Electronic Coding for Abnormal Fecal Immunochemical Test Is Associated With Increased Colonoscopy Completion.

INTRODUCTION: We examined the utility of the International Classification of Disease, Tenth Revision (ICD-10) code, R19.5, for a positive or abnormal fecal immunochemical test (FIT) and its association with colonoscopy completion. METHODS: We identified all patients in a safety-net health system who underwent FITs from January 1, 2020, to August 31, 2021, and extracted the FIT date, FIT result, and ICD-10 code (R19.5) and colonoscopy procedures for each patient. RESULTS: FIT-positive patients who had an R19.5 designation within 90 days (n = 383) were significantly more likely than all other FIT-positive patients (n = 273) to complete a colonoscopy within 6 months (40.9% vs 16.8%, P <0.001). DISCUSSION: We found that less than two-thirds of patients had an ICD-10 code designated in their chart within 30 days of an abnormal FIT. When coding occurred in a timely manner, patients were more likely to complete their colonoscopy within 6 months.

The Influence of a Booster Seat on the Motion of the Reclined Small Female Anthropomorphic Test Device in Low-Acceleration Far-Side Lateral Oblique Impacts.

Belt-positioning booster (BPB) seats may prevent submarining in reclined child occupants in frontal impacts. BPB-seated child volunteers showed reduced lateral displacement in reclined seating in low-acceleration lateral-oblique impacts. As submarining was particularly evident in reclined small adult female occupants, we examined if a booster seat could provide similar effects on the kinematics of the small female occupant to the ones found on the reclined child volunteers in low-acceleration far-side lateral oblique impacts. The THOR-AV-5F was seated on a vehicle seat on a sled simulating a far-side lateral-oblique impact (80 deg from frontal, maximum acceleration ∼2 g, duration ∼170 ms). Lateral and forward head and trunk displacements, trunk rotation, knee-head distance, seatbelt loads, and head acceleration were recorded. Three seatback angles (25 deg, 45 deg, 60 deg) and two booster conditions were examined. Lateral peak head and trunk displacements decreased in more severe reclined seatback angles (25-36 mm decrease compared to nominal). Forward peak head, trunk displacements, and knee-head distance were greater with the seatback reclined and no BPB. Knee-head distance increased in the severe reclined angle also with the booster seat (>40 mm compared to nominal). Seat belt peak loads increased with increased recline angle with the booster, but not without the booster seat. Booster-like solutions may be beneficial for reclined small female adult occupants to reduce head and trunk displacements in far-side lateral-oblique impacts, and knee-head distance and motion variability in severe reclined seatback angles.

Phase I prospective trial of TAS-102 (trifluridine and tipiracil) and radioembolization with 90Y resin microspheres for chemo-refractory colorectal liver metastases.

BACKGROUND: Extrahepatic disease progression limits clinical efficacy of Yttrium-90 (90Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Trifluridine and tipiracil (TAS-102) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer. METHODS: Sequential lobar TARE using 90Y resin microspheres in combination with TAS-102 in 28-day cycles were used to treat adult patients with bilobar liver-dominant chemo-refractory mCRC according to 3 + 3 dose escalation design with a 12-patient dose expansion cohort. Study objectives were to establish safety and determine maximum tolerated dose (MTD) of TAS-102 in combination with TARE. RESULTS: A total of 21 patients (14 women, 7 men) with median age of 60 years were enrolled. No dose limiting toxicities were observed. Treatment related severe adverse events included cytopenias (10 patients, 48%) and radioembolization-induced liver disease (2 patients, 10%). Disease control rate in the liver lobes treated with TARE was 100%. Best observed radiographic responses were partial response for 4 patients (19%) and stable disease for 12 patients (57%). CONCLUSIONS: The combination of TAS-102 and TARE for patients with liver-dominant mCRC is safe and consistently achieves disease control within the liver. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02602327 (first posted 11/11/2015).

The effect of reclined seatback angles on the motion of booster-seated children during lateral-oblique low-acceleration impacts.

