Ketamine in the Management of Acute Pain: A Comprehensive Meta-Analysis.

This review was conducted to find the effectiveness and safety of ketamine in managing acute or sudden pain in the emergency scenarios. The research was carried out using databases such as PubMed, MEDLINE, Cochrane trial registries, and EMBASE from inception up to July 2022. The meta-analysis employed using the random-effects model and presented results as pooled standardised mean difference (SMD) and risk ratio (RR) alongside their 95% confidence intervals (CIs). The pooled SMD for pain assessment within 15 minutes stood at -0.72 (95% CI: -1.55 to 0.12). At 30 minutes, SMD was -0.27 (95% CI: -0.48 to -0.05), and by 45 minutes, it was -0.04 (95% CI: -0.26 to 0.18). Between the 45-minute and 60-minute mark, the SMD was -0.03 (95% CI: -0.22 to 0.17), and after the 60-minute interval, it was registered at 0.11 (95% CI: -0.10 to 0.22). Pooled RR reflecting the requirement for supplementary analgaesics was 0.96 (95% CI: 0.65-1.41). The study found that ketamine's efficacy and safety were comparable or even superior to opioids in addressing sudden pain in the emergency contexts. Key Words: Ketamine, Meta-analysis, Opioids, Acute pain, Emergency.

Sedation efficacy of different dose of remimazolam with sufentanil for nerve block in young and elderly patients: a randomized, controlled study.

PURPOSE: Anxiety and pain commonly occur during nerve block, we aimed to investigate the sedation efficacy of different doses of remimazolam with sufentanil in young and elderly patients. METHODS: In this randomized trial, patients aged 18-85 years who underwent nerve block was enrolled. All patients received sufentanil 0.08 µg/kg for analgesia. Young patients (age < 65 years) were randomized into the control group (Group C, 0.9% saline), medium-dose remimazolam (Group M, 0.06 mg/kg) and high-dose remimazolam group (Group H, 0.08 mg/kg). Elderly patients (age ≥ 65 years) were randomized into the Group C, low-dose remimazolam group (Group L, 0.04 mg/kg) and Group M. Primary outcome was the success rate of procedure sedation. Respiratory depression and hypoxia were the interested safety outcomes. RESULTS: Ninety young and 114 elderly patients were enrolled, respectively. In comparison with Groups C and M, young patients in Group H had the highest success rate of procedure sedation (80.0 vs. 73.3 vs. 43.3%, P = 0.006). Elderly patients in Groups M and L had similar success rates of procedure sedation, which were significantly higher than that in Group C (78.9 vs. 78.9 vs. 50.0%, P = 0.007). In elderly patients, the incidence of respiratory depression and hypoxia tended to be higher in Group M than those in Groups L and C (both P < 0.001). CONCLUSION: Remimazolam 0.08 mg/kg provided the best sedation efficacy in young patients while remimazolam 0.04 mg/kg with the trend of less respiratory adverse events was more optimal for elderly patients. TRIAL REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=122016 .

LncRNAs as biomarkers for predicting radioresistance and survival in cancer: a meta-analysis.

The effect of long noncoding RNAs (lncRNAs) on the radiotherapy response has been gradually revealed. This systematic review and meta-analysis aimed to evaluate the association between the function and underlying mechanism of lncRNAs in regulating the radiosensitivity and radioresistance of different tumors. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to estimate the effect of lncRNAs on cancer patient prognosis, including overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS) and progression-free survival (PFS). Collectively, 23 lncRNAs in 11 cancer types were enrolled. Of them, 13 lncRNAs were downregulated and related to radiosensitivity, 11 lncRNAs were upregulated and related to radioresistance, and 3 lncRNAs were upregulated and related to radiosensitivity in cancers. Furthermore, 17 microRNAs and 20 pathways were targeted by different lncRNAs and contributed to the cancer radiotherapy response in this meta-analysis. The individual pooled HRs (95% CIs) of downregulated radiation-resistant and upregulated radiation-resistant lncRNAs for OS were 0.49 (0.40-0.60) and 1.88 (1.26-2.79), respectively. Our results showed that lncRNAs could modulate tumor radioresistance or sensitivity by affecting radiation-related signaling pathways and serve as potential biomarkers to predict radiotherapy response.

Response to COVID-19 in the Central African Republic: Coping Strategies Combined With China's Experience.

Objectives: The weak health system, domestic political unrest, poverty, and many other factors in the Central African Republic (CAR) have left the country underprepared for the COVID-19 pandemic, resulting in a greater health threat to the entire country. Rapid measures must therefore be taken to prevent the further spread of COVID-19. Methods: This work encompassed a review of relevant literature. We aim to analyze how far Chinese COVID measures can be transferred to the context of the CAR. Results: We argue that the measure that the CAR can learn from China's success is the involvement of community workers and that greater investment in this model may be the optimal solution. Help from the international community is urgently needed. Conclusion: The CAR can benefit from China's successful experience in fighting the epidemic, but the disparity in the combined power of the two countries does not allow for simple replication of China's strategy.

