Long-term outcomes of chemoradiotherapy versus radiotherapy alone in patients with intermediate-risk nasopharyngeal carcinoma: a population-based analysis.

PURPOSE: To investigate the efficacy of chemotherapy among intermediate-risk (stage II/T3N0) nasopharyngeal carcinoma (NPC) patients receiving radiotherapy (RT). METHODS: We identified stage II/T3N0 NPC patients who received radiotherapy with or without chemotherapy from the Surveillance, Epidemiology and End Results database (2004-2019). Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method with log-rank test and Cox proportional hazards models to evaluate the efficacy of chemotherapy. Subgroup analysis was also conducted based on the baseline characteristics. Propensity score matching (PSM) was performed to balance the intergroup covariates. RESULTS: A total of 1623 patients were enrolled in the study, 1444 received chemoradiotherapy (CRT) and 179 received RT alone. CRT, compared to RT alone, was independently associated with a better OS (HR 0.57, 95% CI 0.45-0.71) and CSS (HR 0.55, 95% CI 0.39-0.79). After PSM, similar results were obtained, and CRT was superior to RT alone in terms of OS (HR 0.60, 95% CI 0.39-0.92) and CSS (HR 0.60, 95% CI 0.40-0.91). Subgroup analysis revealed that OS benefits from CRT were mainly observed in T0-2N1(HR 0.51, 95% CI 0.38-0.70) and T3N0 (HR 0.64, 95% CI 0.42-0.98) rather than T2N0 (HR 1.00, 95% CI 0.51-1.94). Interestingly, after PSM, OS benefits were still seen in T0-2N1 (HR 0.44, 95% CI 0.24-0.82), while not seen in T2N0 (HR 1.83, 95% CI 0.56-5.97) and T3N0 (HR 0.56, 95% CI 0.28-1.12). CONCLUSION: For T0-2N1 NPC patients, CRT was superior to RT alone with better survival, whereas, for T2-3N0 patients, CRT was comparable to RT alone. Prospective large studies should be encouraged to verify the results.

Exosomes overexpressing miR-34c inhibit malignant behavior and reverse the radioresistance of nasopharyngeal carcinoma.

BACKGROUND: Malignant behavior and radioresistance, which severely limits the efficacy of radiation therapy (RT) in nasopharyngeal carcinoma (NPC), are associated with tumor progression and poor prognosis. Mesenchymal stem cells (MSCs) are used as a therapeutic tool in a variety of tumors. The aim of this study was to reveal the effect of tumor suppressor microRNA-34c-5p (miR-34c) on NPC development and radioresistance, as well as to confirm that exosomes derived from MSCs overexpressing miR-34c restore the sensitivity to radiotherapy in NPCs. METHODS: Potentially active microRNAs were screened by cell sequencing, Gene Expression Omnibus (GEO) database analysis, and analysis of clinical serum samples from 70 patients. The expression of genes and proteins was detected by Western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemistry (IHC). Proliferation, apoptosis, invasion, migration and radioresistance of NPC were detected. Luciferase reporter assays were used to verify the interactions of microRNAs with their downstream targets. MSCs exosomes were isolated by ultrafiltration and verified by electron microscopy and nanoparticle tracking technology. RESULTS: The expression of miR-34c was associated with the occurrence and radiation resistance of NPC. In vitro and in vivo experiments indicated that overexpression of miR-34c inhibit malignant behavior such as invasion, migration, proliferation and epithelial-mesenchymal transition (EMT) in NPCs by targeting ß-Catenin. In addition, we found alleviated radioresistance upon miR-34c overexpression or ß-catenin knockdown in NPCs. Exosomes derived from miR-34c-transfected MSCs attenuated NPC invasion, migration, proliferation and EMT. Moreover, miR-34c-overexpressing exosomes drastically increased radiation-induced apoptosis in NPC cells. CONCLUSION: miR-34c is a tumor suppressor miR in NPC, which inhibits malignant behavior as well as radioresistance of tumor. Therefore, exogenous delivery of miR-34c to NPCs via MSC exosomes inhibits tumor progression and increases the efficiency of RT. Combination IR with miR-34c-overexpressing exosomes may be effective treatment for radioresistant NPCs.

