From inflammation to sexual dysfunctions: a journey through diabetes, obesity, and metabolic syndrome

Abstract

Metabolic diseases are associated with chronic low-grade inflammation, which has been indicated as a potential mediator of endothelial dysfunction and cardiovascular disease. Visceral adiposity is thought to be the starting condition of the inflammatory state through the release of inflammatory cytokines, including TNF-alpha, CRP, and IL-6, which in turn promote endothelial dysfunction, endothelial expression of chemokines (IL-1) and adhesion molecules (ICAM-1, VCAM-1, and P-selectin), and the inhibition of anti-atherogenic factors (adiponectin). Obesity, metabolic diseases, and diabetes, all conditions characterized by abdominal fat, are well-recognized risk factors for sexual dysfunction in both sexes. Evidence from randomized-controlled trials supports the association between inflammatory milieau and erectile dysfunction in men suffering from metabolic diseases, whereas, in women, this has to be confirmed in further studies. A healthy lifestyle based on dietary pattern with high content of whole grain, fruit, nuts and seeds, and vegetables and low in sodium and saturated fatty acids plus regular physical activity may help to modulate the pro-inflammatory state associated with metabolic diseases and the related burden of sexual dysfunctions.

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Lymph node location is a risk factor for papillary thyroid cancer-related death

Abstract

Purpose

Papillary thyroid cancer (PTC) has good prognosis with a very low chance of mortality. The prognostic role of metastatic lymph node location was judged controversial and more recently (TNM VIII ed.) was considered to have no impact on the prognosis of older patients. The aim of the study was to evaluate the role of metastasized node location on PTC-related mortality.

Methods

PTC-related mortality was analysed in a consecutive retrospective series of 1653 PTC patients followed at our Thyroid Clinic (mean follow-up 5.9 years).

Results

Sixteen out of 1653 patients (0.96%) died because of PTC. Average age was 68 years at presentation and 74.7 at death. F/M ratio was 1:1. The death rate increased in relation to the lymph node status: 0.2% in N0, 0.3% in N1a and 3.0% in N1b.

Conclusions

The presence of lymph node metastases in the N1b compartment should be considered as a risk factor for distant metastatic spread and for cancer-related death and included in post-surgery evaluation.

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Affective and Behavioural Computing: Lessons Learnt from the First Computational Paralinguistics Challenge

Publication date: Available online 15 March 2018
Source:Computer Speech & Language
Author(s): Björn Schuller, Felix Weninger, Yue Zhang, Fabien Ringeval, Anton Batliner, Stefan Steidl, Florian Eyben, Erik Marchi, Alessandro Vinciarelli, Klaus Scherer, Mohamed Chetouani, Marcello Mortillaro
In this article, we review the INTERSPEECH 2013 Computational Paralinguistics ChallengE (ComParE) – the first of its kind – in light of the recent developments in affective and behavioural computing. The impact of the first ComParE installment is manifold: first, it featured various new recognition tasks including social signals such as laughter and fillers, conflict in dyadic group discussions, and atypical communication due to pervasive developmental disorders, as well as enacted emotion; second, it marked the onset of the ComParE, subsuming all tasks investigated hitherto within the realm of computational paralinguistics; finally, besides providing a unified test-bed under well-defined and strictly comparable conditions, we present the definite feature vector used for computation of the baselines, thus laying the foundation for a successful series of follow-up Challenges. Starting with a review of the preceding INTERSPEECH Challenges, we present the four Sub-Challenges of ComParE 2013. In particular, we provide details of the Challenge databases and a meta-analysis by conducting experiments of logistic regression on single features and evaluating the performances achieved by the participants.



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From inflammation to sexual dysfunctions: a journey through diabetes, obesity, and metabolic syndrome

Abstract

Metabolic diseases are associated with chronic low-grade inflammation, which has been indicated as a potential mediator of endothelial dysfunction and cardiovascular disease. Visceral adiposity is thought to be the starting condition of the inflammatory state through the release of inflammatory cytokines, including TNF-alpha, CRP, and IL-6, which in turn promote endothelial dysfunction, endothelial expression of chemokines (IL-1) and adhesion molecules (ICAM-1, VCAM-1, and P-selectin), and the inhibition of anti-atherogenic factors (adiponectin). Obesity, metabolic diseases, and diabetes, all conditions characterized by abdominal fat, are well-recognized risk factors for sexual dysfunction in both sexes. Evidence from randomized-controlled trials supports the association between inflammatory milieau and erectile dysfunction in men suffering from metabolic diseases, whereas, in women, this has to be confirmed in further studies. A healthy lifestyle based on dietary pattern with high content of whole grain, fruit, nuts and seeds, and vegetables and low in sodium and saturated fatty acids plus regular physical activity may help to modulate the pro-inflammatory state associated with metabolic diseases and the related burden of sexual dysfunctions.

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Lymph node location is a risk factor for papillary thyroid cancer-related death

Abstract

Purpose

Papillary thyroid cancer (PTC) has good prognosis with a very low chance of mortality. The prognostic role of metastatic lymph node location was judged controversial and more recently (TNM VIII ed.) was considered to have no impact on the prognosis of older patients. The aim of the study was to evaluate the role of metastasized node location on PTC-related mortality.

Methods

PTC-related mortality was analysed in a consecutive retrospective series of 1653 PTC patients followed at our Thyroid Clinic (mean follow-up 5.9 years).

Results

Sixteen out of 1653 patients (0.96%) died because of PTC. Average age was 68 years at presentation and 74.7 at death. F/M ratio was 1:1. The death rate increased in relation to the lymph node status: 0.2% in N0, 0.3% in N1a and 3.0% in N1b.

Conclusions

The presence of lymph node metastases in the N1b compartment should be considered as a risk factor for distant metastatic spread and for cancer-related death and included in post-surgery evaluation.

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Doble conducto auditivo interno

Publication date: Available online 15 March 2018
Source:Acta Otorrinolaringológica Española
Author(s): María Fernanda Vargas Gamarra, Carlos de Paula Vernetta, Miguel Mazón Momparler




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Predictors of locoregional recurrence in early stage buccal cancer with pathologically clear surgical margins and negative neck

Publication date: Available online 16 March 2018
Source:Acta Otorrinolaringológica Española
Author(s): Shakeel Uz Zaman, Shakil Aqil, Mohammad Ahsan Sulaiman
ObjectiveTo identify the significant predictors of locoregional recurrence in early stage squamous cell carcinoma (SCC) of buccal mucosa with pathologically clear surgical margins and negative neck.MethodSeventy-three patients who underwent per oral wide excision and supraomohyoid neck dissection for early stage buccal SCC with clear surgical margins (>5mm margins each) and negative neck (N0) were included. None of the patients received postoperative radiotherapy or chemotherapy. Univariate and multivariate analyses were used to identify independent predictors of locoregional recurrence.ResultsRecurrence was observed in 22 of 73 (30%) cases. Twelve had local, seven had regional and three developed locoregional recurrences. Both univariate and multivariate analyses demonstrated that lymphovascular invasion (LVI) and non-T4 muscular invasion (non-T4MI) were independent predictors affecting locoregional control.ConclusionLymphovascular invasion (LVI) and non-T4 muscular invasion (non-T4MI) significantly increased the locoregional recurrence rate in early stage buccal SCC with clear surgical margins and negative nodal status. Adjuvant treatment with either radiation or chemoradiation should be considered when one or both of these factors present.



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Sternal semi-closure using a bioresorbable osteosynthesis device: a new method for delayed sternal closure

Abstract

Purpose

To evaluate the safety and efficacy of our new delayed sternal closure (DSC) method, involving sternal semi-closure using a bioresorbable osteosynthesis device and complete skin closure.

Methods

Between 2013 and 2017, 36 patients underwent DCS at our hospital. The patients were divided into two groups based on the method used for DSC. The later conventional DSC group consisted of 18 patients undergoing late complete sternal closure following fixation of pulmonary and hemodynamic instability, and the new DSC group consisted of 18 patients undergoing early sternal semi-closure a few days after surgery. In the new DSC group, the sternum was fixed with Super Fixsorb MX40, followed by complete skin closure.

Results

Respiratory and hemodynamic conditions, such as systolic blood pressure, cardiac index, tidal volume, and regional oxygen saturation, were significantly more stable in the new DCS group than in the conventional DSC group. The hospital stay was also significantly shorter in the new DSC group. Although there were no serious complications, one patient from the new DCS group suffered deformity of the sternum, which was managed successfully.

Conclusion

The sternal semi-closure method decreases pulmonary and cardiac instability during DSC, making early DSC possible.

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Sternal semi-closure using a bioresorbable osteosynthesis device: a new method for delayed sternal closure

Abstract

Purpose

To evaluate the safety and efficacy of our new delayed sternal closure (DSC) method, involving sternal semi-closure using a bioresorbable osteosynthesis device and complete skin closure.

