Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks.

INTRODUCTION: The FDA proposed rule-making to reduce nicotine in cigarettes to minimally addictive levels. Research suggests decreasing nicotine levels (i.e. very low nicotine content cigarettes [VLNCs]) produced greater quit attempts, reduced smoking, and reduced exposure to harmful constituents among smokers. The impact of long-term VLNC use among people who co-use cigarettes and cannabis on non-tobacco-specific toxicant and carcinogen exposure has not been investigated. AIMS AND METHODS: This study presents secondary analyses of a controlled clinical trial examining switching to VLNC (versus a normal nicotine cigarettes control group [NNCs]) between people who co-use cigarettes and cannabis (n = 174) versus smoked cigarettes (n = 555). Linear mixed-effects models compared changes in smoking behavior, and tobacco-specific (i.e. total nicotine equivalents [TNE], 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [NNK; total NNAL]) and non-tobacco-specific (i.e. carbon monoxide (CO), 2-cyanoethylmercapturic acid [CEMA], phenanthrene tetraol [PheT]) toxicant and carcinogen exposure at week 20 (with random intercept for participants). Cannabis use was measured among co-use groups. RESULTS: CO was significantly lower only among the cigarette-only group assigned VLNCs (interaction: p = .015). Although both VLNC groups demonstrated decreased CEMA, greater decreases emerged among the cigarette-only group (interaction: p = .016). No significant interactions emerged for TNE, cigarettes per day (CPD), NNAL, and PheT (ps > .05); both VLNC groups decreased in TNE, CPD, and NNAL. Only the cigarette-only group assigned VLNCs demonstrated decreased PheT (p < .001). The VLNC co-use group showed increased cannabis use over time (p = .012; 0.5 more days per week by week 20). CONCLUSIONS: Those who co-use cannabis and cigarettes may still be at risk for greater exposure to non-tobacco-specific toxicants and carcinogens compared to those who only smoke cigarettes. IMPLICATIONS: The present study is the longest longitudinal, prospective comparison study of smoking behavior and exposure to harmful constituents among those who co-use cigarettes and cannabis versus cigarette-only after immediately switching to very low nicotine content cigarettes (VLNC). Those who co-use experienced similar reductions in CPD and tobacco-specific exposure, compared to those who only use cigarettes. However, co-use groups experienced smaller reductions in non-tobacco-specific toxicants and carcinogens compared to the cigarette-only group, potentially because of combustible cannabis use. Additionally, those who co-use and switched to VLNC may be susceptible to slight increases in cannabis use (approximately two more days per year).

Stability of serial platelet and urine protein measurements in patients receiving nusinersen for spinal muscular atrophy.

INTRODUCTION/AIMS: Patients undergoing nusinersen treatment for spinal muscular atrophy are subject to measurements of platelet count and urine protein before each injection due to concern for platelet depletion and renal dysfunction according to the prescribing information. These tests may be uncomfortable or inconvenient and may cause delays in treatment. However, it is still unclear whether these values have been significantly affected by nusinersen treatment. Our aim in this study was to determine whether these measurements ever reached critical values that necessitated withholding treatment at our center. METHODS: Records from 57 patients treated with nusinersen at our institution between 2017 and 2020 were retrospectively analyzed. Laboratory values for platelet count, random urine protein, and total urine protein:creatinine ratio were collected from all patients before each procedure. RESULTS: Mean patient age was 28.9 years (range, 2-76 years). Mean platelet count was 307 × 109 /L (range, 96-755 × 109 /L; normal lab limits, 150-450 × 109 /L), mean random urine protein was 0.164 g/L (range, <0.05-0.73 g/L), and mean total urine protein:creatinine ratio was 0.885 g per gram creatinine (range, 0.12-9.71 g per gram creatinine). No laboratory values precluded continuing treatment for any patient. DISCUSSION: Although further study on a larger cohort is warranted for more definitive conclusions, it may not be necessary to measure platelet count and urine protein before each nusinersen treatment, particularly in the maintenance phase.

Torcular pseudomass in newborns and its association with delivery: follow up or leave it alone?

