Expression of human and Porphyromonas gingivalis glutaminyl cyclases in periodontitis and rheumatoid arthritis–a pilot study

Publication date: Available online 28 October 2018

Source: Archives of Oral Biology

Author(s): Philip Bender, Andreas Egger, Martin Westermann, Nadine Taudte, Anton Sculean, Jan Potempa, Burkhard Möller, Mirko Buchholz, Sigrun Eick

Abstract

Objectives

Human glutaminyl cyclases (QC and isoQC) play an important role in maintaining inflammatory conditions. Meanwhile a glutaminyl cyclase synthesized by Porphyromonas gingivalis (PgQC), a key pathogen in developing periodontitis and a potential link of periodontitis with rheumatoid arthritis (RA), was discovered. This study was aimed to determine the expression of QC, isoQC and PgQC in patients with chronic periodontitis (CP) and RA.

Design

Thirty volunteers were enrolled in a pilot study and divided into 3 groups (healthy, CP and RA individuals). Blood samples, biofilm and gingival crevicular fluid (GCF) were analysed for mRNA expression of QC, isoQC and P. gingivalis QC. Major bacteria being associated with periodontal disease were quantified in subgingival biofilm and protein levels for monocyte chemoattractant protein (MCP)-1, MCP-3 and interleukin (IL)-1β) were determined in the GCF. Expression of PgQC on the mRNA and protein levels was assessed in two P. gingivalis strains.

Results

PgQC is expressed in P. gingivalis strains and the protein seems to be located mainly in peri-plasmatic space. mRNA expression of QC was significantly increased in the peripheral blood from RA patients vs. healthy subjects and CP patients (p = 0.013 and p = 0.003, respectively). In GCF of RA patients, QC mRNA was detected more frequently than in healthy controls (p = 0.043). In these samples IL-1β levels were also elevated compared to GCF from periodontally healthy individuals (p = 0.003). PgQC was detected in eight out of the 13 P. gingivalis positive biofilm samples.

Conclusion

Activity of QC may play a supportive role in maintaining chronic periodontal inflammation and destruction in RA. PgQC is expressed in vivo but further research is needed to evaluate biological importance of this enzyme and if it constitutes a potential target in periodontal antimicrobial therapy.

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Comparative analysis of blood parameters of the erythrocyte lineage between patients with chronic periodontitis and healthy patients: Results obtained from a meta-analysis

Publication date: Available online 28 October 2018

Source: Archives of Oral Biology

Author(s): Luiz Felipe de Carvalho França, Felipe Rodolfo Pereira da Silva, David di Lenardo, Even Herlany Pereira Alves, Hélio Mateus Silva Nascimento, Isabela Aparecida Tito da Silva, Any Carolina Cardoso Guimarães Vasconcelos, Daniel Fernando Pereira Vasconcelos

Abstract

Objective

Quantitatively evaluate blood parameters of the erythrocyte lineage in patients with chronic periodontitis and healthy controls by means of a meta-analysis.

Material and methods

A review of literature was performed in the scientific databases for studies published before September, 2016. The abstracts were evaluated and the extraction of data performed by two examiners. The parameters assessed were: hemoglobin levels, number of circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in patients with chronic periodontitis and healthy controls. The calculations were obtained through the statistical software Review Manager version 5.3, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05.

Results

Nine case/control studies composed the results with 342 patients with chronic periodontitis and 359 healthy controls. There was a significant decrease in hemoglobin levels (MD = -1.60, 95% CI: -2.72, -0.48, P = 0.005) and number of circulating red blood cells (MD = -0.51, 95% CI: -0.78, -0.24, P = 0.0002), hematocrit (MD = -4.41, IC 95%: -7.13, -1.68, P = 0.002), mean corpuscular hemoglobin (MD = -0.80; IC 95%: -1.38, -0,22, P = 0.007) and mean corpuscular hemoglobin concentration (MD = -0.93, IC 95%: -1.63, -0.23, P = 0.009) in patients with chronic periodontitis when compared to healthy controls. No publication bias was found through the funnel plot asymmetry.

Conclusion

There is an associated of the reduction of hematological parameters (such as levels of hemoglobin and circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) to patients with chronic periodontitis.

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Expression of human and Porphyromonas gingivalis glutaminyl cyclases in periodontitis and rheumatoid arthritis–a pilot study

Publication date: Available online 28 October 2018

Source: Archives of Oral Biology

Author(s): Philip Bender, Andreas Egger, Martin Westermann, Nadine Taudte, Anton Sculean, Jan Potempa, Burkhard Möller, Mirko Buchholz, Sigrun Eick

Abstract

Objectives

Human glutaminyl cyclases (QC and isoQC) play an important role in maintaining inflammatory conditions. Meanwhile a glutaminyl cyclase synthesized by Porphyromonas gingivalis (PgQC), a key pathogen in developing periodontitis and a potential link of periodontitis with rheumatoid arthritis (RA), was discovered. This study was aimed to determine the expression of QC, isoQC and PgQC in patients with chronic periodontitis (CP) and RA.

Design

Thirty volunteers were enrolled in a pilot study and divided into 3 groups (healthy, CP and RA individuals). Blood samples, biofilm and gingival crevicular fluid (GCF) were analysed for mRNA expression of QC, isoQC and P. gingivalis QC. Major bacteria being associated with periodontal disease were quantified in subgingival biofilm and protein levels for monocyte chemoattractant protein (MCP)-1, MCP-3 and interleukin (IL)-1β) were determined in the GCF. Expression of PgQC on the mRNA and protein levels was assessed in two P. gingivalis strains.

Results

PgQC is expressed in P. gingivalis strains and the protein seems to be located mainly in peri-plasmatic space. mRNA expression of QC was significantly increased in the peripheral blood from RA patients vs. healthy subjects and CP patients (p = 0.013 and p = 0.003, respectively). In GCF of RA patients, QC mRNA was detected more frequently than in healthy controls (p = 0.043). In these samples IL-1β levels were also elevated compared to GCF from periodontally healthy individuals (p = 0.003). PgQC was detected in eight out of the 13 P. gingivalis positive biofilm samples.

Conclusion

Activity of QC may play a supportive role in maintaining chronic periodontal inflammation and destruction in RA. PgQC is expressed in vivo but further research is needed to evaluate biological importance of this enzyme and if it constitutes a potential target in periodontal antimicrobial therapy.

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Comparative analysis of blood parameters of the erythrocyte lineage between patients with chronic periodontitis and healthy patients: Results obtained from a meta-analysis

Publication date: Available online 28 October 2018

Source: Archives of Oral Biology

Author(s): Luiz Felipe de Carvalho França, Felipe Rodolfo Pereira da Silva, David di Lenardo, Even Herlany Pereira Alves, Hélio Mateus Silva Nascimento, Isabela Aparecida Tito da Silva, Any Carolina Cardoso Guimarães Vasconcelos, Daniel Fernando Pereira Vasconcelos

Abstract

Objective

Quantitatively evaluate blood parameters of the erythrocyte lineage in patients with chronic periodontitis and healthy controls by means of a meta-analysis.

Material and methods

A review of literature was performed in the scientific databases for studies published before September, 2016. The abstracts were evaluated and the extraction of data performed by two examiners. The parameters assessed were: hemoglobin levels, number of circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in patients with chronic periodontitis and healthy controls. The calculations were obtained through the statistical software Review Manager version 5.3, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05.

Results

Nine case/control studies composed the results with 342 patients with chronic periodontitis and 359 healthy controls. There was a significant decrease in hemoglobin levels (MD = -1.60, 95% CI: -2.72, -0.48, P = 0.005) and number of circulating red blood cells (MD = -0.51, 95% CI: -0.78, -0.24, P = 0.0002), hematocrit (MD = -4.41, IC 95%: -7.13, -1.68, P = 0.002), mean corpuscular hemoglobin (MD = -0.80; IC 95%: -1.38, -0,22, P = 0.007) and mean corpuscular hemoglobin concentration (MD = -0.93, IC 95%: -1.63, -0.23, P = 0.009) in patients with chronic periodontitis when compared to healthy controls. No publication bias was found through the funnel plot asymmetry.

Conclusion

There is an associated of the reduction of hematological parameters (such as levels of hemoglobin and circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) to patients with chronic periodontitis.

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Defining Pollen Seasons: Background and Recommendations

Abstract

Purpose of Review

The definition of a pollen season determines the start and the end of the time period with a certain amount of pollen in the ambient air. Different pollen season definitions were used for a long time including the use of different terms for data and methods used to define a pollen season. Recently suggested pollen season definitions for clinical trials were tested and applied for the first time to more aeroallergens.

Recent Findings

This is a review on pollen season definitions and the latest recommendations. Recently, proposed terminology in aerobiology is promoted here in order to support reproducibility and repeatability in research. Two pollen season definitions, one based on percentages and one based on pollen concentrations, were tested.

Summary

Percentage definitions can be recommended for standard aerobiological routines and for retrospective applications, whereas pollen concentrations definitions can be recommended for prospective applications such as clinical trials.

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Nicotine metabolism, tobacco consumption, and carcinogen exposure among American Indian smokers, electronic nicotine delivery system users, and dual users

Publication date: Available online 28 October 2018

Source: Addictive Behaviors

Author(s): Dana Mowls Carroll, Theodore L. Wagener, Lancer D. Stephens, Lacy S. Brame, David M. Thompson, Laura A. Beebe

Abstract

Background

We tested the hypothesis that in AI tobacco users from the southern plains region of the US tobacco consumption and carcinogen exposure is related to nicotine metabolism whereby a higher nicotine metabolism is associated with higher nicotine and carcinogen exposure.

Methods

Smokers (n = 27), electronic nicotine delivery system (ENDS) users (n = 21), and dual users (n = 25) of AI descent were recruited from a southern plains state. Urinary biomarkers of nicotine metabolism (nicotine metabolite ratio[NMR]), nicotine dose (total nicotine equivalents[TNE]), and a tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides[total NNAL] were measured.

Results

Geometric mean of NMR was 4.47 (95% Confidence Interval(CI):3.19, 5.75), 5.91 (CI:3.91, 7.90), and 4.12 (CI:2.87, 5.37) among smokers, ENDS users, and dual users. Each of the three user groups had relatively low levels of TNE, indicative of light tobacco use. Among smokers, there were inverse relationships between NMR and TNE (r = −0.45) and between NMR and NNAL(r = −0.50). Among dual users, NMR and TNE, and NNAL were unassociated. Among ENDS users, NMR and TNE were unassociated.