Cofilin-2 Acts as a Marker for Predicting Radiotherapy Response and Is a Potential Therapeutic Target in Nasopharyngeal Carcinoma.

BACKGROUND The purpose of this study was to determine whether cofilin-2 could serve as a protein marker for predicting radiotherapy response and as a potential therapeutic target in nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS Cofilin-2 protein levels in serum and tissue samples from patients with NPC were assessed by sandwich ELISA and IHC. In vitro, cofilin-2 levels in CNE-2R cells were significantly higher than those of CNE-2 cells. Meanwhile, CNE-2R cells were silenced for cofilin-2 to obtain a stable cofilin-2-RNAi-LV3 cell line. Then, cell proliferation, radiosensitivity, invasion and migration abilities, cell cycle, and apoptosis were evaluated by Cell Counting Kit 8 assay (CCK-8), flow cytometry (FCM), clone formation assay, and in vitro. RESULTS The secreted levels of the cofilin-2 protein in radioresistant NPC patients were significantly higher than those of radiosensitive cases. After cofilin-2 knockdown in nasopharyngeal carcinoma CNE-2R cells, proliferation was decreased, while apoptosis and radiosensitivity were enhanced; cell cycle distribution was altered, and the transplanted tumors in nude mice grew significantly less. CONCLUSIONS Overall, our findings suggest that cofilin-2 acts as a marker for predicting radiotherapy response and is a potential therapeutic target in nasopharyngeal carcinoma.

Age-based prediction of incidence of complications during inpatient stroke rehabilitation: a retrospective longitudinal cohort study.

BACKGROUND: Stroke complications can occur not only in the acute ward but also during the subsequent rehabilitation period. However, existing studies have not adequately addressed the incidence of various complications among stroke in patients undergoing rehabilitation using a longitudinal method. We aimed to investigate the longitudinal impact of age on complication rates in patients undergoing inpatient stroke rehabilitation at different disease stages. METHODS: Five hundred and sixty-eight first-time stroke patients transferred to the rehabilitation ward between July 2002 and June 2012 were included in the study. Patients were stratified into age groups for comparison: <65 years (young), 65 years to <75 years (younger old), and ≥75 years (older old). In total, 30 different complication types were recorded for analysis. RESULTS: Constipation, shoulder pain, symptomatic urinary tract infection (UTI), and fever were common complications during initial stay in the rehabilitation ward, and incidence was >10% in all three age groups. The frequency of incidence of upper gastrointestinal bleeding (UGIB) was higher in the younger old (17.9%) and older old (20.6%) groups than in the young group (4.1%) during initial stay in the rehabilitation ward (p < 0.001). The incidence of UGIB was higher in the younger old (8.04%) and older old (8.33%) groups than in the young group (0.19%) during subsequent stay in the rehabilitation ward (p = 0.011). The incidence of symptomatic UTI was higher in the younger old (21.0%) and older old (20.0%) groups than in the young group (11.5%) during initial stay in the rehabilitation ward (p = 0.019). The incidence of symptomatic UTI was higher in the older old group (29.17%) than in the younger old (9.21%) and young (3.14%) groups during subsequent stay in the rehabilitation ward (p < 0.001). CONCLUSIONS: Age does not affect every complication type. UGIB and symptomatic UTI occurred more frequently in stroke patients aged ≥65 years during their stay in the rehabilitation ward.

Establishing subdivisions of M1 stage nasopharyngeal carcinoma based on decision tree classification: A multicenter retrospective study.

OBJECTIVES: To meet the demand for personalized treatment, effective stratification of patients with metastatic nasopharyngeal carcinoma (mNPC) is essential. Hence, our study aimed to establish an M1 subdivision for prognostic prediction and treatment planning in patients with mNPC. MATERIALS AND METHODS: This study included 1239 patients with mNPC from three medical centers divided into the synchronous mNPC cohort (smNPC, n = 556) to establish an M1 stage subdivision and the metachronous mNPC cohort (mmNPC, n = 683) to validate this subdivision. The primary endpoint was overall survival. Univariate and multivariate Cox analyses identified covariates for the decision-tree model, proposing an M1 subdivision. Model performance was evaluated using time-dependent receiver operating characteristic curves, Harrell's concordance index, calibration plots, and decision curve analyses. RESULTS: The proposed M1 subdivisions were M1a (≤5 metastatic lesions), M1b (>5 metastatic lesions + absent liver metastases), and M1c (>5 metastatic lesions + existing liver metastases) with median OS of 34, 22, and 13 months, respectively (p < 0.001). This M1 subdivision demonstrated superior discrimination (C-index = 0.698; 3-year AUC = 0.707) and clinical utility over those of existing staging systems. Calibration curves exhibited satisfactory agreement between predictions and actual observations. Internal and mmNPC cohort validation confirmed the robustness. Survival benefits from local metastatic treatment were observed in M1a, while immunotherapy improved survival in patients with M1b and M1c disease. CONCLUSION: This novel M1 staging strategy provides a refined approach for prognostic prediction and treatment planning in patients with mNPC, emphasizing the potential benefits of local and immunotherapeutic interventions based on individualized risk stratification.