PURPOSE: The cranial epidural space (ES) is a potential space and is not generally recognized unless there is underlying pathology. With MRI in newborns, we have frequently observed T2 hyperintense thickening of the ES posterior to the confluence of sinuses, also referred to as "torcular pseudomass" (TP). We aim to identify the frequency of TP and possible associations with delivery. METHODS: Retrospectively, brain MRIs of 194 neonates obtained within the first 2 weeks of life were evaluated. If TP was present, imaging characteristics and thickness were assessed by two observers, using fat-suppressed T2WI/FLAIR, T1WI, and SWI. Exclusion criteria were motion artifact, lack of sagittal T2WI, and lack of clinical data. Medical records were evaluated for demographic and clinical data. Follow-up exams were evaluated if available. Patients with TP and without were compared using Student t and chi-square tests. RESULTS: TP was present in 64/158 (40%). No difference was found between the groups regarding sex, gestational age, birth weight, delivery type, fetal presentation during delivery, birth difficulty, and neurological sequelae (p > 0.05). Eight patients with TP underwent follow-up imaging, and in 6/8, TP completely resolved. Two patients showed persistent TP, improving from 3.2 to 1 mm in one child and from 3.2 to 2.8 mm in the other within a week. CONCLUSION: TP frequently occurs in early newborns. TP does not appear to be associated with factors related to delivery, shows complete resolution in most cases with a follow-up, and is likely of no clinical importance.

A common yet undescribed MRI finding in newborns: posterior epidural space edema of the cervical and upper thoracic spine.

PURPOSE: Posterior spinal epidural space (PSES) is a fat-containing space. We noted numerous spinal MRIs demonstrating T2-hyperintense thickening of the cervical/thoracic PSES in early newborns, resembling epidural edema. Our aim is to describe the appearance/frequency of this finding and explore any associations with delivery. METHODS: Retrospectively, 202 spinal/cranial MRIs, belonging to newborns within the first 2 weeks of life, were evaluated using sagittal fat-suppressed T2, T1-FLAIR, and STIR. Exclusion criteria were motion, incomplete spine imaging, lack of sagittal T2/STIR, and inadequate clinical data. Ninety-three patients were included in the final analysis. We reviewed all cases for T2 hyperintense thickened PSES and, if present, accompanying abnormal T1 signal. The spinal canal and PSES thickness were measured. Clinical and demographic data were collected. Follow-up exams were evaluated, if available. Cases with thickened PSES and without were compared. RESULTS: T2-hyperintense thickened PSES was present in 60/93 (64.5%). Mean PSES thickness was 2.3 mm (0.7-4.6). The mean PSES thickness/spinal canal diameter ratio was 0.2 (0.1-0.5). No cord compression was identified. One had a hyperintense T1 PSES signal, compatible with epidural hemorrhage. No difference was found between those with thickened PSES and without, regarding sex, gestational age, birth weight, birth method, difficult delivery, fetal position, or neurologic status (p>0.05). Follow-up imaging was available in 10, with complete resolution of T2 hyperintense PSES thickening. CONCLUSION: T2 hyperintense PSES thickening is common in imaged newborns and reversible at follow-up. No significant neurologic outcomes were found related to its presence; thus, follow-up does not appear necessary.

Therapeutic Leukapheresis in Pediatric Leukemia: Utilization Trend and Early Outcomes in a US Nationwide Cohort.

Leukapheresis (LA) in pediatric leukemia is performed for leukostasis, a life-threatening emergency in the setting of extremely increased blast cell counts. The authors aimed to assess the epidemiology of pediatric leukemia who received LA. The authors reviewed US nationally representative admission records of patients less than 20 years of age in the Kids' Inpatient Database for the years 2000, 2003, 2006, 2009, 2012, and 2016. Incidence of new leukemia cases who underwent LA were calculated for the years 2009, 2012, and 2016. Cox and logistic regression analyses were performed to ascertain the risk factors for adverse outcomes. There were 526 admissions for pediatric patients with acute lymphoblastic leukemia (ALL) (n=328), acute myeloid leukemia (AML) (n=124), or chronic myeloid leukemia (CML) (n=74) who underwent LA over the study period. The incidence of leukemia cases that required LA was lower in 2016 than in 2009 or 2012 (1.4%, 2.2%, and 2.7%, respectively; P=0.001). In-hospital mortality was higher in AML than ALL (hzard ratio, 3.2; 95% confidence interval, 1.1-9.1). None with CML died during admission. This first population-based study of LA in pediatric leukemia showed a decreased utilization of LA over recent years. The higher inpatient mortality in AML, as compared with ALL or CML, warrant further investigations.

