Associations Among Optimal Lung Cancer Treatment, Clinical Outcomes, and Health Care Utilization in Patients Who Underwent Comprehensive Genomic Profiling.

BACKGROUND: Although immune checkpoint inhibitor immunotherapies are contraindicated as first-line treatment of advanced non-small cell lung cancer (NSCLC) in patients with ALK rearrangement and EGFR mutation, many receive them. The purpose of this study was to examine the association between optimal first-line treatment in this population and clinical outcomes. METHODS: Claims and genomic data from patients with advanced or metastatic NSCLC were extracted from a nationally representative GuardantINFORM dataset. Patients who had their first claim mentioning advanced or metastatic NSCLC between March 2019 and February 2020 and had ALK rearrangement or EGFR mutation detected by comprehensive genomic profiling were included in this study. Patients were classified as having received optimal or suboptimal first-line treatment. Claims were reviewed to determine real-world time to next treatment, real-world time to discontinuation, and health services utilization (emergency department, inpatient, and outpatient) in the 12 months following first-line treatment initiation. Survival analyses were conducted using Kaplan-Meier plots and Cox proportional hazard models. Health services utilization was compared between the groups using t tests and negative binomial models. RESULTS: Of the 359 patients included, 280 (78.0%) received optimal first-line treatment. Optimally treated patients had longer median real-world time to next treatment (11.2 vs 4.4 months; P<.01) and real-world time to discontinuation (10.4 vs 1.9 months; P<.01). The optimal group had significantly fewer emergency department presentations (0.76 vs 1.27; P<.01) and outpatient visits (22.9 vs 42.7; P<.01) than the suboptimal group but did not significantly differ in inpatient utilization. Adjusted utilization analysis yielded similar findings. CONCLUSIONS: Patients with NSCLC who received optimal treatment, as determined by comprehensive genomic profiling using next-generation sequencing-based circulating tumor DNA testing (Guardant360), had significantly superior clinical and utilization outcomes, reinforcing existing guidelines recommending profiling at the onset of treatment.

A Case Report of Congenital Afibrinogenemia and Literature Review of Management of Post-circumcision Bleeding.

We present a case of bleeding from circumcision in a full-term newborn male resulting from a rare coagulopathy, congenital afibrinogenemia, and a review of the literature regarding the management of bleeding after circumcision. Bleeding was managed with silver nitrate, suturing, thrombin powder, AristaTM AH (absorbable hemostatic particles; Becton, Dickinson and Company, Franklin Lakes, USA), FFP (fresh frozen plasma), and cryoprecipitate. The Fibrinogen level was less than 30 mg/dl (ref 150-430 mg/dl). The diagnosis of congenital afibrinogenemia was confirmed by a gene test. The baby was found to have a heterozygous pathogenic variant (c.510+1G>T) and a heterozygous likely pathogenic variant (c.1037del) in the FGA gene.

