Ocean cavity regime shift reversed West Antarctic grounding line retreat in the late Holocene.

Recent geologic and modeled evidence suggests that the grounding line of the Siple Coast of the West Antarctic Ice Sheet (WAIS) retreated hundreds of kilometers beyond its present position in the middle to late Holocene and readvanced within the past 1.7 ka. This grounding line reversal has been attributed to both changing rates of isostatic rebound and regional climate change. Here, we test these two hypotheses using a proxy-informed ensemble of ice sheet model simulations with varying ocean thermal forcing, global glacioisostatic adjustment (GIA) model simulations, and coupled ice sheet-GIA simulations that consider the interactions between these processes. Our results indicate that a warm to cold ocean cavity regime shift is the most likely cause of this grounding line reversal, but that GIA influences the rate of ice sheet response to oceanic changes. This implies that the grounding line here is sensitive to future changes in sub-ice shelf ocean circulation.

Assessment of a Community Pharmacist Remote Monitoring Service in Patients Using Continuous Glucose Monitors (CGMs).

BACKGROUND: Diabetes is the eighth leading cause of death and has a substantial impact on the United States (U.S.) health care system. Recent changes to major insurance formularies allow for increased access to continuous glucose monitors (CGM). Community pharmacists routinely assist and educate patients about diabetes care, including usage of CGM. OBJECTIVES: The purpose of this study was to evaluate the clinical impact of a community pharmacist remote CGM monitoring service on patients' glycemic metrics. Patient completion of comprehensive diabetes standards of care and pharmacist interventions and recommendations were assessed as secondary objectives. METHODS: This study was a prospective, feasibility study conducted at two pharmacies within one regional division of a large community pharmacy chain between November 2022 and June 2023. A pharmacist conducted patient enrollment visits and remotely monitored CGM glycemic metrics via cloud-based platforms per the study protocol. CGM glycemic metrics were evaluated for each patient three months pre- and post-study enrollment, including time above range (TAR), time in range (TIR), time below range (TBR), glucose management indicator (GMI), average glucose, CGM utilization rate, and glucose variability. Metrics were evaluated for statistical significance using the Wilcoxon signed-rank test and descriptive statistics. RESULTS: Pharmacists enrolled 36 patients in this study with 20 patients completing the full three-month study period per protocol. There was a statistically significant improvement in three of eight glycemic metrics (very high TAR, TIR, and average glucose). Specifically, TIR had the largest improvement from 61.8% pre-enrollment to 69.9% (p < 0.006) post-enrollment. All other pertinent glycemic metrics displayed improvements but were not statistically significant. CONCLUSION: The results demonstrate clinically and statistically significant improvements in several glycemic metrics for patients who participated in the community pharmacist-led remote CGM monitoring service, which may result in improved diabetes control and fewer long-term diabetes-related health complications.

Mechanism of actin capping protein recruitment and turnover during clathrin-mediated endocytosis.

Clathrin-mediated endocytosis depends on polymerization of a branched actin network to provide force for membrane invagination. A key regulator in branched actin network formation is actin capping protein (CP), which binds to the barbed end of actin filaments to prevent the addition or loss of actin subunits. CP was thought to stochastically bind actin filaments, but recent evidence shows CP is regulated by a group of proteins containing CP-interacting (CPI) motifs. Importantly, how CPI motif proteins function together to regulate CP is poorly understood. Here, we show Aim21 and Bsp1 work synergistically to recruit CP to the endocytic actin network in budding yeast through their CPI motifs, which also allosterically modulate capping strength. In contrast, twinfilin works downstream of CP recruitment, regulating the turnover of CP through its CPI motif and a non-allosteric mechanism. Collectively, our findings reveal how three CPI motif proteins work together to regulate CP in a stepwise fashion during endocytosis.

Differential encoding of temporal context and expectation under representational drift across hierarchically connected areas.

