Cardiopulmonary Toxicity Following Intensity-Modulated Proton Therapy (IMPT) Versus Intensity-Modulated Radiation Therapy (IMRT) for Stage III Non-Small Cell Lung Cancer
INTRODUCTION/BACKGROUND:Intensity-modulated proton therapy (IMPT) has the potential to reduce radiation dose to normal organs when compared to intensity-modulated radiation therapy (IMRT). We hypothesized that IMPT is associated with a reduced rate of cardiopulmonary toxicities in patients with Stage III NSCLC when compared with IMRT. METHODS:We analyzed 163 consecutively treated patients with biopsy-proven, stage III NSCLC who received IMPT (nÂ =Â 35, 21%) or IMRT (nÂ =Â 128, 79%). Patient, tumor, and treatment characteristics were analyzed. Overall survival (OS), freedom-from distant metastasis (FFDM), freedom-from locoregional relapse (FFLR), and cardiopulmonary toxicities (CTCAE v5.0) were calculated using the Kaplan-Meier estimate. Univariate cox regressions were conducted for the final model. RESULTS:Median follow-up of surviving patients was 25.5 (range, 4.6-58.1) months. Median RT dose was 60 (range, 45-72) Gy [RBE]. OS, FFDM, and FFLR were not different based on RT modality. IMPT provided significant dosimetric pulmonary and cardiac sparing when compared to IMRT. IMPT was associated with a reduced rate of grade more than or equal to 3 pneumonitis (HR 0.25, PÂ =Â .04) and grade more than or equal to 3 cardiac events (HR 0.33, PÂ =Â .08). Pre-treatment predicted diffusing capacity for carbon monoxide less than equal to 57% (HR 2.8, PÂ =Â .04) and forced expiratory volume in the first second less than equal to 61% (HR 3.1, PÂ =Â .03) were associated with an increased rate of grade more than or equal to 3 pneumonitis. CONCLUSIONS:IMPT is associated with a reduced risk of clinically significant pneumonitis and cardiac events when compared with IMRT without compromising tumor control in stage III NSCLC. IMPT may provide a safer treatment option, particularly for high-risk patients with poor pretreatment pulmonary function.
Fatal patients with severe fever with thrombocytopenia syndrome in China
OBJECTIVES/OBJECTIVE:Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with a high case fatality rate. Key gaps remained as to the assessment of the clinical picture in fatal cases. METHODS:A retrospective study was performed on 496 patients with fatal SFTS. The dynamic pattern of clinical manifestations and laboratory indicators were delineated. RESULTS:The mean age of the fatal cases was 69.0 years (standard deviation: 9.3), and 52.8% were male. The median clinical course from disease onset to death was 11 (interquartile range: 10-13) days. A total of 11 laboratory indicators (neutrophil %, platelet, aspartate aminotransferase, aspartate aminotransferase/alanine transaminase, lactate dehydrogenase, creatine kinase, cystatin C, D-dimer, activated partial thromboplastin time, thrombin time, glucose) persistently deviated from normality across hospitalization. The critical time points when the rapid worsening of the indicators was at 6-9 days after disease onset. Alanine transaminase, AST, lactate dehydrogenase, total bile acid, gamma-glutamyl transpeptidase, and glucose were all elevated to a more pronounced level in fatal cases of those aged ≤70 years. CONCLUSION/CONCLUSIONS:The fatal outcome was developed in rather a short course after the disease onset of SFTS. High vigilance should be put on the key time points when the severe worsening and severe complications occur.