Vascular endothelial growth factor levels and bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) regulate both vasculogenesis, the development of blood vessels from precursor cells, and angiogenesis, the formation of blood vessels from preexisting vessels. In the fetal lung, high-affinity receptors for VEGF are expressed mainly in alveolar epithelial cells and myocytes, suggesting a paracrine role for VEGF in modulating activities in adjacent vascular endothelium. Previous studies have shown that vascular growth is impaired in bronchopulmonary dysplasia (BPD). OBJECTIVE: The goal of this study was to examine tracheal (T-VEGF) and gastric (G-VEGF) levels in premature infants in the first and third day of life and examine if these levels were associated with the development of BPD. DESIGN/METHODS: Tracheal aspirates from intubated infants and gastric samples from others were obtained on postnatal days 1 (D1) and 3 (D3) from 43 preterm infants (<2000 g birth weight, ≤34 wks gestation). VEGF was quantified by a VEGF Elisa Kit. Demographic, clinical, and pulmonary outcome data were collected including information on respiratory support (oxygenation index (OI) and ventilatory index (VI)) and on the development of BPD, determined at 36 weeks PMA using NICHD criteria. RESULTS: The mean birth weight was 1060 ± 379 g and gestational age 27.5 ± 2.8 wks. BPD was diagnosed in 26 infants who were less mature than the 17 controls without BPD. Day 1 and day 3T-VEGF concentrations did not correlate, but day 3 levels correlated with gestational age (r = 0.75, p < .05). BPD infants, characterized by longer ventilator, CPAP and oxygen days, had day 1T-VEGF levels similar to control infants (126.6 ± 194.7 vs. 149.7 ± 333.2 pg/ml) but day 3 levels were significantly lower (168.9 ± 218.8 vs. 1041.6 ± 676.7 pg/ml). Day 1G-VEGF levels reflected tracheal samples, trending lower in BPD infants. Mode of delivery, race, sex, antenatal steroid administration, chorioamnionitis, sepsis, or growth restriction did not impact VEGF levels. However, lower VEGF levels were associated with a lower VI and lower OI: Day 3 OI correlated with day 3T-VEGF (r = 0.72, p > .05), albeit not significantly. T-VEGF increased from day 1 to day 3 in controls and decreased in BPD infants. There was no relationship between oxygen, CPAP and ventilator days and day 1 or day 3T-VEGF levels. CONCLUSIONS: BPD may be associated with low-serum VEGF levels during the first week of life. This finding is likely related to decreased expression in the lungs of the less mature infants, who are at the highest risk for BPD.

Serum surfactant protein D as a marker for bronchopulmonary dysplasia.

BACKGROUND: Lung epithelial cells express surfactant protein D (SP-D), a calcium-dependent lectin that plays an important role in antibody-independent pulmonary host defense. Previous studies have shown that it is found in the peripheral circulation in patients with pulmonary disease, likely because of translocation into the blood when lung epithelial barriers are disrupted by inflammation or acute injury. In adults, serum SP-D levels are biomarkers for the progression and severity of chronic lung disease. In neonates, elevated SP-D levels in cord blood and on day 1 have been associated with prenatal risk factors and with an increased risk of respiratory distress syndrome and infections. It is not known whether serum SP-D during the first week of life is a marker for bronchopulmonary dysplasia (BPD), a form of chronic lung disease of prematurity that is associated with lung parenchymal maldevelopment and injury. OBJECTIVE: The goal of this study is to determine whether serum SP-D on days 3 and 7 of life are associated with the development of BPD in preterm infants. DESIGN/METHODS: Serum samples were obtained on postnatal days 3 and 7 from 106 preterm infants (500-2000 g birth weight, 23-32-week gestation). SP-D was quantified by Western blot. BPD was determined at 36 weeks PMA using NICHD criteria. RESULTS: The mean birth weight was 1145 ± 347 g and gestational age 29.2 ± 7.4 weeks. BPD was diagnosed in 7 and "BPD or death" in 16 infants. Days 3 and 7 values tracked significantly (r = 0.648), and did not correlate with birth weight or gestational age. Contrary to expectations, serum SP-D was not associated with BPD. Significant gender differences were noted, with SP-D dropping from day 3 to day 7 in males, while increasing in females (p < .05). CONCLUSION: Elevated serum SP-D does not appear to be a useful marker for BPD. Decreasing serum SP-D levels in males, as compared to females, during the first week of life are likely related to gender differences in lung maturation, consistent with the higher incidence of BPD in males.

High-Deductible Health Plans and the Challenges They Pose to Radiologists.

Patients with high-deductible health plans will increasingly be motivated to contact their hospitals or various websites to try to obtain information about the costs of expensive services like advanced imaging. Unfortunately, they will not find price transparency but rather confusion and opaqueness. Hospital personnel and commercial websites often unwittingly provide erroneous pricing information. The reasons for this are explained. Detailed examples of the erroneous information are provided. State-mandated websites may be somewhat of an improvement, but their methodology seems to vary from state to state, and they too can be confusing. All this obviously creates problems for patients, who are left not knowing what their true costs will be. The situation also creates problems for radiologists and their hospitals. Because of misunderstandings that can occur during the information-gathering phase, the pricing information shown for many hospital facilities may be greatly inflated, placing them at a competitive disadvantage. Certain strategic solutions to the problems are available, and these are discussed.