Conclusions

AI tobacco users with higher rates of nicotine metabolism did not have higher nicotine and carcinogen exposure. This supports prior work among light smokers who do not adjust their tobacco consumption by nicotine metabolism.

Impact

The high smoking prevalence and cancer risks among AI in the southern plains may not be related to nicotine metabolism. Environmental cues may play a more important role in light smokers and this may be particularly true among AI who have strong cultural ties to tobacco.

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Nicotine metabolism, tobacco consumption, and carcinogen exposure among American Indian smokers, electronic nicotine delivery system users, and dual users

Publication date: Available online 28 October 2018

Source: Addictive Behaviors

Author(s): Dana Mowls Carroll, Theodore L. Wagener, Lancer D. Stephens, Lacy S. Brame, David M. Thompson, Laura A. Beebe

Abstract

Background

We tested the hypothesis that in AI tobacco users from the southern plains region of the US tobacco consumption and carcinogen exposure is related to nicotine metabolism whereby a higher nicotine metabolism is associated with higher nicotine and carcinogen exposure.

Methods

Smokers (n = 27), electronic nicotine delivery system (ENDS) users (n = 21), and dual users (n = 25) of AI descent were recruited from a southern plains state. Urinary biomarkers of nicotine metabolism (nicotine metabolite ratio[NMR]), nicotine dose (total nicotine equivalents[TNE]), and a tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides[total NNAL] were measured.

Results

Geometric mean of NMR was 4.47 (95% Confidence Interval(CI):3.19, 5.75), 5.91 (CI:3.91, 7.90), and 4.12 (CI:2.87, 5.37) among smokers, ENDS users, and dual users. Each of the three user groups had relatively low levels of TNE, indicative of light tobacco use. Among smokers, there were inverse relationships between NMR and TNE (r = −0.45) and between NMR and NNAL(r = −0.50). Among dual users, NMR and TNE, and NNAL were unassociated. Among ENDS users, NMR and TNE were unassociated.

Conclusions

AI tobacco users with higher rates of nicotine metabolism did not have higher nicotine and carcinogen exposure. This supports prior work among light smokers who do not adjust their tobacco consumption by nicotine metabolism.

Impact

The high smoking prevalence and cancer risks among AI in the southern plains may not be related to nicotine metabolism. Environmental cues may play a more important role in light smokers and this may be particularly true among AI who have strong cultural ties to tobacco.

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Hearing loss patients at higher risk of hospital readmission

Hard-of-hearing hospital patients who have trouble communicating with medical personnel are more likely to end up back in the hospital within 30 days, compared to patients who don't have trouble hearing, a U.S. study suggests. (Source: Reuters: Health)

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Hearing loss patients at higher risk of hospital readmission

Hard-of-hearing hospital patients who have trouble communicating with medical personnel are more likely to end up back in the hospital within 30 days, compared to patients who don't have trouble hearing, a U.S. study suggests. (Source: Reuters: Health)

MedWorm Message: Have you tried our new medical search engine? More powerful than before. Log on with your social media account. 100% free.

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Improved interaural timing of acoustic nerve stimulation affects sound localization in single-sided deaf cochlear implant users

Publication date: Available online 29 October 2018

Source: Hearing Research

Author(s): J. Seebacher, A. Franke-Trieger, V. Weichbold, P. Zorowka, K. Stephan

Abstract

The main impairment associated with single-sided deafness (SSD) is the loss of binaural hearing. Currently, the most effective treatment to compensate for this deficit is to supply patients suffering from SSD with a cochlear implant (CI) in the deaf ear. With this approach binaural hearing abilities can be restored to a certain extent, which is expressed in an improvement in such patients with regard to sound source localization and speech comprehension in noise after receipt of a CI. However, binaural performance of these listeners does not reach the level of normal-hearing listeners. One of the reasons for this might be that the electrical stimulation via CI and the physiological stimulation via the intact ear are not synchronized: the CI transmits the information to the auditory nerve with different timing than does the intact inner ear. As a result, there is a timing mismatch of the information transfer between the left and the right side, which may account for the limited binaural performance. The effective mismatch in timing depends on the CI system because of different stimulation strategies implemented in devices from different manufacturers. For the particular CI device used in this study (MED-EL Mi1000/Mi1200) electrical stimulation led to faster activation of the auditory nerve than natural for a wide frequency range. In particular, electrical stimulation was about 1 to up to 2 milliseconds ahead of time for frequencies above 1.5 kHz. Hence, it was hypothesized that information transfer between the left and the right ear can be tuned by delaying the CI signal. The goal of the present study was to investigate whether such a delay in the CI signal affects binaural performance of CI users with SSD. For this purpose, sound source localization and speech perception in noise were tested in a sample of 12 CI users with SSD (mean age 51 ± 12 years). The tests were performed for four different delay times of the CI signal applied spontaneously (0.5, 1, 2 and 4 milliseconds) and for the base line condition "no delay" in the CI signal (i.e. everyday use). It was found that delaying the signal had a significant impact on sound source localization. Speech perception in noise was affected, but less pronounced than was sound localization. Regarding sound source localization, a signal delay of 1 millisecond applied to this particular CI device produced the best performance in our patients. It is concluded that improving the synchronization between the CI-transferred signal and the naturally transferred signal could increase binaural hearing performance in CI users with SSD.

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Postoperative Electrocochleography from Hybrid Cochlear Implant users: An Alternative Analysis Procedure

Publication date: Available online 29 October 2018

Source: Hearing Research

Author(s): Jeong-Seo Kim, Viral D. Tejani, Paul J. Abbas, Carolyn J. Brown

Abstract

Objective

Shorter electrode arrays and soft surgical techniques allow for preservation of acoustic hearing in many cochlear implant (CI) users. Recently, we developed a method of using the Neural Response Telemetry (NRT) system built in Custom Sound EP clinical software to record acoustically evoked electrocochleography (ECoG) responses from an intracochlear electrode in Nucleus Hybrid CI users (Abbas, et al., 2017). We recorded responses dominated by the hair cells (cochlear microphonic, CM/DIF) and the auditory nerve (auditory nerve neurophonic, ANN/SUM). Unfortunately, the recording procedure was time consuming, limiting potential clinical applications. This report describes a modified method to record the ECoG response more efficiently. We refer to this modified technique as the "short window" method, while our previous technique (Abbas, et al., 2017) is referred as the "long window" method. In this report, our goal was to 1) evaluate the feasibility of the short window method to record the CM/DIF and ANN/SUM responses, 2) characterize the reliability and sensitivity of the measures recorded using the short window method, and 3) evaluate the relationship between the CM/DIF and ANN/SUM measures recorded using the modified method and audiometric thresholds.

Method

Thirty-four postlingually deafened adult Hybrid CI users participated in this study. Acoustic tone bursts were presented at four frequencies (250, 500, 750, and 1000 Hz) at various stimulation levels via an insert earphone in both condensation and rarefaction polarities. Acoustically evoked ECoG responses were recorded from the most apical electrode in the intracochlear array. These two responses were subtracted to emphasize the CM/DIF responses and added to emphasize the ANN/SUM responses. Response thresholds were determined based on visual inspection of time waveforms, and trough-to-peak analysis technique was used to quantify response amplitudes. Within-subject comparison of responses measured using both short and long window methods were obtained from seven subjects. We also assessed the reliability and sensitivity of the short window method by comparing repeated measures from 19 subjects at different times. Correlations between CM/DIF and ANN/SUM measures using the short window recording method and audiometric thresholds were also assessed.

Results

Regardless of the recording method, CM/DIF responses were larger than ANN/SUM responses. Responses obtained using the short window method were positively correlated to those obtained using the conventional long window method. Subjects who had stable acoustic hearing at two different time points had similar ECoG responses at those points, confirming high test-retest reliability of the short window method. Subjects who lost hearing between two different time points showed increases in ECoG thresholds, suggesting that physiologic ECoG responses are sensitive to audiometric changes. Correlations between CM/DIF and ANN/SUM thresholds and audiometric thresholds at all tested frequencies were significant.

Conclusion

This study compares two different recording methods. Intracochlear ECoG measures recorded using the short window technique were efficient, reliable, and repeatable. We were able to collect more frequency specific data with the short window method, and observed similar results between the long window and short window methods. Correlations between physiological thresholds and audiometric thresholds were similar to those reported previously using the long window method (Abbas, et al., 2017). This is an important finding because it demonstrates that clinically-available software can be used to measure frequency-specific ECoG responses with enhanced efficiency, increasing the odds that this technique might move from the laboratory into clinical practice.

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Hearing loss patients at higher risk of hospital readmission

Hard-of-hearing hospital patients who have trouble communicating with medical personnel are more likely to end up back in the hospital within 30 days, compared to patients who don't have trouble hearing, a U.S. study suggests. (Source: Reuters: Health)

MedWorm Message: Have you tried our new medical search engine? More powerful than before. Log on with your social media account. 100% free.

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Improved interaural timing of acoustic nerve stimulation affects sound localization in single-sided deaf cochlear implant users

Publication date: Available online 29 October 2018

Source: Hearing Research

Author(s): J. Seebacher, A. Franke-Trieger, V. Weichbold, P. Zorowka, K. Stephan

Abstract

The main impairment associated with single-sided deafness (SSD) is the loss of binaural hearing. Currently, the most effective treatment to compensate for this deficit is to supply patients suffering from SSD with a cochlear implant (CI) in the deaf ear. With this approach binaural hearing abilities can be restored to a certain extent, which is expressed in an improvement in such patients with regard to sound source localization and speech comprehension in noise after receipt of a CI. However, binaural performance of these listeners does not reach the level of normal-hearing listeners. One of the reasons for this might be that the electrical stimulation via CI and the physiological stimulation via the intact ear are not synchronized: the CI transmits the information to the auditory nerve with different timing than does the intact inner ear. As a result, there is a timing mismatch of the information transfer between the left and the right side, which may account for the limited binaural performance. The effective mismatch in timing depends on the CI system because of different stimulation strategies implemented in devices from different manufacturers. For the particular CI device used in this study (MED-EL Mi1000/Mi1200) electrical stimulation led to faster activation of the auditory nerve than natural for a wide frequency range. In particular, electrical stimulation was about 1 to up to 2 milliseconds ahead of time for frequencies above 1.5 kHz. Hence, it was hypothesized that information transfer between the left and the right ear can be tuned by delaying the CI signal. The goal of the present study was to investigate whether such a delay in the CI signal affects binaural performance of CI users with SSD. For this purpose, sound source localization and speech perception in noise were tested in a sample of 12 CI users with SSD (mean age 51 ± 12 years). The tests were performed for four different delay times of the CI signal applied spontaneously (0.5, 1, 2 and 4 milliseconds) and for the base line condition "no delay" in the CI signal (i.e. everyday use). It was found that delaying the signal had a significant impact on sound source localization. Speech perception in noise was affected, but less pronounced than was sound localization. Regarding sound source localization, a signal delay of 1 millisecond applied to this particular CI device produced the best performance in our patients. It is concluded that improving the synchronization between the CI-transferred signal and the naturally transferred signal could increase binaural hearing performance in CI users with SSD.

