TAAR1 agonist ulotaront modulates striatal and hippocampal glutamate function in a state-dependent manner.

Aberrant dopaminergic and glutamatergic function, particularly within the striatum and hippocampus, has repeatedly been associated with the pathophysiology of schizophrenia. Supported by preclinical and recent clinical data, trace amine-associated receptor 1 (TAAR1) agonism has emerged as a potential new treatment approach for schizophrenia. While current evidence implicates TAAR1-mediated regulation of dopaminergic tone as the primary circuit mechanism, little is known about the effects of TAAR1 agonists on the glutamatergic system and excitation-inhibition balance. Here we assessed the impact of ulotaront (SEP-363856), a TAAR1 agonist in Phase III clinical development for schizophrenia, on glutamate function in the mouse striatum and hippocampus. Ulotaront reduced spontaneous glutamatergic synaptic transmission and neuronal firing in striatal and hippocampal brain slices, respectively. Interestingly, ulotaront potentiated electrically-evoked excitatory synaptic transmission in both brain regions, suggesting the ability to modulate glutamatergic signaling in a state-dependent manner. Similar striatal effects were also observed with the TAAR1 agonist, RO5166017. Furthermore, we show that ulotaront regulates excitation-inhibition balance in the striatum by specifically modulating glutamatergic, but not GABAergic, spontaneous synaptic events. These findings expand the mechanistic circuit hypothesis of ulotaront and TAAR1 agonists, which may be uniquely positioned to normalize both the excessive dopaminergic tone and regulate abnormal glutamatergic function associated with schizophrenia.

Arthroscopic decompression of calcific tendinitis without cuff repair.

Aims: The aim of this study was to investigate the outcomes of arthroscopic decompression of calcific tendinitis performed without repairing the rotator cuff defect. Methods: A total of 99 patients who underwent treatment between December 2013 and August 2019 were retrospectively reviewed. Visual analogue scale (VAS) and American Shoulder and Elbow Surgeons (ASES) scores were reviewed pre- and postoperatively according to the location, size, physical characteristics, and radiological features of the calcific deposits. Additionally, the influence of any residual calcific deposits shown on postoperative radiographs was explored. The healing rate of the unrepaired cuff defect was determined by reviewing the 29 patients who had follow-up MRIs. Results: Statistically significant improvement from pre- to postoperation was seen in all VAS and ASES scores for each group, but no statistical differences were seen between the postoperative scores according to the differences in the features of the calcific deposits. When residual calcification was observed postoperatively, the mean ASES and VAS (rest) scores improved significantly to 95.0 (SD 5.6) and 0.0 (SD 0.0), respectively (p = 0.006 and p < 0.001), and did not differ from those who had the complete removal. Of 29 patients who had follow-up MRIs, six (20.7%) showed signs of an interstitial tear. This group's mean postoperative ASES and VAS (rest) scores improved to excellent levels of 96.0 (SD 3.7) and 0.0 (SD 0.0), respectively, and were similar to those of the 23 patients with normal MRI appearances. Conclusion: Arthroscopic removal of calcific deposits without repairing the rotator cuff defect resulted in significant improvement in function and pain level, regardless of the deposit's location, size, type, and whether or not complete excision was achieved. Despite leaving the defects unrepaired, in the limited number of patients with follow-up MRIs, 23 of 29 patients (79.3%) showed good healing, and the rest, who had persistent signs of interstitial defects on the MRIs, still had excellent outcomes. The removal of calcific deposits without repairing the cuff defects provided excellent outcomes.

Urine phthalate levels were associated with skin barrier dysfunction and atopic sensitization in children.