Impact of 18-French Rectal Tube Placement on Image Quality of Multiparametric Prostate MRI.

This study compared prostate multiparametric MRI (mpMRI) performed using an 18-French rectal tube in place throughout the examination after initial placement by a technologist (n = 97) with mpMRI performed without rectal tube placement (n = 99). Acquisition parameters were otherwise identical. Two radiologists scored subjective image quality and measured rectal diameter. For both readers, rectal tube placement was associated (p < .001) with improved ADC map quality, decreased DWI distortion, decreased rectal gas, and decreased rectal diameter. Findings support routine rectal tube placement for prostate mpMRI.

Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study.

BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.

Cross-sectional study of sex differences in psychosocial quality of life of long-term melanoma survivors.

PURPOSE: A cancer diagnosis and subsequent treatment can have a significant impact on an individual's quality of life. Differences in quality of life by sex among long-term melanoma survivors remain unclear. The objective of this study was to describe sex differences in cancer-specific psychosocial quality of life of long-term melanoma survivors. METHODS: Melanoma survivors 7-10 years post-diagnosis from a previously conducted population-based case-control study were recruited for a cross-sectional survey. Validated measures of psychosocial quality of life related to melanoma diagnosis were assessed. Outcomes were compared by sex using linear regression models adjusting for age, education, income, and marital status. RESULTS: The survey response rate was 62% (433 females, 291 males; 86% stage I disease). Females were more likely to report changes in their appearance (p = 0.006) and being more fearful of recurrence (p = 0.001) or a second melanoma (p = 0.001) than males but were also more likely to report that melanoma had a positive impact on their lives (p < 0.0001). Males were more likely to agree with statements that emphasized that life's duration is limited (p < 0.0001). CONCLUSION: Long-term melanoma survivors reported generally favorable measures of psychosocial quality of life related to their diagnosis. Females and males reported unique quality of life concerns and may require varied methods of support following a melanoma diagnosis.

CYP51A1 polymorphism and voriconazole-associated hepatotoxicity in children undergoing hematopoietic cell transplant.

Fungal CYP51A (14α-sterol demethylase) is the target of an azole antifungal, voriconazole (VCZ), which also partially inhibits human CYP51A1. Hepatotoxicity is a common adverse effect of azoles, which is reported to be caused by altered gene expressions secondary to cholesterol synthesis inhibition by azoles. This is a post-hoc analysis of a previously conducted phase 1 dose-finding study of prophylactic VCZ in 56 pediatric hematopoietic cell transplant recipients. We explored an association between variants in human CYP51A1 (rs2282976 and rs6465348) and VCZ-induced hepatotoxicity. Genotype A/G or G/G in rs6465348 showed lower odds of hepatotoxicity after adjusting for VCZ area-under-the-curve (OR: 0.10, 95% CI: 0.01 - 0.79, vs. A/A).

Impact of Obesity on Voriconazole Pharmacokinetics among Pediatric Hematopoietic Cell Transplant Recipients.

Voriconazole (VCZ) is an antifungal agent with wide inter- and intrapatient pharmacokinetic (PK) variability and narrow therapeutic index. Although obesity was associated with higher VCZ trough concentrations in adults, the impact of obesity had yet to be studied in children. We characterized the PK of VCZ in obese patients by accounting for age and CYP2C19 phenotype. We conducted intensive PK studies of VCZ and VCZ N-oxide metabolite in 44 hematopoietic stem cell transplantation (HSCT) recipients aged 2 to 21 years who received prophylactic intravenous VCZ every 12 hours (q12h). Blood samples were collected at 5 and 30 minutes; at 1, 3, 6, and 9 hours after infusion completion; and immediately before the next infusion start. We estimated PK parameters with noncompartmental analysis and evaluated for an association with obesity by multiple linear regression analysis. The 44 participants included 9 (20%) with obesity. CYP2C19 metabolism phenotypes were identified as normal in 22 (50%), poor/intermediate in 13 (30%), and rapid/ultrarapid in 9 patients (21%). Obesity status significantly affects the VCZ minimum concentration of drug in serum (Cmin) (higher by 1.4 mg/liter; 95% confidence interval [CI], 0.0 to 2.8; P = 0.047) and VCZ metabolism ratio (VCZRATIO) (higher by 0.4; 95% CI, 0.0 to 0.7; P = 0.03), while no association was observed with VCZ area under the curve (AUC) (P = 0.09) after adjusting for clinical factors. A younger age and a CYP2C19 phenotype were associated with lower VCZ AUC. Obesity was associated with decreased metabolism of VCZ to its inactive N-oxide metabolite and, concurrently, increased VCZ Cmin, which is deemed clinically meaningful. Future research should aim to further characterize its effects and determine a proper dosing regimen for the obese.