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Postoperative Electrocochleography from Hybrid Cochlear Implant users: An Alternative Analysis Procedure

Publication date: Available online 29 October 2018

Source: Hearing Research

Author(s): Jeong-Seo Kim, Viral D. Tejani, Paul J. Abbas, Carolyn J. Brown

Abstract

Objective

Shorter electrode arrays and soft surgical techniques allow for preservation of acoustic hearing in many cochlear implant (CI) users. Recently, we developed a method of using the Neural Response Telemetry (NRT) system built in Custom Sound EP clinical software to record acoustically evoked electrocochleography (ECoG) responses from an intracochlear electrode in Nucleus Hybrid CI users (Abbas, et al., 2017). We recorded responses dominated by the hair cells (cochlear microphonic, CM/DIF) and the auditory nerve (auditory nerve neurophonic, ANN/SUM). Unfortunately, the recording procedure was time consuming, limiting potential clinical applications. This report describes a modified method to record the ECoG response more efficiently. We refer to this modified technique as the "short window" method, while our previous technique (Abbas, et al., 2017) is referred as the "long window" method. In this report, our goal was to 1) evaluate the feasibility of the short window method to record the CM/DIF and ANN/SUM responses, 2) characterize the reliability and sensitivity of the measures recorded using the short window method, and 3) evaluate the relationship between the CM/DIF and ANN/SUM measures recorded using the modified method and audiometric thresholds.

Method

Thirty-four postlingually deafened adult Hybrid CI users participated in this study. Acoustic tone bursts were presented at four frequencies (250, 500, 750, and 1000 Hz) at various stimulation levels via an insert earphone in both condensation and rarefaction polarities. Acoustically evoked ECoG responses were recorded from the most apical electrode in the intracochlear array. These two responses were subtracted to emphasize the CM/DIF responses and added to emphasize the ANN/SUM responses. Response thresholds were determined based on visual inspection of time waveforms, and trough-to-peak analysis technique was used to quantify response amplitudes. Within-subject comparison of responses measured using both short and long window methods were obtained from seven subjects. We also assessed the reliability and sensitivity of the short window method by comparing repeated measures from 19 subjects at different times. Correlations between CM/DIF and ANN/SUM measures using the short window recording method and audiometric thresholds were also assessed.

Results

Regardless of the recording method, CM/DIF responses were larger than ANN/SUM responses. Responses obtained using the short window method were positively correlated to those obtained using the conventional long window method. Subjects who had stable acoustic hearing at two different time points had similar ECoG responses at those points, confirming high test-retest reliability of the short window method. Subjects who lost hearing between two different time points showed increases in ECoG thresholds, suggesting that physiologic ECoG responses are sensitive to audiometric changes. Correlations between CM/DIF and ANN/SUM thresholds and audiometric thresholds at all tested frequencies were significant.

Conclusion

This study compares two different recording methods. Intracochlear ECoG measures recorded using the short window technique were efficient, reliable, and repeatable. We were able to collect more frequency specific data with the short window method, and observed similar results between the long window and short window methods. Correlations between physiological thresholds and audiometric thresholds were similar to those reported previously using the long window method (Abbas, et al., 2017). This is an important finding because it demonstrates that clinically-available software can be used to measure frequency-specific ECoG responses with enhanced efficiency, increasing the odds that this technique might move from the laboratory into clinical practice.

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Design and synthesis of magnetic nanoparticles for biomedical diagnostics

Sensitive and quantitative characterization of clinically relevant biomarkers can facilitate disease diagnosis and treatment evaluation. Magnetic nanomaterials and their biosensing strategies have recently received considerable attention. Magnetic signals experience little interference from native biological background as most biological molecules have negligible magnetic susceptibilities and thus appear transparent to external magnetic fields. Because of this unique property, magnetic sensing can be applied to both in vivo deep tissue imaging as well as ex vivo point-of-care diagnostics. To exploit this mode of magnetic detection, new advancements in both magnetic material syntheses and sensing technologies have been made. This review focuses on recent developments of magnetic nanomaterials as image contrast agents and diagnostic sensors. These developments have not only enabled precise control of magnetic nanomaterial properties but also expanded the reach of magnetic detection for biomedical diagnostics.

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Radiation-induced gray matter atrophy in patients with nasopharyngeal carcinoma after intensity modulated radiotherapy: a MRI magnetic resonance imaging voxel-based morphometry study

Background: Gray matter (GM) damage after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients can result in cognitive impairment, while there may be no visible brain tissue change according to the conventional magnetic resonance imaging (MRI). This study investigated radiation-induced GM volume differences between NPC patients who received RT and those who did not. Methods: High-resolution brain structural MRI data from two groups of patients were acquired. The pre-RT group was composed of 56 newly diagnosed but not yet medically treated NPC patients, while the after-RT group consisted of 40 NPC patients who had completed RT more than 1 year ago. Voxel-based morphometry (VBM) was applied to assess GM volumes. Two sample t-test was used to analyze GM volumes voxel-by-voxel using the VBM8 toolbox built in the SPM software. Radiation-induced cortical volume alteration in all NPC patients after RT and dosimetry of 36 patients were analyzed. Results: Compared to pre-treatment group, cortical volumes of GM were significantly smaller in the left hippocampus, the right pulvinar and the right middle temporal gyrus (MTG, Pmean) for bilateral hippocampal heads were significantly higher than other different parts of the brain (P0.05). Conclusions: Radiation to the NPC patients can not only induce damage of the hippocampus, but also other secondary damages of GM.

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Haemostatic material (Surgicel®

Surgical resection is the first line treatment in the majority of pediatric brain tumors. Even in cases when total resection is not possible, a subtotal debulking is used to reduce mass effect and to provide tissue for histological and molecular diagnosis, necessary to guide oncologic therapies, to assess risk stratification and to predict prognosis (1-3).

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Assessment of positional reproducibility in the head and neck on a 1.5-T MR simulator for an offline MR-guided radiotherapy solution

Background: Recently, a shuttle-based offline magnetic resonance-guided radiotherapy (MRgRT) approach was proposed. This study aims to evaluate the positional reproducibility in the immobilized head and neck using a 1.5-T MR-simulator (MR-sim) on healthy volunteers. Methods: A total of 159 scans of 14 healthy volunteers were conducted on a 1.5-T MR-sim with thermoplastic mask immobilization. MR images with isotropic 1.053 mm3 voxel size were rigidly registered to the first scan based on fiducial, anatomical and gross positions. Mean and standard deviation of positional displacements in translation and rotation were assessed. Systematic error and random errors of positioning in the head and neck on the MR-sim were determined in the translation of, and in the rotation of roll, pitch and yaw. Results: The systematic error (Σ) of translation in left-right (LR), anterior-posterior (AP) and superior-inferior (SI) direction was 0.57, 0.22 and 0.26 mm for fiducial displacement, 0.28, 0.10 and 0.52 mm for anatomical displacement, and 0.53, 0.22 and 0.49 mm for gross displacement, respectively. The random error (σ) in corresponding translation direction was 2.07, 0.54 and 1.32 mm for fiducial displacement, 1.34, 0.73 and 2.04 mm for anatomical displacement, and 2.24, 0.86 and 2.61 mm for gross displacement. The systematic error and random error of rotation were generally smaller than 1°. Conclusions: Our results suggested that high gross positional reproducibility (

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Type II endoleak model creation and intraoperative aneurysmal sac embolization with n-butyl cyanoacrylate-lipiodol-ethanol mixture (NLE) in swine

Background: The purpose of this study was to evaluate the feasibility of type II endoleak model creation and efficacy of intraoperative aneurysmal sac embolization using n-butyl-2-cyanoacrylate-lipiodol-ethanol mixture (NLE) for type II endoleak in swine. Methods: In six swine (mean body weight 53.5 kg), abdominal aortic aneurysm (AAA) was created and then end-to-side anastomosis between the left renal artery and AAA sac was performed. And then, endovascular abdominal aortic aneurysm repair (EVAR) was performed, leading to creation of a type II endoleak model. As control group, EVAR without sac embolization was performed in two swine. In four swine, AAA sac was embolized using NLE immediately after EVAR via the microcatheter placed in AAA sac (NLE embolization group). Follow-up aortography was performed immediately and three days after the procedure, and then the aneurysms were extracted. Results: The AAA sac and type II endoleak model were successfully created in all cases. In control group, type II endoleak persisted three days after the procedure. In NLE embolization group, endoleak disappeared immediately and three days after the procedure. In NLE embolization group, AAA sac was occupied with thrombus and embolic material. Inflammatory changes were recognized in aneurysmal sac wall in NLE embolization group. Conclusions: This experimental study suggests that creation of a type II endoleak model in swine is feasible and that intraoperative AAA sac embolization with NLE during EVAR might reduce the occurrence of type II endoleak.