The classic view that neural populations in sensory cortices preferentially encode responses to incoming stimuli has been strongly challenged by recent experimental studies. Despite the fact that a large fraction of variance of visual responses in rodents can be attributed to behavioral state and movements, trial-history, and salience, the effects of contextual modulations and expectations on sensory-evoked responses in visual and association areas remain elusive. Here, we present a comprehensive experimental and theoretical study showing that hierarchically connected visual and association areas differentially encode the temporal context and expectation of naturalistic visual stimuli, consistent with the theory of hierarchical predictive coding. We measured neural responses to expected and unexpected sequences of natural scenes in the primary visual cortex (V1), the posterior medial higher order visual area (PM), and retrosplenial cortex (RSP) using 2-photon imaging in behaving mice collected through the Allen Institute Mindscope's OpenScope program. We found that information about image identity in neural population activity depended on the temporal context of transitions preceding each scene, and decreased along the hierarchy. Furthermore, our analyses revealed that the conjunctive encoding of temporal context and image identity was modulated by expectations of sequential events. In V1 and PM, we found enhanced and specific responses to unexpected oddball images, signaling stimulus-specific expectation violation. In contrast, in RSP the population response to oddball presentation recapitulated the missing expected image rather than the oddball image. These differential responses along the hierarchy are consistent with classic theories of hierarchical predictive coding whereby higher areas encode predictions and lower areas encode deviations from expectation. We further found evidence for drift in visual responses on the timescale of minutes. Although activity drift was present in all areas, population responses in V1 and PM, but not in RSP, maintained stable encoding of visual information and representational geometry. Instead we found that RSP drift was independent of stimulus information, suggesting a role in generating an internal model of the environment in the temporal domain. Overall, our results establish temporal context and expectation as substantial encoding dimensions in the visual cortex subject to fast representational drift and suggest that hierarchically connected areas instantiate a predictive coding mechanism.

Connecting single-cell transcriptomes to projectomes in mouse visual cortex.

The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge. To address this, we collected coordinated Patch-seq and whole brain morphology data sets of excitatory neurons in mouse visual cortex. From the Patch-seq data, we defined 16 integrated morpho-electric-transcriptomic (MET)-types; in parallel, we reconstructed the complete morphologies of 300 neurons. We unified the two data sets with a multi-step classifier, to integrate cell type assignments and interrogate cross-modality relationships. We find that transcriptomic variations within and across MET-types correspond with morphological and electrophysiological phenotypes. In addition, this variation, along with the anatomical location of the cell, can be used to predict the projection targets of individual neurons. We also shed new light on infragranular cell types and circuits, including cell-type-specific, interhemispheric projections. With this approach, we establish a comprehensive, integrated taxonomy of excitatory neuron types in mouse visual cortex and create a system for integrated, high-dimensional cell type classification that can be extended to the whole brain and potentially across species.

"En-Bloc" Enucleation With Early Apical Release Compared to Standard Holmium Laser Enucleation of the Prostate: A Retrospective Pilot Study During the Initial Learning Curve of a Single Surgeon.

OBJECTIVE: To compare operative efficiency of Holmium laser enucleation of the prostate (HoLEP) using both the standard multi-incisional approach and en-bloc enucleation with early apical release during the initial learning curve. MATERIALS AND METHODS: We retrospectively reviewed the initial 95 consecutive men who underwent HoLEP between April 2019 and September 2020 by a single surgeon. We compared patient demographics, and pre-, intra-, and post-operative metrics between both groups. Differences between groups were evaluated with Mann-Whitney U and Kruskal-Wallis tests. RESULTS: Forty-nine patients underwent the standard HoLEP approach, and 46 patients underwent the en-bloc approach. Compared to a standard HoLEP, the en-bloc approach was associated with decreased operative time (131.11 minutes vs 153.59 minutes, P = .007) with similar weights of tissue removed. Operative efficiency, as measured by grams of prostate tissue removed per minute, was greater for the en-bloc approach (0.49 g/min vs 0.36 g/min, P = .005). There was no difference in length of stay (0.91 days vs 0.96 days, P = .383), laser efficiency (4.41 kJ/g vs 4.83 kJ/g, P = .200), or number of post-operative complications (10 vs 6, P = .236) between the groups. CONCLUSION: Utilization of the en-bloc technique during the initial learning curve allows for a faster, more efficient operation without any difference in functional outcomes or major complications compared to a standard HoLEP.