Efficacy of metastatic lesion radiotherapy in patients with metastatic nasopharyngeal carcinoma: A multicenter retrospective study.

OBJECTIVE: We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). MATERIALS AND METHODS: Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. RESULTS: We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. CONCLUSIONS: MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes.

Efficacy of induction chemotherapy in lymph node-positive stage III nasopharyngeal carcinoma and identification of beneficiaries based on clinical features: A propensity score matching analysis.

PURPOSE: To investigate the role of induction chemotherapy (IC) in lymph node-positive (LN-positive) stage III nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). METHODS: In total, 627 patients with newly diagnosed LN-positive stage III NPC receiving CCRT or IC plus CCRT were included. The primary endpoint was progression-free survival (PFS). Propensity-score matching (PSM) was conducted to balance the intergroup covariates. Kaplan-Meier method with log-rank test was employed to compare survival curves. Subgroup analyses were conducted based on baseline characteristics. RESULTS: After 1:1 PSM, 414 patients were identified (207 patients per group). Compared with CCRT, IC plus CCRT provided better survival (5-year PFS 88.4% vs. 78.6%, P = 0.01; overall survival [OS] 94.8% vs. 85.3%, P = 0.003; and distant metastasis-free survival [DMFS] 93.1% vs. 85.6%, P = 0.03). The IC beneficial effects on PFS were mainly present in patients with grade 2-3 ENE, elevated serum lactate dehydrogenase (LDH > 170U/L), and N2 disease. Patients with grade 2 CNN had comparable PFS benefits to those with grade 0-1 CNN. For patients with grade 0-1 ENE combined with LDH ≤ 170U/L, survival between the two groups was similar with 5-year PFS 93.6% vs. 90.4% (P = 0.50), OS 94.2% vs. 93.0% (P = 0.72), and DMFS 98.6% vs. 97.7% (P = 0.98). CONCLUSION: Adding IC before CCRT improved survival in LN-positive stage III NPC patients. Additional IC did not provide better survival for patients with grade 0-1 ENE combined with LDH ≤ 170U/L and could be avoided in this population. CNN may not be a good risk factor for tailoring a personalized treatment plan.

Incentive spirometry is an effective strategy to improve the quality of postoperative care in patients.

Postoperative pulmonary complications (PPCs) most commonly occur after thoracic surgery. Not only prolonged hospital stay and increased financial expenses but also morbidity and even mortality may be troublesome for those with PPCs. Herein, we aimed to conduct a comprehensive systematic review and meta-analysis of available data to examine the effectiveness of incentive spirometry (IS) to reduce PPCs and shorten hospital stay. This systematic review and meta-analysis included 5 randomized controlled trials (RCT) and 3 retrospective cohort study (10,322 patients in total) in PubMed, Embase and Cochrane Library until September 31, 2021. We assessed the clinical efficacy of IS using length of hospital stay, PPCs, postoperative pneumonia, and postoperative atelectasis with meta-analysis, meta-regression and trial sequential analysis (TSA). With this meta-analysis, the length of hospital stay in patients undergoing IS was significantly shorter (1.8 days) than that in patients not receiving IS (MD = -1.80, 95% CI = -2.95 to -0.65). Patients undergoing IS also had reduced risk of PPCs (32%) and postoperative pneumonia (17.9%) with statistical significance than patients not undergoing IS (PPC: OR = 0.68, 95% CI = 0.51-0.90) (Pneumonia: OR = 0.821, 95% CI = 0.677-0.995).In meta-regression, the benefits of undergoing IS in patients with preoperative predicted FEV1 of <80% in a linear fashion with decreasing PPCs. IS is an effective modality to improve the quality of postoperative care for patients after pulmonary resection, compared with the control group without using IS; and applying IS has favorable outcomes of shorter length of hospital stay (1.8 days) and lower occurrence of PPCs (32% of risk reduction), which are conclusive and robust based on our validation via TSA. Moreover, the IS device is more beneficial for patients with preoperative predicted FEV1 of <80% than that in others.