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Regional cerebral metabolism alterations affect resting-state functional connectivity in major depressive disorder

Background: ¹⁸F-FDG positron emission tomography (PET) is a reliable technique to quantify regional neural glucose metabolism even with major depressive disorder (MDD) heterogeneous features. Previous study proposed that in the resting-state (RS), pairs of brain regions whose regional glucose metabolic rates were significantly correlated were functionally associated. This synchronicity indicates a neuronal metabolic and functional interaction in high energy efficient brain regions. In this study, a multimode method was used to identify the RS-FC patterns based on regional metabolism changes, and to observe its relationship with the severity of depressive symptoms in MDD patients. Methods: The study enrolled 11 medication-naive MDD patients and 14 healthy subjects. All participants received a static ¹⁸F-FDG PET brain scan and a resting-state functional magnetic resonance imaging (RS-fMRI) scan. SPM5 software was used to compare brain metabolism in MDD patients with that in healthy controls, and designated regions with a change in metabolism as regions of interest (ROIs). The glucose metabolism-based regional RS-FC Z values were compared between groups. Then group independent component analysis (ICA) was used to identify the abnormal connectivity nodes in the intrinsic function networks. Finally, the correlation between abnormal RS-FC Z values and the severity of depressive symptoms was evaluated. Results: Patients with MDD had reduced glucose metabolism in the putamen, claustrum, insular, inferior frontal gyrus, and supramarginal gyrus. The metabolic reduction regions impaired functional connectivity (FC) to key hubs, such as the Inferior frontal gyrus (pars triangular), angular gyrus, calcarine sulcus, middle frontal gyrus (MFG), located in dorsolateral prefrontal cortex (DLPFC)/parietal lobe, salience network (SN), primary visual cortex (V1), and language network respectively. There was no correlation between aberrant connectivity and the severity of clinical symptoms. Conclusions: This research puts forward a possibility that focal neural activity alteration may share RS-FC dysfunction and be susceptible to hubs in the functional network in MDD. In particular, the metabolism and function profiles of the Inferior frontal gyrus (pars triangularis) should be emphasized in future MDD studies.

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The modified transforaminal endoscopic technique in treating intracanalicular combining foraminal and/or extraforaminal lumbar disc herniations

Background: To develop a modified transforaminal endoscopic spine system (TESSYS^®) technique for treating intracanalicular combining foraminal and/or extraforaminal lumbar disc herniation (ICFE-LDH), and evaluate the technical efficacy and safety. Methods: Twenty-three patients with ICFE-LDH underwent the modified TESSYS technique were enrolled. Magnetic resonance imaging (MRI) was used to verify the reduction of herniated disc. Pre- and post-operative neurological functions were compared by visual analogue scale (VAS) score, Oswestry disability index (ODI) and the modified MacNab criteria. The technical safety was evaluated by surgical complications. Results: MRI demonstrated reductions of disc herniations in 22 patients (95.7%) after surgeries. The VAS scores were significantly improved at 1 year follow-up (low back: P=0.001, lower limbs: PConclusions: The modified TESSYS technique is a minimally-invasive, effective and safe surgery for treating ICFE-LDHs in selected patients.

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Quantitative CT assessment of lung injury after successful cardiopulmonary resuscitation in a porcine cardiac arrest model of different downtimes

Background: Utilize quantitative computed tomography (QCT) to detect and evaluate the severity of lung injury after successful cardiopulmonary resuscitation (CPR) in a porcine cardiac arrest (CA) model with different downtimes. Methods: Twenty-one male domestic pigs weighing 38±3 kg were randomized into 3 groups: the sham group (n=5), the ventricular fibrillation (VF) 5 min (VF5) group (n=8), and the VF 10 min (VF10) group (n=8). VF was induced and untreated for 5 (VF5 group) or 10 (VF10 group) min before the commencement of manual CPR. Eight animals (8/8, 100%) in VF5 and 6 (6/8, 75%) in VF10 were successfully resuscitated. Chest QCT scans and arterial blood gas tests were performed at baseline and 6 h post-resuscitation. The QCT score, volume, and weight of ground-glass opacification (GGO), which was defined as poorly aerated regions with a CT value ranging from −500 Hounsfield units (HU) to −100 HU, and intense parenchymal opacification (IPO), which was defined as a non-aerated area with a CT value greater than −100 HU, were quantitatively measured. Results: Significantly shorter durations of CPR and fewer defibrillations were observed in the VF5 group compared with the VF10 group [duration of CPR: VF5 (6±0 minutes) versus VF10 (8.3±1.5 minutes), P<0.05; numbers of defibrillation: VF5 (1±0) versus VF10 (2.2±0.8), P<0.05]. Compared with the baseline or sham animals, declining gas exchanges (end-tidal CO₂, PO₂, oxygen index) were observed in both VF groups; however, there were no significant differences in gas exchanges between the VF groups. Compared with the VF5 group, the GGO QCT score, volume, and weight were significantly greater in the VF10 group (P=0.002, 0.001, and 0.002 respectively), while no significant differences were found in the IPO QCT score, volume, or weight between two the VF groups (P=0.354, 0.447, and 0.512 respectively). Conclusions: QCT analysis enables unique non-invasive assessments of different lung injuries (IPO and GGO lesions) that can clearly distinguish heterogeneous lesions and allow for early detection and quantitative monitoring of the severity of lung injury following CPR. QCT could provide a basis for clinical early ventilation strategy management after CPR.

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Rapid tissue histology using multichannel confocal fluorescence microscopy with focus tracking

Background: Simplified hematoxylin and eosin (H&E) staining followed by cryo-sectioning enables rapid identification of cancerous tissue within the procedure room during Mohs micrographic surgery. Yet, a faster evaluation method is desirable as the staining protocol requires physically sectioning of the tissue after freezing, which leads to prolonged sectioning time along with the frozen artifacts that may occur in frozen sectioning. Methods: We present a multichannel confocal microscopy system to rapidly evaluate cancerous tissue. Using the optical sectioning capability of the confocal microscope, optically sectioned images of the freshly excised mouse tissue were acquired and converted into images resembling H&E histology. To show details of the nuclei and structure of the tissue, we applied a newly developed rapid tissue staining method using Hoechst 33342 and Eosin-Y. Line scanning and stitching was performed to overcome the limited field of view of the confocal microscope. Unlike previous confocal systems requiring an additional mechanical device to tilt the sample and match the focus of the objective lens, we developed a focus tracking method to rapidly scan large sample area. The focus tracking provides an effective means of keeping the image of the thick tissue in focus without additional devices. We then evaluated the performance of the confocal microscope to obtain optically sectioned images in thick tissue by comparing fluorescence stained slide images. We also obtained the corresponding H&E histology image to assess the potential of the system as a diagnostic tool. Results: We successfully imaged freshly excised mouse organs including stomach, tumor, and heart within a few minutes using the developed multichannel confocal microscopy and the tissue staining method. Using the pseudocolor method, colors of the acquired confocal grayscale images are converted to furthermore resemble Hematoxylin and Eosin histology. Due to the focus tracking and the line scanning, optically sectioned images were obtained over the large field of view. Comparisons with H&E histology have shown that the confocal images can acquire large details such as the ventricle as well as small details such as muscle fibers and nuclei. Conclusions: This study confirms the use of confocal fluorescence microscopy technique to acquire rapid pathology results using optical sectioning, line scanning and focus tracking. We anticipate that the presented method will enable intraoperative histology and significantly reduce stress on patients undergoing surgery requiring repeated histology examinations.

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Design and synthesis of magnetic nanoparticles for biomedical diagnostics

Sensitive and quantitative characterization of clinically relevant biomarkers can facilitate disease diagnosis and treatment evaluation. Magnetic nanomaterials and their biosensing strategies have recently received considerable attention. Magnetic signals experience little interference from native biological background as most biological molecules have negligible magnetic susceptibilities and thus appear transparent to external magnetic fields. Because of this unique property, magnetic sensing can be applied to both in vivo deep tissue imaging as well as ex vivo point-of-care diagnostics. To exploit this mode of magnetic detection, new advancements in both magnetic material syntheses and sensing technologies have been made. This review focuses on recent developments of magnetic nanomaterials as image contrast agents and diagnostic sensors. These developments have not only enabled precise control of magnetic nanomaterial properties but also expanded the reach of magnetic detection for biomedical diagnostics.

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Radiation-induced gray matter atrophy in patients with nasopharyngeal carcinoma after intensity modulated radiotherapy: a MRI magnetic resonance imaging voxel-based morphometry study

Background: Gray matter (GM) damage after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients can result in cognitive impairment, while there may be no visible brain tissue change according to the conventional magnetic resonance imaging (MRI). This study investigated radiation-induced GM volume differences between NPC patients who received RT and those who did not. Methods: High-resolution brain structural MRI data from two groups of patients were acquired. The pre-RT group was composed of 56 newly diagnosed but not yet medically treated NPC patients, while the after-RT group consisted of 40 NPC patients who had completed RT more than 1 year ago. Voxel-based morphometry (VBM) was applied to assess GM volumes. Two sample t-test was used to analyze GM volumes voxel-by-voxel using the VBM8 toolbox built in the SPM software. Radiation-induced cortical volume alteration in all NPC patients after RT and dosimetry of 36 patients were analyzed. Results: Compared to pre-treatment group, cortical volumes of GM were significantly smaller in the left hippocampus, the right pulvinar and the right middle temporal gyrus (MTG, Pmean) for bilateral hippocampal heads were significantly higher than other different parts of the brain (P0.05). Conclusions: Radiation to the NPC patients can not only induce damage of the hippocampus, but also other secondary damages of GM.

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Haemostatic material (Surgicel®

Surgical resection is the first line treatment in the majority of pediatric brain tumors. Even in cases when total resection is not possible, a subtotal debulking is used to reduce mass effect and to provide tissue for histological and molecular diagnosis, necessary to guide oncologic therapies, to assess risk stratification and to predict prognosis (1-3).

