Introduction: A blood-based MCED test intended to complement, but not replace, recommended USPSTF screening can detect a cancer signal for multiple cancers simultaneously at a specificity of 99.5% (low false positive rate). In the case-control Circulating Cell-free Genome Atlas substudy 3 (CCGA3), MCED test performance across multiple cancer types was evaluated (Table 1). Sensitivity of cancer signal detection (CSD) for colorectal cancer (CRC) was 82.0%. As colon cancer (CC) and rectal cancer (RC) can be clinically distinct (CC is more common than RC, may be more likely to present with no/minimal symptoms, and can develop as interval cancers between colonoscopy or stool-based screenings), we provide a subanalysis of MCED test performance in CC and RC from CCGA3. Methods: The MCED test uses a targeted methylation assay and machine learning classifier to detect a cancer signal in cell-free DNA and predict its origin. We evaluated 197 CCGA3 participants with CRC and used pathology reports to determine tumor location (CC vs RC). Sensitivity of CSD stratified by stage and cancer type (CC vs RC) and overall survival were assessed. Results: There was no significant difference in sensitivity between CC and RC across all stages (p≥0.05) (Figure 1). There was no significant difference in sensitivity for CC between stages II, III and IV (p≥0.05) and a significant difference at stage I (P< 0.05). No significant difference in sensitivity for RC was observed across stages (Figure 1). CRC and CC not detected by the MCED test had significantly better survival than those detected (Table 1; P=0.0038 and P=0.014, respectively); however, no significant difference was found in RC (P=0.11). Conclusion: At a specificity of 99.5%, the MCED test can detect both CC and RC at earlier stages (prior to metastases). It has been shown to detect less-indolent, more aggressive disease (associated with worse survival), allowing opportunity for earlier intervention in higher-risk patients. High sensitivity for CC is especially useful as CC may be associated with fewer symptoms and more likely to present as interval cancers (potentially asymptomatic) between standard screening intervals. A study limitation is relatively low subgroup sizes. Lower sensitivity for stage I CC is explained by shallower depth of tumor invasion. In summary, high sensitivity of this MCED test allows detection of both CC and RC signals, including in those who may not be up to date with standard screening, while also detecting multiple other cancer types.Figure 1.: Sensitivity of detection and survival of CRC, CC and RC in CCGA3. Sensitivities across stages or between colon and rectal cancer were compared using Fisher’s exact test with pairwise comparisons. Rectosigmoid junction cancers were classified as rectal cancer and appendiceal adenocarcinomas were classified as colon cancer. Kaplan-Meier curves were produced and survival was compared using a log-rank test. Table 1. - Examples of Gastrointestinal Cancers Detected by MCED (All Stages) in CCGA3 Cancer Type (total n) CSD Sensitivity % (95% CI) Liver/Bile-duct (46) 93.5 (82.5 - 97.8) Esophagus (100) 85.0 (76.7 - 90.7) Pancreas (135) 83.7 (76.6 - 89.0) Colon/Rectum* (206) 82.0 (76.2 - 86.7) Anus (22) 81.8 (61.5 - 92.7) Gallbladder (17) 70.6 (46.9 - 86.7) Stomach (30) 66.7 (48.8 - 80.8) Sensitivity of cancer signal detection stratified by gastrointestinal cancers with 95% CI (Full list of cancer types detected and corresponding CSD sensitivity previously reported in Klein E et al. Ann Oncol. 2021;32(9):1167-1177.). *CRC subanalysis performed in this analysis. CI, confidence interval; CSD, cancer signal detection.
Background: Type 2 diabetic kidney disease (DKD) is one of the most common and harmful chronic complications in clinical practice, and there is no reliable and targeted treatment plan at present. As a classic complementary and alternative therapy, evidence have shown that warm acupuncture has advantages in the treatment of type 2 DKD. However, there is still a lack of high-quality and long-term follow-up randomized controlled trials of warm acupuncture in the treatment of type 2 DKD. Methods: This is a prospective randomized controlled trial to investigate the efficacy and safety of warm acupuncture in the treatment of type 2 DKD. Participants will be randomly assigned in a 1:1 ratio to either the treatment group (treated with conventional Western medicine) or the control group (treated with warm acupuncture added on the basis of the control group). Both groups will receive 12 weeks of treatment followed by 24 weeks of follow-up. Observation indicators include: 24-hour urinary protein quantification, kidney function, TCM syndrome score and adverse reactions. Finally, SPSS21.0 software will be used to analyze the data. Discussion: This study will evaluate the efficacy and safety of warm acupuncture in the treatment of DKD, and the results of this trial will provide clinical evidence for the treatment of type 2 DKD. Trial registration: The TCTR identification number is TCTR20221104004.
Immunotherapy that inhibits the interaction between programmed death ligand 1 (PD-L1), present on the surface of tumor or antigen-presenting cells, and programmed death 1 (PD-1), present on the surface of activated lymphocytes, is generating much excitement and enthusiasm. Although considerable knowledge has been accumulated on anti-PD-L1 and anti-PD-1 reagents, discovering immunotherapy-associated issues still remains a pressing task for the researchers and clinicians.