OBJECTIVE: Phthalates can cause immunological disorders and aggravate allergic diseases. Thus, we investigated the relationship between urinary phthalate, skin barrier function, and atopic sensitization in children. PATIENTS AND METHODS: In total, 448 school children [334 with severe allergic disease; and 123 with severe atopic dermatitis (AD)] aged 10-12 years were enrolled in this study between June and July 2017. Four high-molecular-weight phthalates (HMWP) [Σ4HMWP] and three low-molecular-weight phthalates (LMWP) [Σ3LMWP] metabolites in urine samples, specific immunoglobulin E (IgE), and total eosinophil count were measured. Four-part trans epidermal water loss (TEWL) (cheek, leg, and upper/lower arm; Σ4TEWL) was measured to evaluate the skin barrier function. RESULTS: After adjusting for confounding variables, Σ4TEWL was significantly associated with the quartiles of urinary Σ4HMWP [adjusted ß=7.897, 95% confidence interval (CI): 0.636-15.158, p=0.033] and Σ3LMWP (adjusted ß=9.670, 95% CI: 2.422-16.919, p=0.009). The adjusted analyses revealed that the quartiles of urinary Σ4HMWP and Σ3LMWP were not significantly associated with total eosinophil count, atopic sensitization, and severe AD (p>0.05). According to the quartiles of urinary Σ4HMWP and Σ3LMWP, there were significant differences in the TEWL of the lower arm and leg (p<0.05) but not in cheek and upper arm. CONCLUSIONS: Exposure to HMWPs and LMWPs was significantly associated with skin barrier dysfunction but not with atopic sensitization. These results suggest that children exposed to phthalates may be more susceptible to fragile skin barrier function.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Serum vitamin D level mitigates fractional exhaled nitric oxide linked to bisphenol-A in school-aged children.

OBJECTIVE: Previous studies on the relationship of bisphenol-A (BPA) with fractional exhaled nitric oxide (FeNO) had conflicting results, suggesting that other factors may modulate this relationship. Thus, we investigated the modulating effect of vitamin D on the relationship of BPA with FeNO in children. PATIENTS AND METHODS: This study recruited 432 children (10 to 12 years old) from the general pediatric population of Korea between June and July 2017. We conducted measurements of urinary BPA, serum vitamin D, specific serum IgE, FeNO, and data from impulse oscillometry (reactance area [AX], airway resistance at 5 Hz [Rrs5] and 20 Hz [Rrs10], and the difference of Rrs5 and Rrs20 [Rrs5-20]). RESULTS: Serum vitamin D (adjusted ß =- 0.014, p=0.002) and urinary BPA (ß = 0.006, p<0.001) level was significantly associated with FeNO. Urinary BPA level was significantly associated with FeNO in children with low vitamin D levels (≤23 ng/mL; αß = 0.006, p < 0.001), but not in children with high vitamin D levels (>23 ng/mL). The interaction of vitamin D and BPA had a significant effect on FeNO (pint = 0.005). There was no relationship with the airway lung function (Rrs5, AX, and Rrs5-20) to serum vitamin D and urinary BPA level. Vitamin D ameliorated the BPA-mediated increase of FeNO in children. CONCLUSIONS: These results suggest that children with low vitamin D levels may be more susceptible to airway inflammation due to BPA.

A NiCoP nanocluster-anchored porous Ti3C2Tx monolayer as high performance hydrogen evolution reaction electrocatalysts.

MXenes have received much attention as promising candidates for noble metal-free hydrogen evolution reaction (HER) electrocatalysts due to their high electrical conductivity, surface hydrophilicity, abundant surface functional groups, and great potential for rational hybridization with other materials. Herein, a novel porous monolayered-Ti3C2Tx@NiCoP (P-Ti3C2Tx@NiCoP) nanostructure was synthesized with uniform distribution of bimetallic compounds for improved charge transfer capability and electrocatalytic activity. In experiments, H2O2-utilized oxidation formed a highly mesoporous structure with a maximized surface area of monolayered MXenes as the support. A subsequent solvothermal process followed by phosphidation enabled successful anchoring of highly HER-active NiCoP nanoclusters onto abundantly exposed terminal edges of the P-Ti3C2Tx support. The structural porosity of the P-Ti3C2Tx nanoflakes played an important role in creating additional room for embedding catalytically active species while stably imparting high electrical conductivity to accelerate charge transfer to NiCoP nanoclusters. With structural modification and effective hybridization, P-Ti3C2Tx@NiCoP showed highly enhanced HER activity with significantly lower overpotentials of 115 and 101 mV at a current density of -10 mA cm-2 in 0.5 M H2SO4 and 1.0 M KOH, respectively, along with showing long-term stability over 60 h. As such, our approach of designing structurally modified-Ti3C2Tx and hybridizing with other electrocatalytically active species would function as a solid platform for implementing Ti3C2Tx-based hetero-nanostructures to achieve state-of-the-art performance in next-generation energy conversion applications.

