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Table of Contents
Year : 2020  |  Volume : 9  |  Issue : 3  |  Page : 189-190

Journal scan

Provenance and Peer Review Commissioned; Internally Peer Reviewed

Date of Web Publication27-Oct-2020

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JCSR.JCSR_67_20

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How to cite this article:
Suresh V, Bitla AR. Journal scan. J Clin Sci Res 2020;9:189-90

How to cite this URL:
Suresh V, Bitla AR. Journal scan. J Clin Sci Res [serial online] 2020 [cited 2021 Aug 3];9:189-90. Available from: https://www.jcsr.co.in/text.asp?2020/9/3/189/298959

Body mass index and hormone receptor status influence recurrence risk in HER2-positive early breast cancer patients

Human epidermal growth factor receptor 2 (HER2)-positive early breast cancer is a heterogeneous disease that has a connection with hormone receptor (HR) status and other categorical variables. Here, the authors assessed the role of body mass index (BMI) and HRs in 238 women who underwent adjuvant chemotherapy (CHT) and 1 year of trastuzumab treatment. A higher 3-year recurrence risk was observed in HR-negative (HR) patients with BMI ≥25 compared with HR + patients with BMI <25, suggesting that these patients might benefit from escalation adjuvant treatment approaches. Kaplan–Meier method survival analysis, multivariate analysis using Cox proportional-hazards model adjusting for HR status, BMI, tumour staging, size, nodal status and type of adjuvant CHT as variables suggested that neither HR status nor BMI alone showed an association with 3-year distant disease-free survival (3-year DDFS). The hazard ratios and Chi-square test resulted that patients with HR-tumours who had BMI ≥25 (3-year DDFS 86.9%; 95% confidence interval [CI], 75.0%–97.7%) were amplified compared with patients possessing HR + tumours and with BMI <25 (3-year DDFS 98%; 95% CI, 94.8%–100.0%) and other subgroups (P = 003) confirmed in multivariate analysis (hazard ratio, 1.79; 95% CI, 1.04–3.07; P = 0.03). The study concluded that patients who are HR − and have BMI ≥25 might benefit from adjuvant chemotherapy escalation approaches, whereas those who are HR + and have BMI <25 might be advised for a shorter duration of adjuvant treatment with anti-HER2 agents.

  Comment Top

In this study, the authors focused on the risk of cancer recurrence in the population of HER2-positive early breast cancer patients by choosing different clinicopathological features, such as staging, node status, BMI and HR status. They related BMI and HR expression in the selected population and concluded that HR negative tumours with BMI more than 25 need escalation approaches (anti-HER2 agents with standard trastuzumab treatment). Escalation and de-escalation approaches are useful for fine-tuning of available adjuvant therapies based on the pathological features of tumour, comorbidities and economic status of the patient. Since this was a retrospective study, confirmation of these findings in a prospective study involving a bigger sample size needs to be carried out.

Cantini L, Pistelli M, Merloni F, Fontana A, Bertolini I, De Angelis C, et al. Body mass index and hormone receptor status influence recurrence risk in HER2-positive early breast cancer patients. Clin Breast Cancer 2020;20:e89-98.

LPS restores protective immunity in macrophages againstMycobacterium tuberculosis via autophagy

Autophagy has been recognised as an essential immune regulatory mechanism. Recent studies interlinked the macrophage autophagy with innate immune responses against Mycobacterium tuberculosis that can survive within macrophages by blocking the phagolysosome formation. Hence, the present study investigated the exogenous autophagy activators rapamycin and LPS in macrophage autophagy and immunity against M. tuberculosis. The findings suggest that autophagy is a regulatable cellular mechanism of M. tuberculosis defence in macrophages by hindering the transcriptomic profiles that affect autophagy-related pathways in human blood of TB patients. The study, in turn, investigated the effects of the autophagy activators to confirm that rapamycin and LPS induce autophagy in M. tuberculosis-infected THP-1-derived macrophages or PMA primed THP-1 macrophages [THP-1 (A)]. LPS restores M. tuberculosis-inhibited interleukin-12 (IL-12) synthesis and secretion in THP-1 (A) cells through autophagy and increases the secretion of effector cytokines IL-12 synthesis that stimulates CD4+ T cells in THP-1(A) cells. Further, the studies illustrated the autophagy importance in M. tuberculosis elimination through macrophages and lead to design novel therapies for tuberculosis and other bacterial infections.

  Comment Top

Authors identified that DEGs involved in the autophagy pathway by comparing the transcriptome of the healthy and patients infected with Mycobacterium. Mycobacterium is protected in macrophages through dysregulation of genes involved in autophagy. The authors confirmed that LPS enhances the autophagy by increased levels of IL-12. Novel therapeutics for multidrug-resistant Mycobacterium can be developed by targeting on autophagy-activating agents.

Fang F, Ge Q, Li R, Lv J, Zhang Y, Feng A, et al. LPS restores protective immunity in macrophages against Mycobacterium tuberculosis via autophagy. Mol Immunol 2020;124:18-24.

Remdesivir for the treatment of COVID-19 – Preliminary report

The study deals with evaluating the preliminary results of the first stage of the Adaptive COVID-19 Treatment Trial (ACTT-1) by comparing remdesivir and placebo. Authors organised a double-blind, randomised, placebo-controlled trial over 1063 COVID-19 adult patients hospitalised with evidence of lower respiratory tract involvement by either administering intravenous remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The prognosis was the recovery time defined by either discharge or hospitalisation for infection control purpose. The study findings observed shortened duration of recovery in the remdesivir group and the preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) after randomisation indicated that remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9–12), as compared with 15 days (95% CI, 13–19) in placebo received patients (rate ratio for recovery, 1.32; 95% CI, 1.12–1.55; P < 0.001). The Kaplan–Meier estimates mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47–1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomisation (21.1%) and 141 of the 522 patients in the placebo group who underwent randomisation (27.0%). Remdesivir was superior to placebo in reducing recovery time in adults hospitalised with COVID-19 having lower respiratory tract infection.

  Comment Top

The FDA has approved the drug remdesivir under the emergency use for the treatment of COVID-19. In this study, the authors conducted phase 3 clinical trials, randomised, double-blind, placebo-controlled trials to evaluate the efficacy and safety of the investigational drug. They found that it is useful for the COVID-19 patients with supplemental oxygen therapy. As the COVID symptoms vary from person to person, combination therapy along with the anti-viral drug is needed for better treatment.

Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of COVID-19 – Preliminary report. N Engl J Med 2020:NEJMoa2007764.

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