Latest articles in this journal
Biomedical Journal; doi:10.1016/j.bj.2021.03.003
Signal transducer and activator of transcription 3 (STAT3) is a key transcription factor involved in regulation of immune cell activation and differentiation. Recent discoveries highlight the role of germline activating STAT3 mutations in inborn errors of immunity characterized by early-onset multi-organ autoimmunity and lymphoproliferation. Much progress has been made in defining the clinical spectrum of STAT3 GOF disease and unraveling the molecular and cellular mechanisms underlying this disease. In this review, we summarize our current understanding of the disease and discuss the clinical phenotype, diagnostic approach, cellular and molecular effects of STAT3 GOF mutations and therapeutic concepts for these patients.
Biomedical Journal; doi:10.1016/j.bj.2021.03.002
Comprehensive Geriatric Assessment (CGA) is the gold standard for detecting frailty in elderly patients with cancer. Since CGA is time- and resource-consuming, many alternative frailty screening tools have been developed; however, it remains unknown whether these tools are suitable for older and adult patients with cancer. Therefore, we used the data collected for a large longitudinal study to compare the diagnostic performances of two frailty screening tools (Geriatric 8 [G8] and Flemish version of the Triage Risk Screening Tool [fTRST]) to identify frailty risk profile among patients with cancer. Patients aged ≥20 years with newly diagnosed cancer were enrolled. Frailty screening with G8, fTRST, and CGA were performed before anti-cancer treatment. Diagnostic characteristics obtained using G8 and fTRST were analyzed by C-index, and the validity of G8 and fTRST was also determined. 40.9% of the 755 patients with cancer displayed frailty on CGA. Both G8 and fTRST showed high sensitivity (80.6–88.4%) and negative predictive value (81.0–81.2%). The C-index of G8 was higher than that of fTRST (0.77 vs 0.71, p = .01). Moreover, the best G8 and fTRST cut-off points were ≤13 and ≥ 2, respectively. The validities of G8 and fTRST were also confirmed; however, frailty age differences were not observed in our study. Frailty is a common problem for patients with cancer, and routine frailty screening is essential for both older and adult patients. G8 and fTRST are simple and useful frailty screening tools, while G8 is more suitable than fTRST for Taiwanese patients with cancer.
Biomedical Journal; doi:10.1016/j.bj.2021.03.006
Biomedical Journal; doi:10.1016/j.bj.2021.03.001
Colorectal cancer (CRC) is a major health concern globally, but exhibits regional and/or environmental distinctions in terms of outcome especially for patients with stage III CRC. From 2014 to 2016, matched pairs of tumor and adjacent normal tissue samples from 60 patients with stage I–IV CRC Chang Gung Memorial Hospital in Taiwan were analyzed using next-generation sequencing. The DNA, mRNA, and miRNA sequences of paired tumor tissues were profiled. An observational study with survival analysis was done. Online datasets of The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) were also integrated and compared. The gene that exhibited the highest mutation rate was adenomatous polyposis coli (APC) (75.0%), followed by TP53 (70.0%), KRAS (56.6%), and TTN (48.3%). APC was also the most frequently mutated gene in TCGA and ICGC datasets. Surprisingly, for non-metastatic cases (stages I-III), CRC patients with mutated APC had better outcome in terms of overall survival (p = 0.041) and recurrence free survival (p = 0.0048). Particularly for stage III CRC, the overall survival rate was 94.4% and 67.7%, respectively (p = 0.018), and the recurrence free survival rate was 94.4% and 16.7%, respectively (p = 0.00044). Further clinical and gene expression analyses revealed that the APC wt specimens to a greater extent exhibit poor differentiation state as well as EGFR upregulation, providing molecular basis for the poor prognosis of these patients. Finally, based on integrated transcriptome analysis, we constructed the mRNA-miRNA networks underlying disease recurrence of the stage III CRC and uncovered potential therapeutic targets for this clinical condition. For stage III CRC, patients with mutated APC had better overall and recurrence free survival.
Biomedical Journal; doi:10.1016/j.bj.2021.03.005
Long noncoding RNAs (lncRNAs) are noncoding RNAs with length greater than 200 nt. The biological roles and mechanisms mediated by lncRNAs have been extensively investigated. Hypoxia is a proven microenvironmental factor that promotes solid tumor metastasis. Epithelial-mesenchymal transition (EMT) is one of the major mechanisms induced by hypoxia to contribute to metastasis. Many lncRNAs have been shown to be induced by hypoxia and their roles have been delineated. In this review, we focus on the hypoxia-inducible lncRNAs that interact with protein/protein complex and chromatin/epigenetic factors, and the mechanisms that contribute to metastasis. The role of a recently discovered lncRNA RP11-390F4.3 in hypoxia-induced EMT is discussed. Whole genome approaches to delineating the association between lncRNAs and histone modifications are discussed. Other topics related to hypoxia-induced tumor progression but require further investigation are also mentioned. The clinical significance and treatment strategy targeted against lncRNAs are discussed. The review aims to identify suitable lncRNA targets that may provide feasible therapeutic venues for hypoxia-involved cancers.