Belt-positioning boosters (BPB) may prevent submarining in novel seating configurations such as seats with reclined seatbacks. However, several knowledge gaps in the motion of reclined child occupants remain as previous reclined child studies only examined responses of a child anthropomorphic test device (ATD) and the PIPER finite element (FE) model in frontal impacts. The aim of this study is to investigate the effect of reclined seatback angles and two types of BPBs on the motion of child volunteer occupants in low-acceleration far-side lateral-oblique impacts. Six healthy children (3 males, 3 females, 6-8 years, seated height: 66±3.2 cm, weight: 25.2±3.2 kg) were seated on two types of low-back BPB (standard and lightweight) on a vehicle seat and restrained by a 3-point simulated-integrated seatbelt on a low-acceleration sled. The sled exposed the participants to a low-speed lateral-oblique (80° from frontal) pulse (2 g). Three seatback recline angles (25°, 45°, 60° from vertical) with two BPB (standard and lightweight) were tested. A 10-camera 3D-motion-capture system (Natural Point Inc.) was used to capture peak lateral head and trunk displacements and forward knee-head distance. Three seat-belt load cells (Denton ATD Inc) captured peak seatbelt loads. Electromyography (EMG, Delsys Inc) recorded muscle activation. Repeated Measure 2-way ANOVAs were performed to evaluate the effect of seatback recline angle and BPB on kinematics. Tukey's post-hoc test for pairwise comparisons was used. P-level was set to 0.05. Peak lateral head and trunk displacement decreased with the increasing seatback recline angle (p < 0.005, p < 0.001, respectively). Lateral peak head displacement was greater in the 25° compared to the 60° condition (p < 0.002) and in the 45° condition compared to the 60° condition (p < 0.04). Lateral peak trunk displacement was greater in the 25° condition than the 45° condition (p < 0.009) and the 60° condition (p < 0.001), and in the 45° condition than the 60° condition (p < 0.03). Overall peak lateral head and trunk displacements and knee-head forward distance were slightly greater in the standard than the lightweight BPB (p < 0.04), however these differences between BPBs were small (∼10 mm). Shoulder belt peak load decreased as the reclined seatback angle increased (p < 0.03): the shoulder belt peak load was statistically greater in the 25° condition than the 60° condition (p < 0.02). Muscle activation from the neck, upper trunk, and lower legs showed great activation. Neck muscles activation increased with the increase in seatback recline angle. Thighs, upper arms, and abdominal muscles showed small activation and no effect of conditions. Child volunteers showed decreased displacement suggesting that reclined seatbacks placed the booster-seated children in a more favorable position within the shoulder belt in a low-acceleration lateral-oblique impact, compared to nominal seatback angles. BPB type seemed to minimally influence the children's motion: the small differences found may have been due to the slight difference in heights between the two BPBs. Future research with more severe pulses is needed to better understand reclined children's motion in far-side lateral-oblique impacts.

Effect of naturalistic seating postures and seatbelt routing on booster-seated Q6 ATD kinematics and kinetics in frontal impacts.

RESEARCH QUESTIONS / OBJECTIVE: Test protocols evaluate restraint performance with pediatric ATDs placed in an ideal seating posture. However, real-world evidence suggests that ideal test conditions do not always reflect actual occupant positions. Prior studies have also shown that booster seat designs affect the position of the seatbelt around the child. Occupants in naturalistic seating postures, coupled with potentially unfavorable seatbelt positions, could result in adverse kinematics and kinetics in a crash. Therefore, the aim of this study was to quantify the effect of different naturalistic seating postures on the response of the Q6 ATD restrained on boosters with varying initial static belt fit in a frontal impact. METHODS/DATA SOURCES: The Q6 ATD was positioned on two booster seats of similar design but varying static belt fit metrics in three seating postures: reference, leaning forward, and leaning inboard. These booster seats were chosen from extensive belt fit studies on human volunteers and ATDs, and were defined as follows:The booster-seated ATD was restrained on the simulated Consumer Reports test buck (2010 Ford Flex 2nd row seat) with a front blocker plate using a 3-point lap-shoulder belt with a retractor and pretensioner. The sled environment was subjected to the FMVSS 213 frontal impact pulse, and each booster and seating posture was evaluated twice (n = 12 sled tests). Kinematic and kinetic measures were recorded. A linear regression analysis was conducted across postures on each booster. Further, a paired t-test analysis was conducted across booster seats for each seating posture. RESULTS: Across seating postures, the reference posture exhibited similar or higher kinematic and kinetic metric values compared to the leaning forward and leaning inboard postures on both boosters. However, both leaning forward (Booster A = 279.5 ± 21.6 mm; Booster B = 298.8 ± 1.5 mm) and leaning inboard (Booster A = 308.7 ± 1.1 mm; Booster B = 331.4 ± 8.5 mm) postures generally resulted in greater head excursion than the reference posture (Booster A = 285.0 ± 16.9 mm; Booster B = 288.1 ± 1.5 mm), indicating greater potential for head contact. Between boosters, Booster A resulted in significantly lower head 3 ms clip acceleration (p = 0.0026), HIC15 (p = 0.0008), upper neck tensile force (Fz)(p = 0.0057), chest 3 ms clip acceleration (p = 0.0013), and right abdominal pressure (p = 0.0163), and significantly higher left ASIS force (Fx)(p = 0.0150) and left (p = 0.0489) and right (p = 0.0088) ASIS moment (My) than Booster B. Upper neck tensile forces on Booster B crossed the 20% and 50% thresholds for AIS3 + injury. Lower abdominal pressure and higher ASIS forces and moments on Booster A suggest that the lap belt loaded the ASIS appropriately, and hence, relatively better kinematics than Booster B. SIGNIFICANCE OF RESULTS: This study shows that booster design affects static belt fit which can have an effect on dynamic crash performance and assessment criteria. By connecting static belt fit to dynamic performance, these effects may have the potential to help guide booster seat design.