The effect of long-term methadone maintenance treatment on coupling among three large-scale brain networks in male heroin-dependent individuals: A resting-state fMRI study
PURPOSE/OBJECTIVE:Methadone maintenance treatment (MMT) is considered as an effective and mainstream therapy for heroin dependence. However, whether long-term MMT would improve the coupling among the three core large-scale brain networks (salience, default mode, and executive control) and its relationship with the craving for heroin is unknown. METHODS:Forty-four male heroin-dependent individuals during long-term MMT, 27 male heroin-dependent individuals after short-term detoxification/abstinence (SA), and 26 demographically matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging. We analyzed the difference in coupling among the salience, default mode, and executive control networks among the three groups and examined how the coupling among these large-scale networks was associated with craving before and after drug-cue exposure. RESULTS:Compared with the SA group, the MMT group showed lower craving before and after cue exposure and stronger connectivity between the dorsal anterior cingulate cortex (a key node of the salience network) and key regions of the bilateral executive control network, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and dorsomedial prefrontal cortex. Among the heroin-dependent individuals, the functional connectivity was negatively correlated with the craving before and after heroin-cue exposure. CONCLUSION/CONCLUSIONS:Our findings suggest that long-term MMT could increase the coupling between the salience and bilateral executive control networks and decrease craving for heroin. These findings contribute to the understanding of the neural mechanism of MMT, from the perspective of large-scale brain networks.
Impact of glycemia and insulin treatment in fatal outcome of severe fever with thrombocytopenia syndrome
BACKGROUND:Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate. How the glucose level might affect the clinical outcome remains obscure. METHODS:A multicenter study was performed in 2 hospitals from 2011 to 2021. Patients with SFTS and acute hyperglycemia (admission fasting plasma glucose [FPG] â‰¥7 mmol/L), postadmission hyperglycemia (admission FPG <7 mmol/L but FPG â‰¥7 mmol/L after admission), and euglycemia (FPG <7 mmol/L throughout hospitalization) were compared for their clinical progress and outcomes. RESULTS:A total of 3225 patients were included in this study, 37.9% of whom developed acute hyperglycemia and 7.6% postadmission hyperglycemia. The presence of acute hyperglycemia, with or without known diabetes, was associated with increased risk of death (odds ratio [OR]: 1.63; 95% confidence interval [CI]: 1.29-2.05) compared with euglycemia. This effect, however, was only determined in female patients (OR: 2.15; 95% CI: 1.54-2.93). Insulin treatment of patients with SFTS and acute hyperglycemia without previous diabetes was associated with significantly increased mortality (OR: 1.58; 95% CI: 1.16-2.16). CONCLUSION/CONCLUSIONS:Acute hyperglycemia can act as a strong predictor of SFTS-related death in female patients. Insulin treatment of hyperglycemia in patients with SFTS without pre-existing diabetes has adverse effects.
Clinical efficacy and safety evaluation of favipiravir in treating patients with severe fever with thrombocytopenia syndrome
BACKGROUND:Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality, however with no effective therapy available. METHODS:The effect of favipiravir (FPV) in treating SFTS was evaluated by an integrated analysis on data collected from a single-arm study (n=428), a surveillance study (n=2350) and published data from a randomized controlled trial study (n=145). A 1:1 propensity score matching was performed to include 780 patients: 390 received FPV and 390 received supportive therapy only. Case fatality rates (CFRs), clinical progress, and adverse effects were compared. FINDINGS/RESULTS:copies/mL. Age-stratified analysis revealed no benefit in the aging group >70 years, regardless of their sex, onset-to-admission interval, therapy duration or baseline viral load. However, for both â‰¤60 and 60-70 years groups, therapy duration and baseline viral load differentially affected FPV therapy efficiency. Hyperuricemia and thrombocytopenia, as the major adverse response of FPV usage, were observed in >70 years patients. INTERPRETATION/CONCLUSIONS:FPV was safe in treating SFTS patients but showed no benefit for those aged >70 years. Instant FPV therapy could highly benefit SFTS patients aged 60-70 years. FUNDING/BACKGROUND:China Natural Science Foundation (No. 81825019, 82073617 and 81722041) and China Mega-project for Infectious Diseases (2018ZX10713002Â and 2015ZX09102022).
Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356