EGFR Mutation Testing Practice in Advanced Non-Small Cell Lung Cancer

Purpose

Testing tumor samples for the presence of a mutation in the epithelial growth factor receptor (EGFR) gene is recommended for advanced non-squamous non-small cell lung cancer (NSCLC) patients. We aimed to collect data about common practice among Medical Oncologists treating lung cancer patients, regarding EGFR mutation testing in advanced NSCLC patients.

Methods

An internet-based survey was conducted among members of the Israeli Society for Clinical Oncology and Radiotherapy involved in the treatment of lung cancer patients.

Results

24 Oncologists participated in the survey. The participants encompass the Oncologists treating most of the lung cancer patients in Israel. 79 % of them use EGFR testing routinely for all advanced NSCLC patients. Opinions were split regarding the preferable biopsy site for EGFR testing material. 60 % of participants recommend waiting for EGFR test results prior to initiation of first-line therapy.

Conclusions

EGFR testing is requested in Israel routinely by most treating Oncologists for all advanced NSCLC patients, regardless of histology. In most cases, systemic treatment is deferred until the results of this test are received.     

Inverse correlation between coronary and retinal blood flows in patients with normal coronary arteries and slow coronary blood flow

Background

The “Slow Coronary Flow” (SCF) phenomenon in the presence of angiographically normal coronaries is attributed to microvascular and endothelial dysfunction. The microcirculation can be non-invasively assessed by measuring retinal blood flow velocity.The aim of the present study was to evaluate the efficacy of the “Retinal Functional Imager” (RFI) device as a noninvasive method of diagnosing patients with slow coronary flow.

Methods

Coronary blood flow velocity assessed by corrected TIMI Frame Count and retinal arterioles blood flow assessed by RFI were measured in 28 consecutive patients with normal coronary arteries. The patients were divided into 2 groups: a slow coronary flow (SCF) and a normal coronary flow (NCF) groups.

Results

Inverse correlation was found between retinal and coronary blood flows so that higher retinal arterial flow velocity was observed in the SCF group (3.8 ± 1.1 mm/s vs. 2.9 ± 0.61 mm/s, respectively, p = 0.022). RFI provided 73% sensitivity and 77% specificity for diagnosing SCF using ROC analysis. Additionally, patients with SCF had higher values of serum LDL cholesterol (104.7 ± 18.93 mg/dl vs. 81.55 ± 14.62 mg/dl in NCF, p = 0.005), Glucose (96.9 ± 23.0 mg/dl vs. 83.55 ± 9.7 mg/dl in NCF, p = 0.024), and lower percentage of statin consumption (40.0% vs. 76.9% in NCF, p = 0.049).

Conclusions

Slow coronary blood flow can be non-invasively diagnosed with Retinal Functional Imager. Patients with normal coronary arteries and slow coronary blood flow have high retinal arteriolar blood flow. Early non-invasive diagnosis of SCF might help detect individuals who are at higher risk to develop coronary atherosclerosis, and to provide them with early preventive measures.     

Daily Mean Temperature and Clinical Kidney Stone Presentation in Five U.S. Metropolitan Areas: A Time-Series Analysis

Background: High ambient temperatures are a risk factor for nephrolithiasis, but the precise relationship between temperature and kidney stone presentation is unknown.Objectives: Our objective was to estimate associations between mean daily temperature and kidney stone presentation according to lag time and temperatures.Methods: Using a time-series design and distributed lag nonlinear models, we estimated the relative risk (RR) of kidney stone presentation associated with mean daily temperatures, including cumulative RR for a 20-day period, and RR for individual daily lags through 20 days. Our analysis used data from the MarketScan Commercial Claims database for 60,433 patients who sought medical evaluation or treatment of kidney stones from 2005–2011 in the U.S. cities of Atlanta, Georgia; Chicago, Illinois; Dallas, Texas; Los Angeles, California; and Philadelphia, Pennsylvania.Results: Associations between mean daily temperature and kidney stone presentation were not monotonic, and there was variation in the exposure–response curve shapes and the strength of associations at different temperatures. However, in most cases RRs increased for temperatures above the reference value of 10°C. The cumulative RR for a daily mean temperature of 30°C versus 10°C was 1.38 in Atlanta (95% CI: 1.07, 1.79), 1.37 in Chicago (95% CI: 1.07, 1.76), 1.36 in Dallas (95% CI: 1.10, 1.69), 1.11 in Los Angeles (95% CI: 0.73, 1.68), and 1.47 in Philadelphia (95% CI: 1.00, 2.17). Kidney stone presentations also were positively associated with temperatures < 2°C in Atlanta, and < 10°C in Chicago and Philadelphia. In four cities, the strongest association between kidney stone presentation and a daily mean temperature of 30°C versus 10°C was estimated for lags of ≤ 3 days.Conclusions: In general, kidney stone presentations increased with higher daily mean temperatures, with the strongest associations estimated for lags of only a few days. These findings further support an adverse effect of high temperatures on nephrolithiasis.Citation: Tasian GE, Pulido JE, Gasparrini A, Saigal CS, Horton BP, Landis JR, Madison R, Keren R, for the Urologic Diseases in America Project. 2014. Daily mean temperature and clinical kidney stone presentation in five U.S. metropolitan areas: a time-series analysis. Environ Health Perspect 122:1081–1087; http://dx.doi.org/10.1289/ehp.1307703     

Lifestyle Modification Parallels to Sleeve Success

Background

The role of laparoscopic sleeve gastrectomy (LSG) has increased over the past 10 years. We present our results of patients who were 5 years out from surgery with regard to safety and long-term efficacy.