Methods

Between 2013 and 2017, 36 patients underwent DCS at our hospital. The patients were divided into two groups based on the method used for DSC. The later conventional DSC group consisted of 18 patients undergoing late complete sternal closure following fixation of pulmonary and hemodynamic instability, and the new DSC group consisted of 18 patients undergoing early sternal semi-closure a few days after surgery. In the new DSC group, the sternum was fixed with Super Fixsorb MX40, followed by complete skin closure.

Results

Respiratory and hemodynamic conditions, such as systolic blood pressure, cardiac index, tidal volume, and regional oxygen saturation, were significantly more stable in the new DCS group than in the conventional DSC group. The hospital stay was also significantly shorter in the new DSC group. Although there were no serious complications, one patient from the new DCS group suffered deformity of the sternum, which was managed successfully.

Conclusion

The sternal semi-closure method decreases pulmonary and cardiac instability during DSC, making early DSC possible.

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A standardized analysis of the current surgical and non-surgical treatment selection process for men with localized prostate cancer

Abstract

Robot-assisted radical prostatectomy to treat localized prostate cancer has increased in popularity, although other options exist, including radiotherapy and active surveillance. The decision about choosing the right treatment has become pertinent for many patients. This literature review aimed to assess the current state-of-the-art regarding decisional aids and the associated decisional outcomes for the purpose of designing a method for both patients and doctors to use to make the best treatment decision for the patient. A literature search was conducted via MEDLINE, Embase, and Web of Science databases using the keywords "prostate" and "cancer" and "impact" and "decisio*" and "treatment." Articles were included that focused on treatment outcomes, decision-making processes, and the use of decisional aids for localized prostate cancer. Articles that investigated prostate cancer in general or prostate cancer screening were excluded, as were articles that were not written in English. Altogether, 13 articles were finally critically reviewed for this study. Results were conflicting regarding the relations between patient factors, use of decisional aids, and decisional outcomes. There was a large gap in the literature regarding the optimal decision-making process for men with localized prostate cancer. The role of currently available decisional aids is limited to helping patients make the right decisions. There is a need to develop a novel decisional aid in which patient–physician discussion—involving evaluation of a spectrum of patient-, doctor-, and treatment-related factors—is included.

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Upper gastrointestinal malignancies in 2017: current perspectives and future approaches

Future Oncology, Ahead of Print.


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Insights into the hepatocellular carcinoma patient journey: results of the first global quality of life survey

Future Oncology, Ahead of Print.


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The role of IDH mutations in acute myeloid leukemia

Future Oncology, Ahead of Print.


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Incidental Histopathologic Finding of Sinonasal Inverted Papilloma Among Surgically Excised Polyps Increases the Risk of Tumor Recurrence

Abstract

Inverted papilloma (IP) is a benign tumor remarkable for its tendency toward recurrence. Local relapse implicates incomplete resection concerning the bone adjacent to tumor base. The high false negative rates on biopsies, mainly when nasal polyps coexist, may affect the surgical management and outcomes. Our objective was to study the impact of preoperative histologic diagnosis in IP recurrence, particularly in patients with pre-surgical diagnosis of inflammatory polyps. A retrospective analysis of 62 patients treated for IP was conducted. Demographic data and information about smoking status, alcohol intake, tumor location, histology, presence of nasal polyps, staging, malignancy, previous biopsies and surgical approach were evaluated to identify factors associated with recurrence. Prevalence of nasal polyps was higher in patients with recurrence. Smoking history, alcohol abuse, staging, histologic type, malignancy and surgical approach were not associated with recurrence. The presence of nasal polyps at endoscopy was inversely associated with the diagnosis of IP at incisional biopsy. Incidental histologic diagnosis of IP after surgery increased the risk of recurrence more than tenfold. Biopsy reporting the diagnosis of IP previous to surgery was inversely associated to recurrence. In patients with IP, coexistence of nasal polyps at initial endoscopy and lack of pathological IP diagnosis prior to surgery are strongly associated with a higher risk of recurrence. When excisional biopsy reports IP incidentally, an early revision surgery should be considered in order to avoid future aggressive surgeries because of tumor recurrence.

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NFLPA Annual Meeting: Dr. Shad Morris, DMD, Sets Example For Sleep Dentists Nationally In Former NFL Player Health Assessment

Dr. Shad Morris and Andre Collins, Executive Director of Player Athletes Foundation

The National Football League Players Association (NFLPA) Former Players Convention is an annual meeting for retired NFL players who come together for days of "innovative professional and personal development workshops, networking, guest speakers and family fun". A growing topic among the former player community, as well as the world population in recent years, has been health. So much so, that a health assessment planned and organized by Living Heart Foundation was included in the official agenda on two days of the three day conference where players were assessed for body composition, blood pressure, pulmonary function, hearing, sleep apnea and more.

Dr. Shad Morris Demonstrating Digital Scanning

David Gergen, CEO of Pro Player Health Alliance (PPHA), was appointed by Andre Collins who is the Executive Director of the Players Athletes Foundation to oversee the sleep apnea component of the health assessments. Gergen selected a team of sleep dentists who need to meet a number of requirements to participate: They must be Diplomates of the American Sleep and Breathing Academy (ASBA), have a strong community presence and have the capability to treat Medicare patients. Dr. Shad Morris, DMD, led the team of ASBA Diplomates which included Dr. Ronald Rosenbaum, DMD, and Dr. Edward Hobbs, DDS. The board certified sleep physician who worked in collaboration with Dr. Morris was Dr. Cliff Molin. Project Rose provided the sleep testing equipment for the event and were able to provide a home sleep test to every player who were found to be at high risk of sleep apnea. Founded by Earl Campbell and Gary Baxter, Project Rose Sleep Program is a premier sleep program that test, treat and do research in the field of sleep for better health and wellness outcomes. The initial testing reports from this event found that 93% of former players who were tested came back positive for sleep apnea.

NFL Hall of fame CB Mike Haynes and Dr. Shad Morris

Dr. Shad Morris impressed everyone who was involved with his dedication, professionalism and attention to detail as well as his demonstration of digital scanners. When asked why Dr. Morris was selected to be the point man for the health assessment, David Gergen said, "Shad has donated time and money to help elderly in his community with holiday church functions for years. He has explained to me that his grandparents forged the way for his future. Although many dentists stay away from Medicare because the reimbursement isn't good and contains so many regulations, Dr. Morris doesn't mind because he believes in doing the right thing and helping those who worked hard to give him the opportunities to thrive today; giving back is the right thing to do. When I interviewed him for the position in December of 2017, he told me it's not about the money it's about successful outcomes, I knew he was the right guy to bring that same attitude to treating members of the NFLPA." In a separate meeting with Gergen, Morris and NFL Hall of Fame CB Mike Haynes, Gergen mentioned Dr. Morris as the perfect candidate to be the sleep dentists for the newly relocated Las Vegas Raiders because of his thousands of successful outcomes.

ASBA members are the only qualified sleep dentists to treat the former NFL players for obstructive sleep apnea when medically indicated. To attend the ASBA Annual Meeting and become a member of the ASBA, visit Sleep-Conference.Com or email David Gergen at gxployer@aol.com.

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Academy News – March PM&R Journal

As the primary medical society for the specialty of PM&R, your Academy is focused on moving the specialty and you forward. Academy membership supports initiatives to assist our members with:

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Information for Authors

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Table of Contents

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Instrumental Variables: Uses and Limitations

Observational studies are limited by the issue of confounding. For example, light-to-moderate drinkers tend to have lower risk of cardiovascular disease than nondrinkers. This association could be due to a causal effect of alcohol on the body, or it could be due to other attributes of light-to-moderate drinkers, such as high socioeconomic status or the ability to practice moderation across a range of behaviors. Statistical adjustment only imperfectly addresses confounding [1]: Confounders such as socioeconomic status may be crudely measured, resulting in residual confounding; plus, some confounders—such as intangible attributes like the ability to practice moderation—may remain unmeasured.

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Copyright Page

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Editorial Board

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Spanish Translated Abstracts

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ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment

Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including Estrogen receptor-α (ER). Here we describe a new, orally bioavailable CDK7 inhibitor, ICEC0942. It selectively inhibits CDK7, with an IC50 of 40nM; IC50 values for CDK1, CDK2, CDK5 and CDK9 were 45-, 15-, 230- and 30-fold higher. In vitro studies show that a wide range of cancer types are sensitive to CDK7 inhibition with GI50 values ranging between 0.2-0.3 µM. In xenografts of both breast and colorectal cancers, the drug has substantial anti-tumor effects. Additionally, combination therapy with tamoxifen showed complete growth arrest of ER-positive tumor xenografts. Our findings reveal that CDK7 inhibition provides a new approach, especially for ER-positive breast cancer and identify ICEC0942 as a prototype drug with potential utility as a single agent or in combination with hormone therapies for breast cancer. ICEC0942 may also be effective in other cancers that display characteristics of transcription factor addiction, such as acute leukaemia, and small-cell lung cancer.