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Assessment of positional reproducibility in the head and neck on a 1.5-T MR simulator for an offline MR-guided radiotherapy solution

Background: Recently, a shuttle-based offline magnetic resonance-guided radiotherapy (MRgRT) approach was proposed. This study aims to evaluate the positional reproducibility in the immobilized head and neck using a 1.5-T MR-simulator (MR-sim) on healthy volunteers. Methods: A total of 159 scans of 14 healthy volunteers were conducted on a 1.5-T MR-sim with thermoplastic mask immobilization. MR images with isotropic 1.053 mm3 voxel size were rigidly registered to the first scan based on fiducial, anatomical and gross positions. Mean and standard deviation of positional displacements in translation and rotation were assessed. Systematic error and random errors of positioning in the head and neck on the MR-sim were determined in the translation of, and in the rotation of roll, pitch and yaw. Results: The systematic error (Σ) of translation in left-right (LR), anterior-posterior (AP) and superior-inferior (SI) direction was 0.57, 0.22 and 0.26 mm for fiducial displacement, 0.28, 0.10 and 0.52 mm for anatomical displacement, and 0.53, 0.22 and 0.49 mm for gross displacement, respectively. The random error (σ) in corresponding translation direction was 2.07, 0.54 and 1.32 mm for fiducial displacement, 1.34, 0.73 and 2.04 mm for anatomical displacement, and 2.24, 0.86 and 2.61 mm for gross displacement. The systematic error and random error of rotation were generally smaller than 1°. Conclusions: Our results suggested that high gross positional reproducibility (

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Type II endoleak model creation and intraoperative aneurysmal sac embolization with n-butyl cyanoacrylate-lipiodol-ethanol mixture (NLE) in swine

Background: The purpose of this study was to evaluate the feasibility of type II endoleak model creation and efficacy of intraoperative aneurysmal sac embolization using n-butyl-2-cyanoacrylate-lipiodol-ethanol mixture (NLE) for type II endoleak in swine. Methods: In six swine (mean body weight 53.5 kg), abdominal aortic aneurysm (AAA) was created and then end-to-side anastomosis between the left renal artery and AAA sac was performed. And then, endovascular abdominal aortic aneurysm repair (EVAR) was performed, leading to creation of a type II endoleak model. As control group, EVAR without sac embolization was performed in two swine. In four swine, AAA sac was embolized using NLE immediately after EVAR via the microcatheter placed in AAA sac (NLE embolization group). Follow-up aortography was performed immediately and three days after the procedure, and then the aneurysms were extracted. Results: The AAA sac and type II endoleak model were successfully created in all cases. In control group, type II endoleak persisted three days after the procedure. In NLE embolization group, endoleak disappeared immediately and three days after the procedure. In NLE embolization group, AAA sac was occupied with thrombus and embolic material. Inflammatory changes were recognized in aneurysmal sac wall in NLE embolization group. Conclusions: This experimental study suggests that creation of a type II endoleak model in swine is feasible and that intraoperative AAA sac embolization with NLE during EVAR might reduce the occurrence of type II endoleak.

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Regional cerebral metabolism alterations affect resting-state functional connectivity in major depressive disorder

Background: ¹⁸F-FDG positron emission tomography (PET) is a reliable technique to quantify regional neural glucose metabolism even with major depressive disorder (MDD) heterogeneous features. Previous study proposed that in the resting-state (RS), pairs of brain regions whose regional glucose metabolic rates were significantly correlated were functionally associated. This synchronicity indicates a neuronal metabolic and functional interaction in high energy efficient brain regions. In this study, a multimode method was used to identify the RS-FC patterns based on regional metabolism changes, and to observe its relationship with the severity of depressive symptoms in MDD patients. Methods: The study enrolled 11 medication-naive MDD patients and 14 healthy subjects. All participants received a static ¹⁸F-FDG PET brain scan and a resting-state functional magnetic resonance imaging (RS-fMRI) scan. SPM5 software was used to compare brain metabolism in MDD patients with that in healthy controls, and designated regions with a change in metabolism as regions of interest (ROIs). The glucose metabolism-based regional RS-FC Z values were compared between groups. Then group independent component analysis (ICA) was used to identify the abnormal connectivity nodes in the intrinsic function networks. Finally, the correlation between abnormal RS-FC Z values and the severity of depressive symptoms was evaluated. Results: Patients with MDD had reduced glucose metabolism in the putamen, claustrum, insular, inferior frontal gyrus, and supramarginal gyrus. The metabolic reduction regions impaired functional connectivity (FC) to key hubs, such as the Inferior frontal gyrus (pars triangular), angular gyrus, calcarine sulcus, middle frontal gyrus (MFG), located in dorsolateral prefrontal cortex (DLPFC)/parietal lobe, salience network (SN), primary visual cortex (V1), and language network respectively. There was no correlation between aberrant connectivity and the severity of clinical symptoms. Conclusions: This research puts forward a possibility that focal neural activity alteration may share RS-FC dysfunction and be susceptible to hubs in the functional network in MDD. In particular, the metabolism and function profiles of the Inferior frontal gyrus (pars triangularis) should be emphasized in future MDD studies.

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The modified transforaminal endoscopic technique in treating intracanalicular combining foraminal and/or extraforaminal lumbar disc herniations

Background: To develop a modified transforaminal endoscopic spine system (TESSYS^®) technique for treating intracanalicular combining foraminal and/or extraforaminal lumbar disc herniation (ICFE-LDH), and evaluate the technical efficacy and safety. Methods: Twenty-three patients with ICFE-LDH underwent the modified TESSYS technique were enrolled. Magnetic resonance imaging (MRI) was used to verify the reduction of herniated disc. Pre- and post-operative neurological functions were compared by visual analogue scale (VAS) score, Oswestry disability index (ODI) and the modified MacNab criteria. The technical safety was evaluated by surgical complications. Results: MRI demonstrated reductions of disc herniations in 22 patients (95.7%) after surgeries. The VAS scores were significantly improved at 1 year follow-up (low back: P=0.001, lower limbs: PConclusions: The modified TESSYS technique is a minimally-invasive, effective and safe surgery for treating ICFE-LDHs in selected patients.

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Quantitative CT assessment of lung injury after successful cardiopulmonary resuscitation in a porcine cardiac arrest model of different downtimes

Background: Utilize quantitative computed tomography (QCT) to detect and evaluate the severity of lung injury after successful cardiopulmonary resuscitation (CPR) in a porcine cardiac arrest (CA) model with different downtimes. Methods: Twenty-one male domestic pigs weighing 38±3 kg were randomized into 3 groups: the sham group (n=5), the ventricular fibrillation (VF) 5 min (VF5) group (n=8), and the VF 10 min (VF10) group (n=8). VF was induced and untreated for 5 (VF5 group) or 10 (VF10 group) min before the commencement of manual CPR. Eight animals (8/8, 100%) in VF5 and 6 (6/8, 75%) in VF10 were successfully resuscitated. Chest QCT scans and arterial blood gas tests were performed at baseline and 6 h post-resuscitation. The QCT score, volume, and weight of ground-glass opacification (GGO), which was defined as poorly aerated regions with a CT value ranging from −500 Hounsfield units (HU) to −100 HU, and intense parenchymal opacification (IPO), which was defined as a non-aerated area with a CT value greater than −100 HU, were quantitatively measured. Results: Significantly shorter durations of CPR and fewer defibrillations were observed in the VF5 group compared with the VF10 group [duration of CPR: VF5 (6±0 minutes) versus VF10 (8.3±1.5 minutes), P<0.05; numbers of defibrillation: VF5 (1±0) versus VF10 (2.2±0.8), P<0.05]. Compared with the baseline or sham animals, declining gas exchanges (end-tidal CO₂, PO₂, oxygen index) were observed in both VF groups; however, there were no significant differences in gas exchanges between the VF groups. Compared with the VF5 group, the GGO QCT score, volume, and weight were significantly greater in the VF10 group (P=0.002, 0.001, and 0.002 respectively), while no significant differences were found in the IPO QCT score, volume, or weight between two the VF groups (P=0.354, 0.447, and 0.512 respectively). Conclusions: QCT analysis enables unique non-invasive assessments of different lung injuries (IPO and GGO lesions) that can clearly distinguish heterogeneous lesions and allow for early detection and quantitative monitoring of the severity of lung injury following CPR. QCT could provide a basis for clinical early ventilation strategy management after CPR.

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Rapid tissue histology using multichannel confocal fluorescence microscopy with focus tracking

Background: Simplified hematoxylin and eosin (H&E) staining followed by cryo-sectioning enables rapid identification of cancerous tissue within the procedure room during Mohs micrographic surgery. Yet, a faster evaluation method is desirable as the staining protocol requires physically sectioning of the tissue after freezing, which leads to prolonged sectioning time along with the frozen artifacts that may occur in frozen sectioning. Methods: We present a multichannel confocal microscopy system to rapidly evaluate cancerous tissue. Using the optical sectioning capability of the confocal microscope, optically sectioned images of the freshly excised mouse tissue were acquired and converted into images resembling H&E histology. To show details of the nuclei and structure of the tissue, we applied a newly developed rapid tissue staining method using Hoechst 33342 and Eosin-Y. Line scanning and stitching was performed to overcome the limited field of view of the confocal microscope. Unlike previous confocal systems requiring an additional mechanical device to tilt the sample and match the focus of the objective lens, we developed a focus tracking method to rapidly scan large sample area. The focus tracking provides an effective means of keeping the image of the thick tissue in focus without additional devices. We then evaluated the performance of the confocal microscope to obtain optically sectioned images in thick tissue by comparing fluorescence stained slide images. We also obtained the corresponding H&E histology image to assess the potential of the system as a diagnostic tool. Results: We successfully imaged freshly excised mouse organs including stomach, tumor, and heart within a few minutes using the developed multichannel confocal microscopy and the tissue staining method. Using the pseudocolor method, colors of the acquired confocal grayscale images are converted to furthermore resemble Hematoxylin and Eosin histology. Due to the focus tracking and the line scanning, optically sectioned images were obtained over the large field of view. Comparisons with H&E histology have shown that the confocal images can acquire large details such as the ventricle as well as small details such as muscle fibers and nuclei. Conclusions: This study confirms the use of confocal fluorescence microscopy technique to acquire rapid pathology results using optical sectioning, line scanning and focus tracking. We anticipate that the presented method will enable intraoperative histology and significantly reduce stress on patients undergoing surgery requiring repeated histology examinations.

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Prevalence of contact allergy in the general population: A systematic review and meta‐analysis

Contact Dermatitis, EarlyView.


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Prevalence of contact allergy in the general population: A systematic review and meta‐analysis

Contact Dermatitis, EarlyView.