The evaluation of mandatory alerts on long-acting opioid prescriptions and the use of a community pharmacy naloxone protocol.

BACKGROUND: Opioid overdose deaths accounted for approximately 69.5% of the total drug overdoses in the United States in 2018. In the same year, the Centers for Disease Control and Prevention estimates that around 9 million opportunities to dispense naloxone to high-risk patients were missed. Community pharmacists are equipped to help all patients obtain naloxone to prevent opioid-related overdoses. OBJECTIVES: The purpose of this study was to determine the impact of mandatory alerts on the dispensing of naloxone by pharmacists using a physician-approved protocol. The primary objective of this study was to evaluate the change in the number of dispensed naloxone prescriptions via physician-approved protocol compared with the same time period in the previous year. The secondary objective was to evaluate the pharmacists' knowledge and confidence dispensing naloxone via physician-approved protocol. PRACTICE DESCRIPTION: A system-generated mandatory alert that prompted pharmacists to assess the need for naloxone and initiate and dispense as appropriate via a physician-approved protocol was implemented in 5 pharmacies of a large community pharmacy chain between June and July 2020. PRACTICE INNOVATION: A technology enhancement was designed that automatically created a mandatory alert in the pharmacy management system for all patients who were dispensed a long-acting opioid medication to prompt pharmacists to initiate and dispense naloxone as appropriate. EVALUATION METHODS: The impact of the mandatory alert was evaluated by assessing patients' medication fill history in the pharmacy management system to determine the change in naloxone prescriptions dispensed. RESULTS: During the intervention period, pharmacists initiated and dispensed 34 incremental naloxone prescriptions via a physician-approved protocol compared with the same time period in the previous year. CONCLUSION: The results illustrated that system-generated mandatory alerts prompting pharmacist intervention can effectively increase pharmacist utilization of a physician-approved protocol, resulting in increased naloxone prescriptions dispensed to high-risk patients.

Survey of spiking in the mouse visual system reveals functional hierarchy.

The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically1. However, direct observation of cellular-level functional interactions across this hierarchy is lacking due to the challenge of simultaneously recording activity across numerous regions. Here we describe a large, open dataset-part of the Allen Brain Observatory2-that surveys spiking from tens of thousands of units in six cortical and two thalamic regions in the brains of mice responding to a battery of visual stimuli. Using cross-correlation analysis, we reveal that the organization of inter-area functional connectivity during visual stimulation mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas3. We find that four classical hierarchical measures-response latency, receptive-field size, phase-locking to drifting gratings and response decay timescale-are all correlated with the hierarchy. Moreover, recordings obtained during a visual task reveal that the correlation between neural activity and behavioural choice also increases along the hierarchy. Our study provides a foundation for understanding coding and signal propagation across hierarchically organized cortical and thalamic visual areas.

Implementation of a depression screening as part of a holistic adherence assessment in a large community pharmacy chain.

BACKGROUND: Medication nonadherence is associated with increased morbidity and mortality, higher rates of hospital admissions, and increased health care costs. Nearly half of patients do not take their medications as prescribed leading to poor outcomes. Patients with chronic conditions, especially those with depression, demonstrate lower adherence to their medications. Community pharmacists routinely address demographic and sociocultural barriers and are equipped to screen for and assist with behavioral barriers to medication adherence. OBJECTIVES: The purpose of this study was to assess the feasibility and impact of conducting a depression screening as part of a holistic adherence assessment. The primary objective of this project was to evaluate the impact of a holistic adherence assessment on medication adherence. The secondary objectives evaluated patients' barriers to adherence, Patient Health Questionnaires 2 and 9 (PHQ-2 and 9) results, and pharmacist interventions. PRACTICE DESCRIPTION: Pharmacists conducted a holistic adherence assessment and performed a depression screening for patients who were nonadherent or at risk of becoming nonadherent to their chronic medications. PRACTICE INNOVATION: A pharmacist-led holistic adherence assessment implemented in 2 pharmacies of a large community pharmacy chain between January and May 2020. EVALUATION METHODS: The impact on medication adherence was evaluated by assessing if patients received the next fill of their chronic medication on time after the holistic adherence assessment. RESULTS: During the study period, 69 patients completed the holistic adherence assessment and were screened for depression. A total of 12 patients (17.4%) screened positive on the PHQ-2, and 6 patients (8.7%) screened positive on the PHQ-9. After the intervention, 42 patients (60.9%) received the next fill of their targeted chronic medication on time, and 27 patients (39.1%) were late to pick up their next fill. CONCLUSION: The results illustrated that community pharmacists can incorporate a depression screening into a holistic adherence assessment effectively to screen for behavioral barriers that may affect medication adherence.