Background: Thymic carcinoid is a rare highly differentiated neuroendocrine neoplasm, which can manifest as endocrine disorders caused by ectopic adrenocorticotrophic hormone (ACTH) syndrome.Although clinical manifestations such as hypertension and hypokalemia are common manifestations in patients with ectopic ACTH syndrome, clinicians should also be aware of the mental and behavioral abnormalities that may initially appear in patients.It is extremely rare for patients with ectopic ACTH syndrome caused by thymic carcinoid to concurrently exhibit abnormal mental behavior, especially as the initial clinical manifestation of the tumor.Studies have suggested that abnormal mental behavior may be related to elevated blood cortisol levels.Case Description: A patient was admitted to hospital due to abnormal mental behavior, manifesting as hyperphasia involving gibberish and illogical language, trance, and a state of suspicion.The patient had experienced persecutory delusion.Auxiliary examination revealed elevated cortisol and ACTH.Chest computed tomography (CT) showed right anterior mediastinal tumor.After discussion, the multidisciplinary team (MDT) concluded that ectopic ACTH syndrome derived from the thymus should be considered.After excluding surgical contraindications, a thymic tumor was resected, and the postoperative pathology confirmed that it was thymic carcinoid.At 6 postoperative months, the results were as follows: cortisol at 8:00 am 196.50 nmol/L; and ACTH at 8:00 am 28.63 pg/mL.The patient's mental behavior had returned to normal, and normal communication was possible.The postoperative symptoms and signs of the patient were improved, which reiterated the presence ectopic ACTH syndrome caused by thymic carcinoid.Conclusions: Thymic carcinoid with ectopic ACTH syndrome is very rare in clinical practice, and it is easily missed and misdiagnosed.Although clinical manifestations such as hypertension and hypokalemia are common manifestations in patients with Cushing's syndrome, clinicians should be aware that patients with Cushing's syndrome may initially exhibit abnormal mental behavior.Clinically, if the patient exhibits abnormal mental behavior accompanied by symptoms such as hypokalemia, hypertension, and diabetes, blood cortisol and ACTH hormone levels should be screened without delay.If the levels are found to be significantly increased, ACTH syndrome should be highly suspected.
Tuberculosis seriously threatens human health even though medicine rapidly developed today.And our country is also under a high burden of tuberculosis.Methods of TB diagnosis are still limited, especially in active pulmonary tuberculosis diagnosis.Sputum culture is regarded as the gold standard of TB diagnosis for now, but time-consuming and low positive rate limit the diagnosis efficiency.Recent studies show that interferon-gamma release assay has a certain value in TB diagnosis and treatment efficacy evaluation.This paper aims to discuss the application value of interferon-gamma release assay in TB diagnosis and treatment efficacy based on recent literatures.
Key words:
Tuberculosis; Interferon-gamma release assay
Background: Recently, the SARS-CoV-2 variant of concern, Omicron (B.1.1.529), was identified as responsible for a novel wave of COVID-19 worldwide. Here, we compared initial clinical features of hospitalized COVID-19 patients during recent wave (Omicron Variant) with those in ancestral variant wave (2020). Methods: This is a cohort study of electronic health record (EHR) data from a signal center in the China. The clinical data of 116 cases of Omicron hospitalized in 2022 and 87 cases hospitalized in 2020 were collected. The comparisons were performed with the Mann–Whitney U test, Fisher exact test or the chi-square test, and multivariable logistic regression analysis. Results: Clinically, compared with 2020-cohort, Omicron-cohort was more inclined to cluster in younger population and had more nonsymptomatic (25.0%) and nonsevere cases, as well as suffered from comparable extrapulmonary complication. Radiologically, although the major computed tomography (CT) findings of both cohorts were ground-glass opacities (GGOs), crazy-paving pattern was relatively less seen in the Omicron-cohort. Based on multiple logistic regression analysis, Omicron-cohort was associated with a lower risk of complaining with fever, the presence of lung opacity, and increased Sequential Organ Failure Assessment (SOFA) score. Conclusion: This study provided the data of different patterns of clinic characteristics and reduced severity from infections that occurred in Omicron variant as compared with the outbreak of the epidemic in 2020 wave (ancestral variant).
H7N9 influenza is a recently emerging infection with a high mortality rate. The aim of the present study was to investigate dynamic fluctuations of peripheral blood immune cell subgroups in patients with critical H7N9 infection. Flow cytometry was used to assess the cells in whole blood samples from 9 cases. With regard to the innate immune system, in the majority of patients, the natural killer (NK) cell counts were similar to those of monocytes, which demonstrated a gradual increase in the progression period and an early increase followed by a reduction during recovery. B cells exhibited a reduction during progression and were further decreased during recovery. The CD4+T cells of all patients decreased during progression, and further decreased during recovery. By contrast, CD8+T cells increased in the majority of patients in the progression stage, and underwent an initial reduction followed by a gradual increase during recovery. However, CD8+ programmed death (PD)‑1+T cell and T helper (Th) 1 cell frequencies demonstrated a moderate increase in all patients during the progression stage, and regulatory T cell (Treg) frequencies tended to be reduced during progression and increased during recovery. Notably, this preliminary data also showed that the frequencies of B cells, Th2 cells and Th17 cells in the progression period were higher than those in the recovery period. The frequencies of monocytes, CD4+T cell, CD8+T cell, CD4+PD‑1+T cells and CD8+PD‑1+T cells in the progression period were lower than those during recovery. In conclusion, different levels of peripheral blood immune cell subgroups during the pathogenesis of H7N9 infection may be associated with elimination of the virus and immune damage.
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