Three-dimensional measurement of radiographic bone-implant contact lengths of zygomatic implants in zygomatic bone: a retrospective study of 66 implants in 28 patients.

Zygomatic implant treatment is widely applied for severe maxillary atrophy to help rehabilitate the maxillary dentition. This retrospective study was performed to evaluate the actual radiographic bone-implant contact (rBIC) lengths of zygomatic implants. The records of 28 patients who underwent zygomatic implant surgery and subsequent follow-up examinations between August 2013 and September 2018 in the Department of Oral and Maxillofacial Surgery, Taipei Tzu Chi Hospital were reviewed. The surgeries were performed by a single surgeon using the same treatment protocol. All patients had a computed tomography scan at 1year after the surgery. Using three-dimensional imaging software, an investigator measured the rBIC lengths of 66 implants and documented their clinical status. The implant survival rate was 100%. The mean rBIC length was significantly longer in male patients than in female patients (20.80±5.88mm versus 17.79±6.34mm; P=0.028). The mean rBIC length of double zygomatic implants was significantly longer when compared to that of single implants (21.11±6.23mm versus 17.75±5.85mm; P=0.027). This article is novel in reporting the exact rBIC lengths of zygomatic implants in a clinical setting. The results showed that zygomatic implants are a viable treatment modality for full-mouth rehabilitation.

Diagnostic patterns of non-small-cell lung cancer at Princess Margaret Cancer Centre.

Background: Accurate classification of lung cancer subtypes has become critical in tailoring lung cancer treatment. Our study aimed to evaluate changes in diagnostic testing and pathologic subtyping of advanced non-small-cell lung cancer (nsclc) over time at a major cancer centre. Methods: In a review of patients diagnosed with advanced nsclc at Princess Margaret Cancer Centre between 2007-2009 and 2013-2015, diagnostic method, sample type and site, pathologic subtype, and use of immunohistochemistry (ihc) staining and molecular testing were abstracted. Results: The review identified 238 patients in 2007-2009 and 283 patients in 2013-2015. Over time, the proportion of patients diagnosed with adenocarcinoma increased to 73.1% from 60.9%, and diagnoses of nsclc not otherwise specified (nos) decreased to 6.4% from 18.9%, p < 0.0001. Use of diagnostic bronchoscopy decreased (26.9% vs. 18.4%), and mediastinal sampling procedures, including endobronchial ultrasonography, increased (9.2% vs. 20.5%, p = 0.0001). Use of ihc increased over time to 76.3% from 41.6% (p < 0.0001). Larger surgical or core biopsy samples and those for which ihc was performed were more likely to undergo biomarker testing (both p < 0.01). Conclusions: Customizing treatment based on pathologic subtype and molecular genotype has become key in treating patients with advanced lung cancer. Greater accuracy of pathology diagnosis is being achieved, including through the routine use of ihc.

Knowledge Assessment of Military Personnel, Veterans, and Family Taking Dietary Supplements.

Dietary supplements (DS) pose many side effects and multiple interactions with perioperative medications, which may increase surgical morbidity and mortality. Descriptive empirical data are essentially nonexistent related to DS consumption and patient knowledge of DS. The aims of this study were to investigate the prevalence of use, type of supplements used, and the knowledge base among military beneficiaries and veterans consuming DS during the preoperative period. This descriptive cross-sectional study solicited data from 2,623 volunteer, preoperative patients at 6 different military medical centers throughout the United States. Of the 2,623 participants, 847 (32.3%) reported taking at least 1 DS. Relevant to the surgical population, 154 (18.1%) of participants reported consuming DS that are associated with an increased risk of bleeding. Importantly, we found that 89.7% of patients taking DS were not aware of any potential side effects, and 97.1% lacked knowledge regarding any potential medication interactions between the supplement consumed and their prescribed medications. This vast knowledge gap could have deleterious effects on surgical outcomes. An increase in DS research is needed, and patient education should be incorporated routinely during preoperative assessments provided by military and Veterans Affairs healthcare facilities.