A Comparison of Methods for High-Spatial-Resolution Diffusion-weighted Imaging in Breast MRI.

Background Diffusion-weighted imaging (DWI) shows promise in detecting and monitoring breast cancer, but standard spin-echo (SE) echo-planar DWI methods often have poor image quality and low spatial resolution. Proposed alternatives include readout-segmented (RS) echo-planar imaging and axially reformatted (AR)-simultaneous multislice (SMS) imaging. Purpose To compare the resolution and image quality of standard SE echo-planar imaging DWI with two high-spatial-resolution alternatives, RS echo-planar and AR-SMS imaging, for breast imaging. Materials and Methods In a prospective study (2016-2018), three 5-minute DWI protocols were acquired at 3.0 T, including standard SE echo-planar imaging, RS echo-planar imaging with five segments, and AR-SMS imaging with four times slice acceleration. Participants were women undergoing breast MRI either as part of a treatment response clinical trial or undergoing breast MRI for screening or suspected cancer. A commercial breast phantom was imaged for resolution comparison. Three breast radiologists reviewed images in random order, including clinical images indicating the lesion, images with b value of 800 sec/mm2, and apparent diffusion coefficient (ADC) maps from the three randomly labeled DWI methods. Readers measured the longest dimension and lesion-average ADC on three DWI methods, reported measurement confidence, and rated or ranked the quality of each image. The scores were fit to a linear mixed-effects model with intercepts for reader and subject. Results The smallest feature (1 mm) was only detectible in a phantom on images from AR-SMS DWI. Thirty lesions from 28 women (mean age, 50 years ± 13 [standard deviation]) were evaluated. On the five-point Likert scale for image quality, AR-SMS imaging scored 1.31 points higher than SE echo-planar imaging and 0.74 points higher than RS echo-planar imaging, whereas RS echo-planar imaging scored 0.57 points higher than SE echo-planar imaging (all P < .001). Conclusion The axially reformatted simultaneous multislice protocol was rated highest for image quality, followed by the readout-segmented echo-planar imaging protocol. Both were rated higher than the standard spin-echo echo-planar imaging. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Partridge in this issue.

The Role of Dual-Phase FDG PET/CT in the Diagnosis and Follow-Up of Brain Tumors.

OBJECTIVE. FDG PET/CT of brain tumors is limited by background activity. Dual-phase FDG PET/CT can eliminate this limitation and allow discernment of viable tumors. Our aim was to assess the diagnostic capability of dual-phase FDG PET/CT qualitatively and quantitatively and to determine cutoff values for dual-phase FDG PET/CT in brain tumor imaging. MATERIALS AND METHODS. Retrospectively, 51 malignant brain tumors were evaluated with dual-phase FDG PET/CT in 32 patients. Acquisitions were performed 30 minutes (time 1) and 3 hours (time 2) after administration of 10 mCi (370 MBq) FDG and 6 hours of fasting. Two observers independently and qualitatively evaluated lesions. A weighted Cohen kappa was used to calculate interrater reliability and accuracy. Quantitatively, maximum standardized uptake value (SUVmax) was measured in the lesions, contralateral white matter (CWM), contralateral caudate nucleus head, and ipsilateral cerebellar cortex (CC). Lesion-to-CWM SUVmax, lesion-to-contralateral caudate nucleus head SUVmax, and lesion-to-ipsilateral CC SUVmax ratios at time 1 and time 2 were calculated. ROC analysis was used to determine optimum cutoff values, and AUC ratios were compared among quantitative parameters. Lesion outcome was determined by pathologic results (available in 15 lesions), lesion stability on serial MRI examinations (representing nonviable tumor), or decreased tumor size on serial MRI examinations after new treatment (representing viable tumor). RESULTS. Thirty-seven viable and 14 nonviable lesions were evaluated. Qualitatively, the diagnostic accuracy (first observer: κ = 0.45 to κ = 0.59; second observer: κ = 0.41 to κ = 0.66) and interrater reliability (at time 1: κ = 0.51; at time 2: κ = 0.83) improved with delayed imaging. AUC and ROC analysis showed comparably high sensitivity, specificity, and accuracy profiles for early and delayed dual-phase FDG PET/CT. Some of the proposed cutoff values were as follows: lesion SUVmax at time 1, 7.20 (sensitivity, 89.2%; specificity, 85.7%); lesion SUVmax at time 2, 7.80 (sensitivity, 97.3%; specificity, 71.4%); lesion-to-CWM SUVmax at time 1, 2.05 (sensitivity, 78.4%; specificity, 92.9%); and lesion-to-CWM SUVmax at time 2, 2.36 (sensitivity, 81.1%; specificity, 85.7%). CONCLUSION. Dual-phase FDG PET/CT improves lesion detection and diagnostic accuracy in malignant brain tumors.