Measurement and monitoring of electrocardiogram belt tension in premature infants for assessment of respiratory function.

BACKGROUND: Monitoring of the electrocardiogram (ECG) in premature infants with conventional adhesive-backed electrodes can harm their sensitive skin. Use of an electrode belt prevents skin irritation, but the effect of belt pressure on respiratory function is unknown. A strain gauge sensor is described which measures applied belt tension. METHOD: The device frame was comprised of an aluminum housing and slide to minimize the device weight. Velcro tabs connected housing and slide to opposite tabs located at the electrode belt ends. The slide was connected to a leaf spring, to which were bonded two piezoresistive transducers in a half-bridge circuit configuration. The device was tested for linearity and calibrated. The effect on infant respiratory function of constant belt tension in the normal range (30 g-90 g) was determined. RESULTS: The mechanical response to a step input was second order (fn = 401 Hz, zeta = 0.08). The relationship between applied tension and output voltage was linear in the range 25-225 gm of applied tension (r2 = 0.99). Measured device sensitivity was 2.18 mV/gm tension using a 5 V bridge excitation voltage. When belt tension was increased in the normal range from 30 gm to 90 gm, there was no significant change in heart rate and most respiratory functions during monitoring. At an intermediate level of tension of 50 gm, pulmonary resistance and work of breathing significantly decreased. CONCLUSION: The mechanical and electrical design of a device for monitoring electrocardiogram electrode belt tension is described. Within the typical range of application tension, cardiovascular and respiratory function are not substantially negatively affected by electrode belt force.

A Large State Medicaid Outpatient Advanced Imaging Utilization Management Program: Substantial Savings Without the Need for Denials.

A decade of rapidly rising outpatient advanced imaging utilization ended toward the end of the past decade, with slow growth since. This has been attributed to repetitive reimbursement cuts, medical radiation exposure concerns, increasing deductibles and patient copayments, and the influence of radiology benefit management companies. State Medicaid programs have been reluctant to institute radiology benefit management preauthorization programs since the time burden for obtaining test approval could cause providers to drop out. Also, these patients may lack the knowledge to appeal denials, and medically necessary tests could be denied with adverse outcomes. Little data exist demonstrating the efficacy of such programs in decreasing utilization and cost. We report a 2-year experience with an outpatient advanced imaging prior notification program for a large state Medicaid fee-for-service population. The program did not allow any denials, but nevertheless the data reveal a large, durable decrease in advanced imaging utilization and cost.

Angiographic imaging of the lower extremities with multidetector CT.

Multidetector CT (MDCT) has improved imaging of the arteries in the lower extremities. The main advantages of this novel technology are the exceptionally fast scan times, high spatial resolution, increased anatomic coverage, and capability to generate high-quality multiplanar reformations and three-dimensional (3-D) renderings from raw data that can be reprocessed easily and quickly. The applications of MDCT in imaging the lower extremities are multiple and varied. They include the evaluation of peripheral arterial occlusive and aneurysmal disease, the patency and integrity of bypass grafts, and arterial injury owing to trauma. This article describes the techniques of lower extremity MDCT angiography and its use in a few clinical applications.

Umbilical vein interleukin-6 levels in very low birth weight infants developing intraventricular hemorrhage.