Differential Coupling of Adult-Born Granule Cells to Parvalbumin and Somatostatin Interneurons.

A strong GABAergic tone imposes sparse levels of activity in the dentate gyrus of the hippocampus. This balance is challenged by the addition of new granule cells (GCs) with high excitability. How developing GCs integrate within local inhibitory networks remains unknown. We used optogenetics to study synaptogenesis between new GCs and GABAergic interneurons expressing parvalbumin (PV-INs) and somatostatin (SST-INs). PV-INs target the soma, and synapses become mature after 6 weeks. This transition is accelerated by exposure to an enriched environment. PV-INs exert efficient control of GC spiking and participate in both feedforward and feedback loops, a mechanism that would favor lateral inhibition and sparse coding. SST-INs target the dendrites, and synapses mature after 8 weeks. Outputs from GCs onto PV-INs develop faster than those onto SST-INs. Our results reveal a long-lasting transition wherein adult-born neurons remain poorly coupled to inhibition, which might enhance activity-dependent plasticity of input and output synapses.

Case Start Time Affects Intraoperative Transfusion Rates in Adult Cardiac Surgery: A Single-Center Retrospective Analysis.

OBJECTIVE: The goal of the study was to investigate the role time of day plays in perioperative outcomes. The authors examined intraoperative transfusion rates throughout the day in adult cardiac surgery patients. They hypothesized that the rate of transfusion changes with later case start times in scheduled cardiac surgery. DESIGN: Retrospective observational study. SETTING: Single academic medical center. PARTICIPANTS: Adults undergoing cardiac surgery involving cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite variable of transfusion. The association between the time of day and the rate of transfusion was explored with a multivariate logistic regression to fit the effect of starting time as a cubic spline. There were 1,421 cases that met inclusion criteria. There were 1,220 cases that were matched for modeling. The estimated probability of a patient receiving a transfusion changed significantly with later case start times in the multivariable model after adjusting for initial hemoglobin, age, sex, height, ideal body weight, diabetes, peripheral vascular disease, stroke, chronic kidney disease, chronic obstructive pulmonary disease, duration of cardiopulmonary bypass, aortic cross clamp time, attending surgeon, and attending anesthesiologist (p = 0.032, C-statistic = 0.807, n = 1220). The estimated probability of receiving an intraoperative red blood cell transfusion increased with later case start times in the multivariable model (p = 0.027, C-statistic = 0.902, n = 1220). There was no difference in the probability of transfusion for plasma, cryoprecipitate, or platelets. CONCLUSIONS: The observed rate of intraoperative blood product transfusion changed with later case start times in a multivariable model of scheduled cardiac surgery.

Nuclear Medicine and Resources for Patients: How Complex Are Online Patient Educational Materials?

The Internet is a major source of health care information for patients. The American Medical Association and the National Institutes of Health recommend that consumer health care websites be written at a third- to seventh-grade level. The purpose of this study was to evaluate the level of readability of patient education websites pertaining to nuclear medicine. Methods: We searched for 10 terms on Google, collected the top 10 links for each term, and analyzed their level of readability using 10 well-established readability scales. Results: Collectively, the 99 articles were written at a grade level of 11.8 (SD, 3.4). Only 5 of the 99 articles were written at the third- to seventh-grade level recommended by the National Institutes of Health and the American Medical Association. Conclusion: There is a clear discordance between the readability level of nuclear medicine-related imaging terms and the National Institutes of Health and American Medical Association guidelines. This discordance may have a negative impact on patient understanding, contributing to poor health outcomes.

Investigation of the Anxiolytic and Antidepressant Effects of Crocin, a Compound from Saffron (Crocus sativus L), in the Male Sprague-Dawley Rat.

