Hengjia Tu

To the Editor The study by Tsukita et al presents valuable insights. However, there were several critical limitations that warrant discussion, along with

To the Editor We have some concerns about a recent study about phosphorylated α-synuclein as a diagnostic biomarker for synucleinopathies.First, the use

To the Editor Although a recent study about the therapeutic potential of aspirin in managing MASLD without cirrhosis provided valuable insights, we have

Patients with breast cancer undergoing chemotherapy are susceptible to prolonged and severe neutropenia. Multiple biosimilars of long-acting granulocyte colony-stimulating factors (LA-G-CSFs) have been newly developed to prevent this disease. Nonetheless, which LA-G-CSF regimen has the optimal balance of efficacy and safety remains controversial. Moreover, there is a lack of evidence supporting clinical decisions on LA-G-CSF dose escalation in poor conditions. PubMed, Embase, Cochrane Library, Web of Science, and several Chinese databases were searched (December 2022) to collect randomized controlled trials (RCTs) about LA-G-CSFs preventing chemotherapy-induced neutropenia in breast cancer patients. No restrictions were imposed on language. A Bayesian network meta-analysis was performed. We assessed the incidence of severe neutropenia (SN) and febrile neutropenia (FN), the duration of SN (DSN), and the absolute neutrophil account recovery time (ANCrt) for efficacy, while the incidence of severe adverse events (SAE) was assessed for safety. The study was registered in PROSPERO (CRD42022361606). A total of 33 RCTs were included. Our network meta-analysis demonstrated that lipegfilgrastim 6 mg and eflapegrastim 13.2 mg outperformed other LA-G-CSFs with high efficacy rates and few safety concerns (SUCRA of lipegfilgrastim 6 mg: ANC rt 95.2%, FN 97.4%; eflapegrastim 13.2 mg: FN 87%, SN 89.3%). Additionally, 3.6 mg, 4.5 mg, 6 mg, and 13.2 mg dosages all performed significantly better than 1.8 mg in reducing the duration of SN (3.6 mg: DSN, SMD −0.68 [−1.13, −0.22; moderate]; 4.5 mg: −0.87 [−1.57, −0.17; low]; 6 mg: −0.89 [−1.49, −0.29; moderate]; 13.2 mg: −1.02 [1.63, −0.41; high]). Increasing the dosage from the guideline-recommended 6 mg to 13.2 mg can reduce both the duration and incidence of SN (SMD −0.13 [−0.24 to −0.03], RR 0.65 [0.43 to 0.96], respectively), with no significant difference in SAE. For patients with breast cancer, lipegfilgrastim 6 mg and eflapegrastim 13.2 mg might be the most effective regimen among LA-G-CSFs. Higher doses of LA-G-CSF may enhance efficacy without causing additional SAEs.

Background: Exploring the cancer risks of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARDs) can help detect, evaluate, and treat malignancies at an early stage for these patients. Thus, a comprehensive analysis was conducted to determine the cancer risk of RA patients using different types of DMARDs and analyze their relationship with tumor mutational burdens (TMBs) reflecting immunogenicity.Methods: A thorough search of PubMed, EMBASE, Web of Science, and Medline was conducted up to 20 August 2022. Standardized incidence ratios (SIRs) were constructed with a random-effect model to determine risks for different types of malignancies in comparison with the general population. We also analyzed the correlation between SIRs and TMBs using linear regression (LR).Results: From a total of 22 studies, data on 371,311 RA patients receiving different types of DMARDs, 36 kinds of malignancies, and four regions were available. Overall cancer risks were 1.15 (SIR 1.15; 1.09–1.22; p < 0.001) and 0.91 (SIR 0.91; 0.72–1.14; p = 0.402) in RA populations using conventional synthetic DMARDs (csDMARDs) and biologic DMARDs (bDMARDs), respectively. RA patients taking csDMARDs displayed a 1.77-fold lung cancer risk (SIR 1.77; 1.50–2.09; p < 0.001), a 2.15-fold lymphoma risk (SIR 2.15; 1.78–2.59; p < 0.001), and a 1.72-fold melanoma risk (SIR 1.72; 1.26–2.36; p = 0.001). Correlation coefficients between TMBs and SIRs were 0.22 and 0.29 from those taking csDMARDs and bDMARDs, respectively.Conclusion: We demonstrated a cancer risk spectrum of RA populations using DMARDs. Additionally, TMBs were not associated with elevated cancer risks in RA patients following immunosuppressive therapy, which confirmed that iatrogenic immunosuppression might not increase cancer risks in patients with RA.Interpretation: Changes were similar in cancer risk after different immunosuppressive treatments, and there was a lack of correlation between SIRs and TMBs. These suggest that we should look for causes of increased risks from the RA disease itself, rather than using different types of DMARDs.