Candida auris Direct Detection from Surveillance Swabs, Blood, and Urine Using a Laboratory-Developed PCR Method.

Candida auris is an emerging fungal pathogen with cases reported in countries around the world and in 19 states within the United States as of August 2020. The CDC has recommended that hospitals perform active surveillance upon admission for patients with the appropriate risk factors. Currently, active surveillance requires that local hospitals send surveillance swabs to a public health laboratory for analysis. In this work, a real-time PCR assay was developed for the specific detection of C. auris from surveillance swabs, blood, and urine to enable rapid detection of this pathogen. The assay uses commercially available primers and reporter probes and it was verified on the LightCycler 480 PCR platform. Contrived specimens and prospectively collected composite groin/axilla surveillance swabs were used to validate the assay. The performance of the PCR assay on surveillance swabs was also compared to a second PCR assay targeting C. auris that was performed at the Minnesota Department of Health-Public Health Laboratory (MDH-PHL). Our PCR assay is able to detect and differentiate C. auris from closely related Candida species such as C. duobushaemulonii, C. haemulonii, and C. pseudohaemulonii on the basis of melting curve temperature differences.

Impact of an adherence intervention program on patient adherence and star ratings measures in a large community pharmacy chain.

OBJECTIVE: This study aimed to determine the impact of an adherence intervention program on medication adherence rates and performance on the Centers for Medicare and Medicaid Services star ratings measures. SETTING: The study was conducted in a large community pharmacy chain comprising more than 2200 pharmacies and 7000 pharmacists across 36 states. PRACTICE DESCRIPTION: Pharmacists conducted adherence interventions with patients with a proportion of days covered (PDC) of less than 80% for hypertension, cholesterol, and diabetes star ratings medications. PRACTICE INNOVATION: A longitudinal, pharmacist-led adherence intervention program with automated follow-up interventions was implemented between June 2017 and December 2017. EVALUATION: The percentage of patients with a PDC of greater than or equal to 80% and performance on CMS star ratings measures were evaluated for Medicare Part D Prescription Drug Plan (PDP) and Medicare Advantage Prescription Drug (MAPD) Plan populations in 2017 compared with that of 2015 and 2016. Patient-level PDC change, pharmacist intervention completion, and pharmacist recommendation of additional pharmacy services were also measured. RESULTS: A total of 241,261 interventions were generated in the electronic dispensing systems. Pharmacists enrolled 60,232 patients and completed 75.4% of follow-up interventions, with an average of 1.3 follow-ups per patient. For the Medicare PDP population, improvement in the percentage of adherent patients ranged from 1.1% to 1.2% and 0.9% to 1.8% for 2015-2016 and 2016-2017, respectively, whereas improvement ranged from 2.1% to 2.5% and 2.0% to 3.0% for 2015-2016 and 2016-2017, respectively, for the MAPD Plan population. In 2016 and 2017, performance on cholesterol and diabetes measures achieved the 4-star cut point, and the hypertension measure achieved the 5-star cut point. CONCLUSION: This study demonstrated the successful implementation and pharmacist participation in an adherence intervention program in a large community pharmacy chain. Compared with the previous year, medication adherence improved for patients attributed to hypertension, cholesterol, and diabetes measures, and performance on CMS star rating measures was maintained, despite an increase in cut points.

Diagnostic capability of dynamic ultrasound evaluation of supination-external rotation ankle injuries: a cadaveric study.