Association between age at initial diagnosis and post-metastasis mortality among women with recurrent metastatic breast cancer in China.

BACKGROUND: Little is known about whether age at initial diagnosis influences the prognosis of recurrent metastatic breast cancer (rMBC). Here, we analyzed the association between age at initial diagnosis and rMBC mortality in China. METHODS: A total of 1636 women diagnosed with rMBC between 1989 and 2020 at West China Hospital, Sichuan University were included in this study. The age at initial diagnosis was categorized as young (≤ 40 years), middle-aged (41-64 years) and elderly (≥ 65 years). Post-metastasis mortality was the primary outcome and its associated factors were analyzed by Cox proportional hazards models. RESULTS: During a median follow-up of 5.2 years after initial diagnosis of breast cancer, 620 deaths were identified. Compared with middle-aged patients, elderly patients had a 70% increased risk of post-metastasis mortality (95%CI, 1.24-2.33) after adjusting for demographics, tumor characteristics and treatment modes. Similarly, elderly patients were associated with a 75% increased risk of post-metastasis mortality (95%CI, 1.19-2.59) compared with young patients. Subgroup analyses also showed similar trends. CONCLUSION: Our findings suggest that in breast cancer, elderly patients at initial diagnosis face a higher risk of post-metastasis mortality.

Impact of time to initiation of postoperative radiotherapy after neoadjuvant chemotherapy on the prognosis of breast cancer: A retrospective cohort study in China.

The optimal time to the initiation of postoperative radiotherapy (TTR) in breast cancer patients after neoadjuvant chemotherapy (NAC) and surgery is unclear. We explored the association between TTR and outcomes among breast cancer females to determine the optimal timing for radiotherapy. We included 1022 women with breast cancer who underwent NAC and surgery between 1997 and 2019. Patients were categorized into three groups based on the TTR: <8 weeks, 8 to 16 weeks and >16 weeks. We used Cox proportional hazards models and analyzed the hazard ratios (HRs) for breast cancer-specific mortality (BCSM) and all-cause mortality (ACM). The median TTR for the cohort was 97 days. Compared to patients with TTRs of 8 to 16 weeks, those with TTRs <8 weeks or >16 weeks had an increased risk of BCSM (HR, 2.59; 95% confidence interval [CI], 1.26-5.36 and HR, 2.01; 95% CI, 1.24-3.28, respectively) and ACM (HR, 2.32; 95% CI, 1.17-4.56 and HR, 1.92; 95% CI, 1.24-2.98, respectively) after adjusting for the confounders. Furthermore, at TTR of >16 weeks, each additional week of TTR was associated with a 3% increase in BCSM risk and 2% increase in ACM risk. Our findings suggest that patients who have undergone NAC and surgery show lower BCSM and ACM risks at TTR of 8 to 16 weeks compared to <8 weeks or >16 weeks.

Surgery of the primary tumor improves survival in women with stage IV breast cancer in Southwest China: A retrospective analysis.

The International Consensus Guidelines for advanced breast cancer (ABC) considers that the surgery of the primary tumor for stage IV breast cancer patients does not usually improve the survival. However, studies have showed that resection of the primary tumor may benefit these patients. The correlation between surgery and survival remains unclear.The impact of surgery and other clinical factors on overall survival (OS) of stage IV patients is investigated in West China Hospital. Female patients diagnosed with stage IV breast cancer between 1999 and 2014 were included (N = 223). Univariate and multivariate analysis assessed the association between surgery and OS.One hundred seventy-seven (79.4%) underwent surgery for the primary tumor, and 46 (20.6%) had no surgery. No significant differences were observed in age at diagnosis, T-stage, N-stage, histological grade, molecular subtype, hormone receptor (HR), and number of metastatic sites between 2 groups. Patients in the surgery group had dramatically longer OS (45.6 vs 21.3 months, log-rank P < .001). In univariate analysis, survival was associated with surgical treatment, residence, tumor size, lymph node, HR status, hormonal therapy, and radiotherapy. In multivariate analysis, surgery was an independent prognostic factor for OS [hazard ratio (HR), 0.569; 95% confidence interval (CI) 0.329-0.984, P = .044]. Additional independent prognostic factors were hormonal therapy (HR, 0.490; 95% CI 0.300-0.800) and radiotherapy (HR, 0.490; 95% CI 0.293-0.819). In addition, a favorable impact of surgery was observed by subgroup analysis.Our study showed that surgery of the primary breast tumor has a positive impact on OS in with stage IV breast cancer patients.