Increased risk of second primary hematologic and solid malignancies in patients with mycosis fungoides: A Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: Mycosis fungoides (MF) is associated with increased risk of second primary hematologic malignancies, but its association with second primary solid tumors is less well characterized. OBJECTIVE: This retrospective analysis seeks to assess the risk of being diagnosed with a second primary hematologic or solid malignancy in patients with MF. DESIGN: We performed an analysis of patients diagnosed with MF from 2000 through 2015 in the United States cancer registries of SEER-18 (N = 6742). RESULTS: Relative risks were estimated by using standardized incidence ratios (SIRs). Among 6742 patients, there were 511 (7.5%) second cancer events (SIR, 10.15; 95% confidence interval [CI], 9.29-11.07). These included 184 (36.0%) hematologic malignancies (SIR, 39.71; 95% CI, 34.05-46.05) and 327 (64.0%) solid tumor malignancies (SIR, 7.33; 95% CI, 6.56-8.17). Patients with MF were at increased risk for non-Hodgkin lymphoma; Hodgkin lymphoma; melanoma; and lung, female breast, prostate, colon, and renal cancers. Females were at higher risk than males (P < .05). All ethnic groups showed a statistically significant elevation in SIRs. Elevation of SIRs was observed across all stages of MF. CONCLUSIONS AND RELEVANCE: Patients with MF are at increased risk for diagnosis of second primary malignancies and should be carefully screened for discernable signs and symptoms of second malignancies.

Smoking Topography Characteristics During a 6-Week Trial of Very Low Nicotine Content Cigarettes in Smokers With Serious Mental Illness.

INTRODUCTION: A nicotine-reduction policy could have major benefits for smokers with serious mental illness (SMI). However, potential unintended consequences, such as compensatory smoking, should be considered to ensure that such a policy does not negatively affect this population. The purpose of this secondary analysis was to examine the impact of smoking very low nicotine content (VLNC) cigarettes for 6 weeks on smoking topography characteristics, indicators of compensatory smoking, among smokers with SMI. AIMS AND METHODS: After a baseline usual brand smoking phase, smokers with SMI (N = 58) were randomly assigned under double-blind conditions to receive either VLNC (0.4 mg nicotine per g tobacco) or normal nicotine content (NNC; 15.8 mg nicotine per g tobacco) research cigarettes for 6 weeks. During two study visits scheduled 6 weeks apart, participants smoked either their usual brand (baseline) or assigned study cigarettes (postrandomization) through a handheld smoking topography device. Univariate analysis of variance compared smoking topography indices with cigarette condition (VLNC vs. NNC) as the between-subjects factor with corresponding baseline topography results included as covariates. RESULTS: At week 6, participants in the VLNC condition smoked fewer puffs per cigarette and had shorter interpuff intervals compared to participants in the NNC condition (ps < .05). There were no differences between research cigarette conditions at week 6 for cigarette volume, puff volume, puff duration, peak flow rate, or carbon monoxide boost. CONCLUSIONS: Findings are consistent with acute VLNC cigarette topography studies and indicate that a nicotine-reduction policy is unlikely to lead to compensation among smokers with SMI. IMPLICATIONS: Given the high smoking rates among people with SMI, understanding how a nicotine-reduction policy may affect this population is critically important. When considering the smoking topography results as a whole, smokers with SMI did not engage in compensatory smoking behavior when using VLNC cigarettes during a 6-week trial. Study findings suggest that compensatory smoking is not likely to occur among smokers with SMI if nicotine content is lowered to minimally addictive levels.