Individualized number of induction chemotherapy cycles for locoregionally advanced nasopharyngeal carcinoma patients based on early tumor response.

BACKGROUND: The optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is unclear. We aimed to combine the tumor response during IC and tumor stage to individualize the number of IC cycles. METHODS: Totally, 498 LANPC patients who received IC plus CCRT between 2014 and 2018 were reviewed. Tumor response during IC was used to stratify patients with different risks. All patients were classified into those who received two cycles of IC and those who were treated with three cycles. Propensity score matching methods were performed to compare the treatment efficiency. RESULTS: After two cycles of IC, 340/498 (68.3%) cases showed complete tumor response (CR)/partial response (PR) and 158 (31.7%) achieved stable disease (SD)/disease progression (PD). Unfavorable responders (SD/PD) exhibited poor survival outcomes. The three-cycle IC regimen was correlated with better OS and PFS than the two-cycle regimen for N2-3 patients in the CR/PR group. However, the use of different IC cycle strategies achieved similar survival outcomes for SD/PD or N0-1 patients. The incidences of acute toxicities were higher in the IC = 3 group. CONCLUSIONS: Tumor response during IC could be a powerful predictor of LANPC and could be used to guide the individualized number of IC cycles. A three-cycle IC regimen seemed to be preferable for N2-3 patients who received CR/PR during IC. However, an additional cycle of IC could not benefit N0-1 or SD/PD patients, and the optimal treatment strategies for these patients require further consideration.

Diastole/Body Mass Index Ratio Can Predict Post-Thoracoscopic Surgery Metastasis in Stage I Lung Adenocarcinoma.

BACKGROUND: According to recent animal models for lung adenocarcinoma metastasis, cardiac function may be related to the clinical outcome. The aim of this study is to identify a predictable index for postoperative metastasis (POM) that is associated with cardiac function. METHODS: Two hundred and seven consecutive patients who underwent thoracoscopic resection for stage I lung adenocarcinoma were included. Disease-free survival (DFS), overall survival (OS), and patients' clinical and pathological characteristics were analyzed. RESULTS: Among the 207 patients, 17 cases demonstrated metastasis, 110 cases received a preoperative echocardiogram, and six cases had POM. Mitral valve peak A velocity, which is one of the left ventricular diastolic function parameters affected by BMI (MVPABMI), was associated with a negative factor for POM (hazard ratio (HR): 2.139, p = 0.019) and a poor 5-year DFS in the above median (100% vs. 87%, p = 0.014). The predictable rate increased from 30.7% to 75% when the MVPABMI was above the median = 3.15 in the solid subtype). CONCLUSIONS: MVPABMI is a novel index for POM prediction in early-stage lung adenocarcinoma. This is a pilot study and the first attempt at research to verify that the diastole and the BMI may be associated with POM in early-stage lung adenocarcinoma.

Development of A Nomogram for Progression-free Survival in Patients with Stage II/T3N0 Nasopharyngeal Carcinoma to Explore Different Treatment Modalities.

Purpose To explore the prognostic value of clinical and serological risk factors for progression-free survival (PFS) in stage II and T3N0 nasopharyngeal carcinoma (NPC) and construct a nomogram based on these factors. Additionally, to investigate the long-term survival and short-term toxic reactions of patients in different risk stratification under different treatment modalities. Methods The patients were randomly divided into training and validation cohorts in a 7:3 ratio. Independent prognostic factors were identified using Cox regression analysis, and a nomogram was constructed by combining these predictive factors with the TNM staging system. The nomogram was then validated in the validation cohort, and patients were classified into different risk groups based on the nomogram. The PFS, overall survival (OS), and acute toxicities were compared among different treatment modalities after balancing baseline characteristics. Results Multivariate Cox regression analysis indicated that pathological type, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were independent prognostic factors(p<0.05) in this study. The nomogram showed good prognostic accuracy in both the training and validation cohorts (C-index of 0.73 and 0.70, respectively). In the different risk subgroups, there were no statistically significant differences in PFS and OS between radiotherapy and chemoradiotherapy groups(p>0.05). The treatment modality of combined chemotherapy was associated with more acute toxic reactions. Conclusion We established and validated a nomogram for predicting PFS in patients with stage II/T3N0 NPC. Intensity-modulated radiation therapy (IMRT) combined with chemotherapy did not provide additional survival benefits for these patients and was associated with more chemotherapy-related side effects.