To assess the relationship between perinatal infection/inflammation as reflected by umbilical vein interleukin-6 (IL-6) levels and the development of periventricular-intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants, we tested the hypothesis that VLBW infants who develop IVH have higher concentrations of IL-6 in an umbilical vein sample compared to infants without IVH. An inception cohort of 69 VLBW infants was followed from birth until discharge or death to determine the development of IVH by serial neuroultrasounds. Umbilical vein IL-6 levels were measured using commercially available ELISA kit (Endogen Laboratories, Woburn, MA) and compared in IVH and control cohorts. Twenty-two (32%) infants developed IVH, including 18 (82%) with grade I or II and 4 (18%) with grade III or IV. One of these infants also developed periventricular leukomalacia. The umbilical vein IL-6 levels were significantly elevated in infants with IVH with median value of 87 pg/ml (25th percentile value 30 pg/ml and 75th percentile value 310 pg/ml) compared with infants without IVH, with a median value of 0 pg/ml (25th percentile value 0 pm/ml and 75th percentile value 4 pg/ml) (P = 0.007). Umbilical vein IL-6 levels are elevated in neonates who subsequently develop IVH.

Surveillance for endoleaks: how to detect all of them.

Endovascular aneurysm repair has proven to be a valuable alternative to open repair in selected patients. This less invasive procedure, however, requires long-term surveillance for its own set of potential complications, including perigraft leakage, or endoleak. This article focuses on the detection of these leaks, first defining and classifying endoleaks and then describing various means of detecting them, including computed tomographic angiography, magnetic resonance angiography, color-flow duplex ultrasonography, and conventional angiography.

Resolution of peripheral artery catheter-induced ischemic injury following prolonged treatment with topical nitroglycerin ointment in a newborn: a case report.

Tissue ischemia, necrosis, and gangrene are uncommon but well-described complications of arterial catheterization in the neonate. Treatment options for progressive tissue necrosis following arterial embolization and/or vasospasm are limited in these patients secondary to unpredictable pharmacokinetics and risks associated with systemic anticoagulation or vasodilatation in newborns. We report a case of a multidose regimen of topical 2% nitroglycerin ointment for reversing severe tissue ischemia following peripheral arterial line placement. The favorable response in this infant suggests that topical nitroglycerin therapy should be considered as potential therapy to ameliorate the effects of vascular compromise following arterial line placement in neonates.

Impact of race and ethnicity on the outcome of preterm infants below 32 weeks gestation.

OBJECTIVES: To determine the impact of race/ethnicity on mortality and morbidity such as intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD) and bacteriologically confirmed sepsis, assisted ventilation, surfactant administration, intrauterine growth retardation (IUGR), and patent ductus arteriosus (PDA) among very prematurely delivered infants. STUDY DESIGN: Retrospective study of a cohort of 1006 preterm neonates with gestational age ranging from 22 to 32 weeks discharged from the Neonatal Intensive Care Unit (NICU) between 1998 and 2001. Subgroup analysis according to gestational age (GA) (22 to 24, 25 to 28, and 29 to 32 weeks) and plurality (singleton and multiple) was performed using the chi(2) test and an analysis of variance. RESULTS: Of the 1006 infants, 54.3% were white, 21.7% black, 13.7% Hispanic, and 10.3% were classified as Other. Multiple births among white infants were approximately twice that in (42.4%) black infants (22.1%), and was also significantly higher than in the Hispanic (28.3%) and other race/ethnic groups (25.2%). Overall, a higher proportion of black infants were born with a GA

Risk of cranial ultrasound abnormalities in very-low-birth-weight infants conceived with assisted reproductive techniques.

OBJECTIVE: To evaluate risks of cranial ultrasound abnormalities among very-low-birth-weight (VLBW) infants conceived with fertility therapy (ovulation induction only or with assisted reproductive techniques [ART]) and of multiple gestation pregnancies. STUDY DESIGN: The incidences of cranial ultrasound abnormalities in 1473 VLBW infants conceived with and without fertility therapy and born of multiple versus singleton pregnancies were compared, using logistic regression models. RESULTS: Infants conceived with ART were less likely to have intraventricular hemorrhage (IVH). Twins and triplets had risks of cranial ultrasound abnormalities similar to those of singletons. Twins and triplets conceived with ART were at lower risk of IVH. CONCLUSION: VLBW infants conceived with ART do not appear to be at increased risk of cranial ultrasound abnormalities. Likewise, twins and triplets were not at increased risk of these abnormalities.

