The human microbiome mainly consists of bacteria and interacts closely with the immune system. Immune checkpoint inhibitors (ICI) are used to treat several types of cancers. Recently, it has been identified that the gut microbiome plays a role in the effectiveness of immunotherapy. This study aims to analyze the effect of microbiome and antibiotics on the effectiveness of ICI in cancer patients and the measures to improve efficacy based on that. A detailed review was conducted on articles published in PubMed and Science Direct in the last five years i.e., 2016 to 2021. A total of 16 articles involving 1293 patients with cancer who were receiving immunotherapy, were deemed eligible to be included in the final review. Data were extracted from the eligible articles and were checked for quality appraisal. All 16 articles revealed the effect of either gut microbiome or antibiotics or both on ICI. Based on our findings, we found that the microbiome enriched in different microorganisms responded differently to the ICI and that antibiotics negatively impacted the effectiveness of ICI. The time at which patients receiving ICI were prescribed antibiotics influenced the effect of ICI. Antibiotics and different microbiome also affected progression-free survival (PFS) and overall survival (OS).
Antigen detection rapid diagnostic tests (Ag-RDTs) used for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein are inexpensive, faster and easy to use alternative of Nucleic Acid Amplification Test (NAAT) for diagnosis of Coronavirus disease 2019 (COVID-19). In this systematic review and meta-analysis, we assessed the diagnostic accuracy of Ag-RDTs in low and middle-income countries (LMICs). We included studies that evaluated the diagnostic accuracy of Ag-RDTs (sensitivity and specificity) against reverse transcription-polymerase chain reaction (RT-PCR) as a reference standard. The study population comprised of people living in LMICs irrespective of age and gender, who had undergone testing for COVID-19. We included peer reviewed prospective or retrospective cohort studies, cross-sectional studies, case control studies, randomized clinical trials (RCTs) as well as non-randomized experimental studies which addressed the review question. A systematic search was conducted in PubMed, CINAHL, Embase, Scopus, and Google Scholar to identify studies published between 1 January, 2020 and 15 August, 2021. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool was used to assess the methodological quality of studies. The analysis was done using Review Manager 5.4 and R software 4.0.2. From the total of 12 diagnostic accuracy studies with 4,817 study participants, pooled sensitivity and specificity were 78.2% and 99.5% respectively. Sensitivity was marginally higher in subgroup analysis based on studies with low risk of bias and applicability concerns (78.9%) and studies using SD Biosensor Ag-RDT (79.4%). However, an inverse relation between cycle threshold (Ct) and sensitivity of Ag-RDT was not seen. The review demonstrated pooled sensitivity value approaching the minimum performance requirement for diagnosis of COVID-19 by WHO with specificity value meeting the specified requirement. Ag-RDTs, therefore have the potential to be used as a screening tool for SARS-CoV-2 detection in low resource settings where RT-PCR might not be readily accessible. However, false negative results need to be interpreted with caution.
Takayasu's arteritis (TAK) is a rare large vessel vasculitis of unknown etiology that chiefly targets the aorta and its branches. It predominantly affects females under 50 years of age. A relationship between TAK and Mycobacterium tuberculosis (TB) has been suggested for a long time, but only a few systematic studies have been done centering on this association. The present systematic review aimed to analyze the possible association between TAK and TB based on the studies conducted previously. A detailed search was conducted until April 2021 using three databases: PubMed, Cochrane Library, and MedlinePlus. PubMed search on the related topic identified 1053 articles, four on Cochrane Library, and three on MedlinePlus. Finally, 13 papers were pertinent for our review. The appropriate data was extracted from these articles, and the risk of bias assessment was done. The systematic review of these finalized articles found that the majority of the current studies supported the presence of TB in patients with TAK. Out of 13 final observational studies, only one study failed to detect a link between TAK and TB. However, data are still lacking that show a direct link between them. Future large-scale studies are needed to probe the exact role of Mycobacterium tuberculosis infection in the etiopathogenesis of TAK.
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a rare disease with a progressive nature, eventually leading to lung fibrosis. Nintedanib, a tyrosine kinase inhibitor, is a widely accepted drug for treating idiopathic pulmonary fibrosis (IPF), a disease that shares some similarities with SSc-ILD regarding pathological disease processes. In this review, we aim to discuss the pathogenesis of SSc-ILD and the overall role of nintedanib in the management of SSc-ILD. SSc-ILD involves multiple pathological mediators contributing to various pathways that ultimately cause lung fibrosis. The pathogenesis of SSc-ILD is a complex phenomenon and still needs further study. Nintedanib has demonstrated its efficacy in the treatment of SSc-ILD by reducing the progression of the pathological process. It has also proven its clinical significance in the management of SSc-ILD. However, the currently available literature does not have any evidence to compare the effectiveness of nintedanib with the already available treatment modalities such as cyclophosphamide (CYC), mycophenolate mofetil (MMF), and azathioprine (AZT). The current literature also lacks information about nintedanib's long-term consequences on patients with SSc-ILD. Therefore, to create better evidence-based treatment guidelines, we recommend that researchers conduct randomized clinical trials comparing nintedanib to MMF, CYC, AZT, etc., and continue surveillance to explore the longterm consequences of nintedanib.
Prothrombin gene mutation (prothrombin thrombophilia) is an inherited disorder that increases the risk of venous thrombosis. However, limited data exist on the risk of arterial stroke in an at-risk population. Several meta-analyses report slightly increased risk in specific populations. We report a 10-year-old Hispanic girl who presented to the emergency department with a seizure. This seizure occurred five days after she tripped and fell without any initial associated symptoms. She had left-sided hemiparesis on physical examination after the seizure. Imaging revealed internal carotid artery (ICA) dissection with thrombus, right caudate nucleus and putamen infarcts, and ischemic penumbra. She subsequently had an endovascular thrombectomy of the right ICA with reperfusion. Genetic testing showed a prothrombin gene mutation (G20210A). Prothrombin gene mutation was the most likely explanation for her stroke in the absence of a significant risk factor for arterial thrombosis or an underlying hypercoagulable disorder. Further investigations are required to determine the risks and evaluate the correlation between prothrombin gene mutation and ischemic stroke in children.
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