Modulation of myeloid and T cells in vivo by Bruton's tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma.

BACKGROUND: In preclinical studies of pancreatic ductal adenocarcinoma (PDAC), ibrutinib improved the antitumor efficacy of the standard of care chemotherapy. This led to a phase 1b clinical trial to determine the safety, tolerability, and immunologic effects of ibrutinib treatment in patients with advanced PDAC. METHODS: Previously untreated patients with PDAC were enrolled in a phase 1b clinical trial (ClinicalTrials.gov) to determine the safety, toxicity, and maximal tolerated dose of ibrutinib when administered with the standard regimen of gemcitabine and nab-paclitaxel. To study the immune response to ibrutinib alone, the trial included an immune response arm where patients were administered with ibrutinib daily for a week followed by ibrutinib combined with gemcitabine and nab-paclitaxel. Endoscopic ultrasonography-guided primary PDAC tumor biopsies and blood were collected before and after ibrutinib monotherapy. Changes in abundance and functional state of immune cells in the blood was evaluated by mass cytometry by time of flight and statistical scaffold analysis, while that in the local tumor microenvironment (TME) were assessed by multiplex immunohistochemistry. Changes in B-cell receptor and T-cell receptor repertoire were assessed by sequencing and analysis of clonality. RESULTS: In the blood, ibrutinib monotherapy significantly increased the frequencies of activated inducible T cell costimulator+(ICOS+) CD4+ T cells and monocytes. Within the TME, ibrutinib monotherapy led to a trend in decreased B-cell abundance but increased interleukin-10+ B-cell frequency. Monotherapy also led to a trend in increased mature CD208+dendritic cell density, increased late effector (programmed cell death protein 1 (PD-1-) eomesodermin (EOMES+)) CD8+ T-cell frequency, with a concomitantly decreased dysfunctional (PD-1+ EOMES+) CD8+ T-cell frequency. When ibrutinib was combined with chemotherapy, most of these immune changes were not observed. Patients with partial clinical responses had more diverse T and B cell receptor repertoires prior to therapy initiation. CONCLUSION: Ibrutinib monotherapy skewed the immune landscape both in the circulation and TME towards activated T cells, monocytes and DCs. These effects were not observed when combining ibrutinib with standard of care chemotherapy. Future studies may focus on other therapeutic combinations that augment the immunomodulatory effects of ibrutinib in solid tumors. TRIAL REGISTRATION NUMBER: NCT02562898.

Biofidelic Evaluation of the Large Omni-Directional Child Anthropomorphic Test Device in Low Speed Loading Conditions.

Motor vehicle crashes remain the leading cause of death for children. Traditionally, restraint design has focused on the crash phase of the impact with an optimally seated occupant. In order to optimize restrain design for real-world scenarios, research has recently expanded its focus to non-traditional loading conditions including pre-crash positioning and lower speed impacts. The goal of this study was to evaluate the biofidelity of the large omni-directional child (LODC) ATD in non-traditional loading conditions by comparing its response to pediatric volunteer data in low-speed sled tests. Low-speed (2-4 g, 1.9-3.0 m/s) frontal (0°), far-side oblique (60°), and far-side lateral (90º) sled tests, as well as lateral swerving (0.72 g, 0.5 Hz) tests, were conducted using the LODC. The LODC was restrained using a 3-point-belt with an electromechanical motorized seat belt retractor, or pre-pretensioner. Motion capture markers were placed on the head, torso, and belt. The LODC was compared to previously collected pediatric volunteer data as well as the HIII 10 and Q10. Significant difference between the pediatric volunteers and ATDs were identified by comparing the mean ATD response to the pediatric volunteer 95% CI. The LODC exhibited lower forward head excursion (262 mm) compared to pediatric volunteers (263 - 333 mm) in low-speed frontal sled tests (p<0.05), but was closer to the pediatric volunteers than the HIII 10 (179 mm) and Q10 (171 mm). In lateral swerving, the LODC (429 mm) exhibited greater lateral head excursion (p<0.05) compared to pediatric volunteers (115 - 171 mm). The LODC exhibited a greater reduction in kinematics compared to the pediatric volunteers in all loading conditions with a pre-pretensioner. These data provide valuable insight into the biofidelity of the LODC in non-traditional loading conditions, such as evaluating pre-crash maneuvers on occupant response.