Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed with dermatoscopy. If a melanoma is suspected, a histopathological examination is always required. Sequential digital dermatoscopy and full body photography can be used in high-risk patients to improve the detection of early melanoma. Where available, confocal reflectance microscopy can also improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the American Joint Committee on Cancer classification. Thin melanomas up to 0.8 mm tumor thickness do not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC onwards whole-body examinations with computed tomography (CT) or positron emission tomography CT (PET-CT) in combination with brain magnetic resonance imaging are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to define the frequency and extent of examinations. A stage-based follow-up scheme is proposed which, according to the experience of the guideline group, covers the optimal requirements, but further studies may be considered. This guideline is valid until the end of 2024. 

http://www.ejcancer.com/article/S0959804922001526/pdf

European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022.

Background: The albumin levels may potentially be used as a prognostic biomarker in patients with cancertreated with immune checkpoint inhibitors (ICIs) due to its close relationship with nutritional and inflammatory status. However, the available data is limited with heterogeneous patient cohorts, sample sizes and variable cut-offs. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between survival outcomes and albumin levels in patients treated with ICIs. Methods: We conducted a systematic review using the PubMed, Web of Science, and Embase databases to filter the published studies up to 1 June 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model due to the high degree of heterogeneity. The primary outcome measure was hazard ratio (HR) with 95% confidence intervals (CI). The study protocol was registered with the PROSPERO registry (Registration Number: CRD42022337746). Results: Thirty-six studies encompassing 8406 cancer patients with advanced disease were included in the meta-analyses. Almost half of the studies were conducted in NSCLC cohorts (n = 15), and 3.5 gr/dL was the most frequently used albumin cut-off in the included studies (n = 20). Patients with lower albumin levels had a significantly increased risk of death (HR: 1.65, 95% CI: 1.52–1.80, p < 0.0001) than patients with higher albumin levels. Subgroup analyses for study location, sample size, tumor type and albumin cut-off were demonstrated consistent results. Furthermore, in the subgroup analysis of eight studies using albumin levels as a continuous prognostic factor, every 1 gr/dL decrease in albumin levels was associated with significantly increased risk of death by a factor of 10% (HR: 1.10, 95% CI: 1.05–1.16, p = 0.0002). Similar to analyses with overall survival, the patients with lower albumin levels had an increased risk of progression or death compared to patients with higher albumin levels (HR: 1.76, 95% CI: 1.40–2.21, p < 0.001). Conclusion: The available evidence demonstrates that albumin levels may be a prognostic biomarker in advanced cancer patients treated with ICIs. Further research is needed to delineate the role of albumin levels in patients treated with ICIs in the adjuvant setting, as well as the possible benefit of therapeutic approaches to improve hypoalbuminemia.

/pdf/the-association-between-albumin-levels-and-survival-in-2n9gens7.pdf

The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) about 22 nucleotides in size, which play an important role in gene regulation and are involved in almost all major cellular physiological processes. In recent years, the abnormal expression of miRNAs has been shown to be associated with human diseases including cancer. In the past ten years, the link between miRNAs and various cancers has been extensively studied, and the abnormal expression of miRNAs has been reported in various malignant tumors, such as lung cancer, gastric cancer, colorectal cancer, liver cancer, breast cancer, and prostate cancer. Due to the high malignancy grade of these cancers, it is more necessary to develop the related diagnostic and prognostic methods. According to the study of miRNAs, many potential cancer biomarkers have been proposed for the diagnosis and prognosis of diseases, especially cancer, thus providing a new theoretical basis and perspective for cancer screening. The use of miRNAs as biomarkers for diagnosis or prognosis of cancer has the advantages of being less invasive to patients, with better accuracy and lower price. In view of the important clinical significance of miRNAs in human cancer research, this article reviewed the research status of miRNAs in the above-mentioned cancers in 2021, especially in terms of diagnosis and prognosis, and provided some new perspectives and theoretical basis for the diagnosis and treatment of cancers.

https://www.mdpi.com/1422-0067/23/19/11389/pdf?version=1665452714

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021

Melanoma is one of the seven most common cancers in the United States, and its incidence is still increasing. Since 2011, developments in targeted therapies and immunotherapies have been essential for significantly improving overall survival rates. Prior to the advent of targeted and immunotherapies, metastatic melanoma was considered a death sentence, with less than 5% of patients surviving more than 5 years. With the implementation of immunotherapies, approximately half of patients with metastatic melanoma now survive more than 5 years. Unfortunately, this also means that half of the patients with melanoma do not respond to current therapies and live less than 5 years after diagnosis. One major factor that contributes to lower response in this population is acquired or primary resistance to immunotherapies via tumor immune evasion. To improve the overall survival of melanoma patients new treatment strategies must be designed to minimize the risk of acquired resistance and overcome existing primary resistance. In recent years, many advances have been made in identifying and understanding the pathways that contribute to tumor immune evasion throughout the course of immunotherapy treatment. In addition, results from clinical trials focusing on treating patients with immunotherapy-resistant melanoma have reported some initial findings. In this review, we summarize important mechanisms that drive resistance to immunotherapies in patients with cutaneous melanoma. We have focused on tumor intrinsic characteristics of resistance, altered immune function, and systemic factors that contribute to immunotherapy resistance in melanoma. Exploring these pathways will hopefully yield novel strategies to prevent acquired resistance and overcome existing resistance to immunotherapy treatment in patients with cutaneous melanoma.