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Photo-polymerization properties of Type-II photoinitiator systems based on 2-chlorohexaaryl biimidazole (o-Cl-HABI) and various N-phenylglycine (NPG) derivatives

Photochem. Photobiol. Sci., 2018, Accepted Manuscript
DOI: 10.1039/C8PP00300A, Paper

Yung-Chung Chen, Yuan-Tsung Kao, Tsung-Han Ho
A series of p-substituted NPG derivatives (Cl-NPG, OMe-NPG and NO2-NPG) comprising different push-pull characteristics have been synthesized and characterized. The NPG derivatives have good thermal stability and rather-red shifted absorption...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Photo-polymerization properties of Type-II photoinitiator systems based on 2-chlorohexaaryl biimidazole (o-Cl-HABI) and various N-phenylglycine (NPG) derivatives

Photochem. Photobiol. Sci., 2018, Accepted Manuscript
DOI: 10.1039/C8PP00300A, Paper

Yung-Chung Chen, Yuan-Tsung Kao, Tsung-Han Ho
A series of p-substituted NPG derivatives (Cl-NPG, OMe-NPG and NO2-NPG) comprising different push-pull characteristics have been synthesized and characterized. The NPG derivatives have good thermal stability and rather-red shifted absorption...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Improvement of exertional dyspnea and breathing pattern of inspiration to expiration after bronchial thermoplasty

Bronchial thermoplasty (BT) is a bronchoscopic treatment that can ameliorate the symptoms of severe asthma. However, little is known about the mechanism by which BT improves exertional dyspnea without signific...

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First reported case in Canada of anaphylaxis to lupine in a child with peanut allergy

Lupine is a member of the legume family and is often used in many food products in Europe (e.g. pasta, pizza, sauces, etc.) as a wheat or soy substitute. Lupine cross-reacts with peanut, and cases of allergic ...

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Improvement of exertional dyspnea and breathing pattern of inspiration to expiration after bronchial thermoplasty

Bronchial thermoplasty (BT) is a bronchoscopic treatment that can ameliorate the symptoms of severe asthma. However, little is known about the mechanism by which BT improves exertional dyspnea without signific...

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First reported case in Canada of anaphylaxis to lupine in a child with peanut allergy

Lupine is a member of the legume family and is often used in many food products in Europe (e.g. pasta, pizza, sauces, etc.) as a wheat or soy substitute. Lupine cross-reacts with peanut, and cases of allergic ...

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Targeting Chemokines and Chemokine Receptors in Melanoma and Other Cancers

Nicolas Jacquelot, Connie P. M. Duong, Gabrielle T. Belz, Laurence Zitvogel (Source: Frontiers in Immunology)

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Outer-Membrane-Vesicle –Associated O Antigen, a Crucial Component for Protecting Against Bordetella parapertussis Infection

Daniela Bottero, Mar ía Eugenia Zurita, María Emilia Gaillard, Francisco Carriquiriborde, Pablo Martin Aispuro, Maia Elizagaray, Erika Bartel, Celina Castuma, Daniela Hozbor (Source: Frontiers in Immunology)

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Rainbow Trout Erythrocytes ex vivo Transfection With a DNA Vaccine Encoding VHSV Glycoprotein G Induces an Antiviral Immune Response

Sara Puente-Marin, Ivan Nombela, Veronica Chico, Sergio Ciordia, Maria Carmen Mena, Julio Coll, Luis Mercado, Maria Del Mar Ortega-Villaizan (Source: Frontiers in Immunology)

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Divergent lncRNA GATA3-AS1 Regulates GATA3 Transcription in T-Helper 2 Cells

Hunter R. Gibbons, Guzel Shaginurova, Laura C. Kim, Nathaniel Chapman, Charles F. Spurlock, Thomas M. Aune (Source: Frontiers in Immunology)

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Rheumatoid Arthritis Patients With Circulating Extracellular Vesicles Positive for IgM Rheumatoid Factor Have Higher Disease Activity

Onno J. Arntz, Bartijn C. H. Pieters, Rogier M. Thurlings, Mark H. Wenink, Peter L. E. M. van Lent, Marije I. Koenders, Frank H. J. van den Hoogen, Peter M. van der Kraan, Fons A. J. van de Loo (Source: Frontiers in Immunology)

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Hormonal Regulation of Physiology, Innate Immunity and Antibody Response to H1N1 Influenza Virus Infection During Pregnancy

Elizabeth Q. Littauer, Ioanna Skountzou (Source: Frontiers in Immunology)

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Pre-emptive Allogeneic Hematopoietic Stem Cell Transplantation in Ataxia Telangiectasia

Shahrzad Bakhtiar, Sandra Woelke, Sabine Huenecke, Matthias Kieslich, Alexander Malcolm Taylor, Ralf Schubert, Stefan Zielen, Peter Bader (Source: Frontiers in Immunology)

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Baseline Circulating Activated TFH and Tissue-Like Exhausted B Cells Negatively Correlate With Meningococcal C Conjugate Vaccine Induced Antibodies in HIV-Infected Individuals

Lucimar Milagres, Giselle Silva, W ânia Pereira-Manfro, Ana Cristina Frota, Cristina Hofer, Bianca Ferreira, Daniela Barreto, Marcelo Figueredo, Barbara Coelho, Lucia Villela, Constantinos Petrovas, Richard Koup (Source: Frontiers in Immunology)

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Maternal immunization downregulates offspring TCD4 regulatory cells (Tregs) thymic maturation without implications for allergy inhibition

Scandinavian Journal of Immunology, EarlyView. (Source: Scandinavian Journal of Immunology)

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Primary Prevention of Asthma: Will It Be Possible in the Future?

AbstractPurpose of ReviewAsthma is a major public health problem in both the developed and developing world. Asthma is a complex heterogeneous disease with a multifactorial etiology involving genetic, epigenetic, viral, microbial and environmental exposures.Recent FindingsNew studies have provided significant novel information on the interplay between inherited and modifiable risk factors in the development of asthma, suggesting possible primary preventive measures.SummaryMulti-faceted interventional strategies targeted to the personalized risk profile will likely be most effective in primary prevention of asthma. (Source: Current Treatment Options in Allergy)

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First reported case in Canada of anaphylaxis to lupine in a child with peanut allergy

Lupine is a member of the legume family and is often used in many food products in Europe (e.g. pasta, pizza, sauces, etc.) as a wheat or soy substitute. Lupine cross-reacts with peanut, and cases of allergic ... (Source: Allergy, Asthma and Clinical Immunology)

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House Dust Mite Tablets Now Officially Accepted as Treatment in GINA: What Is the Evidence and What ’s Next?

AbstractPurpose of ReviewThis review analyzes the growing evidence regarding the standardized quality house dust mite (SQ-HDM) sublingual immunotherapy (SLIT) tablets as a valuable therapeutic option in asthma, as recently included in the treatment algorithm of the Global Initiative for Asthma (GINA) as an add-on treatment for adult patients with allergic asthma not well controlled with inhaled corticosteroids (ICS).Recent FindingsEvidence from well-designed randomized placebo-controlled clinical trials shows that the SQ-HDM SLIT tablet is effective vs. placebo in reducing both asthma symptoms and the need for ICS, as well as the risk of experiencing a moderate/severe asthma exacerbation following ICS reduction, besides having a very good safety profile and tolerability. However, some unme...

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Diagnosis and Management of Shellfish Allergy: Current Approach and Future Needs

AbstractPurpose of reviewShellfish allergy is an increasing health concern worldwide with over 2% of the population affected and higher rates in countries with high consumption. Shellfish includes both crustaceans and mollusks and constitutes one of the major food groups triggering allergic reactions.Recent findingsShrimp is the best-studied crustacean, in which the major shellfish allergen, tropomyosin, was initially characterized. Nevertheless, several other allergens have been identified and should be considered despite prevalence of sensitization being lower than tropomyosin (e.g., arginine kinase, myosin light chain, and sarcoplasmic calcium-binding protein).SummaryDiagnosis is not always straightforward; due to the conserved nature of most allergens, there is extensive cross-reactivi...

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IgE-Mediated Food Allergy

AbstractFood allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the immune system, causing a T helper 2 response which results in IgE binding to Fcε receptors on effector cells like mast cells and basophils. The activation of these cells causes release of histamine and other preformed mediators, and rapid symptom onset, in contrast with non-IgE-mediated food allergy which is more delayed in onset. The diagnosis of IgE-mediated food allergy re quires a history of classic clinical symptoms and evidence of foo...

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A Low Frequency of IL-17-Producing CD8+ T-Cells Is Associated With Persistent Immune Activation in People Living With HIV Despite HAART-Induced Viral Suppression

Federico Perdomo-Celis, Manuel G. Feria, Natalia A. Taborda, Maria T. Rugeles (Source: Frontiers in Immunology)

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Induction of Tolerance Through Early Weaning and Oral Immunotherapy

AbstractPurpose of reviewThe increase in IgE-mediated food allergy in the world with prevalence of egg, milk, peanut, and wheat allergies presenting and coexisting as multiple food allergies in young children.Recent findingsEarlier initiation in weaning and timing of exposure of specific food allergens to an atopic infant appears to affect the trajectory and progression of acquiring tolerance in these children for specific foods. In this review, the allergen-specific strategies for increasing tolerance (desensitization) and hastening the resolution of food allergy (SU) are reviewed for treatment of food allergy.SummaryPhenotypic complexity of the individual (eczema, asthma, rhinitis), age of the child at presentation and severity of food reactions, alongside skin test size and IgE levels c...