ADAMTS6 suppresses tumor progression via the ERK signaling pathway and serves as a prognostic marker in human breast cancer.

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is involved in tumor development. However, how ADAMTS6 influences cancer remains unknown. We investigated the biological function and clinical implications of ADAMTs6 in breast cancer (BC). Its functional significance in BC cell lines was confirmed by ADAMTs6 overexpression or downregulation both in vitro and in vivo studies. Enhanced ADAMTS6 expression suppressed cell migration, invasion, and tumorigenesis, whereas knockdown promoted these characteristics. The extracellular signal-regulated kinase (ERK) pathway was partially involved in ADAMTS6-mediated inhibition of BC development, and miR-221-3p was identified as a predicted target for ADAMTS6. Results from the luciferase assay confirmed that miR-221-3p directly inhibited ADAMTS6 expression by binding its 3'-untranslated region. In addition, immunohistochemistry data from specimens from 182 BC patients showed that high ADAMTS6 expression was significantly correlated with favorable disease-free survival (DFS, p = 0.045). Subgroup analysis of patients with ER positive, PR positive or HER-2 negative tumors revealed that high ADAMTS6 expression more strongly extended DFS compared to low expression (p = 0.004, p = 0.009, p = 0.017). Multivariate analyses confirmed that ADAMTS6 expression was an independent risk factor for DFS (p = 0.011). Together, these data demonstrate that ADAMTS6 inhibits tumor development by regulating the ERK pathway via binding of miR-221-3p. Thus, its expression may be a potential prognostic biomarker for BC.

IκB kinase α functions as a tumor suppressor in epithelial-derived tumors through an NF-κB-independent pathway (Review).

Recent studies have shown that IκB kinase α (IKKα) plays an important role in human skin cancer and acts as a major regulator for keratinocyte terminal differentiation and proliferation. IKKα deficiency or mutation is associated with human tumor development; thus, overexpression of IKKα could prevent tumor progression. However, findings suggest that IKKα is equally essential for many other epithelial-derived tumors. In the present study, we discussed the role of IKKα as a tumor suppressor in IKKα-mediated epithelial­derived tumors and its activation pathway, which is different from the traditional NF-κB pathway. The present study provides theoretical basis for understanding the molecular mechanisms involved in IKKα-related tumors.

Downregulation of MDC1 and 53BP1 by short hairpin RNA enhances radiosensitivity in laryngeal carcinoma cells.

DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) are among the most cytotoxic types of DNA damage. The DNA damage response (DDR) may be a reason for the cancer cell resistance to radiotherapy using IR. Identified as critical upstream mediators of the phosphorylation of ataxia telangiectasia-mutated (ATM) pathway, mediator of DNA damage checkpoint 1 (MDC1) and p53-binding proteins 1 (53BP1) may affect the radiosensitivity of tumor cells. In the present study, we generated two HEP-2 cell lines with a stable knockdown of MDC1 or 53BP1 with short hairpin RNA (shRNA), respectively, and investigated the effect of MDC1 and 53BP1 on cell radiosensitivity, cell cycle distribution and the formation of cell foci. Downregulation of the two proteins reduced the number of clonogenic cells that treated with IR. Accumulation of G2/M phase cells was detected after the MDC1 and 53BP1 downregulation. These results indicated that the expression of MDC1 or 53BP1 limited tumor cell sensitivity to radiotherapy and may play an important role in the DNA repair progression. Furthermore, the MDC1 foci was identified and presented in the 53BP1-inhibited cells. By contrast, the 53BP1 foci was absent from the MDC1-inhibited cells. The results confirmed that the recruitment of 53BP1 into the foci occurred in an MDC1-dependent manner.

Recurrent desmoid tumor of the mediastinum: A case report.

Desmoid tumors (DTs) are rare, benign soft-tissue tumors that have the potential for local invasion, but not for metastasis. The tumors are commonly characterized by a palpable mass, but present a variable and unpredictable clinical course. The current study presents the case of a giant mediastinal DT exhibiting lung involvement. A 50-year-old female was referred to the West China Hospital (Chengdu, Sichuan, China) due to a recurrent DT that was identified one year following radical surgery. The patient subsequently received radiation therapy. The DT arose from the mediastinum, unlike the usual presentation, and recurrence presented as extensive invasion into the lung tissue, almost being misdiagnosed as lung cancer with brain metastasis. Tumor recurrence was diagnosed through contrast-enhanced computed tomography and histological examination of the tumor. A routine follow-up revealed no further tumor progression at 9 months post-admission. Taking into account the unpredictable treatment complications, recurrent DTs can be managed simply and efficiently. A 'wait-and-see' policy could be a viable therapeutic option for this disease.