Biomedical Journal; doi:10.1016/j.bj.2021.03.004
The most commonly encountered tumour of the spine is metastasis, and thoracic spine is the most commonly metastatic spine. Controversy exists regarding the optimal surgical approach for this kind of patient. The author conducted a study to assess the differences between anterior thoracotomy and a posterior approach in patients with malignant epidural cord compression in the thoracic spine. Between January 2004 and December 2017, 97 patients with metastatic thoracic lesion were stratified into two groups by approach method to the lesion site: Group A - mean anterior thoracotomy, decompression and fixation; and Group P - represented posterior decompression and fixation. Survival time, neurologic status, each complication by surgery or in hospital, and days in intensive care unit were compared. Twenty-five patients were grouped in Group A, and 72 patients belonged to Group P. Lung cancer was the most common primary cancer in both groups. Operation time (213.0 vs. 199.2 minutes, p=0.380) and blood loss (912.5 vs. 834.4 ml, p=0.571) were not statistically significantly different between the two groups. Six patients in Group A (24%) and 6 in Group P (8.3%) developed complications (p=0.040). Patients in Group A required more days of care in intensive care units (2.36 vs. 0.19 days, p<0.001). The longer survival was seen in Group P (15.4 vs. 11.2 months) but with no significant difference. A lower surgical complication rate and fewer days of care in intensive care unit were seen in Group P. The authors would prefer a posterior approach for those with thoracic metastatic tumour.
Biomedical Journal; doi:10.1016/j.bj.2021.02.005
The purpose of this study was to evaluate the stability on dental and skeletal aspect after surgical advancement and counterclockwise rotation for the correction of the mandibular deficiency in patients with high mandibular plane angle (MPA). We analyzed the records of patients who had undergone surgical treatment for dentofacial deformities with mandibular deficiency and high MPA. Clinical and radiological data were taken 1 month before surgery (T0), 6 weeks after surgery (T1) and 1 year after surgery (T2). Cephalometric values of the MPA were recorded and compared. The cephalometric changes in the different time periods were defined as follows: A: postsurgical changes (T0–T1), B: one-year changes (T1–T2), and C: short term changes (T0–T2). Twenty-seven patients had prominent mandibular deficiency with an MPA of over 35° (high angle). The mean age of patients at surgery was 29.7 years. Seven patients had a single jaw procedure, 20 patients had bilateral sagittal split osteotomy (BSSO) combined with a Le Fort I osteotomy, and 14 patients had additional genioplasty. MPA values differed significantly between the time periods (p < 0.05) with an observed relapse of the angle. However, satisfactory clinical improvement was achieved in the dental and skeletal presentation. The overjet improvement was evident from 8.815 ± 2.085 mm (T0) to 3.426 ± 1.253 mm (T2). Counterclockwise surgical advancement of the mandible to correct mandibular deficiency in patients with a high mandibular plane angle showed an overall acceptable stability during one-year follow-up.
Biomedical Journal; doi:10.1016/j.bj.2021.02.008
COVID-19, an infectious disease caused by a novel coronavirus (SARS-CoV-2) has emerged as global pandemic. Here, we are describing the changes in microbiota of upper respiratory tract by analyzing the publically available RNA-sequencing data of SARS-CoV-2 infected ferrets. The bacterial dysbiosis due to SARS-CoV-2 is largely inversely proportional to the dysbiosis caused by influenza-A virus. The bacterial taxa, which are defined as healthy ecostate are significantly reduced during SARS-CoV-2 infection. Altogether, this preliminary study provides a new insight on the possible role of bacterial communities of upper respiratory tract in determining the immunity, susceptibility, and mortality for COVID-19.
Biomedical Journal; doi:10.1016/j.bj.2021.02.003
Copy number variants (CNVs) were the subject of extensive research in the past years. They are common features of the human genome that play an important role in evolution, contribute to population diversity, development of certain diseases, and influence host–microbiome interactions. CNVs have found application in the molecular diagnosis of many diseases and in non-invasive prenatal care, but their full potential is only emerging. CNVs are expected to have a tremendous impact on screening, diagnosis, prognosis, and monitoring of several disorders, including cancer and cardiovascular disease. Here, we comprehensively review basic definitions of the term CNV, outline mechanisms and factors involved in CNV formation, and discuss their evolutionary and pathological aspects. We suggest a need for better defined distinguishing criteria and boundaries between known types of CNVs.
Biomedical Journal; doi:10.1016/j.bj.2021.02.007
Clostridium difficile infection (CDI) is a leading cause of healthcare-associated diarrhea worldwide. In this study, risk factors associated with the development of severe-complicated and recurrent outcomes in CDI patients in different age groups, including the non-elderly, were assessed in a third-level hospital. CDI cases were detected by clinical data and polymerase-chain-reaction (PCR). Clinical, demographic, epidemiological, and microbiological risk factors for CDI were evaluated. During the study period, 248 out of 805 patients with nosocomial diarrhea were diagnosed with CDI and the majority were severe-complicated cases (87.90%). Female gender (OR 3.19, 95% CI 1.19–8.55, p = 0.02) and lymphoma (OR 3.95, 95% CI 1.03–15.13, p = 0.04) were risk factors for severe-complicated CDI. Mature adulthood (51–60 years) (OR 5.80, 95% CI 1.56–21.62, p = 0.01), previous rifampicin use (OR 7.44, 95% CI 2.10–26.44, p = 0.00), and neoplasm (solid malignant neoplasm or hematological malignancies) (OR 4.12, 95% CI 1.01–16.83, p = 0.04) were risk factors for recurrent infection. Autoimmune disorders (OR 6.62, CI 95% 1.26–34.73, p = 0.02), leukemia (OR 4.97, 95% CI 1.05–23.58, p = 0.04), lymphoma (OR 3.79, 95% CI 1.03–12.07, p = 0.04) and previous colistin treatment (OR 4.97, 95% CI 1.05–23.58, p = 0.04) were risk factors for 30-day mortality. Newly identified risk factors for recurrent CDI were rifampicin treatment and age between 51 and 60 years; colistin treatment was identified as a risk factor for 30-day mortality. Previously identified risk factors for severe-complicated CDI were confirmed, but with a major impact on non-elderly patients.