Measurements by semivolatile thermal desorption aerosol gas chromatography (SV-TAG) were used to investigate how semivolatile organic compounds (SVOCs) partition among indoor reservoirs in (1) a manufactured test house under controlled conditions (HOMEChem campaign) and (2) a single-family residence when vacant (H2 campaign). Data for phthalate diesters and siloxanes suggest that volatility-dependent partitioning processes modulate airborne SVOC concentrations through interactions with surface-laden condensed-phase reservoirs. Airborne concentrations of SVOCs with vapor pressures in the range of C13 to C23 alkanes were observed to be correlated with indoor air temperature. Observed temperature dependencies were quantitatively similar to theoretical predictions that assumed a surface-air boundary layer with equilibrium partitioning maintained at the air-surface interface. Airborne concentrations of SVOCs with vapor pressures corresponding to C25 to C31 alkanes correlated with airborne particle mass concentration. For SVOCs with higher vapor pressures, which are expected to be predominantly gaseous, correlations with particle mass concentration were weak or nonexistent. During primary particle emission events, enhanced gas-phase emissions from condensed-phase reservoirs partitioned to airborne particles, contributing substantially to organic particulate matter. An emission event related to oven-usage was inferred to deposit siloxanes in condensed-phase reservoirs throughout the house, leading to the possibility of reemission during subsequent periods with high particle loading.

It is important to improve our understanding of exposure to particulate matter (PM) in residences because of associated health risks. The HOMEChem campaign was conducted to investigate indoor chemistry in a manufactured test house during prescribed everyday activities, such as cooking, cleaning, and opening doors and windows. This paper focuses on measured size distributions of PM (0.001-20 μm), along with estimated exposures and respiratory-tract deposition. Number concentrations were highest for sub-10 nm particles during cooking using a propane-fueled stovetop. During some cooking activities, calculated PM_2.5 mass concentrations (assuming a density of 1 g cm^-3) exceeded 250 μg m^-3, and exposure during the postcooking decay phase exceeded that of the cooking period itself. The modeled PM respiratory deposition for an adult residing in the test house kitchen for 12 h varied from 7 μg on a day with no indoor activities to 68 μg during a simulated day (including breakfast, lunch, and dinner preparation interspersed by cleaning activities) and rose to 149 μg during a simulated Thanksgiving day.

Inhalation of particulate matter is associated with adverse health outcomes. The fluorescent portion of supermicron particulate matter has been used as a proxy for bioaerosols. The sources and emission rates of fluorescent particles in residential environments are not well-understood. Using an ultraviolet aerodynamic particle sizer (UVAPS), emissions of total and fluorescent supermicron particles from common human activities were investigated during the HOMEChem campaign, a test-house investigation of the chemistry of indoor environments. Human occupancy and activities, including cooking and mopping, were found to be considerable sources of indoor supermicron fluorescent particles, which enhanced the indoor particle concentrations by two orders of magnitude above baseline levels. The estimated total (fluorescent) mass emission rates for the activities tested were in the range of 4-30 (1-11) mg per person meal for cooking and 0.1-4.9 (0.05-4.7) mg/h for occupancy and mopping. Model calculations indicate that, once released, the dominant fate of coarse particles (2.5-10 micrometer in diameter) was deposition onto indoor surfaces, allowing for the possibility of subsequent resuspension and consequent exposures over durations much longer than the ventilation time scale. Indoor coarse particle deposition would also contribute to soiling of indoor surfaces.

BACKGROUND: The absence of consensus for outcomes in pediatric antibiotic trials is a major barrier to research harmonization and clinical translation. We sought to develop expert consensus on study outcomes for clinical trials of children with mild community-acquired pneumonia (CAP). METHODS: Applying the Delphi method, a multispecialty expert panel ranked the importance of various components of clinical response and treatment failure outcomes in children with mild CAP for use in research. During Round 1, panelists suggested additional outcomes in open-ended responses that were added to subsequent rounds of consensus building. For Rounds 2 and 3, panelists were provided their own prior responses and summary statistics for each item in the previous round. The consensus was defined by >70% agreement. RESULTS: The expert panel determined that response to and failure of treatment should be addressed at a median of 3 days after initiation. Complete or substantial improvement in fever, work of breathing, dyspnea, tachypnea when afebrile, oral intake, and activity should be included as components of adequate clinical response outcomes. Clinical signs and symptoms including persistent or worsening fever, work of breathing, and reduced oral intake should be included in treatment failure outcomes. Interventions including receipt of parenteral fluids, supplemental oxygen, need for high-flow nasal cannula oxygen therapy, and change in prescription of antibiotics should also be considered in treatment failure outcomes. CONCLUSIONS: Clinical response and treatment failure outcomes determined by the consensus of this multidisciplinary expert panel can be used for pediatric CAP studies to provide objective data translatable to clinical practice.