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Metformin suppresses tumor progression by inactivating stromal fibroblasts in ovarian cancer

Ovarian cancer (OC) is a devastating disease due to its high incidence of relapse and chemoresistance. The tumor microenvironment, especially the tumor stroma compartment, was proven to contribute tremendously to the unsatisfactory chemotherapeutic efficacy in OC. Cytotoxic agents not only effect tumor cells, but also modulate the phenotype and characteristics of the vast stromal cell population, which can in turn alter the tumor cell response to chemointervention. In this study, we focused on the tumor stroma response to cytotoxic agents and the subsequent effect on the OC tumor cells. First, we found a significant stromal overexpression of IL6 in patient samples that received cisplatin-based treatment, which was further validated in purified fibroblasts challenged with cisplatin. Stromal fibroblast derived IL6 was proven to mediate OC tumor cell chemoresistance. For the first time we found that the tumor stroma of patients with routine metformin administration exhibited lower IL6 expression. Thus, we presumed that metformin was a potent alleviator of stromal inflammation in OC. We found that metformin partly reversed cisplatin-stimulated IL6 secretion in the stromal fibroblasts and attenuated fibroblast-facilitated tumor growth in 3D organotypic co-cultures and murine xenograft models. Mechanistically, we found that metformin inhibited IL6 secretion via suppressing NF-B signaling, an upstream controller of stromal inflammation. Collectively, our findings introduced a novel mechanism of metformin in suppressing OC progression through diminishing chemotherapy-induced stromal activation. Therefore, we provide an alternative therapeutic option in targeting stromal inflammation and a potential scheme of combination therapy to improve the chemosensitivity in OC.

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A miR-29b Byproduct Sequence Exhibits Potent Tumor Suppressive Activities via Inhibition of NF-{kappa}B Signaling in KRAS Mutant Colon Cancer Cells

We previously demonstrated that miR-29b-3p is a hopeful microRNA (miRNA)-based therapies against colorectal cancer (CRC). In this study, we aimed to clarify a value of miR-29b-1-5p as a next generation treatment, especially for KRAS mutant CRC. RT-PCR assay showed that expression of miR-29b-3p was high and its partner strand, miR-29b-1-5p level was only negligible in clinical CRC samples. Mimic-miR-29b-1-5p significantly inhibited proliferation of KRAS mutant CRC cell lines DLD1 and SW480 and KRAS wild type HT29 cells. Proliferative activity was further examined by either miR-29b-1-5p strand or its opposite complementary sequence because miR-29b-1-5p is a passenger miRNA and may have no physiological function. We found that completely opposite complementary strand to miR-29b-1-5p, but not miR-29b-1-5p possessed a potent anti-tumor effect and named this byproduct miRNA sequence "MIRTX." MIRTX directly targeted the 3'-UTR of CXCR2 and PIK3R1 mRNA and suppressed the NF-B signaling pathway in KRAS mutated CRC cells. in KRAS mutant CRC cells. MIRTX induced apoptosis in DLD1 with down-regulation of anti-apoptotic BCL2, BCL-xL, and MCL1 and up-regulation of cleaved caspase 3 and cleaved PARP. In mouse xenograft models, systemic administration of MIRTX using a super carbonate apatite as a delivery vehicle significantly inhibited tumor growth of DLD1 and HT29 cells without any particular toxicities. In conclusion, these findings indicate that inhibition of NF-B signaling by this novel miRNA-based therapeutic could be a promising treatment against refractory KRAS mutant CRC and KRAS wild CRC.

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Acquired resistance to a MET antibody in vivo can be overcome by the MET antibody mixture Sym015

Failure of clinical trials due to development of resistance to MET-targeting therapeutic agents is an emerging problem. Mechanisms of acquired resistance to MET tyrosine kinase inhibitors are well described, whereas characterization of mechanisms of resistance toward MET-targeting antibodies is limited. This study investigated mechanisms underlying in vivo resistance to two antibody therapeutics currently in clinical development: an analogue of the MET-targeting antibody emibetuzumab and Sym015, a mixture of two antibodies targeting non-overlapping epitopes of MET. Upon long-term in vivo treatment of a MET-amplified gastric cancer xenograft model (SNU-5), emibetuzumab-resistant, but not Sym015-resistant, tumors emerged. Resistant tumors were isolated and used to establish resistant cell lines. Characterization of both tumors and cell lines using extensive protein and signaling pathway activation mapping along with next-generation sequencing revealed two distinct resistance profiles, one involving PTEN loss and the other involving activation of the PI3Kinase pathway, likely via MYC and ERBB3 copy number gains. PTEN loss left one model unaffected by PI3Kinase/AKT-targeting but sensitive to mTOR-targeting, while the PI3Kinase pathway-activated model was partly sensitive to targeting of multiple PI3Kinase pathway proteins. Importantly, both resistant models were sensitive to treatment with Sym015 in vivo due to antibody-dependent cellular cytotoxicity-mediated tumor growth inhibition, MET degradation, and signaling inhibition. Taken together, our data provide key insights into potential mechanisms of resistance to a single MET-targeting antibody, demonstrate superiority of Sym015 in preventing acquired resistance, and confirm Sym015 anti-tumor activity in tumors resistant to a single MET antibody.

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Bi-hemispheric repetitive transcranial magnetic stimulation for upper limb motor recovery in chronic stroke: A feasibility study

Publication date: Available online 15 March 2018
Source:Brain Stimulation
Author(s): Raffaella Chieffo, Giuseppe Scopelliti, Mario Fichera, Roberto Santangelo, Simone Guerrieri, Abraham Zangen, Giancarlo Comi, Letizia Leocani




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A response to comments by Dr. Mohammad Alwardat on “Safety of repeated sessions of transcranial direct current stimulation: A systematic review”

Publication date: Available online 15 March 2018
Source:Brain Stimulation
Author(s): Stevan Nikolin, Colleen K. Loo, Donel M. Martin




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Short-interval and long-interval intracortical inhibition of TMS-evoked EEG potentials

Publication date: Available online 15 March 2018
Source:Brain Stimulation
Author(s): Isabella Premoli, Julia Király, Florian Müller-Dahlhaus, Carl M. Zipser, Pierre Rossini, Christoph Zrenner, Ulf Ziemann, Paolo Belardinelli
BackgroundInhibition in the human motor cortex can be probed by means of paired-pulse transcranial magnetic stimulation (ppTMS) at interstimulus intervals of 2–3 ms (short-interval intracortical inhibition, SICI) or ∼100 ms (long-interval intracortical inhibition, LICI). Conventionally, SICI and LICI are recorded as motor evoked potential (MEP) inhibition in the hand muscle. Pharmacological experiments indicate that they are mediated by GABAA and GABAB receptors, respectively.Objective/Hypothesis: SICI and LICI of TMS-evoked EEG potentials (TEPs) and their pharmacological properties have not been systematically studied. Here, we sought to examine SICI by ppTMS-evoked compared to single-pulse TMS-evoked TEPs, to investigate its pharmacological manipulation and to compare SICI with our previous results on LICI.MethodsPpTMS-EEG was applied to the left motor cortex in 16 healthy subjects in a randomized, double-blind placebo-controlled crossover design, testing the effects of a single oral dose 20 mg of diazepam, a positive modulator at the GABAA receptor, vs. 50 mg of the GABAB receptor agonist baclofen on SICI of TEPs.ResultsWe found significant SICI of the N100 and P180 TEPs prior to drug intake. Diazepam reduced SICI of the N100 TEP, while baclofen enhanced it. Compared to our previous ppTMS-EEG results on LICI, the SICI effects on TEPs, including their drug modulation, were largely analogous.ConclusionsFindings suggest a similar interaction of paired-pulse effects on TEPs irrespective of the interstimulus interval. Therefore, SICI and LICI as measured with TEPs cannot be directly derived from SICI and LICI measured with MEPs, but may offer novel insight into paired-pulse responses recorded directly from the brain rather than muscle.