Is direct transport to a trauma centre best for patients with severe traumatic brain injury? A study in south-central Taiwan.

OBJECTIVE: This study attempted to identify any differences between the outcomes of patients with severe traumatic brain injury (TBI) who were directly transported to Chang Gung Memorial Hospital and those who were stabilised initially at other hospitals in south-central Taiwan. METHODS: A retrospective review of the records of 254 patients with isolated severe TBI who visited this hospital's emergency department from July 2003 to June 2008, of whom 167 were referred from other hospitals. Logistic regression was used to assess the effects of transfer and its components on mortality. RESULTS: Transfer from another hospital was not significantly correlated with mortality in this study (OR 0.513, 95% CI 0.240 to 1.097). Moreover, neither intubation (OR 1.356, 95% CI 0.445 to 4.133) nor transfer time over 4 h (OR 0.549, 95% CI 0.119 to 1.744) had a significant effect on mortality. CONCLUSION: No differences in outcome were found between patients with isolated severe TBI who were directly transported and those transferred to this hospital's emergency room.

A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma.

Purpose: The role of concurrent chemoradiotherapy (CCRT) in stage II nasopharyngeal carcinoma (NPC) is still controversial. Our objective is to evaluate the value of concurrent chemotherapy in stage II NPC receiving radiotherapy (RT). Methods: We searched the PubMed, Embase, and Scopus databases for studies comparing CCRT versus RT alone in stage II NPC with survival outcomes and toxicities, including locoregional recurrence-free survival (LRFS), metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and grade 3-4 acute toxicities. The hazard ratios (HRs) of survival outcomes and risk ratios (RRs) of toxicities were extracted for meta-analysis. Subgroup analysis for stage N1 patients was performed to further explore whether these populations can earn benefits from concurrent chemotherapy. Results: Nine eligible studies with a total of 4,092 patients were included. CCRT was associated with a better OS (HR = 0.61, 95% CI 0.44-0.82), LRFS (HR = 0.62, 95% CI 0.50-0.78), and PFS (HR = 0.65, 95% CI 0.54-0.79), but with similar DMFS (HR = 0.81, 95% CI = 0.46-1.45) compared with two-dimensional RT (2DRT) alone. However, CCRT showed no survival benefit in terms of OS (HR = 0.84, 95% CI 0.62-1.15), LRFS (HR = 0.85, 95% CI 0.54-1.34), DMFS (HR = 0.96, 95% CI 0.60-1.54), and PFS (HR = 0.96, 95% CI 0.66-1.37) compared with intensity-modulated RT (IMRT) alone. Subgroup analyses indicated that CCRT had similar OS (HR = 1.04, 95% CI 0.37-2.96), LRFS (HR = 0.70, 95% CI 0.34-1.45), DMFS (HR = 1.03, 95% CI 0.53-2.00), and PFS (HR = 1.04, 95% CI 0.58-1.88) in the stage N1 populations. Meanwhile, compared to RT alone, CCRT significantly increased the incidence of grade 3-4 leukopenia (RR = 4.00, 95% CI 2.29-6.97), mucositis (RR = 1.43, 95% CI 1.16-1.77), and gastrointestinal reactions (RR = 8.76, 95% CI 2.63-29.12). No significant differences of grade 3-4 toxicity in thrombocytopenia (RR = 3.45, 95% CI 0.85-13.94) was found between the two groups. Conclusion: For unselected patients with stage II NPC, CCRT was superior to 2DRT alone with better LRFS, PFS, and OS, while adding concurrent chemotherapy to IMRT did not significantly improve survival but exacerbated acute toxicities. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022318253.