BACKGROUND: Ankle syndesmosis injuries are common and range in severity from subclinical to grossly unstable. Definitive diagnosis of these injuries can be made with plain film radiographs, but are often missed when severity or image quality is low. Computed tomography (CT) and magnetic resonance imaging (MRI) can provide definitive diagnosis, but are costly and introduce the patient to radiation when CT is used. Ultrasonography may circumvent many of these disadvantages by being inexpensive, efficient, and able to detect injuries without radiation exposure. The purpose of this study was to evaluate the ability of ultrasonography to detect early stage supination-external rotation (SER) ankle syndesmosis injuries with a dynamic external rotational stress test. METHODS: Nine, all male, fresh frozen specimens were secured to an ankle rig and stress tested to 10 Nm of external rotational torque with ultrasonography at the tibiofibular clear space. The ankles were subjected to syndesmosis ligament sectioning and repeat stress measurements of the tibiofibular clear space at peak torque. Stress tests and measurements were repeated three times and averaged and analyzed using a repeated one-way analysis of variance (ANOVA). There were six ankle injury states examined including: Intact State, 75% of AITFL Cut, 100% of AITFL Cut, Fibula FX - Cut 8 cm proximal, 75% PITFL Cut, and 100% PITFL Cut. RESULTS: Dynamic external rotation stress evaluation using ultrasonography was able to detect a significant difference between the uninjured ankle with a tibiofibular clear space of 4.5 mm and the stage 1 complete injured ankle with a clear space of 6.0 mm (P < .02). Additionally, this method was able to detect significant differences between the uninjured ankle and the stage 2-4 injury states. CONCLUSION: Dynamic external rotational stress evaluation using ultrasonography was able to detect stage 1 Lauge-Hansen SER injuries with statistical significance and corroborates criteria for diagnosing a syndesmosis injury at ≥6.0 mm of tibiofibular clear space widening.

Novel Use of the Epic Electronic Medical Record Platform to Identify Lost Ureteral Stents.

Introduction and Objective: Ureteral stents are utilized in the management of many urologic conditions including nephrolithiasis, ureteral strictures, ureteral injuries, and malignant obstruction. Prolonged placement has a risk of stent failure with obstruction, infection, and encrustation. We describe the novel use of the Epic electronic medical record (EMR) platform to identify patients lost to follow-up after ureteral stent placement. We additionally identified risk factors for lost stents. Methods: A methodology was created in Epic to log ureteral stent insertion and removal, with automated reporting of stents implanted for >90 days. Starting in January 2015, a nurse reviewed the reports monthly and contacted lost patients to arrange follow-up. We retrospectively reviewed patient charts for clinical characteristics including age, gender, race, surgical urgency (elective vs emergent), and insurance status to identify risk of failure to follow-up. Results: We identified 1788 patients who underwent ureteral stent placement over the study period. Sixteen patients (0.9%) failed to follow-up for ureteral stent explantation. Using multivariate logistic regression, stents placed in an emergent setting (odds ratio [OR] 3.5, p = 0.018) and black race (OR 4.03, p = 0.018) were independent predictors of failure to follow-up. Age, gender, and insurance status were not predictors of follow-up. On average, explanted stents were in place for 15 days vs 165 days among those patients lost to follow-up. Conclusions: Lost ureteral stents are rare, however, potentially high impact events. Automated data collected through an EMR such as Epic facilitates easy identification of these events before potential complications. Stents placed in an emergent setting are at a higher risk of poor follow-up as they may not be readily connected in the health care system or misunderstand discharge instructions, creating barriers to follow-up. Black race is an independent predictor of a stent being retained and is of uncertain etiology, which will require further investigation to clarify.

Behavioral effects of chronic WIN 55,212-2 administration during adolescence and adulthood in mice.