Anxiety and depression are debilitating, costly psychological disorders that account for more than $133 billion annually in direct medical expenses in the United States. Finding alternative treatments to reduce the personal and financial burden for patients with these disorders, while maintaining patient safety, is vital. The purposes of this study were to determine if crocin, a compound from saffron (Crocus sativus L), produces anxiolytic and/or antidepressant effects using rat models for anxiety and behavioral despair and to determine the effects of crocin at the benzodiazepine site on the γ-aminobutyric acid type A receptor. Fifty-five male Sprague Dawley rats were randomly assigned to 1 of 5 groups: vehicle (dimethyl sulfoxide), crocin, midazolam, flumazenil plus crocin, and midazolam plus crocin. Behavioral analyses were conducted in the elevated plus-maze and the forced swim test. Data were analyzed using multivariate analysis of variance and a least significant difference post hoc test. Data from the elevated plus-maze suggested crocin may attenuate the anxiolytic effects of midazolam, while not affecting psychomotor activity. Data from the forced swim test showed a significant increase in mean time mobile in the midazolam plus crocin group, suggesting a decrease in behavioral despair because of the interaction between crocin and midazolam.

A study of the probable transmission routes of MERS-CoV during the first hospital outbreak in the Republic of Korea.

Infections caused by the Middle East respiratory syndrome coronavirus (MERS-CoV) are a serious health issue due to their prevalence and associated mortality. However, the transmission routes of the virus remain unclear, and thus, the current recommended control strategies are not evidence based. In this study, we investigated the transmission routes of MERS-CoV during the first nosocomial outbreak in the Republic of Korea in May 2015 using a multi-agent modeling framework. We identified seven hypothesized transmission modes based on the three main transmission routes (long-range airborne, close contact, and fomite). The infection risks for each hypothesis were estimated using the multi-agent modeling framework. Least-squares fitting was conducted to compare the distribution of the predicted infection risk in the various scenarios with that of the reported attack rates and to identify the hypotheses with the best fit. In the scenarios in which the index patient was a super-spreader, our model simulations suggested that MERS-CoV probably spread via the long-range airborne route. However, it is possible that the index patient shed an average viral load comparable to the loads reported in the literature, and that transmission occurred via a combined long-range airborne and close contact route.

Immune enhancement effect of an herb complex extract through the activation of natural killer cells and the regulation of cytokine levels in a cyclophosphamide-induced immunosuppression rat model

Objective:To investigate the effects of a herb complex extract (HCE) prepared from Cornus officinalis Sieb. Et Zucc., Eriobotrya japonica Lindley, and olive leaves on immune response of mouse spleen NK cells in vitro and in vivo analysis.Methods:The activity of natural killer (NK) cells was measured in splenocytes and YAC-1 cells. Mice were immunosuppressed using cyclophosphamide (5 mg/kg body weight). Three different doses of HCE (200, 400, and 800 mg/kg body weight) and red ginseng extract (800 mg/kg body weight) which was used as standard immunomodulatory herb were administered orally for 4 weeks. The body weight, dietary, water intake, organs (liver, thymus, and spleen) weight, completed blood count, and cytokines (tumor necrosis factor alpha, interferon gamma, and interleukin-2) production was measured.Results:At the maximum concentration of HCE, the activity of NK cells was increased by 48.5%. HCE increased liver, spleen, and thymus weights without altering numbers of white blood cells, lymphocytes, and neutrophils in a cyclophosphamide-induced immunosuppression rat model. However, HCE recovered the inhibited cytokine expression; HCE (800 mg/kg) increased cytokines levels. The results indicate the immune enhancement potential of this HCE.Conclusion:The HCE enhances immunity by increasing NK cell activity, regulating cytokine levels, and maintaining spleen weight. Therefore, it may be used as a potential immunity enhancer.

Predicting the risk of parafoveal scotoma in myopic normal tension glaucoma: role of optic disc tilt and rotation.