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Novel application of virtual reality in patient engagement for Deep Brain Stimulation: A Pilot study

Publication date: Available online 15 March 2018
Source:Brain Stimulation
Author(s): Malie K. Collins, Victoria Y. Ding, Robyn L. Ball, Dana L. Dolce, Jaimie M. Henderson, Casey H. Halpern




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Dualistic effect of pallidal deep brain stimulation on motor speech disorders in dystonia

Publication date: Available online 15 March 2018
Source:Brain Stimulation
Author(s): Jan Rusz, Tereza Tykalová, Anna Fečíková, Daniela Šťastná, Dušan Urgošík, Robert Jech
BackgroundAlthough pallidal deep brain stimulation (GPi-DBS) is an effective treatment for dystonia, it may cause important stimulation-induced side-effects such as hypokinetic dysarthria or stuttering. However, the reasons behind the occurrence of these side-effects remain unknown.ObjectiveTo objectively investigate the impact of GPi-DBS on patients with dystonia on speech fluency, intelligibility, and key aspects of hyperkinetic and hypokinetic dysarthria.MethodsSpeech was systematically evaluated in 19 dystonic patients with GPi-DBS. Each patient was tested twice within one day in both the GPi-DBS ON and GPi-DBS OFF stimulation conditions. A control sample of 19 matched healthy speakers underwent the same speech assessment.ResultsWe observed an improvement of hyperkinetic dysarthria symptoms in 47% and an aggravation of hypokinetic dysarthria symptoms in 26% of patients with the GPi-DBS switched ON. A higher stimulus intensity was found in a group of patients in whom the hypokinetic dysarthria worsened with the GPi-DBS ON when compared to other dystonic patients (p = 0.02). Furthermore, we revealed a significant increase of dysfluent words in the GPi-DBS ON when compared to OFF condition (p = 0.001) associated with the shorter distance of the active contact localization along the medio-lateral direction (r = −0.70, p = 0.005).ConclusionThis study provides evidence of dualistic effects of GPi-DBS on speech in dystonia manifested as an improvement of hyperkinetic or a deterioration of hypokinetic dysarthria. Our findings suggest that lower stimulation parameters and placement of active contacts more laterally in the internal globus pallidus should be preferred to avoid the possible side effects of hypokinetic dysarthria and dysfluency.



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New opportunities for kinase drug repurposing and target discovery

New opportunities for kinase drug repurposing and target discovery

New opportunities for kinase drug repurposing and target discovery, Published online: 16 March 2018; doi:10.1038/s41416-018-0045-6

New opportunities for kinase drug repurposing and target discovery

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The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes, Published online: 16 March 2018; doi:10.1038/s41416-018-0038-5

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

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Mutant IDH1 cooperates with ATRX loss to drive the alternative lengthening of telomere (ALT) phenotype in glioma

A subset of tumors use a recombination-based alternative lengthening of telomere (ALT) pathway to resolve telomeric dysfunction in the absence of TERT. Loss-of-function mutations in the chromatin remodeling factor ATRX are associated with ALT but are insufficient to drive the process. Because many ALT tumors express the mutant isocitrate dehydrogenase IDH1 R132H, including all lower-grade astrocytomas (LGA) and secondary glioblastoma, we examined an hypothesized role for IDH1 R132H in driving the ALT phenotype during gliomagenesis. In p53/pRb-deficient human astrocytes, combined deletion of ATRX and expression of mutant IDH1 were sufficient to create tumorigenic cells with ALT characteristics. The telomere capping complex component RAP1 and the non-homologous DNA end-joining repair factor XRCC1 were each downregulated consistently in these tumorigenic cells, where their coordinate re-expression was sufficient to suppress the ALT phenotype. RAP1 or XRCC1 downregulation cooperated with ATRX loss in driving the ALT phenotype. RAP1 silencing caused telomere dysfunction in ATRX deficient cells, whereas XRCC1 silencing suppressed lethal fusion of dysfunctional telomeres, by allowing IDH1-mutant ATRX deficient cells to use homologous recombination and ALT to resolve telomeric dysfunction and escape cell death. Overall, our studies show how expression of mutant IDH1 initiates telomeric dysfunction and alters DNA repair pathway preferences at telomeres, cooperating with ATRX loss to defeat a key barrier to gliomagenesis.

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Folate Receptor Alpha Peptide Vaccine generates immunity in Breast and Ovarian Cancer Patients

Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients. Experiment Design: We conducted a Phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to one year later. Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in greater than 90% of patients examined. Unlike recall immunity to tetanus toxoid, FR T cell responses developed slowly over the course of vaccination with a median time to maximal immunity at 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months. Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen and the developed vaccine is testable for therapeutic activity in the majority of patients whose tumors express FR, regardless of HLA genotype.

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Multivalent binding and biomimetic cell rolling improves the sensitivity and specificity of circulating tumor cell capture

Purpose: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in cancer patients undergoing radiotherapy (RT) treatment. Experimental Design: Patients with histologically confirmed primary carcinoma undergoing RT, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to 5 time points, including prior to RT, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of RT. CTC capture was accomplished using a nanotechnology-based assay (CapioCyte) functionalized with aEpCAM, aHER-2, and aEGFR. Results: CapioCyte was able to detect CTCs in all 24 cancer patients enrolled. Multivalent binding via poly(amidoamine) dendrimers further improved capture sensitivity. We also showed that cell rolling effect can improve CTC capture specificity (% of captured cells that are CK+/CD45-/DAPI+) up to 38%. Among the 18 patients with sequential CTC measurements, the median CTC decreased from 113 CTCs/mL before RT to 32 CTCs/mL at completion of RT (p = 0.001). CTCs declined throughout RT in patients with complete clinical and/or radiographic response, in contrast to an elevation in CTCs at mid or post-RT in the 2 patients with known pathologic residual disease. Conclusions: Our study demonstrated that multivalent binding and cell rolling can improve the sensitivity and specificity of CTC capture compared to multivalent binding alone, allowing reliable monitoring of CTC changes during and after treatment.

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Effective Use of Auditory Bombardment as a Therapy Adjunct for Children With Developmental Language Disorders

Purpose

Modeling of grammatical forms has been used in conjunction with conversational recast treatment in various forms. This study tests the relative effect of providing bombardment prior to or after recast treatment.

Method

Twenty-eight children with developmental language disorder participated in daily conversational recast treatment for morpheme errors. This treatment was either preceded or followed by a brief period of intensive auditory bombardment. Generalization to untreated lexical contexts was measured throughout the treatment period to assess the degree of learning and how quickly the onset of measurable learning occurred.

Results

There were no significant differences in elicited use of morphemes for the groups of children who received auditory bombardment before or after enhanced conversational recast treatment. However, there was a difference in the number of children who could be considered treatment responders versus nonresponders, favoring those who received auditory bombardment after recast treatment.

Conclusion

A brief period of auditory bombardment is a relatively low cost addition to recast treatment methods, given how little time it takes. There is a small but measurable advantage to following recast treatment with a period of auditory bombardment.

Supplemental Material

https://doi.org/10.23641/asha.5960005

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Communicative Function Use of Preschoolers and Mothers From Differing Racial and Socioeconomic Groups

Purpose

This study explores whether communicative function (CF: reasons for communicating) use differs by socioeconomic status (SES), race/ethnicity, or gender among preschoolers and their mothers.

Method

Mother–preschooler dyads (N = 95) from the National Center for Early Development and Learning's (2005) study of family and social environments were observed during 1 structured learning and free-play interaction. CFs were coded by trained independent raters.

Results

Children used all CFs at similar rates, but those from low SES homes produced fewer utterances and less reasoning, whereas boys used less self-maintaining and more predicting. African American mothers produced more directing and less responding than European American and Latino American mothers, and Latino American mothers produced more utterances than European American mothers. Mothers from low SES homes did more directing and less responding.

Conclusions

Mothers exhibited more sociocultural differences in CFs than children; this suggests that maternal demographic characteristics may influence CF production more than child demographics at school entry. Children from low SES homes talking less and boys producing less self-maintaining coincided with patterns previously detected in pragmatic literature. Overall, preschoolers from racial/ethnic minority and low SES homes were not less deft with CF usage, which may inform how their pragmatic skills are described.

Supplemental Material

https://doi.org/10.23641/asha.5890255

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The Use of Nerve Transfers to Restore Upper Extremity Function in Cervical Spinal Cord Injury

Nerve transfer surgery to restore upper extremity (UE) function in cervical spinal cord injury (SCI) is novel and may transform treatment. Determining candidacy even years post-SCI is ill-defined and deserves investigation.

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Sound energy absorbance characteristics of cartilage grafts used in type 1 tympanoplasty

The purpose of this prospective case-control study is to evaluate the sound energy absorbance characteristics of cartilage grafts in patients, who have undergone type 1 cartilage tympanoplasty.

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Systematic review of professional liability when prescribing beta-lactams for patients with a known penicillin allergy

To describe medical negligence and malpractice cases in which a patient with a known penicillin allergy received a beta-lactam and experienced an adverse reaction related to the beta-lactam.

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Paediatric asthma treatment: what to do when international guidelines' recommendations don't agree?

Authors' contributions

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Do Participants Report Any Undesired Effects in Ultrasound Speech Therapy?

Purpose

Ultrasound visual feedback of the tongue is increasingly used as a component of speech therapy in clinical research and practice. The purpose is to offer a preliminary summary of the nature of participant-reported undesired effects related to ultrasound visual feedback.

Method

Sixty-two participants across 3 sites (mean age = 11.9 years) and 38 parents responded to a 2-item verbal questionnaire following 14–16 hr of treatment regarding any aspects of the treatment they did not like. Responses were thematically categorized.

Results

The 62 participants provided 65 distinct responses, which were categorized as follows: 31% no concerns, 40% gel-related (e.g., cold, sticky), 21% positioning of the probe (e.g., uncomfortable, annoying), 3% chin hurting (qualified as being minor in nature), and 5% other (i.e., unrelated to the use of the ultrasound). Responses from all parents suggested no concerns about the use of ultrasound; however, 8% expressed concerns unrelated to ultrasound use (e.g., fatigue).