Background: One of the most frequent malignancies of the digestive system is stomach adenocarcinoma (STAD). Recent research has demonstrated how cuproptosis (copper-dependent cell death) differs from other cell death mechanisms that were previously understood. Cuproptosis regulation in tumor cells could be a brand-new treatment strategy. Our goal was to create a cuproptosis-related lncRNA signature. Additionally, in order to evaluate the possible immunotherapeutic advantages and drug sensitivity, we attempted to study the association between these lncRNAs and the tumor immune microenvironment of STAD tumors. Methods: The TCGA database was accessed to download the RNA sequencing data, genetic mutations, and clinical profiles for TCGA STAD. To locate lncRNAs related to cuproptosis and build risk-prognosis models, three techniques were used: co-expression network analysis, Cox-regression techniques, and LASSO techniques. Additionally, an integrated methodology was used to validate the models’ predictive capabilities. Then, using GO and KEGG analysis, we discovered the variations in biological functions between each group. The link between the risk score and various medications for STAD treatment was estimated using the tumor mutational load (TMB) and tumor immune dysfunction and rejection (TIDE) scores. Result: We gathered 22 genes linked to cuproptosis based on the prior literature. Six lncRNAs related to cuproptosis were used to create a prognostic marker (AC016394.2, AC023511.1, AC147067.2, AL590705.3, HAGLR, and LINC01094). After that, the patients were split into high-risk and low-risk groups. A statistically significant difference in overall survival between the two groups was visible in the survival curves. The risk score was demonstrated to be an independent factor affecting the prognosis by both univariate and multivariate Cox regression analysis. Different risk scores were substantially related to the various immunological states of STAD patients, as further evidenced by immune cell infiltration and ssGSEA analysis. The two groups had differing burdens of tumor mutations. In addition, immunotherapy was more effective for STAD patients in the high-risk group than in the low-risk group, and risk scores for STAD were substantially connected with medication sensitivity. Conclusions: We discovered a marker for six cuproptosis-associated lncRNAs linked to STAD as prognostic predictors, which may be useful biomarkers for risk stratification, evaluation of possible immunotherapy, and assessment of treatment sensitivity for STAD.

Previous studies have reached different conclusions regarding the effect of vitamin D supplementation and the incidence of fractures in the elderly. As more and more high-quality studies are published, an updated Meta-analysis is needed. We searched the PubMed, Cochrane Library, Embase, and Web of Science databases (from creation date to September 10, 2022) using the keywords vitamin D and fracture. We also searched at https://clinicaltrials.gov/ to search for unpublished clinical studies. Randomized clinical trials comparing vitamin D supplements with a placebo or no treatment for fracture incidence in community-dwelling adults older than 50 years was included. Hip fracture was defined as the primary outcome. Secondary outcomes were total fracture, vertebral fracture, and nonvertebral fracture. The protocol is available in PROSPERO (ID: CRD42022360619). A total of 15 randomized trials involving 53291 participants fulfilled the inclusion criteria. Supplementing with vitamin D had no significant effect on reducing the incidence of hip fracture (RR = 1.18, [95% CI, 0.99 − 0.41]), total fracture (RR = 1.01, [95% CI, 0.92–1.11]), vertebral fracture (RR = 0.97, [95% CI, 0.54–1.77]), or non-vertebral fracture (RR = 1.04, [95% CI, 0.97–1.12]). On the contrary, taking high doses of vitamin D once a year may increase the incidence of hip fractures (OR = 1.44, [95% CI, 1.03–2.02]). Besides, being in a low-light environment increased the incidence of hip fractures (OR = 1.25, [95% CI, 1.01–1.55]). There were no significant findings from subgroup analyses based on sex, fracture history, calcium consumption, baseline 25-hydroxyvitamin levels, or trial durations. Vitamin D use in community-dwelling older adults does not reduce the risk of fracture. High doses of vitamin D at one-year intervals may even increase the risk of fracture. In addition, older adults in low sunlight exposure areas had a higher risk of fracture regardless of vitamin D use.

MEN2B is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and without hyperparathyroidism, over 95% of which patients have mutations in codon M918T (at exon 16). Early diagnosis of MEN2B has important implications for the treatment and prognosis of the disease, as thyroidectomy has the potential to cure patients. In this case, the patient was a 31-year-old man presented with low back pain as the initial and primary symptom. In addition to MTC and PHEO, the examination showed that he also had hyperparathyroidism, which led to the misjudgment of MEN typing at first. We finally diagnosed this patient as MEN2B based on the results of genetic testing. After the operation and treatment, the patient recovered well. Early diagnosis is the key to the MEN2B treatment. Whether MEN2A and MEN2B can be distinguished by the presence of parathyroidism still needs more researches to verify. RET gene detection plays an important role in the diagnosis and prognosis of MEN2B and surgery is the first choice for the treatment of MEN2B.