future vaccination strategies, schedules, and combinations. Thus, we investigated a cohort of individuals pre- and post-vaccination to understand the humoral and cellular immune response against different COVID-19 vaccines, including recombinant adenoviral vector (rAdVV) and mRNA-based vaccines. Single-cell RNA sequencing allowed characterization of monocytes, T, NK and B cell activation at the transcriptomics/proteomic level, in response to different COVID-19 vaccines. Our data revealed that different COVID-19 vaccines elicit a unique and distinct mechanism of action. Specifically, we revealed that rAdVV vaccines negatively regulate CD4+ T cell activation, leukocytes chemotaxis, IL-18 signalling and antigen presentation by monocytes whilst mRNA vaccines positively regulate NKT cell activation, platelets activation and chemokine signalling pathways. An antigen-specific T cell response was already observed following the 1st vaccine dose and was not further augmented after the subsequent 2nd dose of the same vaccine and it was dependent on the type of vaccination used. Our integrated three layered-analyses highlights that COVID-19 vaccines evoke a strong but divergent immune response at the RNA, protein, and cellular levels. Our approach is able to pinpoint efficacy and mechanisms controlling immunity to vaccination and open the door for better vaccination which could induce innate and adaptive immunity equally in the long term. Decrease in major three cell types classical and non-classical monocytes and NK type III cells after COVID-19 vaccination Individual vaccination (AZ, JJ, MD, PB) has differential effect on various immune cell subsets and regulates unique cell populations, whilst no change was observed for CV vaccination rAdVV and mRNA vaccines have different mechanism of action for activation of lymphocytes and monocytes, respectively rAdVV vaccines negatively regulates CD4+ T cell activation, leukocytes chemotaxis, IL-18 signalling and antigen presentation whilst mRNA vaccines positively regulate NKT cell activation, platelets activation and chemokine signalling pathways. An antigen-specific T cell response was prompted after the 1st vaccine dose and not augmented after the subsequent 2nd dose of the same vaccine.