Conclusion

These data inform clinicians and researchers about participant's experience and highlight the type of comments most likely to be encountered with ultrasound in speech therapy. Although the reported adverse effects can be considered minor, they should be weighed against the potential benefits of visual feedback in treatment.

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Clinician-Driven Design of –An Intelligent Monitoring and Communication Device to Improve Patient Safety in the Intensive Care Unit

The pediatric intensive care unit (ICU) is a complex environment, in which a multidisciplinary team of clinicians (registered nurses, respiratory therapists, and physicians) continually observe and evaluate patient information. Data are provided by multiple, and often physically separated sources, cognitive workload is high, and team communication can be challenging. Our aim is to combine information from multiple monitoring and therapeutic devices in a mobile application, the VitalPAD, to improve the efficiency of clinical decision-making, communication, and thereby patient safety. We observed individual ICU clinicians, multidisciplinary rounds, and handover procedures for 54 h to identify data needs, workflow, and existing cognitive aid use and limitations. A prototype was developed using an iterative participatory design approach; usability testing, including general and task-specific feedback, was obtained from 15 clinicians. Features included map overviews of the ICU showing clinician assignment, patient status, and respiratory support; patient vital signs; a photo-documentation option for arterial blood gas results; and team communication and reminder functions. Clinicians reported the prototype to be an intuitive display of vital parameters and relevant alerts and reminders, as well as a user-friendly communication tool. Future work includes implementation of a prototype, which will be evaluated under simulation and real-world conditions, with the aim of providing ICU staff with a monitoring device that will improve their daily work, communication, and decision-making capacity. Mobile monitoring of vital signs and therapy parameters might help improve patient safety in wards with single-patient rooms and likely has applications in many acute and critical care settings.

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Influence of Language Load on Speech Motor Skill in Children With Specific Language Impairment

Purpose

Children with specific language impairment (SLI) show particular deficits in the generation of sequenced action: the quintessential procedural task. Practiced imitation of a sequence may become rote and require reduced procedural memory. This study explored whether speech motor deficits in children with SLI occur generally or only in conditions of high linguistic load, whether speech motor deficits diminish with practice, and whether it is beneficial to incorporate conditions of high load to understand speech production.

Method

Children with SLI and typical development participated in a syntactic priming task during which they generated sentences (high linguistic load) and, then, practiced repeating a sentence (low load) across 3 sessions. We assessed phonetic accuracy, speech movement variability, and duration.

Results

Children with SLI produced more variable articulatory movements than peers with typical development in the high load condition. The groups converged in the low load condition. Children with SLI continued to show increased articulatory stability over 3 practice sessions. Both groups produced generated sentences with increased duration and variability compared with repeated sentences.

Conclusions

Linguistic demands influence speech motor production. Children with SLI show reduced speech motor performance in tasks that require language generation but not when task demands are reduced in rote practice.

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Acoustic Predictors of Pediatric Dysarthria in Cerebral Palsy

Purpose

The objectives of this study were to identify acoustic characteristics of connected speech that differentiate children with dysarthria secondary to cerebral palsy (CP) from typically developing children and to identify acoustic measures that best detect dysarthria in children with CP.

Method

Twenty 5-year-old children with dysarthria secondary to CP were compared to 20 age- and sex-matched typically developing children on 5 acoustic measures of connected speech. A logistic regression approach was used to derive an acoustic model that best predicted dysarthria status.

Results

Results indicated that children with dysarthria secondary to CP differed from typically developing children on measures of multiple segmental and suprasegmental speech characteristics. An acoustic model containing articulation rate and the F2 range of diphthongs differentiated children with dysarthria from typically developing children with 87.5% accuracy.

Conclusion

This study serves as a first step toward developing an acoustic model that can be used to improve early identification of dysarthria in children with CP.

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Psychophysical Boundary for Categorization of Voiced–Voiceless Stop Consonants in Native Japanese Speakers

Purpose

The purpose of this study was to investigate the psychophysical boundary used for categorization of voiced–voiceless stop consonants in native Japanese speakers.

Method

Twelve native Japanese speakers participated in the experiment. The stimuli were synthetic stop consonant–vowel stimuli varying in voice onset time (VOT) with manipulation of the amplitude of the initial noise portion and the first formant (F1) frequency of the periodic portion. There were 3 tasks, namely, speech identification to either /d/ or /t/, detection of the noise portion, and simultaneity judgment of onsets of the noise and periodic portions.

Results

The VOT boundaries of /d/–/t/ were close to the shortest VOT values that allowed for detection of the noise portion but not to those for perceived nonsimultaneity of the noise and periodic portions. The slopes of noise detection functions along VOT were as sharp as those of voiced–voiceless identification functions. In addition, the effects of manipulating the amplitude of the noise portion and the F1 frequency of the periodic portion on the detection of the noise portion were similar to those on voiced–voiceless identification.

Conclusion

The psychophysical boundary of perception of the initial noise portion masked by the following periodic portion may be used for voiced–voiceless categorization by Japanese speakers.

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Vocalization Subsystem Responses to a Temporarily Induced Unilateral Vocal Fold Paralysis

Purpose

The purpose of this study is to quantify the interactions of the 3 vocalization subsystems of respiration, phonation, and resonance before, during, and after a perturbation to the larynx (temporarily induced unilateral vocal fold paralysis) in 10 vocally healthy participants. Using dynamic systems theory as a guide, we hypothesized that data groupings would emerge revealing context-dependent patterns in the relationships of variables representing the 3 vocalization subsystems. We also hypothesized that group data would mask important individual variability important to understanding the relationships among the vocalization subsystems.

Method

A perturbation paradigm was used to obtain respiratory kinematic, aerodynamic, and acoustic formant measures from 10 healthy participants (8 women, 2 men) with normal voices. Group and individual data were analyzed to provide a multilevel analysis of the data. A 3-dimensional state space model was constructed to demonstrate the interactive relationships among the 3 subsystems before, during, and after perturbation.

Results

During perturbation, group data revealed that lung volume initiations and terminations were lower, with longer respiratory excursions; airflow rates increased while subglottic pressures were maintained. Acoustic formant measures indicated that the spacing between the upper formants decreased (F3–F5), whereas the spacing between F1 and F2 increased. State space modeling revealed the changing directionality and interactions among the 3 subsystems.

Conclusions

Group data alone masked important variability necessary to understand the unique relationships among the 3 subsystems. Multilevel analysis permitted a richer understanding of the individual differences in phonatory regulation and permitted subgroup analysis. Dynamic systems theory may be a useful heuristic to model the interactive relationships among vocalization subsystems.

Supplemental Material

https://doi.org/10.23641/asha.5913532

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Pitch and Time Processing in Speech and Tones: The Effects of Musical Training and Attention

Purpose

Musical training is often linked to enhanced auditory discrimination, but the relative roles of pitch and time in music and speech are unclear. Moreover, it is unclear whether pitch and time processing are correlated across individuals and how they may be affected by attention. This study aimed to examine pitch and time processing in speech and tone sequences, taking musical training and attention into account.

Method

Musicians (16) and nonmusicians (16) were asked to detect pitch or timing changes in speech and tone sequences and make a binary response. In some conditions, the participants were focused on 1 aspect of the stimulus (directed attention), and in others, they had to pay attention to all aspects at once (divided attention).

Results

As expected, musicians performed better overall. Performance scores on pitch and time tasks were correlated, as were performance scores for speech and tonal stimuli, but most markedly in musicians. All participants performed better on the directed versus divided attention task, but again, musicians performed better than nonmusicians.

Conclusion

In general, this experiment shows that individuals with a better sense of pitch discrimination also have a better sense of timing discrimination in the auditory domain. In addition, although musicians perform better overall, these results do not support the idea that musicians have an added advantage for divided attention tasks. These findings serve to better understand how musical training and attention affect pitch and time processing in the context of speech and tones and may have applications in special populations.

Supplemental Material

https://doi.org/10.23641/asha.5895997

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Deep Brain Stimulation of the Subthalamic Nucleus Parameter Optimization for Vowel Acoustics and Speech Intelligibility in Parkinson's Disease

Purpose

The settings of 3 electrical stimulation parameters were adjusted in 12 speakers with Parkinson's disease (PD) with deep brain stimulation of the subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and speech intelligibility.

Method

Participants were tested under permutations of low, mid, and high STN-DBS frequency, voltage, and pulse width settings. At each session, participants recited a sentence. Acoustic characteristics of vowel production were extracted, and naive listeners provided estimates of speech intelligibility.

Results

Overall, lower-frequency STN-DBS stimulation (60 Hz) was found to lead to improvements in intelligibility and acoustic vowel expansion. An interaction between speaker sex and STN-DBS stimulation was found for vowel measures. The combination of low frequency, mid to high voltage, and low to mid pulse width led to optimal speech outcomes; however, these settings did not demonstrate significant speech outcome differences compared with the standard clinical STN-DBS settings, likely due to substantial individual variability.