Mechanisms of Immunotherapy Resistance in Cutaneous Melanoma: Recognizing a Shapeshifter

Purpose Immunotherapy is regarded as the most promising treatment for cancer. However, immune checkpoint inhibitors (ICIs) are not effective for all patients. Herein, we conducted a systematic review and meta-analysis to explore whether tumor mutational burden (TMB) can be used as a potential prognostic biomarker for cancer patients treated with ICIs. Methods We systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to December 28, 2020. All cohort studies and clinical trials that reported hazard ratios (HRs) for overall (OS) and progression-free survival (PFS), as well as the corresponding 95% confidence intervals (CIs) of high and low TMB patients, were included. All statistical analyses were performed using the R software. Results Pooled results from a total of 32 studies with 6,131 participants showed significantly increased OS (HR: 0.61, 95% CI: 0.53-0.71; P <0.01) and PFS (HR: 0.51, 95% CI: 0.44-0.60; P <0.01) for the high TMB group receiving ICIs as compared to the low TMB group. Particularly, results were found to be more significant in studies with larger sample sizes (≥30), Western patients, higher TMB cutoff values (≥20 mut/Mb), anti-PD-1 therapy, and when the sample source was tissue and tumor type was either melanoma, small cell lung cancer, or gastric cancer. Conclusion TMB is a promising independent prognostic biomarker for cancer patients receiving ICIs, which could provide a new potential therapeutic strategy for high TMB patients who have failed traditional therapy. Furthermore, consistency in the key aspects of TMB assessment is expected in the future. Systematic Review Registration [https://www.crd.york.ac.uk/PROSPERO], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42021229016.

/pdf/prognostic-role-of-tumor-mutational-burden-in-cancer-3pwduu1det.pdf

Prognostic Role of Tumor Mutational Burden in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced a worldwide pandemic. The main clinical manifestations of COVID-19 patients have been fever, cough, dyspnea, and other respiratory symptoms. However, some patients’ initial symptoms have been nausea, vomiting, diarrhea and other gastrointestinal symptoms, and SARS-CoV-2 RNA could be found in their stool samples. Studies have shown that the gastrointestinal tract highly-expressed angiotensin-converting enzyme 2 is used by SARS-CoV-2 to enter cells. Therefore, exploring the damage caused by SARS-CoV-2 to the gastrointestinal tract and whether it could replicate in the gastrointestinal tract and transmit through fecal-oral route has significance for the diagnosis, treatment and prevention of COVID-19. We combined the current clinical data about COVID-19 patients with gastrointestinal symptoms as well as its pathogenic mechanism and prevention methods herein to review the relationship between the disease and gastrointestinal symptoms.

/pdf/progress-on-gastrointestinal-symptoms-treatment-and-2iwcx8i3c2.pdf

Progress on Gastrointestinal Symptoms, Treatment and Protection in COVID-19 Patients

Approximately half of the world's gastric cancer cases and deaths occur in China. In addition, the incidence and mortality rates of gastric cancer in Gansu province in China are much higher than the average nationwide levels. The present study investigated microRNA (miRNA/miR) profiles in early gastric cancer (EGC) without specific symptoms. miRNA expression levels in five pairs of EGC tissues and adjacent non-cancerous mucosa tissues of patients from Gansu province in China were analyzed using a miRNA microarray. A total of 47 differentially expressed miRNAs (DEMs) were identified. Subsequently, mRNA expression profiles of three pairs of cancer tissues and adjacent non-cancerous tissues from 3 Asian patients with stage I or stage II gastric cancer (stage I/II; American Joint Committee on Cancer classification, Eighth Edition) were obtained from The Cancer Genome Atlas database, and differentially expressed genes (DEGs) were identified. The target genes of DEMs were filtered from the DEGs using the miRDB database and a miRNA-gene network was constructed. The functions of DEMs were evaluated using the tool for annotations of human miRNAs database, and via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and Gene Set Enrichment Analysis of the target genes. Finally, survival analyses of DEMs, which were in the miRNA-gene network, was performed. The results suggested that a number of miRNAs, including hsa-let-7a-5p, hsa-miR-27a-3p, hsa-miR-126-5p and hsa-miR-424-5p, may serve critical roles in EGC. The present study could provide a basis for the identification of EGC screening biomarkers. Furthermore, the present study may provide a basis for the exploration of the cause of the high incidence of gastric cancer in Gansu province from the perspective of miRNAs.

/pdf/microrna-profiles-in-five-pairs-of-early-gastric-cancer-3tvwmfx08y.pdf

MicroRNA profiles in five pairs of early gastric cancer tissues and adjacent non-cancerous tissues.

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Prognostic Role of Tumor Mutational Burden in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Progress on Gastrointestinal Symptoms, Treatment and Protection in COVID-19 Patients

MicroRNA profiles in five pairs of early gastric cancer tissues and adjacent non-cancerous tissues.