Cigarette Smokers Versus Cousers of Cannabis and Cigarettes: Exposure to Toxicants.

INTRODUCTION: Cannabis and tobacco couse is common and could expose users to higher levels of toxicants. No studies have examined biomarkers of toxicant exposure in cousers of cannabis and cigarettes, compared with cigarette smokers (CS). AIMS AND METHODS: Adult daily CS were recruited from 10 US sites for a study of reduced nicotine cigarettes. In this analysis of baseline data, participants were categorized as either cousers of cannabis and tobacco (cousers; N = 167; urine positive for 11-nor-9-carboxy-Δ 9-tetrahydrocannnabinol and self-reported cannabis use ≥1×/week), or CS (N = 911; negative urine and no self-reported cannabis use). Participants who did not meet either definition (N = 172) were excluded. Self-reported tobacco and cannabis use and tobacco and/or combustion-related biomarkers of exposure were compared between groups. RESULTS: Compared to CS, cousers were younger (couser Mage = 38.96, SD = 13.01; CS Mage = 47.22, SD = 12.72; p < .001) and more likely to be male (cousers = 67.7%, CS = 51.9%, p < .001). There were no group differences in self-reported cigarettes/day, total nicotine equivalents, or breath carbon monoxide, but cousers had greater use of non-cigarette tobacco products. Compared to CS, cousers had higher concentrations of 3-hydroxypropylmercapturic acid, 2-cyanoethylmercapturic acid, S-phenylmercapturic acid, 3-hydroxy-1-methylpropylmercapturic acid (ps < .05), and phenanthrene tetraol (p < .001). No biomarkers were affected by number of cannabis use days/week or days since last cannabis use during baseline (ps > .05). CONCLUSIONS: Cousers had higher concentrations of biomarkers of exposure than CS, but similar number of cigarettes per day and nicotine exposure. Additional studies are needed to determine whether cannabis and/or alternative tobacco products are driving the increased toxicant exposure. IMPLICATIONS: Cousers of cannabis and tobacco appear to be exposed to greater levels of harmful chemicals (ie, volatile organic compounds and polycyclic aromatic hydrocarbons), but similar levels of nicotine as CS. It is unclear if the higher levels of toxicant exposure in cousers are due to cannabis use or the increased use of alternative tobacco products compared with CS. It is important for studies examining biomarkers of exposure among CS to account for cannabis use as it may have a significant impact on outcomes. Additionally, further research is needed examining exposure to harmful chemicals among cannabis users.

Role of adjuvant radiation or re-excision for early stage vulvar squamous cell carcinoma with positive or close surgical margins.

OBJECTIVES: This study aims to evaluate whether re-excision or adjuvant radiation for stage I vulvar squamous cell carcinoma (SCC) with either a close or positive surgical margin improves recurrence-free survival. METHODS: Patients with pathologically confirmed FIGO stage I vulvar SCC who underwent primary surgical management between January 1, 1995 and September 30, 2017 and had positive or close (<8 mm) surgical margins were included. Kaplan-Meier curves were generated and compared using the log-rank test. RESULTS: Of 150 patients with stage I vulvar SCC, 47 (31.3%) had positive or close margins. Median follow-up time was 25 months (IQR 13-59 months). Twenty-one (44.6%) patients received additional treatment with re-excision (n = 17) or vulvar radiation (n = 4); 26 (55.3%) patients received no additional therapy. Patients with positive margins were more likely to receive additional therapy compared to patients with close margins (80% vs 35.1%, p = 0.03). The 2-year recurrence rates were similar between the no further therapy and the re-excision/vulvar radiation groups (11.5% vs 4.8%, p = 0.62). Local recurrence-free survival (RFS) and overall survival (OS) were similar between patients who received re-excision/vulvar radiation and patients who received no further therapy (p = 0.10 and p = 0.16, respectively). Subgroup analysis of the 37 patients with close margins demonstrated no difference in RFS or OS when patients received re-excision or adjuvant vulvar radiation compared to no additional therapy (p = 0.74 and p = 0.82, respectively). CONCLUSIONS: In our study, any additional treatment following primary surgical resection did not improve RFS or OS in stage IA and IB vulvar SCC. Larger studies are warranted in order to definitively determine the role of re-excision and adjuvant radiation in early stage disease.