Conclusions

Although lower-frequency STN-DBS stimulation was found to yield consistent improvements in speech outcomes, it was not found to necessarily lead to the best speech outcomes for all participants. Nevertheless, frequency may serve as a starting point to explore settings that will optimize an individual's speech outcomes following STN-DBS surgery.

Supplemental Material

https://doi.org/10.23641/asha.5899228

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Targeting Complex Sentences in Older School Children With Specific Language Impairment: Results From an Early-Phase Treatment Study

Purpose

This study investigated the effects of a complex sentence treatment at 2 dosage levels on language performance of 30 school-age children ages 10–14 years with specific language impairment.

Method

Three types of complex sentences (adverbial, object complement, relative) were taught in sequence in once or twice weekly dosage conditions. Outcome measures included sentence probes administered at baseline, treatment, and posttreatment phases and comparisons of pre–post performance on oral and written language tests and tasks. Relationships between pretest variables and treatment outcomes were also explored.

Results

Treatment was effective at improving performance on the sentence probes for the majority of participants; however, results differed by sentence type, with the largest effect sizes for adverbial and relative clauses. Significant and clinically meaningful pre–post treatment gains were found on a comprehensive oral language test, but not on reading and writing measures. There was no treatment advantage for the higher dosage group. Several significant correlations indicated a relationship between lower pretest scores and higher outcome measures.

Conclusions

Results suggest that a focused intervention can produce improvements in complex sentence productions of older school children with language impairment. Future research should explore ways to maximize gains and extend impact to natural language contexts.

Supplemental Material

https://doi.org/10.23641/asha.5923318

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Dysarthria in Mandarin-Speaking Children With Cerebral Palsy: Speech Subsystem Profiles

Purpose

This study explored the speech characteristics of Mandarin-speaking children with cerebral palsy (CP) and typically developing (TD) children to determine (a) how children in the 2 groups may differ in their speech patterns and (b) the variables correlated with speech intelligibility for words and sentences.

Method

Data from 6 children with CP and a clinical diagnosis of moderate dysarthria were compared with data from 9 TD children using a multiple speech subsystems approach. Acoustic and perceptual variables reflecting 3 speech subsystems (articulatory-phonetic, phonatory, and prosodic), and speech intelligibility, were measured based on speech samples obtained from the Test of Children's Speech Intelligibility in Mandarin (developed in the lab for the purpose of this research).

Results

The CP and TD children differed in several aspects of speech subsystem function. Speech intelligibility scores in children with CP were influenced by all 3 speech subsystems, but articulatory-phonetic variables had the highest correlation with word intelligibility. All 3 subsystems influenced sentence intelligibility.

Conclusion

Children with CP demonstrated deficits in speech intelligibility and articulation compared with TD children. Better speech sound articulation influenced higher word intelligibility, but did not benefit sentence intelligibility.

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Reading Behind the Lines: The Factors Affecting the Text Reception Threshold in Hearing Aid Users

Purpose

The visual Text Reception Threshold (TRT) test (Zekveld et al., 2007) has been designed to assess modality-general factors relevant for speech perception in noise. In the last decade, the test has been adopted in audiology labs worldwide. The 1st aim of this study was to examine which factors best predict interindividual differences in the TRT. Second, we aimed to assess the relationships between the TRT and the speech reception thresholds (SRTs) estimated in various conditions.

Method

First, we reviewed studies reporting relationships between the TRT and the auditory and/or cognitive factors and formulated specific hypotheses regarding the TRT predictors. These hypotheses were tested using a prediction model applied to a rich data set of 180 hearing aid users. In separate association models, we tested the relationships between the TRT and the various SRTs and subjective hearing difficulties, while taking into account potential confounding variables.

Results

The results of the prediction model indicate that the TRT is predicted by the ability to fill in missing words in incomplete sentences, by lexical access speed, and by working memory capacity. Furthermore, in line with previous studies, a moderate association between higher age, poorer pure-tone hearing acuity, and poorer TRTs was observed. Better TRTs were associated with better SRTs for the correct perception of 50% of Hagerman matrix sentences in a 4-talker babble, as well as with better subjective ratings of speech perception. Age and pure-tone hearing thresholds significantly confounded these associations. The associations of the TRT with SRTs estimated in other conditions and with subjective qualities of hearing were not statistically significant when adjusting for age and pure-tone average.

Conclusions

We conclude that the abilities tapped into by the TRT test include processes relevant for speeded lexical decision making when completing partly masked sentences and that these processes require working memory capacity. Furthermore, the TRT is associated with the SRT of hearing aid users as estimated in a challenging condition that includes informational masking and with experienced difficulties with speech perception in daily-life conditions. The current results underline the value of using the TRT test in studies involving speech perception and aid in the interpretation of findings acquired using the test.

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Development of Velopharyngeal Closure for Vocalization During the First 2 Years of Life

Purpose

The vocalizations of young infants often sound nasalized, suggesting that the velopharynx is open during the 1st few months of life. Whereas acoustic and perceptual studies seemed to support the idea that the velopharynx closes for vocalization by about 4 months of age, an aeromechanical study contradicted this (Thom, Hoit, Hixon, & Smith, 2006). Thus, the current large-scale investigation was undertaken to determine when the velopharynx closes for speech production by following infants during their first 2 years of life.

Method

This longitudinal study used nasal ram pressure to determine the status of the velopharynx (open or closed) during spontaneous speech production in 92 participants (46 male, 46 female) studied monthly from age 4 to 24 months.

Results

The velopharynx was closed during at least 90% of the utterances by 19 months, though there was substantial variability across participants. When considered by sound category, the velopharynx was closed from most to least often during production of oral obstruents, approximants, vowels (only), and glottal obstruents. No sex effects were observed.

Conclusion

Velopharyngeal closure for spontaneous speech production can be considered complete by 19 months, but closure occurs earlier for speech sounds with higher oral pressure demands.

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Tutorial and Guidelines on Measurement of Sound Pressure Level in Voice and Speech

Purpose

Sound pressure level (SPL) measurement of voice and speech is often considered a trivial matter, but the measured levels are often reported incorrectly or incompletely, making them difficult to compare among various studies. This article aims at explaining the fundamental principles behind these measurements and providing guidelines to improve their accuracy and reproducibility.

Method

Basic information is put together from standards, technical, voice and speech literature, and practical experience of the authors and is explained for nontechnical readers.

Results

Variation of SPL with distance, sound level meters and their accuracy, frequency and time weightings, and background noise topics are reviewed. Several calibration procedures for SPL measurements are described for stand-mounted and head-mounted microphones.

Conclusions

SPL of voice and speech should be reported together with the mouth-to-microphone distance so that the levels can be related to vocal power. Sound level measurement settings (i.e., frequency weighting and time weighting/averaging) should always be specified. Classified sound level meters should be used to assure measurement accuracy. Head-mounted microphones placed at the proximity of the mouth improve signal-to-noise ratio and can be taken advantage of for voice SPL measurements when calibrated. Background noise levels should be reported besides the sound levels of voice and speech.

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Statistical Methodology for the Analysis of Repeated Duration Data in Behavioral Studies

Purpose

Repeated duration data are frequently used in behavioral studies. Classical linear or log-linear mixed models are often inadequate to analyze such data, because they usually consist of nonnegative and skew-distributed variables. Therefore, we recommend use of a statistical methodology specific to duration data.

Method

We propose a methodology based on Cox mixed models and written under the R language. This semiparametric model is indeed flexible enough to fit duration data. To compare log-linear and Cox mixed models in terms of goodness-of-fit on real data sets, we also provide a procedure based on simulations and quantile–quantile plots.

Results

We present two examples from a data set of speech and gesture interactions, which illustrate the limitations of linear and log-linear mixed models, as compared to Cox models. The linear models are not validated on our data, whereas Cox models are. Moreover, in the second example, the Cox model exhibits a significant effect that the linear model does not.

Conclusions

We provide methods to select the best-fitting models for repeated duration data and to compare statistical methodologies. In this study, we show that Cox models are best suited to the analysis of our data set.

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What Does a Cue Do? Comparing Phonological and Semantic Cues for Picture Naming in Aphasia

Purpose

Impaired naming is one of the most common symptoms in aphasia, often treated with cued picture naming paradigms. It has been argued that semantic cues facilitate the reliable categorization of the picture, and phonological cues facilitate the retrieval of target phonology. To test these hypotheses, we compared the effectiveness of phonological and semantic cues in picture naming for a group of individuals with aphasia. To establish the locus of effective cueing, we also tested whether cue type interacted with lexical and image properties of the targets.

Method

Individuals with aphasia (n = 10) were tested with a within-subject design. They named a large set of items (n = 175) 4 times. Each presentation of the items was accompanied by a different cueing condition (phonological, semantic, nonassociated word and tone). Item level variables for the targets (i.e., phoneme length, frequency, imageability, name agreement, and visual complexity) were used to test the interaction of cue type and item variables. Naming accuracy data were analyzed using generalized linear mixed effects models.

