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Fulltext Comparing Efficacy and Safety of Empirical vs. Guided Therapy for Non-cardiac Chest Pain: A Pragmatic Randomized Trial

Abdul Kadir NP, Ma ZF, Abdul Hafidz MI, Annamalai C, Jayaraman T, Hamid N, et al.

Front Med (Lausanne), 2021;8:605647.
PMID: 33659261 DOI: 10.3389/fmed.2021.605647

Background: Non-cardiac chest pain is common with two-thirds due to gastroesophageal reflux disease (GERD). Objective: To evaluate the effectiveness and safety of guided vs. empirical therapy in non-cardiac chest pain. Methods: Adults with normal angiogram or stress test were randomized into either a guided or empirical group. In the guided group, after the ambulatory pH-impedance test, if GERD then dexlansoprazole 30 mg/day for 8 weeks, but if functional or hypersensitive chest pain, then theophylline SR 250 mg/day for 4 weeks. In the empirical group, dexlansoprazole 60 mg/day was given for 2 weeks. The primary outcome was global chest pain visual analog score (VAS) and secondary outcomes were Quality of Life in Reflux and Dyspepsia (QOLRAD), GERD questionnaire (GERDQ), and pH parameters, all determined at baseline, 2nd and 8th weeks. Results: Of 200 screened patients, 132 were excluded, and of 68 randomized per-protocol, 33 were in the guided group and 35 in the empirical group. For between-group analysis, mean global pain scores were better with guided vs. empirical group at 8th week (P = 0.005) but not GERDQ or QOLRAD or any of pH measures (all P > 0.05). For within-group analysis, mean QOLRAD improved earliest at 8th week vs. baseline (P = 0.006) in the guided group and 2nd week vs. baseline (P = 0.011) in the empirical group but no differences were seen in other secondary outcomes (P > 0.05). No serious adverse events were reported. Conclusions: Guided approach may be preferred over short-term empirical therapy in symptom response, however QOLRAD, acid-related symptoms, or pH measures are not significantly different (trial registration ID no. NCT03319121).
Fulltext Differential polarization and the expression of efferocytosis receptor MerTK on M1 and M2 macrophages isolated from coronary artery disease patients

Mohd Idrus FN, Ahmad NS, Hoe CH, Azlan M, Norfuad FA, Yusof Z, et al.

BMC Immunol, 2021 03 24;22(1):21.
PMID: 33761885 DOI: 10.1186/s12865-021-00410-2

BACKGROUND: Differential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis. Higher expression of Mer proto-oncogene tyrosine kinase (MerTK) on M2 macrophage helps in maintaining macrophage efferocytic efficiency. In healthy individuals, macrophage polarization into M1 and M2 occurs in tissues in concomitance with the acquisition of functional phenotypes depending on specific microenvironment stimuli. However, whether the macrophage differential polarization and MerTK expression vary in coronary artery disease (CAD) patients remain unknown.
OBJECTIVE: This study aimed to elucidate the polarization of M1 and M2 macrophage from CAD patients as well as to investigate the expression of MerTK in these macrophage phenotypes.
METHODS: A total of 14 (n) CAD patients were recruited and subsequently grouped into "no apparent CAD", "non-obstructive CAD" and "obstructive CAD" according to the degree of stenosis. Thirty ml of venous blood was withdrawn to obtain monocyte from the patients. The M1 macrophage was generated by treating the monocyte with GMCSF, LPS and IFN-γ while MCSF, IL-4 and IL-13 were employed to differentiate monocyte into M2 macrophage. After 7 days of polarization, analysis of cell surface differentiation markers (CD86+/CD80+ for M1 and CD206+/CD200R+ for M2) and measurement of MerTK expression were performed using flow cytometry.
RESULTS: Both M1 and M2 macrophage expressed similar level of CD86, CD80 and CD206 in all groups of CAD patients. MerTK expression in no apparent CAD patients was significantly higher in M2 macrophage compared to M1 macrophage [12.58 ± 4.40 vs. 6.58 ± 1.37, p = 0.040].
CONCLUSION: Differential polarization of macrophage into M1 and M2 was highly dynamic and can be varied due to the microenvironment stimuli in atherosclerotic plaque. Besides, higher expression of MerTK in patients with the least coronary obstructive suggest its vital involvement in efferocytosis.
Findings from a Malaysian multicentre study on oropharyngeal squamous cell carcinoma

Sathasivam HP, Davan SP, Chua SM, Rohaizat RF, Japar R, Zakaria Z, et al.

Infect Agent Cancer, 2023 Nov 28;18(1):74.
PMID: 38017493 DOI: 10.1186/s13027-023-00557-0

BACKGROUND: In addition to the conventional aetiologic agents of oropharyngeal squamous cell carcinoma (OPSCC) such as tobacco usage, alcohol consumption and betel quid usage, it has been established that a proportion of OPSCC are driven by persistent oncogenic human papillomavirus (HPV) infections. Currently, there is a lack of data on the burden of HPV- associated OPSCC in Asian countries including Malaysia.
METHODS: A cross-sectional multicentre study with tissue analysis of Malaysian patients diagnosed with primary OPSCC within a five-year period, from 2015 to 2019 between 01/01/2015 to 31/12/2019 was undertaken. Determination of HPV status was carried out using p16INK4a immunohistochemistry on tissue microarrays constructed from archived formalin-fixed paraffin-embedded tissue.
RESULTS: From the cases identified, 184 cases had sufficient tissue material for analysis. Overall, median age at diagnosis was 63.0 years (IQR = 15) and 76.1% of patients were males. In our cohort, 35.3% of patients were Indian, 34.2% were Chinese, 21.2% were Malay and 9.2% were from other ethnicities. The estimated prevalence of HPV-associated OPSCC in our cohort was 31.0% (CI 24.4-38.2%). The median age for the HPV-associated OPSCC sub-group of patients was not significantly lower than the median age of patients with HPV-independent OPSCC. More than half of HPV-associated OPSCC was seen in patients of Chinese ethnicity (54.4%). Patients with HPV-associated OPSCC had a much better overall survival than patients with HPV-independent OPSCC (Log rank test; p

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