Background

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: Open or closed abdominal technique.

Aim

To evaluate the impact of HIPEC method on post-operative and long-term survival outcomes.

Methods

Patients undergoing CRS with HIPEC from 2000-2017 were identified in the United States HIPEC collaborative database. Post-operative, recurrence, and overall survival outcomes were compared between those who received open vs closed HIPEC.

Results

Of the 1812 patients undergoing curative-intent CRS and HIPEC, 372 (21%) patients underwent open HIPEC and 1440 (79%) underwent closed HIPEC. There was no difference in re-operation or severe complications between the two groups. Closed HIPEC had higher rates of 90-d readmission while open HIPEC had a higher rate of 90-d mortalities. On multi-variable analysis, closed HIPEC technique was not a significant predictor for overall survival (hazards ratio: 0.75, 95% confidence interval: 0.51-1.10, P = 0.14) or recurrence-free survival (hazards ratio: 1.39, 95% confidence interval: 1.00-1.93, P = 0.05) in the entire cohort. These findings remained consistent in the appendiceal and the colorectal subgroups.

Conclusion

In this multi-institutional analysis, the HIPEC method was not independently associated with relevant post-operative or long-term outcomes. HIPEC technique may be left to the discretion of the operating surgeon.

Background

Postoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on the survival of patients with appendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown.

Methods

The US HIPEC Collaborative (2000-2017) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. The analysis was stratified by noninvasive appendiceal neoplasm versus invasive appendiceal/colorectal adenocarcinoma. The POCs were grouped into infectious, cardiopulmonary, thromboembolic, and intestinal dysmotility. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS).

Results

Of the 1304 patients, 33% had noninvasive appendiceal neoplasm (n = 426), and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the noninvasive appendiceal cohort, POCs were identified in 55% of the patients (n = 233). The 3-year OS and RFS did not differ between the patients who experienced a complication and those who did not (OS, 94% vs 94%, p = 0.26; RFS, 68% vs 60%, p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased 3-year OS (59% vs 74%; p < 0.001) and RFS (32% vs 42%; p < 0.001). Infectious POCs were the most common (35%; n = 196). In Multivariable analysis accounting for gender, peritoneal cancer index (PCI), and incomplete resection (CCR1), infectious POCs in particular were associated with decreased OS compared with no complication (hazard ratio [HR] 2.08; p < 0.01) or other types of complications (HR, 1.6; p < 0.01). Similarly, infectious POCs were independently associated with worse RFS (HR 1.61; p < 0.01).

Conclusion

Postoperative complications are associated with decreased OS and RFS after CRS/HIPEC for invasive histology, but not for an indolent disease such as noninvasive appendiceal neoplasm, and this association is largely driven by infectious complications. The exact mechanism is unknown, but may be immunologic. Efforts must target best practices and standardized prevention strategies to minimize infectious postoperative complications.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000-2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.

Background

While parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC.

Methods

Patients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS).

Results

A total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p < .001) per patient and required more reoperations (22% vs. 11%; p = .007) and readmissions (39% vs. 25%; p = .014) than non-LR patients. LR patients had decreased OS (2-year OS 62% vs. 79%, p < .001), even when accounting for peritoneal carcinomatosis index and histology type. Preoperative factors associated with decreased OS on multivariable analysis in LR patients included age < 60 years (HR, 3.61; 95% CI, 1.10-11.81), colorectal histology (HR, 3.84; 95% CI, 1.69-12.65), and multiple liver tumors (HR, 3.45; 95% CI, 1.21-9.85) (all p < .05). When assigning one point for each factor, there was an incremental decrease in 2-year survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%).

Conclusions

As CRS/HIPEC + LR has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC + LR. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in OS.