Methods

Retrospective analysis was carried out from prospectively collected data of patients who underwent LSG for morbid obesity. Bariatric Analysis and Reporting Outcome System (BAROS) and Food Tolerance Scores (FTS) were assessed. At 5 years, two lifestyle modification questions (regarding nutrition habits and physical fitness) were separately assessed.

Results

One hundred fourteen patients underwent LSG and were available for postoperative visits. Mean excess weight loss (EWL) was >65 % during the initial 3 years and declined to 45.3 % in 5 years. Of the patients, 71.92 % did not reach 50 % EWL at 60 months and were considered objective failures. BAROS and FTS scores were 7.15 and 4.32, and 23.5 and 22.5 at 30 and 60 months, respectively. Analyzing the 32 patients with EWL >50 % in the 5-year group, 26 (81.25 %) of them had scored ≥0.5 on the two lifestyle modification questions compared with 6 (18.75 %) that scored <0.5 (P?<?0.001).

Conclusion

LSG is an effective bariatric surgical procedure with significant long-term (5 year) weight loss, resolution of comorbid medical conditions and significant improvement in the quality of life. The basis for this success, which must be always emphasized preoperatively by the bariatric team, is knowledge and implementation of better nutritional habits and increasing physical fitness or, in other words, in significant lifestyle modification.     

Blood pressure reaction to negative stimuli: Insights from continuous recording and analysis

Individuals with a tendency toward abnormally enhanced cardiovascular responses to stress are at greater risk of developing essential hypertension later in life. Accurate profiling of continuous blood pressure (BP) reactions in healthy populations is crucial for understanding normal and abnormal emotional reaction patterns. To this end, we examined the continuous time course of BP reactions to aversive pictures among healthy participants. In two experiments, we showed participants negative and neutral pictures while simultaneously measuring their continuous BP and heart rate (HR) reactions. In this study, BP reactions were analyzed continuously, in contrast to previous studies, in which BP responses were averaged across blocks. To compare time points along a temporal continuum, we applied a multi-level B-spline model, which is innovative in the context of BP analysis. Additionally, HR was similarly analyzed in order to examine its correlation with BP. Both experiments revealed a similar pattern of BP reactivity and association with HR. In line with previous studies, a decline in BP and HR levels was found in response to negative pictures compared to neutral pictures. In addition, in both conditions, we found an unexpected elevation of BP toward the end of the stimuli exposure period. These findings may be explained by the recruitment of attention resources in the presence of negative stimuli, which is alleviated toward the end of the stimulation. This study highlights the importance of continuous measurement and analysis for characterizing the time course of BP reactivity to emotional stimuli.     

Bilateral polymicrogyria associated with dystonia: A new neurogenetic syndrome?

The clinical presentation of bilateral perisylvian polymicrogyria (PMG) is highly variable, including oromotor dysfunction, epilepsy, intellectual disability, and pyramidal signs. Extrapyramidal features are extremely rare. We present four apparently unrelated patients with a unique association of PMG with dystonia. The clinical, genetic, and radiologic features are described and possible mechanisms of dystonia are discussed. All patients were female and two were born to consanguineous families. All presented with early childhood onset dystonia. Other neurologic symptoms and signs classically seen in bilateral perisylvian PMG were observed, including oromotor dysfunction and speech abnormalities ranging from dysarthria to anarthria (4/4), pyramidal signs (3/4), hypotonia (3/4), postnatal microcephaly (1/4), and seizures (1/4). Neuroimaging showed a unique pattern of bilateral PMG with an infolded cortex originating primarily from the perisylvian region in three out of four patients. Whole exome sequencing was performed in two out of four patients and did not reveal pathogenic variants in known genes for cortical malformations or movement disorders. The dystonia seen in our patients is not described in bilateral PMG and suggests an underlying mechanism of impaired connectivity within the motor network or compromised cortical inhibition. The association of bilateral PMG with dystonia in our patients may represent a new neurogenetic disorder.     

A single-session testing protocol to determine critical power and W′

Purpose

Critical power (CP), and the finite capacity to perform work above CP (W′), can be determined using a 3-min “all-out” cycling test (3MT). This protocol requires two laboratory visits: an incremental exercise test, followed by a 3MT on a separate day. The purpose of this study was to establish whether an incremental exercise test and a 3MT performed during a single laboratory visit can be used to accurately determine CP and W′.

Methods

Twelve participants completed two experimental protocols: (1) Combined protocol: an incremental exercise test followed by a 3MT, with 20 min of recovery between exercise bouts; and (2) Independent protocol: the conventional 3MT protocol, performed on a separate day.

Results

CP determined from the Combined (254 ± 117 W) and Independent (256 ± 118 W) protocols were not different (p = 0.40). Similarly, W′ was not different (p = 0.96) between the Combined (13.7 ± 3.9 kJ) and Independent (13.7 ± 4.5 kJ) protocols. Linear regression revealed a strong level of measurement agreement between the protocols for CP and W′, evidenced by high R ² values (≥0.85) and marginal standard errors of the estimates (CP = 5 W; W′ = 1.81 kJ).

Conclusion

A Combined protocol, consisting of an incremental exercise test followed by a 3MT, provides an accurate and valid method to determine an individual’s CP and, to a lesser extent, W′. Furthermore, this protocol permits the measurement of the gas-exchange threshold and peak O₂ uptake and, consequently, the moderate, heavy, and severe exercise-intensity domains may be defined within a single exercise-testing session.