Development and validation of prognostic nomograms in patients with ascending type of nasopharyngeal carcinoma: Retrospective study based on SEER database.

BACKGROUND: Nomograms specifically used to predict the prognosis of ascending type nasopharyngeal carcinoma (NPC) have not been constructed. METHODS: Data of ascending type (T3-4N0-1M0) NPC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were extracted. RESULTS: Altogether 862 patients with ascending type NPC were enrolled, including 603 in training cohort and 259 in validation cohort. Age, marital status, pathology, grade, tumor size, T classification, and chemotherapy were the independent prognostic factors for overall survival (OS). Age, marital status, pathology, grade, and chemotherapy were the independent prognostic factors for cancer-specific survival (CSS). In training cohort, the concordance index of the OS and CSS nomograms were 0.694 (95% confidence interval [CI], 0.677-0.711) and 0.678 (95%CI, 0.659-0.697), respectively, while those in validation cohort were 0.740 (95%CI, 0.715-0.765) and 0.708 (95%CI, 0.679-0.737), separately. CONCLUSION: The as-constructed nomograms for ascending type NPC could provide accurate prognostic predictions of OS and CSS.

Association between selective serotonin reuptake inhibitor and risk of peripheral artery disease in diabetes mellitus: Propensity score matching and landmark analysis.

ABSTRACT: An increasing number of studies have demonstrated the bidirectional hemostatic effect of selective serotonin reuptake inhibitors (SSRIs) on the risk of cerebrovascular and cardiovascular diseases. However, no previous study has focused on the relationship between SSRI and the risk of peripheral artery disease (PAD) in diabetes mellitus (DM). We sought to evaluate the association between SSRIs and the PAD risk in individuals with DM.We conducted a retrospective, population-based cohort study using data from the Longitudinal Health Insurance Database from 1999 to 2010 in Taiwan. A total of 5049 DM patients were included and divided into 2 groups: DM with SSRI users and DM with SSRI non-users. Propensity score matching and 1-year landmark analysis were used for our study design. Stratified Cox proportional hazard regressions were used to analyze the hazard ratio of the PAD risk in certain subgroups.DM with SSRI users did not affect the PAD risk compared to DM with SSRI non-users. These findings were consistent with all sensitivity analyses (i.e., age, sex, SSRI doses, antithrombotic medication use, and medical and psychiatric comorbidities).In this study, we found that there was no significant difference of PAD risk between DM with SSRI users and DM with SSRI non-users. DM with SSRI user did not affect PAD risk across any SSRI dose, age, sex, antithrombotic medications, and multiple comorbidities in the subgroup analysis.

Promising Effects of Digital Chest Tube Drainage System for Pulmonary Resection: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: The chest tube drainage system (CTDS) of choice for the pleural cavity after pulmonary resection remains controversial. This systematic review and network meta-analysis (NMA) aimed to assess the length of hospital stay, chest tube placement duration, and prolonged air leak among different types of CTDS. METHODS: This systemic review and NMA included 21 randomized controlled trials (3399 patients) in PubMed and Embase until 1 June 2021. We performed a frequentist random effect in our NMA, and a P-score was adopted to determine the best treatment. We assessed the clinical efficacy of different CTDSs (digital/suction/non-suction) using the length of hospital stay, chest tube placement duration, and presence of prolonged air leak. RESULTS: Based on the NMA, digital CTDS was the most beneficial intervention for the length of hospital stay, being 1.4 days less than that of suction CTDS (mean difference (MD): -1.40; 95% confidence interval (CI): -2.20 to -0.60). Digital CTDS also had significantly reduced chest tube placement duration, being 0.68 days less than that of suction CTDSs (MD: -0.68; 95% CI: -1.32 to -0.04). Neither digital nor non-suction CTDS significantly reduced the risk of prolonged air leak. CONCLUSIONS: Digital CTDS is associated with better outcomes than suction and non-suction CTDS for patients undergoing pulmonary resections, specifically 0.68 days shorter chest tube duration and 1.4 days shorter hospital stay than suction CTDS.