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Improvement of exertional dyspnea and breathing pattern of inspiration to expiration after bronchial thermoplasty

Bronchial thermoplasty (BT) is a bronchoscopic treatment that can ameliorate the symptoms of severe asthma. However, little is known about the mechanism by which BT improves exertional dyspnea without signific... (Source: Allergy, Asthma and Clinical Immunology)

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Targeting Chemokines and Chemokine Receptors in Melanoma and Other Cancers

Nicolas Jacquelot, Connie P. M. Duong, Gabrielle T. Belz, Laurence Zitvogel (Source: Frontiers in Immunology)

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Outer-Membrane-Vesicle –Associated O Antigen, a Crucial Component for Protecting Against Bordetella parapertussis Infection

Daniela Bottero, Mar ía Eugenia Zurita, María Emilia Gaillard, Francisco Carriquiriborde, Pablo Martin Aispuro, Maia Elizagaray, Erika Bartel, Celina Castuma, Daniela Hozbor (Source: Frontiers in Immunology)

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Rainbow Trout Erythrocytes ex vivo Transfection With a DNA Vaccine Encoding VHSV Glycoprotein G Induces an Antiviral Immune Response

Sara Puente-Marin, Ivan Nombela, Veronica Chico, Sergio Ciordia, Maria Carmen Mena, Julio Coll, Luis Mercado, Maria Del Mar Ortega-Villaizan (Source: Frontiers in Immunology)

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Divergent lncRNA GATA3-AS1 Regulates GATA3 Transcription in T-Helper 2 Cells

Hunter R. Gibbons, Guzel Shaginurova, Laura C. Kim, Nathaniel Chapman, Charles F. Spurlock, Thomas M. Aune (Source: Frontiers in Immunology)

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Rheumatoid Arthritis Patients With Circulating Extracellular Vesicles Positive for IgM Rheumatoid Factor Have Higher Disease Activity

Onno J. Arntz, Bartijn C. H. Pieters, Rogier M. Thurlings, Mark H. Wenink, Peter L. E. M. van Lent, Marije I. Koenders, Frank H. J. van den Hoogen, Peter M. van der Kraan, Fons A. J. van de Loo (Source: Frontiers in Immunology)

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Hormonal Regulation of Physiology, Innate Immunity and Antibody Response to H1N1 Influenza Virus Infection During Pregnancy

Elizabeth Q. Littauer, Ioanna Skountzou (Source: Frontiers in Immunology)

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Pre-emptive Allogeneic Hematopoietic Stem Cell Transplantation in Ataxia Telangiectasia

Shahrzad Bakhtiar, Sandra Woelke, Sabine Huenecke, Matthias Kieslich, Alexander Malcolm Taylor, Ralf Schubert, Stefan Zielen, Peter Bader (Source: Frontiers in Immunology)

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Baseline Circulating Activated TFH and Tissue-Like Exhausted B Cells Negatively Correlate With Meningococcal C Conjugate Vaccine Induced Antibodies in HIV-Infected Individuals

Lucimar Milagres, Giselle Silva, W ânia Pereira-Manfro, Ana Cristina Frota, Cristina Hofer, Bianca Ferreira, Daniela Barreto, Marcelo Figueredo, Barbara Coelho, Lucia Villela, Constantinos Petrovas, Richard Koup (Source: Frontiers in Immunology)

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Maternal immunization downregulates offspring TCD4 regulatory cells (Tregs) thymic maturation without implications for allergy inhibition

Scandinavian Journal of Immunology, EarlyView. (Source: Scandinavian Journal of Immunology)

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Primary Prevention of Asthma: Will It Be Possible in the Future?

AbstractPurpose of ReviewAsthma is a major public health problem in both the developed and developing world. Asthma is a complex heterogeneous disease with a multifactorial etiology involving genetic, epigenetic, viral, microbial and environmental exposures.Recent FindingsNew studies have provided significant novel information on the interplay between inherited and modifiable risk factors in the development of asthma, suggesting possible primary preventive measures.SummaryMulti-faceted interventional strategies targeted to the personalized risk profile will likely be most effective in primary prevention of asthma. (Source: Current Treatment Options in Allergy)

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First reported case in Canada of anaphylaxis to lupine in a child with peanut allergy

Lupine is a member of the legume family and is often used in many food products in Europe (e.g. pasta, pizza, sauces, etc.) as a wheat or soy substitute. Lupine cross-reacts with peanut, and cases of allergic ... (Source: Allergy, Asthma and Clinical Immunology)

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House Dust Mite Tablets Now Officially Accepted as Treatment in GINA: What Is the Evidence and What ’s Next?

AbstractPurpose of ReviewThis review analyzes the growing evidence regarding the standardized quality house dust mite (SQ-HDM) sublingual immunotherapy (SLIT) tablets as a valuable therapeutic option in asthma, as recently included in the treatment algorithm of the Global Initiative for Asthma (GINA) as an add-on treatment for adult patients with allergic asthma not well controlled with inhaled corticosteroids (ICS).Recent FindingsEvidence from well-designed randomized placebo-controlled clinical trials shows that the SQ-HDM SLIT tablet is effective vs. placebo in reducing both asthma symptoms and the need for ICS, as well as the risk of experiencing a moderate/severe asthma exacerbation following ICS reduction, besides having a very good safety profile and tolerability. However, some unme...

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Diagnosis and Management of Shellfish Allergy: Current Approach and Future Needs

AbstractPurpose of reviewShellfish allergy is an increasing health concern worldwide with over 2% of the population affected and higher rates in countries with high consumption. Shellfish includes both crustaceans and mollusks and constitutes one of the major food groups triggering allergic reactions.Recent findingsShrimp is the best-studied crustacean, in which the major shellfish allergen, tropomyosin, was initially characterized. Nevertheless, several other allergens have been identified and should be considered despite prevalence of sensitization being lower than tropomyosin (e.g., arginine kinase, myosin light chain, and sarcoplasmic calcium-binding protein).SummaryDiagnosis is not always straightforward; due to the conserved nature of most allergens, there is extensive cross-reactivi...

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IgE-Mediated Food Allergy

AbstractFood allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the immune system, causing a T helper 2 response which results in IgE binding to Fcε receptors on effector cells like mast cells and basophils. The activation of these cells causes release of histamine and other preformed mediators, and rapid symptom onset, in contrast with non-IgE-mediated food allergy which is more delayed in onset. The diagnosis of IgE-mediated food allergy re quires a history of classic clinical symptoms and evidence of foo...

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A Low Frequency of IL-17-Producing CD8+ T-Cells Is Associated With Persistent Immune Activation in People Living With HIV Despite HAART-Induced Viral Suppression

Federico Perdomo-Celis, Manuel G. Feria, Natalia A. Taborda, Maria T. Rugeles (Source: Frontiers in Immunology)

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Induction of Tolerance Through Early Weaning and Oral Immunotherapy

AbstractPurpose of reviewThe increase in IgE-mediated food allergy in the world with prevalence of egg, milk, peanut, and wheat allergies presenting and coexisting as multiple food allergies in young children.Recent findingsEarlier initiation in weaning and timing of exposure of specific food allergens to an atopic infant appears to affect the trajectory and progression of acquiring tolerance in these children for specific foods. In this review, the allergen-specific strategies for increasing tolerance (desensitization) and hastening the resolution of food allergy (SU) are reviewed for treatment of food allergy.SummaryPhenotypic complexity of the individual (eczema, asthma, rhinitis), age of the child at presentation and severity of food reactions, alongside skin test size and IgE levels c...

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Improvement of exertional dyspnea and breathing pattern of inspiration to expiration after bronchial thermoplasty

Bronchial thermoplasty (BT) is a bronchoscopic treatment that can ameliorate the symptoms of severe asthma. However, little is known about the mechanism by which BT improves exertional dyspnea without signific... (Source: Allergy, Asthma and Clinical Immunology)

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Patterns of Hysteresis Between Induction and Emergence of Neuroanesthesia are Present in Spinal and Intracranial Surgeries

Background: Recovery of consciousness is usually seen as a passive process, with emergence from anesthesia depicted as the inverse process of induction resulting from the elimination of anesthetic drugs from their central nervous system sites of action. However, that need not be the case. Recently it has been argued that we might encounter hysteresis to changes in the state of consciousness, known as neural inertia. This phenomenon has been debated in neuroanesthesia, as manipulation of the brain might further influence recovery of consciousness. The present study is aimed at assessing hysteresis between induction and emergence under propofol-opioid neuroanesthesia in humans using estimated propofol concentrations in both spinal and intracranial surgeries. Methods: We identified the moments of loss (LOR) and recovery of responsiveness (ROR) in 21 craniotomies and 25 spinal surgeries. Propofol was given slowly until loss of responsiveness and stopped at the end of surgery. An opioid was present at induction and recovery. Propofol infused was recorded and plasma and effect-site concentrations were estimated using 2 pharmacokinetic models. Dose-response curves were generated. Estimated propofol plasma and effect-site concentrations were compared to assess hysteresis. Results: Estimated propofol concentrations at LOR and ROR showed hysteresis. Whether for spinal or intracranial surgeries, the EC50 of propofol at which half of the patients entered and exited the state of responsiveness was significantly different. Conclusions: Hysteresis was observed between propofol concentrations at LOR and ROR, in both patients presenting for spinal and intracranial surgeries. Manipulation of the brain does not appear to change patterns of hysteresis, suggesting that neural inertia may occur in humans, in a way similar to that found in animal species. These findings justify performing a clinical study in patients using measured propofol concentrations to assess neural inertia. Supported by the Fundação para a Ciência e Tecnologia with the reference projects SFRH/BD/98915/2013 and UID/SEM/50022/2013. The authors have no conflicts of interest to disclose. Address correspondence to: Ana Leitão Ferreira, MSc, MS, Center of Clinical Investigation in Anesthesiology, Service of Anesthesiology, Hospital Center of Porto, Largo Professor Abel Salazar, 4099-001 Porto, Portugal (e-mail: ana.leitao.ferreira@gmail.com). Received April 12, 2018 Accepted September 14, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Journal Club

No abstract available

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Patterns of Hysteresis Between Induction and Emergence of Neuroanesthesia are Present in Spinal and Intracranial Surgeries

Background: Recovery of consciousness is usually seen as a passive process, with emergence from anesthesia depicted as the inverse process of induction resulting from the elimination of anesthetic drugs from their central nervous system sites of action. However, that need not be the case. Recently it has been argued that we might encounter hysteresis to changes in the state of consciousness, known as neural inertia. This phenomenon has been debated in neuroanesthesia, as manipulation of the brain might further influence recovery of consciousness. The present study is aimed at assessing hysteresis between induction and emergence under propofol-opioid neuroanesthesia in humans using estimated propofol concentrations in both spinal and intracranial surgeries. Methods: We identified the moments of loss (LOR) and recovery of responsiveness (ROR) in 21 craniotomies and 25 spinal surgeries. Propofol was given slowly until loss of responsiveness and stopped at the end of surgery. An opioid was present at induction and recovery. Propofol infused was recorded and plasma and effect-site concentrations were estimated using 2 pharmacokinetic models. Dose-response curves were generated. Estimated propofol plasma and effect-site concentrations were compared to assess hysteresis. Results: Estimated propofol concentrations at LOR and ROR showed hysteresis. Whether for spinal or intracranial surgeries, the EC50 of propofol at which half of the patients entered and exited the state of responsiveness was significantly different. Conclusions: Hysteresis was observed between propofol concentrations at LOR and ROR, in both patients presenting for spinal and intracranial surgeries. Manipulation of the brain does not appear to change patterns of hysteresis, suggesting that neural inertia may occur in humans, in a way similar to that found in animal species. These findings justify performing a clinical study in patients using measured propofol concentrations to assess neural inertia. Supported by the Fundação para a Ciência e Tecnologia with the reference projects SFRH/BD/98915/2013 and UID/SEM/50022/2013. The authors have no conflicts of interest to disclose. Address correspondence to: Ana Leitão Ferreira, MSc, MS, Center of Clinical Investigation in Anesthesiology, Service of Anesthesiology, Hospital Center of Porto, Largo Professor Abel Salazar, 4099-001 Porto, Portugal (e-mail: ana.leitao.ferreira@gmail.com). Received April 12, 2018 Accepted September 14, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Journal Club

No abstract available

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Cutaneous localization of angioimmunoblastic T‐cell lymphoma may masquerade as B cell lymphoma or classical Hodgkin lymphoma: a histologic diagnostic pitfall

Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.