Marijuana, a psychoactive drug that activates cannabinoid-1 (CB1) receptors in the brain, is the most prevalently abused illicit drug among American adolescents and young adults. However, the long-term consequences of adolescent exposure to cannabinoids on the brain and behavior remain poorly understood. In both humans and nonhumans, adolescence is characterized by the maturation of the endocannabinoid neurotransmitter system in the prefrontal cortex and striatum-brain regions that underlie choice and decision making and are densely packed with CB1 receptors. In the current study, the effects of chronic WIN 55,212-2 (a CB1 agonist) exposure during adolescence on reversal learning and delay discounting were compared with those of adult-onset exposure using mice. Mice were administered 3.0 mg/kg/day WIN 55,212-2 or vehicle for 21 days beginning in adolescence (postnatal days 28-49) or adulthood (postnatal days 90-111). For the reversal-learning task, there was no difference in errors or omissions to criterion following a reversal in adolescent-exposed mice but adult-exposed mice showed a delay in beginning the reversal, suggesting that adolescents, but not adults, are resilient to this drug. Adult mice given WIN 55,212-2 in adolescence displayed greater impulsivity in the form of preference for smaller-sooner reinforcers over larger-delayed ones in the delay-discounting procedure, but this was seen to a lesser extent with adult-onset exposure. These data underscore the importance of variables related to the timing and duration of exposure as well as the specific and persistent behavioral endpoints affected by chronic cannabinoid administration. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Glycoprotein-130 Expression Is Associated with Aggressive Bladder Cancer and Is a Potential Therapeutic Target.

Predicting bladder cancer progression is important in selecting the optimal treatment for bladder cancer. Because current diagnostic factors regarding progression are lacking, new factors are needed to further stratify the curative potential of bladder cancer. Glycoprotein-130 (GP130), a transmembrane protein, is central to a number of signal transduction pathways involved in tumor aggressiveness, making it an attractive target. We hypothesize that if GP130 is found in an aggressive population of bladder tumors, then blocking GP130 expression may inhibit bladder cancer growth. Herein, we quantitatively show, using 11 patient samples and four bladder cancer cell lines, that GP130 is expressed in the aggressive human bladder tumors and in high-grade bladder cancer cell lines. Moreover, GP130 is significantly correlated with tumor grade, node category, tumor category, and patient outcome. We demonstrated a tumor-specific GP130 effect by blocking GP130 expression in bladder tumor cells, which resulted in decreased cell viability and reduced cell migration. Furthermore, we reduced tumor volume by approximately 70% compared with controls by downregulating GP130 expression using chitosan-functionalized nanoparticles encapsulating GP130 siRNA in an in vivo bladder cancer xenograft mouse model. Our results indicate that GP130 expression is linked to the aggressiveness of bladder tumors, and blocking GP130 has therapeutic potential in controlling tumor growth.

Survival outcomes for patients with localised upper tract urothelial carcinoma managed with non-definitive treatment.

OBJECTIVE: To investigate the outcomes of patients with upper tract urothelial carcinoma (UTUC) with non-definitive therapy, which currently remains unknown. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify individuals with a localised, histologically confirmed kidney/renal pelvis and ureteric UC. Survival analysis using the Kaplan-Meier method was performed. A competing risk model evaluated the cumulative incidence and predictors of cancer-specific mortality (CSM). RESULTS: We identified 633 (7.6%) individuals who did not receive surgery. These individuals were significantly older (median age 81 vs 71 years, P < 0.001) than surgically managed patients. The median overall survival (OS) was significantly shorter compared to the surgical cohort (1.9 vs 7.8 years, P < 0.001). The 3-year disease-specific survival (DSS) for patients without surgery was significantly lower compared to those with surgery, at 73.7% vs 92.4%, respectively (P < 0.001). The 3-year DSS for patients with high-grade tumours was worse when compared to patients with low-grade tumours, at 65.1% vs 82.9%, respectively (P < 0.001). The 3-year cumulative CSM was 26.3%. On multivariable analysis, older age (hazard ratio [HR] 1.05, P < 0.001) and high tumour grade (HR 1.88, P < 0.001) were predictors of worse outcomes. CONCLUSIONS: In this population-based cohort, 7.6% of patients with UTUC were managed with a non-definitive approach. The median OS for the untreated cohort was significantly shorter compared to the surgical cohort (1.9 vs 7.8 years, respectively). These data may be helpful in counselling patients who are poor surgical candidates, as non-definitive therapy may provide reasonable oncological outcomes.

Outcomes of a Highly Selective Surgical Approach to Oligometastatic Lung Cancer.