PurposeThe purpose of the study was to evaluate the factors associated with development of parafoveal scotoma in early myopic normal tension glaucoma (NTG).Patients and methodsNinety-nine myopic NTG patients with mean deviation (MD) >-6.0 decibels (dB) were enrolled. Parafoveal scotoma was defined as a visual field (VF) defect within 10° of fixation with at least one point at P<1% lying at the four innermost central points. Systemic factors, optic disc characteristics including tilt ratio, rotation degree, ß-zone parapapillary atrophy, disc hemorrhage, and peripapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer (mGCIPL) thickness parameters using optical coherence tomography were evaluated. Logistic regression analysis was performed to identify factors associated with the development of parafoveal scotoma.ResultsThe mean spherical equivalent refractive error and MD were -6.07±2.83 diopters and -3.29±1.70 dB, respectively. Among 99 eyes, 42 (42.42%) showed parafoveal scotoma. Eyes with parafoveal scotoma had greater disc tilt, lesser disc rotation, lower MD, thinner minimum mGCIPL, and a higher proportion of VF defect in the superior hemifield than eyes without parafoveal scotoma. Multivariate logistic regression showed that all these parameters were significantly associated with development of parafoveal scotoma (P=0.047, P=0.011, P=0.032, P=0.010, and P=0.001, respectively).ConclusionIn addition to the previously reported risk factors, optic disc characteristics, such as tilt ratio and optic disc rotation, were also significantly associated with development of parafoveal scotoma in patients with myopic NTG.

Stroke and Intracranial Hemorrhage in HeartMate II and HeartWare Left Ventricular Assist Devices: A Systematic Review.

BACKGROUND: Ischemic stroke and intracranial hemorrhage (ICH) following left ventricular assist device (LVAD) placement are major causes of morbidity. The incidence and mortality associated with these events stratified by device type have not been systematically explored. METHODS: A systematic review of PubMed was conducted from January 2007 through June 2016 for all English-language articles involving HeartMate II (HMII) and HeartWare LVAD patients. Ischemic stroke and/or ICH incidence (events per patient-year) and associated mortality rates were abstracted for each device type. RESULTS: Of 735 articles reviewed, 48 (11,310 patients) met inclusion criteria (33 HMII, six HeartWare, eight both devices, and one unspecified). The median duration of device support was 112 days (total 13,723 patient-years). Overall, ischemic stroke or ICH occurred in 9.8% (1110 persons and 0.08 events per patient year [EPPY]). Ischemic stroke occurred in a median of 6.0% or 0.06 EPPY (range 0-16% or 0-0.21 EPPY) of HMII patients versus 7.5% or 0.09 EPPY (range 4-17.1% or 0.01-0.94 EPPY) of HeartWare patients. ICH occurred in a median of 3.0% or 0.04 EPPY (range 0-13.5% or 0-0.13 EPPY) of HMII and 8.0% or 0.08 EPPY (range 3-23% or 0.01-0.56 EPPY) of HeartWare patients. The median mortality rate for LVAD-associated ischemic stroke was 31% (HMII: 33%, [range 2.4-75%] and HeartWare: 11.5% [range 3.9-40%]), and the median mortality rate following ICH was 71% (HMII: 75%, [range 3.9-100%] and HeartWare: 44%, [range 3.1-88%]). CONCLUSIONS: Ischemic stroke and ICH are common after LVAD placement, but heterogeneous event rates are reported in the literature. Given the high associated mortality, further prospective study is warranted.

Approach to biomarker testing: perspectives from various specialties.

BACKGROUND: Despite its importance for patient outcomes, biomarker testing for lung cancer is not uniformly integrated into the Canadian health care system. To better understand current practice patterns for lung cancer biomarker testing, we assessed physician perspectives by specialty and region. METHODS: A national survey of Canadian lung cancer specialists was conducted to understand their perspectives on biomarker testing in lung cancer. The 11-item survey assessed the current practice and challenges of testing. The survey was sent to 375 specialists. RESULTS: The overall response rate for the survey was 36%. Nearly all specialists reported that knowing tumour genotyping results affects patient outcome and influences the treatment decision. Medical oncologists most commonly initiated molecular testing; however, most respondents suggested a shared model involving medical oncologists and pathologists. More than half of all responding specialists had the perception that fewer than 25% of test results are available for first-line treatment decisions. Identified barriers to routine testing for all lung cancer patients included cost, lack of funding, tissue availability, and sample quality. CONCLUSIONS: There was clear agreement that biomarker testing is important in determining appropriate treatment for patients. There is a need for general consensus on who should initiate molecular testing. Clear clinical guidance for pathologists has to be established for molecular testing, including defining the population to be tested, the timing of testing, and the tests to be performed. Testing could be facilitated by including more information on diagnostic sample requisitions, such as clinical suspicion of primary lung cancer, cancer history, and other samples already collected.