The effect of a no-denial policy on imaging utilization.

PURPOSE: Seeking to control advanced diagnostic imaging costs, health insurance plans have instituted broad-based utilization management systems. Most processes ultimately contain denial provisions, meaning that the health plans will refuse to pay for requested studies if performed. The aim of this analysis was to determine whether removal of a denial provision would result in increased utilization of imaging services. METHODS: A major US health plan used a no-denial preauthorization system in all but 4 geographic markets for all CT, MRI, PET, and nuclear cardiac imaging studies, constituting the experimental group. This study consisted of a retrospective review of 247,117 advanced imaging requests 21 months before and 16 months after the elimination of the denial provision in the experimental group. A matched population with no such change in the review process served as the control group. Population-normalized utilization rates were measured for both pooled groups before and after the change. RESULTS: Utilization decreased slightly more in the experimental group than in the control group (-0.10 requests per 1,000 covered lives; 95% confidence interval, -0.20 to 0.00; P = .050) after elimination of the denial provision. The rates of request approval, examination modification, withdrawal, and no consensus after peer-to-peer consultation did not significantly change. CONCLUSIONS: Eliminating denial provisions in utilization management for advanced diagnostic imaging does not result in increased utilization of such imaging.

Early risk, attention, and brain activation in adolescents born preterm.

The relations among early cumulative medical risk, cumulative environmental risk, attentional control, and brain activation were assessed in 15-16-year-old adolescents who were born preterm. Functional magnetic resonance imaging found frontal, temporal, and parietal cortex activation during an attention task with greater activation of the left superior-temporal and left supramarginal gyri associated with better performance. Individual differences in early cumulative risk are related to patterns of brain activation such that medical risk is related to left parietal cortex activation and environmental risk is related to temporal lobe activation. The findings suggest that early risk is related to less mature patterns of brain activation, including reduced efficiency of processing and responding to stimuli.

The Effect of Auditory Stimulation upon Cerebral Blood Oxygenation in Infants: Measurements by Light Emitting Diode (LED) Near Infrared Spectroscopy.

This study assessed the feasibility of neonatal cerebral oxygen monitoring by near-infrared light spectroscopy (NIRS) using a light emitting diode (LED) based system. We aimed to measure the changes in cerebral oxygen saturation, as regional oxygen saturation and tissue oxygenation index, in response to auditory stimuli. Documenting changes in oxygenation in response to such stimuli will help validate the usefulness of LED-NIRS as a tool in the study of cerebral oxygen saturation in neonates.

Umbilical cord unbound free fatty acid concentration and low apgar score.

Increased levels of unbound Free Fatty acid (FFAu) have been found in adults undergoing coronary angioplasty as a result of acute hypoxia-ischemia. We hypohesized that infants suffering from a 1-minute Apgar score of less than 5 will demonstrate elevated FFAu levels in the cord blood. One hundred ninety-nine infants between 25 and 41 weeks gestational age were enrolled in the study. Infants with an Apgar score of less than 5 at 1 minute served as the study group. Blood samples were collected from the umbilical cord and serum FFAu levels were measured with the fluorescent probe acrylodan-derivatized intestinal fatty acid binding protein. The low Apgar score group (n=32, birthweight 3153+/-780 g, gestational age 37.9+/-3.1 weeks) and normal Apgar score group (n=167, birthweight 3067+/-847 g, gestational age 37.5+/-3.5 weeks) were significantly different with respect to Apgar score at 1 minute (3.0+/-1.2 versus 8.4+/-1.1), Apgar score at 5 minutes (6.9+/-versus 8.9+/-0.5), cord pH (7.16+/-0.12 versus 7.28+/-0.07), and in the frequency of meconium passage (40.6% versus 14.9%). Cord FFAu levels were 4.4+/-1.7 versus 3.2+/-1.2 nM (p<0.001), respectively. Cord FFAu correlated inversely with Apgar score at 1 minute (r=-0.31, p<0.05) and with cord pH (r=-0.12, p<0.05), but not with birthweight or gestational age. In infants with low 1-minute Apgar scores, cord free fatty acid levels were significantly elevated compared with those from controls.