BACKGROUND: A highly selected subset of patients with oligometastatic non-small cell lung cancer (NSCLC) will be cured after all sites of established disease (primary and metastases) have been eliminated by surgery or radiation (ie, "curative intent" approach). Mediastinal lymph node metastases (N2) have been found retrospectively to predict a poor prognosis in this setting (5-year survival of 4% for N2-positive versus 31% for N2-negative). Hence, our institution has programmatically limited the use of curative intent local therapy to oligometastatic NSCLC patients confirmed to be free of N2 disease. However, it is unclear whether the exclusion of N2-positive patients is an effective prospective selection step to aggressively treat oligometastatic NSCLC. METHODS: A prospectively maintained institutional tumor registry was reviewed for oligometastatic stage IV NSCLC patients evaluated for curative intent treatment from 2005 to 2014. RESULTS: All synchronous oligometastatic NSCLC cases were evaluated by invasive mediastinal staging before treatment. Twenty-two patients without N2 disease underwent curative intent treatment, and 13 patients with N2 disease were treated palliatively. The groups were similar by bivariate analyses. The N2-negative patients treated with curative intent had a superior 5-year survival compared with N2-positive patients treated palliatively (58% versus 0%, respectively; p = 0.028). CONCLUSIONS: Using invasive mediastinal staging to exclude N2 disease has a role in surgical decision making and achieving long-term survival among oligometastatic NSCLC patients. Further study is warranted to determine whether a subset of patients with N2 disease also have the potential for long-term survival with local therapy.

Spectrum of FDG uptake in large (>10 cm) esophageal leiomyomas.

Esophageal leiomyomas are rare benign tumors that can be treated successfully with limited surgical resection. It is occasionally important to distinguish leiomyomas from more aggressive submucosal esophageal tumors, most notably gastrointestinal stromal tumors (GISTs). GISTs have a worse prognosis, particularly when they are large (>10 cm). Increased uptake of (18)F-fluorodeoxyglucose on positron emission tomography (PET) scans is common in GISTs, potentially allowing PET scanning to differentiate between GIST and benign esophageal tumors. Three patients presented with large (>10 cm) esophageal masses of ranging PET avidity [maximum standardized uptake value (SUVmax) of 1.3-10.1]. All were treated surgically and histologically confirmed to be esophageal leiomyomas. Unfortunately, the wide range of PET uptake precludes PET scanning from differentiating large leiomyomas from more aggressive lesions.

Is directly measured low-density lipoprotein clinically equivalent to calculated low-density lipoprotein?

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) can either be calculated or measured directly. Clinical guidelines recommend the use of calculated LDL-C (C-LDL-C) to guide therapy because the evidence base for cholesterol management is derived almost exclusively from trials that use C-LDL-C, with direct measurement of LDL-C (D-LDL-C) being reserved for those patients who are nonfasting or with significant hypertriglyceridemia. OBJECTIVE: Our aim was to determine the clinical equivalence of directly measured-LDL-C, using a Siemens Advia Chemistry System, and fasting C-LDL-C. METHODS: Eighty-one subjects recruited for two cholesterol treatment studies had at least one C-LDL-C and D-LDL-C performed simultaneously; 64 had a repeat lipid assessment after 4 to 6 weeks of therapy, resulting in 145 pairs of C-LDL-C and D-LDL-C. RESULTS: There was significant correlation between D-LDL-C and C-LDL-C (r² = 0.86). Correlation was significantly better in those with lower total cholesterol, triglycerides, and high-density lipoprotein. In 60% of subjects, the difference between D-LDL-C and C-LDL-C was more than 5 mg/dL and greater than 6%. Clinical concordance between D-LDL-C and C-LDL-C was present in 40% of patients, whereas clinical discordance was noted in 25%. One-third had greater than a 15 mg/dL difference between D-LDL-C and C-LDL-C, whereas 25% had a greater than 20 mg/dL difference. In 47% of subjects, the difference between D-LDL-C and C-LDL-C at baseline and follow-up changed by a minimum of 10% or 10 mg/dL. CONCLUSIONS: Our findings suggest that D-LDL-C is not clinically equivalent to C-LDL-C. This puts into question the current recommendation of using D-LDL-C in situations in which C-LDL-C would be inaccurate.