Results

Phonological cues were more effective than semantic cues, improving accuracy across individuals. However, phonological cues did not interact with phonological or lexical aspects of the picture names (e.g., phoneme length, frequency). Instead, they interacted with properties of the picture itself (i.e., visual complexity), such that phonological cues improved naming accuracy for items with low visual complexity.

Conclusions

The findings challenge the theoretical assumptions that phonological cues map to phonological processes. Instead, phonological information benefits the earliest stages of picture recognition, aiding the initial categorization of the target. The data help to explain why patterns of cueing are not consistent in aphasia; that is, it is not the case that phonological impairments always benefit from phonological cues and semantic impairments form semantic cues. A substantial amount of the literature in naming therapy focuses on picture naming paradigms. Therefore, the results are also critically important for rehabilitation, allowing for therapy development to be more rooted in the true mechanisms through which cues are processed.

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Poor Speech Perception Is Not a Core Deficit of Childhood Apraxia of Speech: Preliminary Findings

Purpose

Childhood apraxia of speech (CAS) is hypothesized to arise from deficits in speech motor planning and programming, but the influence of abnormal speech perception in CAS on these processes is debated. This study examined speech perception abilities among children with CAS with and without language impairment compared to those with language impairment, speech delay, and typically developing peers.

Method

Speech perception was measured by discrimination of synthesized speech syllable continua that varied in frequency (/dɑ/–/ɡɑ/). Groups were classified by performance on speech and language assessments and compared on syllable discrimination thresholds. Within-group variability was also evaluated.

Results

Children with CAS without language impairment did not significantly differ in syllable discrimination compared to typically developing peers. In contrast, those with CAS and language impairment showed significantly poorer syllable discrimination abilities compared to children with CAS only and typically developing peers. Children with speech delay and language impairment also showed significantly poorer discrimination abilities, with appreciable within-group variability.

Conclusions

These findings suggest that speech perception deficits are not a core feature of CAS but rather occur with co-occurring language impairment in a subset of children with CAS. This study establishes the significance of accounting for language ability in children with CAS.

Supplemental Materials

https://doi.org/10.23641/asha.5848056

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Masked Repetition Priming Treatment for Anomia

Purpose

Masked priming has been suggested as a way to directly target implicit lexical retrieval processes in aphasia. This study was designed to investigate repeated use of masked repetition priming to improve picture naming in individuals with anomia due to aphasia.

Method

A single-subject, multiple-baseline design was used across 6 people with aphasia. Training involved repeated exposure to pictures that were paired with masked identity primes or sham primes. Two semantic categories were trained in series for each participant. Analyses assessed treatment effects, generalization within and across semantic categories, and effects on broader language skills, immediately and 3 months after treatment.

Results

Four of the 6 participants improved in naming trained items immediately after treatment. Improvements were generally greater for items that were presented in training with masked identity primes than items that were presented repeatedly during training with masked sham primes. Generalization within and across semantic categories was limited. Generalization to broader language skills was inconsistent.

Conclusion

Masked repetition priming may improve naming for some individuals with anomia due to aphasia. A number of methodological and theoretical insights into further development of this treatment approach are discussed.

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Speech Adaptation to Kinematic Recording Sensors: Perceptual and Acoustic Findings

Purpose

This study used perceptual and acoustic measures to examine the time course of speech adaptation after the attachment of electromagnetic sensor coils to the tongue, lips, and jaw.

Method

Twenty native English speakers read aloud stimulus sentences before the attachment of the sensors, immediately after attachment, and again 5, 10, 15, and 20 min later. They read aloud continuously between recordings to encourage adaptation. Sentence recordings were perceptually evaluated by 20 native English listeners, who rated 150 stimuli (which included 31 samples that were repeated to assess rater reliability) using a visual analog scale with the end points labeled as "precise" and "imprecise." Acoustic analysis began by segmenting and measuring the duration of the fricatives /s/ and /ʃ/ as well as the whole sentence. The spectral center of gravity and spectral standard deviation of the 2 fricatives were measured using Praat. These phonetic targets were selected because the standard placement of sensor coils on the lingual surface was anticipated to interfere with normal fricative production, causing them to become distorted.

Results

Perceptual ratings revealed a decrease in speech precision after sensor attachment and evidence of adaptation over time; there was little perceptual change beyond the 10-min recording. The spectral center of gravity for /s/ decreased, and the spectral standard deviation for /ʃ/ increased after sensor attachment, but the acoustic measures showed no evidence of adaptation over time.

Conclusion

The findings suggest that 10 min may be sufficient time to allow speakers to adapt before experimental data collection with Northern Digital Instruments Wave electromagnetic sensors.

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An Initial Investigation of the Neural Correlates of Word Processing in Preschoolers With Specific Language Impairment

Purpose

Previous behavioral studies have found deficits in lexical–semantic abilities in children with specific language impairment (SLI), including reduced depth and breadth of word knowledge. This study explored the neural correlates of early emerging familiar word processing in preschoolers with SLI and typical development.

Method

Fifteen preschoolers with typical development and 15 preschoolers with SLI were presented with pictures followed after a brief delay by an auditory label that did or did not match. Event-related brain potentials were time locked to the onset of the auditory labels. Children provided verbal judgments of whether the label matched the picture.

Results

There were no group differences in the accuracy of identifying when pictures and labels matched or mismatched. Event-related brain potential data revealed that mismatch trials elicited a robust N400 in both groups, with no group differences in mean amplitude or peak latency. However, the typically developing group demonstrated a more robust late positive component, elicited by mismatch trials.

Conclusions

These initial findings indicate that lexical–semantic access of early acquired words, indexed by the N400, does not differ between preschoolers with SLI and typical development when highly familiar words are presented in isolation. However, the typically developing group demonstrated a more mature profile of postlexical reanalysis and integration, indexed by an emerging late positive component. The findings lay the necessary groundwork for better understanding processing of newly learned words in children with SLI.

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Metapragmatic Explicitation and Social Attribution in Social Communication Disorder and Developmental Language Disorder: A Comparative Study

Purpose

The purposes of this study are to investigate metapragmatic (MP) ability in 6–11-year-old children with social communication disorder (SCD), developmental language disorder (DLD), and typical language development and to explore factors associated with MP explicitation and social understanding (SU).

Method

In this cross-sectional study, all participants (N = 82) completed an experimental task, the Assessment of Metapragmatics (Collins et al., 2014), in which pragmatic errors are identified in filmed interactions. Responses were scored for complexity/type of explicitation (MP score) and attribution of social characteristics to the films' characters (SU score).

Results

Groups with SCD and DLD had significantly lower MP scores and less sophisticated explicitation than the group with typical language development. After controlling for language and age, the group with SCD had significantly lower SU scores than the group with DLD. Significant correlations were found between MP scores and age/language ability but not with pragmatic impairment.

Conclusions

Children with SCD or DLD performed poorly on an MP task compared with children who are typically developing but do not differ from each other in ability to reflect verbally on pragmatic features in interactions. MP ability appears to be closely related to structural language ability. The limited ability of children with SCD to attribute social/psychological states to interlocutors may indicate additional social attribution limitations.

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Inter-institutional Travel Fellowships—a Need for the Young Surgical Oncologists

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Seeing structure: Shape skeletons modulate perceived similarity

Abstract

An intrinsic part of seeing objects is seeing how similar or different they are relative to one another. This experience requires that objects be mentally represented in a common format over which such comparisons can be carried out. What is that representational format? Objects could be compared in terms of their superficial features (e.g., degree of pixel-by-pixel overlap), but a more intriguing possibility is that they are compared on the basis of a deeper structure. One especially promising candidate that has enjoyed success in the computer vision literature is the shape skeleton—a geometric transformation that represents objects according to their inferred underlying organization. Despite several hints that shape skeletons are computed in human vision, it remains unclear how much they actually matter for subsequent performance. Here, we explore the possibility that shape skeletons help mediate the ability to extract visual similarity. Observers completed a same/different task in which two shapes could vary either in their skeletal structure (without changing superficial features such as size, orientation, and internal angular separation) or in large surface-level ways (without changing overall skeletal organization). Discrimination was better for skeletally dissimilar shapes: observers had difficulty appreciating even surprisingly large differences when those differences did not reorganize the underlying skeletons. This pattern also generalized beyond line drawings to 3-D volumes whose skeletons were less readily inferable from the shapes' visible contours. These results show how shape skeletons may influence the perception of similarity—and more generally, how they have important consequences for downstream visual processing.