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Cutaneous localization of angioimmunoblastic T‐cell lymphoma may masquerade as B cell lymphoma or classical Hodgkin lymphoma: a histologic diagnostic pitfall

Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.


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Pathological Features and Clinical Course in Patients With Recurrent or Malignant Orbital Solitary Fibrous Tumor/Hemangiopericytoma

Purpose: A risk assessment score for metastasis based on age, tumor size, and mitotic figures has been suggested for nonorbital solitary fibrous tumor (SFT)/hemangiopericytoma. The authors herein examine the clinicopathological features of recurrent and metastatic orbital SFT and evaluate the existing risk assessment score for orbital SFT. Methods: The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried for patients with recurrent or malignant orbital hemangiopericytoma/SFT. The medical records were reviewed for clinical and pathologic findings, treatments, and outcomes. Results: Eight patients from 3 institutions were identified with recurrent orbital hemangiopericytoma/SFT. Median age at diagnosis was 59 years, and 4 patients were women. The mean size of tumor was 2.1 ± 1.1 cm. All patients were initially treated with surgery and experienced local recurrence after a median of 4 (range 0.5–10) years. Five patients were treated with orbital radiation. Two patients also developed distant metastases and eventually died of their disease. Median Ki-67 was 5% (range 1–65%) and 5 mitotic figures/10 high-power fields (range 2–30). The previously described risk stratification model for nonorbital SFT did not correlate with the propensity to develop metastases in this cohort; however, both patients with distant metastasis had > 4 mitotic figures /10 high-power fields. Conclusions: In this cohort of recurrent orbital hemangiopericytoma/SFT, median time to recurrence was 4 years underscoring the importance of careful continued follow-up. The current risk stratification models have limited use for orbital lesions, mostly due to the fact that orbital SFTs are smaller than even the smallest size criteria in this risk assessment model. Accepted for publication June 17, 2018. This work was supported in part by the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) Foundation through their support of the ASOPRS Oncology Database at MD Anderson Cancer Center. The authors have no conflicts of interest to disclose. Presented at the American Society of Oculoplastic and Reconstructive Surgery Fall Meeting on November 10, 2017 in New Orleans, LA. Address correspondence and reprint requests to Bita Esmaeli, M.D., F.A.C.S., Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, Unit 1488, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. E-mail: besmaeli@mdanderson.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Pathological Features and Clinical Course in Patients With Recurrent or Malignant Orbital Solitary Fibrous Tumor/Hemangiopericytoma

Purpose: A risk assessment score for metastasis based on age, tumor size, and mitotic figures has been suggested for nonorbital solitary fibrous tumor (SFT)/hemangiopericytoma. The authors herein examine the clinicopathological features of recurrent and metastatic orbital SFT and evaluate the existing risk assessment score for orbital SFT. Methods: The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried for patients with recurrent or malignant orbital hemangiopericytoma/SFT. The medical records were reviewed for clinical and pathologic findings, treatments, and outcomes. Results: Eight patients from 3 institutions were identified with recurrent orbital hemangiopericytoma/SFT. Median age at diagnosis was 59 years, and 4 patients were women. The mean size of tumor was 2.1 ± 1.1 cm. All patients were initially treated with surgery and experienced local recurrence after a median of 4 (range 0.5–10) years. Five patients were treated with orbital radiation. Two patients also developed distant metastases and eventually died of their disease. Median Ki-67 was 5% (range 1–65%) and 5 mitotic figures/10 high-power fields (range 2–30). The previously described risk stratification model for nonorbital SFT did not correlate with the propensity to develop metastases in this cohort; however, both patients with distant metastasis had > 4 mitotic figures /10 high-power fields. Conclusions: In this cohort of recurrent orbital hemangiopericytoma/SFT, median time to recurrence was 4 years underscoring the importance of careful continued follow-up. The current risk stratification models have limited use for orbital lesions, mostly due to the fact that orbital SFTs are smaller than even the smallest size criteria in this risk assessment model. Accepted for publication June 17, 2018. This work was supported in part by the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) Foundation through their support of the ASOPRS Oncology Database at MD Anderson Cancer Center. The authors have no conflicts of interest to disclose. Presented at the American Society of Oculoplastic and Reconstructive Surgery Fall Meeting on November 10, 2017 in New Orleans, LA. Address correspondence and reprint requests to Bita Esmaeli, M.D., F.A.C.S., Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, Unit 1488, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. E-mail: besmaeli@mdanderson.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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A Stab in the Back: An Unusual Case of Cutaneous Neural Infiltration as a Manifestation of Chronic Lymphoproliferative Disorder of Natural Killer Cells

Abstract: Chronic lymphoproliferative disorder of natural killer cells (CLPDNK) is a rare heterogenous indolent disorder comprising a persistent peripheral blood cell count of more than ≥2 × 109/L natural killer cells for over 6 months. We report an unusual case of cutaneous neural infiltration as a manifestation of CLPDNK. A 52-year-old woman with a background of CLPDNK was referred to dermatology with a painful rash primarily affecting her back. Skin biopsies revealed a neurotropic atypical lymphoid infiltration. Results of immunohistochemistry studies showed CD8, CD56, granzyme B, perforin positivity, and CD3 negativity in keeping with an atypical neurotropic lymphoid infiltrate consistent with cutaneous involvement by the patient's known CLPDNK. Cutaneous lesions and peripheral neuropathy in patients with CLPDNK have been reported; however, the involvement of cutaneous peripheral nerves as described in our case has not been reported before. Correspondence: Sarah Ní Mhaolcatha, Department of Pathology, Cork University Hospital, Cork, Ireland (e-mail: Sarah.Nimhaolcatha@hse.ie). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A Granular Cell Tumor Appearing at a Vaccination Site, a Possible Reaction to Trauma?

No abstract available

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Syringotropic Lichen Planus: A Potential Histopathologic Mimicker of Syringotropic Mycosis Fungoides

Abstract: Perieccrine inflammation may be observed in several different dermatoses, but true permeation of the secretory coil by lymphocytes (lymphocytic syringotropism) is a rather uncommon finding, usually observed in mycosis fungoides (MF—syringotropic MF). Rare cases of syringotropic lichen striatus and lymphocytic autoimmune hidradenitis showing a similar pattern have been described as well. We describe an exceptional case of lichen planus (LP) characterized by marked lymphocytic syringotropism with focal hyperplasia of the eccrine epithelium. Histopathology was characterized by the combination of features of conventional LP, prominent permeation of the secretory portion of the eccrine glands by reactive lymphocytes, and focal involvement of a hair follicle. Syringotropic LP may be regarded as a histologic mimicker of syringotropic MF, thus representing a potential diagnostic pitfall. Correspondence: Lorenzo Cerroni, MD, Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria (e-mail: lorenzo.cerroni@medunigraz.at). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Violaceous Plaques and Nodules: Challenge

No abstract available

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A Stab in the Back: An Unusual Case of Cutaneous Neural Infiltration as a Manifestation of Chronic Lymphoproliferative Disorder of Natural Killer Cells

Abstract: Chronic lymphoproliferative disorder of natural killer cells (CLPDNK) is a rare heterogenous indolent disorder comprising a persistent peripheral blood cell count of more than ≥2 × 109/L natural killer cells for over 6 months. We report an unusual case of cutaneous neural infiltration as a manifestation of CLPDNK. A 52-year-old woman with a background of CLPDNK was referred to dermatology with a painful rash primarily affecting her back. Skin biopsies revealed a neurotropic atypical lymphoid infiltration. Results of immunohistochemistry studies showed CD8, CD56, granzyme B, perforin positivity, and CD3 negativity in keeping with an atypical neurotropic lymphoid infiltrate consistent with cutaneous involvement by the patient's known CLPDNK. Cutaneous lesions and peripheral neuropathy in patients with CLPDNK have been reported; however, the involvement of cutaneous peripheral nerves as described in our case has not been reported before. Correspondence: Sarah Ní Mhaolcatha, Department of Pathology, Cork University Hospital, Cork, Ireland (e-mail: Sarah.Nimhaolcatha@hse.ie). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A Granular Cell Tumor Appearing at a Vaccination Site, a Possible Reaction to Trauma?

No abstract available

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Syringotropic Lichen Planus: A Potential Histopathologic Mimicker of Syringotropic Mycosis Fungoides

Abstract: Perieccrine inflammation may be observed in several different dermatoses, but true permeation of the secretory coil by lymphocytes (lymphocytic syringotropism) is a rather uncommon finding, usually observed in mycosis fungoides (MF—syringotropic MF). Rare cases of syringotropic lichen striatus and lymphocytic autoimmune hidradenitis showing a similar pattern have been described as well. We describe an exceptional case of lichen planus (LP) characterized by marked lymphocytic syringotropism with focal hyperplasia of the eccrine epithelium. Histopathology was characterized by the combination of features of conventional LP, prominent permeation of the secretory portion of the eccrine glands by reactive lymphocytes, and focal involvement of a hair follicle. Syringotropic LP may be regarded as a histologic mimicker of syringotropic MF, thus representing a potential diagnostic pitfall. Correspondence: Lorenzo Cerroni, MD, Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria (e-mail: lorenzo.cerroni@medunigraz.at). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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