Dosimetric Risk Factors for Acute Radiation Pneumonitis in Patients With Prior Receipt of Immune Checkpoint Inhibitors.

Purpose: Dosimetric parameters (e.g., mean lung dose (MLD), V20, and V5) can predict radiation pneumonitis (RP). Constraints thereof were formulated before the era of combined immune checkpoint inhibitors (ICIs) and radiotherapy, which could amplify the RP risk. Dosimetric predictors of acute RP (aRP) in the context of ICIs are urgently needed because no data exist thus far. Methods and Materials: All included patients underwent thoracic intensity-modulated radiotherapy, previously received ICIs, and followed-up at least once. Logistic regression models examined predictors of aRP (including a priori evaluation of MLD, V20, and V5), and their discriminative capacity was assessed by receiver operating characteristic analysis. Results: Median follow-up of the 40 patients was 5.3 months. Cancers were lung (80%) or esophageal (20%). ICIs were PD-1 (85%) or PD-L1 (15%) inhibitors (median 4 cycles). Patients underwent definitive (n=19), consolidative (n=14), or palliative (n=7) radiotherapy; the median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR, 51.8-64 Gy). Grades 1-5 aRP occurred in 25%, 17.5%, 15%, 2.5%, and 5%, respectively. The only variables associated with any-grade aRP were V20 (p=0.014) and MLD (p=0.026), and only V20 with grade ≥2 aRP (p=0.035). Neither the number of prior ICI cycles nor the delivery of concurrent systemic therapy significantly associated with aRP risk. Graphs were constructed showing the incrementally increasing risk of aRP based on V20 and MLD (continuous variables). Conclusions: This is the first study illustrating that V20 and MLD may impact aRP in the setting of prior ICIs. However, these data should not be extrapolated to patients without pre-radiotherapy receipt of prior ICIs, or to evaluate the risk of chronic pulmonary effects. If these results are validated by larger studies with more homogeneous populations, the commonly accepted V20/MLD dose constraints could require revision if utilized in the setting of ICIs.

Acute fatal chest pain: optimized procedure in emergency department.

OBJECTIVE: To explore the diagnostic procedure of acute fatal chest pain in emergency department (ED) in order to decrease the misdiagnosis rate and shorten the definite time to diagnosis. The ultimate aim is to rescue the patients timely and effectively. METHODS: Three hundreds and two patients (56.9 ± 11.8 Years, 72% men) complained with acute chest pain and chest distress presenting to our ED were recruited. They were divided into two groups according to visiting time (Group I: from October 2010 to March 2011, Group II: from October 2011 to March 2012). The misdiagnosis rate, definite time for diagnosis and medical expense were analyzed. Patients of Group I were diagnosed by initial doctors who made their diagnosis according to personal experience in outpatient service or rescue room in ED. While patients of Group II were all admitted to rescue room and were diagnosed and rescued according to the acute chest pain screening flow-process diagram. Differences inter-group was compared. RESULTS: The misdiagnosis rate of fatal chest pain in Group I and Group II was 6.8% and 0% respectively, and there was statistic difference (P=0.000). The definite time to diagnosis was 65.3 min and 40.1 min in control and Group II respectively, the difference had statistic significance (P=0.000). And the mean cost for treatment was 787.5/124.5 ¥/$ and 905.5/143.2 ¥/$ respectively, and there was statistic difference too (P=0.012). CONCLUSION: Treating emergency patients with acute chest pain according to the acute chest pain screening flow-process diagram in rescue room will decrease misdiagnosis apparently, and it can also shorten the definite time to correct diagnosis. It has a remarkable positive role in rescuing patients with acute chest pain timely and effectively.

Co-exposure to noise, N,N-dimethylformamide, and toluene on 24-hour ambulatory blood pressure in synthetic leather workers.