Association of lipid peroxidation with hepatocellular injury in preterm infants.

INTRODUCTION: We wished to determine whether cholestasis induced by total parenteral nutrition (TPN) in preterm newborn infants is associated with increased oxidative stress secondary to increased reactive oxygen intermediates. We hypothesized that elevated urinary thiobarbituric-acid-reacting substances (TBARS), a marker of oxidative stress, would be associated with hepatocellular injury as measured by serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. MATERIALS AND METHODS: Preterm infants (<35 weeks' gestation) admitted to the neonatal intensive care unit were enrolled (with their parents' informed consent) in either the 'cholestasis' group (if their direct bilirubin was >2 mg/dl [34.2 micromol/l] and duration of TPN was > or = 10 days [n = 27]) or in the control group. Urine samples for measurement of TBARS (proportionate to lipid peroxidation) and blood specimens for analysis of serum bilirubin, ALT, AST, and alkaline phosphatase were obtained within 24 hours of enrollment. RESULTS: The cholestasis and control groups were comparable with respect to gestational age, birth weight, Apgar score, maximum FiO2, and duration of supplemental oxygen administration. Median serum direct bilirubin concentrations in the cholestasis and control groups were, respectively, 3.3 mg/dl (56.4 micromol/l) and 1.7 mg/dl (29.1 micromol/l) (P < 0.001). Serum ALT and AST levels were also elevated in the cholestasis group, but alkaline phosphatase levels did not differ significantly between the groups. Urinary levels of TBARS in all the infants were correlated with ALT and AST but did not differ significantly between cholestatic and control infants. DISCUSSION: Our findings suggest that oxidant stress is associated with hepatocellular injury in preterm infants. This effect is not correlated with the degree of cholestasis.

Cerebral vascular responses to changes in carbon dioxide tension in term and preterm infants with apnea.

Carbon dioxide (CO(2)) plays important roles in regulating both respiratory drive and cerebral blood flow. These effects are mediated, in part, by activity of the sympathetic nervous system. We hypothesized that the presence of acute life-threatening events or apnea in term or preterm infants, respectively, would serve as a marker for immaturity of cerebral autonomic innervation and that such infants would display a reduced cerebral vascular response to elevated pCO(2). Therefore, we evaluated the cerebral vascular response during CO(2) challenge tests in groups of term and preterm infants with primary apnea. In term infants (39 +/- 2 weeks gestation) with acute life-threatening events, elevated pCO(2) was accompanied by decreasing pulsatility index and increasing mean anterior cerebral blood flow velocity. However, in preterm infants (29 +/- 2 weeks' gestation) with apnea, pulsatility index and anterior cerebral artery flow velocity did not significantly change in response to CO(2) supplementation. We conclude that preterm, but not term, infants with apnea exhibit impaired vascular responses to hypercarbia.

Power spectral analysis of heart rate in relation to sleep position.

We used spectral analysis of heart rate variability, as a measure of autonomic tone, to determine spectral power differences in infants sleeping supine and prone. We studied 29 infants with a birth weight of 1,915 +/- 939 g, at the postconceptional age of 36 +/- 2 weeks. We then calculated total power (TP), low-frequency power (LF, 0.03-0.15 Hz), and high-frequency power (HF, 0.5-1.0 Hz). TP corresponds to overall heart rate variability, LF to both sympathetic and parasympathetic activity, and HF to parasympathetic activity only. Median (25th, 75th percentile) TP (beats/min2) in the supine position was 32.60 (23.12, 59.90), which was significantly higher than the prone position of 25.87 (14.94, 35.57). Similarly, LF (beats/min2) in the supine position of 13.82 (8.63, 23.31) was significantly higher than the prone position of 9.79 (5.46, 14.33). No significant difference was seen in the HF. We conclude that the prone position is associated with decreased heart rate variability and probably decreased sympathetic tone, which imply decreased autonomic stability in this position.