The efficacy of fluoroscopy-guided epidural blood patch in the treatment of spontaneous and iatrogenic cerebrospinal fluid leakage.

OBJECTIVE: To evaluate patient outcomes following fluoroscopy-guided epidural blood patch (FGEBP), factors affecting the outcome, and to identify the rate of fluoroscopy-guided lumbar punctures (FGLP) requiring FGEBP. METHODS: All FGLPs and FGEBPs between January 2014 and May 2017 were retrospectively evaluated. Information regarding patient characteristics, details of previous dural puncture (DP), details of the FGEBP, and FGEBP outcome were recorded. The outcome was classified into three categories as "complete response", "partial response", and "no response". Patients with "complete response" were compared to the combined group of "no response" and "partial response", classified as "incomplete response". Two-sample/Fisher's exact (continued/categorical variables) tests were used (p < 0.05). RESULTS: Sity-seven FGEBPs were performed in 63 patients (female/male, 36/27; mean age/BMI 38/28.2). Fifty-nine were referred following DP; 31 were performed by radiologists. The rate of FGLPs requiring FGEBP was 1.78% within 3.5 years. The mean DP-FGEBP interval was 4.8 days. "Complete response" was achieved in 56 (84.8%), "no response" was found following 4 (6%) procedures. Average applied blood volume was 16 cc (5-30 cc). No difference was found between "complete response" and "incomplete response" groups regarding age, sex, BMI, DP performer, DP level, DP fluoroscopy time, DP needle caliber/type, FGEBP level, FGEBP needle caliber/type, FGEBP fluoroscopy time, FGEBP performer, and applied blood volume (p > 0.05). Despite approaching significance, no statistically significant difference was found regarding the presence of previous DP (p = 0.06). CONCLUSIONS: The efficacy of FGEBP is high in a group of patients referred to radiology for treatment of CSF leakage with complete response in 84.8% of patients. KEY POINTS: • Fluoroscopy-guided epidural blood patch completely resolved symptoms in 85% of post-dural puncture headaches. • The success approaches 95% when including the patients with partial resolution of symptoms. • Epidural blood patch rate is found 1.8% following 1703 fluoroscopy-guided lumbar punctures.

Effects of 6-Week Use of Very Low Nicotine Content Cigarettes in Smokers With Serious Mental Illness.

INTRODUCTION: The US Food and Drug Administration is considering implementing a reduced-nicotine standard for cigarettes. Given the high rate of smoking among people with serious mental illness (SMI), it is important to examine the responses of these smokers to very low nicotine content (VLNC) cigarettes. METHODS: This trial compared the effects of VLNC (0.4 mg nicotine/g tobacco) and normal nicotine content cigarettes (15.8 mg/g) over a 6-week period in non-treatment-seeking smokers with schizophrenia, schizoaffective disorder, or bipolar disorder (n = 58). Linear regression was used to examine the effects of cigarette condition on cigarettes per day, subjective responses, nicotine and tobacco toxicant exposure, craving, withdrawal symptoms, and psychiatric symptoms. RESULTS: At week 6, participants in the VLNC condition smoked fewer cigarettes per day, had lower breath carbon monoxide levels, lower craving scores, and rated their study cigarettes lower in satisfaction, reward, enjoyment, and craving reduction than those in the normal nicotine content condition (ps < .05). Week 6 psychiatric and extrapyramidal symptoms did not differ by condition, except for scores on a measure of parkinsonism, which were lower in the VLNC condition (p < .05). There were no differences across conditions on total nicotine exposure, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, withdrawal symptoms, or responses to abstinence. CONCLUSIONS: These results suggest that a reduced-nicotine standard for cigarettes would reduce smoking among smokers with SMI. However, the lack of effect on total nicotine exposure indicates VLNC noncompliance, suggesting that smokers with SMI may respond to a reduced-nicotine standard by substituting alternative forms of nicotine. IMPLICATIONS: Results from this trial suggest that a reduced-nicotine standard for cigarettes would reduce smoking rates and smoke exposure in smokers with SMI, without increasing psychiatric symptoms. However, noncompliance with VLNC cigarettes was observed, suggesting that these smokers might respond to a reduced-nicotine standard by substituting alternative forms of nicotine.