Independent exposure to noise, N,N-dimethylformamide (DMF), or toluene has been associated with cardiovascular effects, but the combined effects are not clear. This study investigated ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) in workers co-exposed to noise, DMF, and toluene. Twenty workers in a synthetic leather manufacturing company were recruited as study subjects. Personal noise exposure and ambulatory blood pressure were measured concomitantly for 24 hr; airborne co-exposure to DMF and toluene during the working period was also analyzed to identify solvents exposure. Linear mixed-effects regressions were used to estimate effects on ambulatory blood pressure by controlling potential confounders. Four high-combined-exposure workers (83 +/- 8 dBA; DMF: 3.23 +/- 2.15 ppm, toluene: 1.09 +/- 1.13 ppm) had the higher means of 16 +/- 7 mmHg in 24-hr DBP (p = 0.027) and 21 +/- 8 mmHg in working-time DBP (p = 0.048) than seven low-combined-exposure workers (73 +/- 12 dBA; DMF: 0.41 +/- 0.02 ppm, toluene: 0.12 +/- 0.01 ppm). Three high-noise-exposure workers (84 +/- 7 dBA) also had a marginal increase of 13 +/- 6 mmHg in DBP at work (p = 0.076) compared with the control group. No significant differences in SBP and DBP were found between six high-solvent-exposure workers (DMF: 1.24 +/- 1.25 ppm, toluene: 2.63 +/- 1.29 ppm) and office workers during any periods. After the Bonferroni correction, there were no significant differences in ambulatory blood pressure between three high-exposure groups and the low-exposure groups. Our findings suggest no interactive effects of co-exposure to noise, DMF, and toluene on workers' ambulatory blood pressure.

Effects of co-exposure to noise and mixture of organic solvents on blood pressure.

OBJECTIVES: Independent exposure to noise or organic solvents is reported to be associated with cardiovascular effects, but the effect of joint exposure is unclear. The present study aimed to investigate effects of noise, a mixture of organic solvents (N,N-dimethylformamide (DMF) and toluene) and their interaction on hypertension. METHODS: We recruited 59 volunteers working in a synthetic leather manufacturing company during 2005-2006. Both personal noise exposure and airborne co-exposure to DMF and toluene at work were measured and used to calculate the mixed hazard index (HI). Multivariate logistic regressions were conducted to estimate between-group differences of hypertension by controlling for potential confounders. RESULTS: We found that 18 co-exposure workers (82.22 +/- 2.70 dBA and a mixed HI of 0.53 +/- 0.20) had the highest prevalence of hypertension (55.6%) compared to 15 solvent-exposure workers (a mixed HI of 0.32 +/- 0.18; 46.7%), 9 noise-exposure workers (84.13 +/- 2.30 dBA; 44.4%) and 17 low-exposure workers (11.8%). The adjusted odds ratio (OR) of hypertension compared to low-exposure workers increased from 7.9 times (95% confidence interval (CI)=0.9-66.3; p=0.06) in solvent-exposure workers and 9.1 times (OR=9.1, 95% CI=1.0-81.1; p<0.05) in noise-exposure workers to 13.5 times (95% CI=1.5-117.8; p<0.05) in co-exposure workers. CONCLUSIONS: Our findings suggest that co-exposure to noise, DMF and toluene is associated with hypertension in synthetic leather workers. Simultaneous exposure to noise and a mixture of organic solvents may have a sub-additive effect on the risk of hypertension.

Effects of occupational noise exposure on 24-hour ambulatory vascular properties in male workers.

BACKGROUND: Epidemiologic studies have demonstrated that occupational noise exposure is associated with hypertension, but the related mechanism in vascular structural changes is unclear. OBJECTIVE: This panel study aimed to investigate effects of occupational noise exposure on ambulatory vascular structural properties in male workers. METHODS: We recruited 20 volunteers and divided them into a high-noise-exposure group of 15 and a low-noise-exposure group of 5 based on environmental noise measurement in an automobile manufacturing company. We determined individual noise exposure and measured personal ambulatory vascular property parameters simultaneously during 24 hr. Linear mixed-effects regression models were used to estimate transient and sustained effects of noise exposure on vascular parameters by adjusting some confounders collected from self-administrated questionnaires and health checkups. RESULTS: The high-noise-exposed (85 +/- 8 dBA) workers had significantly higher systemic vascular resistance (SVR) than the low-noise-exposed workers (59 +/- 4 dBA) during work and sleep periods. Contrarily, low-noise-exposed workers had significantly higher brachial artery compliance (BAC), brachial artery distensibility (BAD), and systemic vascular compliance (SVC; marginal, p = 0.07) than high-noise-exposed workers during off-duty periods. We also found that high-noise-exposed workers had significantly lower BAC (1.38 +/- 0.55 %mL/mmHg) and BAD (1.29 +/- 0.51 %/mmHg), as well as lower SVC (0.24 +/- 0.10 mL/L/mmHg), but higher SVR (1.93 +/- 0.67 mL/L/min) compared with low-noise-exposed workers over a 24-hr period. CONCLUSIONS: Our findings suggest that in automobile workers, occupational noise exposure may have sustained, not transient, effects on vascular properties and also enhances the development of hypertension.