A nomogram based on tumor response to induction chemotherapy may predict survival in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: To evaluate the clinical significance of tumor response to induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients and further to develop a nomogram for predicting survival prognosis. METHODS: A total of 498 patients with stage III-IVA NPC applying IC and concurrent chemotherapy were reviewed (training cohort, n = 376; validation cohort, n = 122). RESULTS: Tumor response was an independent predictor for clinical outcomes. The nomogram included age, N stage, pretreatment Epstein-Barr virus DNA, lymphocyte-to-monocyte ratio, and tumor response achieved an ideal C-index of 0.703 (95% CI 0.655-0.751) in the validation cohort for predicting overall survival (OS), which outperformed than that of the TNM system alone (C-index, 0.670, 95% CI: 0.622-0.718). In addition, the nomogram could successfully classified patients into different risk groups. CONCLUSIONS: We established and validated a precise and convenient nomogram based on tumor response for predicting the OS of LANPC patients.

Prognostic significance of wait time for radical radiotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: The prognostic significance of wait time between definite diagnosis and initial radical radiotherapy is not well established in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) receiving both induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT). METHODS: From 2010 to 2018, 648 patients with LA-NPC treated with IC followed by CCRT were included. RESULTS: A total of 172 pairs of patients with LA-NPC were selected by propensity score matching (PSM). Compared to patients with an acceptable wait time (≤75 days), patients with a prolonged wait time (>75 days) had a significant lower 5-year DMFS rate (86.6% vs. 74.1%, p = 0.006). Subgroup analyses indicated that the unfavorable effects of longer waiting times were mainly seen among stage IVa patients. CONCLUSIONS: A prolonged wait time (>75 days) between definite diagnosis and initial radical radiotherapy has negative prognostic effects on patients with LA-NPC receiving IC plus CCRT, particularly those with IVa stage.

Efficiency of high cumulative cisplatin dose in high- and low-risk patients with locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high-and low-risk patients with LA-NPC. METHODS: Data from 472 LA-NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram-defined high- and low-risk groups. Additionally, acute toxicities were evaluated comparatively between the high- and low-CCD groups. RESULTS: After matching, there was no difference between different CCD groups for all patients in terms of 3-year overall survival (OS), distant metastasis-free survival (DMFS), locoregional recurrence-free survival (LRRFS), or progression-free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post-IC EBV DNA, post-IC primary gross tumor and lymph node volumes obtained a C-index of 0.674. The high-risk group determined by the nomogram had poorer 3-year PFS, OS, DMFS, and LRRFS than the low-risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3-year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high-risk group but not in the low-risk group. Moreover, the high CCD increased treatment-related acute toxicities. CONCLUSIONS: A high CCD was associated with better 3-year PFS and DMFS rates than a low dose for high-risk patients but could not produce a survival benefit for low-risk patients.

A nomogram to predict survival and guide individualized induction chemotherapy in T3-4N1M0 nasopharyngeal carcinoma.

Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) and CCRT alone were the optional treatment regimens for T3-4N1M0 nasopharyngeal carcinoma (NPC) patients. Therefore, we established a nomogram to predict clinical prognosis and guide individualized IC in T3-4N1M0 NPC. Overall, 699 T3-4N1M0 NPC patients treated with CCRT with or without IC between January 2010 and December 2018 were examined. Overall survival (OS) was the main endpoint. A nomogram was developed that included prognostic variables selected by multivariable analysis. The risk score, which was calculated according to the nomogram, was used for risk stratification. The survival difference of patients undergoing CCRT with or without IC was then compared in risk-stratified subgroups. The nomogram yielded C-indexes of 0.708 (95% confidence interval [CI]: 0.682-0.734) in the training cohort and 0.670 (95% CI: 0.625-0.715) in the validation cohort. Calibration curves for 1-, 3- and 5-year OS suggested a good association between the nomogram predicted and observed probabilities. High-risk patients stratified by nomogram benefited from IC (IC + CCRT vs CCRT: 5-year OS: 77.8% vs 58.8%; P = 0.040; 5-year disease-free survival: 75.0% vs 58.2%; P = 0.017), whereas in the low-risk group, the application of IC was associated with worse locoregional recurrence-free survival and distant metastasis-free survival. This nomogram can serve as a reliable model for prognostic prediction and can be used to guide individualized treatment of T3-4N1M0 NPC. High-risk patients are candidates for IC before CCRT, while the use of IC for low-risk patients should be considered carefully.