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American Indian Women Cancer Survivor’s Needs and Preferences: Community Support for Cancer Experiences

Abstract

Cancer (the focus of this inquiry) is the leading cause of death among American Indian and Alaska Native women. The purpose of this study was to identify American Indian women cancer survivors' needs and preferences related to community supports for their cancer experience. This qualitative study examined female American Indian cancer survivors' needs and preferences about community support. The sample included 43 American Indian women cancer survivors (the types of cancer survivors included cervical cancer: n = 14; breast cancer: n = 14; and colon and other types: n = 15) residing in the Northern Plains region, in the state of South Dakota. Data were analyzed using qualitative content analysis and were collected between June of 2014 and February of 2015. When asked about their needs and preferences, 82% of participants (n = 35) of female American Indian cancer survivors reported at least one of the following most commonly reported themes: cancer support groups (n = 31, 72%), infrastructure for community support (n = 17, 40%), and cancer education (n = 11, 26%). In addition to the aforementioned themes, 33% of participants (n = 14) indicated the need for an improved healthcare system, with 11% (n = 5) of participants expressly desiring the integration of spirituality and holistic healing options. The majority of American Indian women cancer survivor participants of this study identified a need for more community-based support systems and infrastructures to aid with the cancer survivor experience. Results warrant a community approach to raise awareness, education, and support for American Indian cancer survivors.

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American Indian Women Cancer Survivor’s Needs and Preferences: Community Support for Cancer Experiences

Abstract

Cancer (the focus of this inquiry) is the leading cause of death among American Indian and Alaska Native women. The purpose of this study was to identify American Indian women cancer survivors' needs and preferences related to community supports for their cancer experience. This qualitative study examined female American Indian cancer survivors' needs and preferences about community support. The sample included 43 American Indian women cancer survivors (the types of cancer survivors included cervical cancer: n = 14; breast cancer: n = 14; and colon and other types: n = 15) residing in the Northern Plains region, in the state of South Dakota. Data were analyzed using qualitative content analysis and were collected between June of 2014 and February of 2015. When asked about their needs and preferences, 82% of participants (n = 35) of female American Indian cancer survivors reported at least one of the following most commonly reported themes: cancer support groups (n = 31, 72%), infrastructure for community support (n = 17, 40%), and cancer education (n = 11, 26%). In addition to the aforementioned themes, 33% of participants (n = 14) indicated the need for an improved healthcare system, with 11% (n = 5) of participants expressly desiring the integration of spirituality and holistic healing options. The majority of American Indian women cancer survivor participants of this study identified a need for more community-based support systems and infrastructures to aid with the cancer survivor experience. Results warrant a community approach to raise awareness, education, and support for American Indian cancer survivors.

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Are surgeons overdosing patients with lidocaine?

Publication date: Available online 14 March 2018
Source:American Journal of Otolaryngology
Author(s): Laura Garcia-Rodriguez, Jeffrey Spiegel




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The Imperative of Addressing Cancer Drug Costs and Value

The President's Cancer Panel has released its latest report, Promoting Value, Affordability, and Innovation in Cancer Drug Treatment. The report recommends six actions to maximize the value and affordability of cancer drug treatment.

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Comparison of the Effects of Vonoprazan and Lansoprazole for Treating Endoscopic Submucosal Dissection-Induced Artificial Ulcers

Abstract

Background

Vonoprazan exhibits a more potent, rapid, and longer-lasting inhibitory effect on gastric acid secretion than proton pump inhibitors; however, whether it is more effective than PPI for treating endoscopic submucosal dissection (ESD)-induced artificial ulcers remains controversial.

Aim

This study aimed to assess and compare the effects of vonoprazan and lansoprazole for treating ESD-induced artificial ulcers.

Methods

This prospective, randomized controlled trial enrolled 149 patients who underwent ESD for the treatment of early gastric neoplasms from April 2015 to May 2017. They were randomly treated with either 20 mg/day vonoprazan (V group) or 30 mg/day lansoprazole (L group) orally. The primary end points were the area and shrinkage ratio of the ulcers at 4 and 8 weeks post-ESD.

Results

Data from 127 patients were analyzed, which showed that the 4- and 8-week healing ratios were not significantly different between the V and L groups (4 weeks, 16.3 vs. 25.8%; 8 weeks, 86.9 vs. 90.9%, respectively). Similarly, the shrinkage ratio, categorized as less than 90%, 90% or more but less than 100%, or 100% at 4 weeks and as less than 100% or 100% at 8 weeks were not statistically different between the V and L groups (4 weeks: 12, 41, 8 vs. 13, 41, 12, p = 0.7246; 8 weeks: 9, 52 vs. 9, 57, p = 0.8568). Delayed bleeding was also not significantly different between both the groups (5.4 vs. 5.3%; p = 0.9844).

Conclusions

Vonoprazan is as effective as lansoprazole in treating ESD-induced ulcers.

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A Tribute to Paul H. Guth, MD (1927–2017)

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An Analysis of the Clinical, Laboratory, and Histological Features of Striped, Punctate, and Nodular Gastric Antral Vascular Ectasia

Abstract

Background

Gastric antral vascular ectasia (GAVE) commonly presents as linear striped ("watermelon stomach") or punctate phenotypes, to which a newly discovered nodular form was recently added.

Aims

We performed a retrospective cohort study to detail and compare the clinical and histological characteristics of major GAVE phenotypes.

Methods

In 136 GAVE patients (tertiary care ambulatory and inpatient, median age 61.3 years, 73 men, and 63 women), clinical and laboratory results were recorded, with comorbidities, endoscopy indications, and complications of cirrhosis. In 74 patients, GAVE histopathology was cataloged by a pathologist masked to endoscopy results.

Results

Median age 61.3 years, 73 men, and 63 women. GAVE phenotypes were: linear striped—62 (46%), punctate—32 (24%), and nodular—41 (30%). Endoscopy was commonly performed for variceal screening in linear striped (45%) and nodular (34%) GAVE and for gastrointestinal bleeding in punctate (41%) and nodular (29%) GAVE, respectively. Of 89 cirrhotic patients, 37.5% each had linear striped or nodular GAVE, 24.7% had punctate forms (p = 0.03). Child–Turcotte–Pugh and Model for End-Stage Liver Disease scores were similar among phenotypes. Histologically, reactive epithelial hyperplasia and vascular ectasia were universal; smooth muscle proliferation was more common and consistent (78–86%) than microvascular thrombi (27–59%) and fibrohyalinosis (18–53%), which each varied with phenotype.

Conclusions

Nodular GAVE is a gastric mucosal abnormality that is similar to the linear striped and punctate phenotypes, yet has distinct clinical and histological features. Increased awareness of nodular GAVE by endoscopists is needed to avoid its misdiagnosis as nonspecific antral nodules.

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Autophagy Strengthens Intestinal Mucosal Barrier by Attenuating Oxidative Stress in Severe Acute Pancreatitis

Abstract

Background

Intestinal mucosal barrier dysfunction can be caused by severe acute pancreatitis (SAP). It is normally associated with changes to mucosal autophagy and oxidative stress.

Objective

The aim of this study was to investigate the correlation between autophagy and oxidative stress on the intestinal mucosal barrier of SAP rat model.

Methods

SAP was induced by retrograde injection of sodium taurocholate (5%) into the biliopancreatic duct. Bacterial translocation (BT) was detected by 16S rDNA sequencing analysis. Morphological alterations in the pancreas and gut were determined by hematoxylin–eosin staining. Oxidative stress status was determined by measuring the level of intestinal malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Western blot, RT-PCR, and immunofluorescent staining were preformed to analyze the expression of tight junction and autophagy proteins.

Results

According to the sequencing analysis, rats in SAP group were divided into BT (+) group (n = 9) and BT (−) group (n = 8). Pancreatic and intestinal injuries in SAP group were significantly higher than sham operation group. The content of MDA was clearly elevated, and SOD as well as GPx activities were decreased in BT (+) group as compared with BT (−) group. The expression of LC3II and Beclin1 in BT (−) group was higher than that observed in BT (+). In contrast, BT (+) group had a higher level of claudin-2 and a lower level of zonula occluden-1, occludin, and claudin-1.

Conclusion

These results suggest that activated autophagy may attenuate intestinal mucosal barrier dysfunction by preventing and reducing the oxidative stress in SAP.

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Effect of Bifidobacterium infantis 35624 (Align) on the Lactulose Breath Test for Small Intestinal Bacterial Overgrowth

Abstract

Background

Small intestinal bacterial overgrowth (SIBO) may cause symptoms in patients with abdominal bloating, distension, and gas. SIBO can be assessed using the lactulose breath test (LBT). A commonly used probiotic supplement is Align containing Bifidobacterium infantis 35624. The aim of this study was to determine the effect of B. infantis 35624 on hydrogen and methane excretion during LBT.

Methods

Healthy subjects underwent LBT before and after 2 weeks of daily Align administration. Hydrogen and methane concentrations were measured for each breath sample. Results are expressed as mean ± SE and analyzed using repeated measures ANCOVA. A breath test was considered positive if hydrogen and/or methane increased > 20 ppm above baseline by 90 min of the test or if a dual hydrogen peak was present.

Results

Nineteen healthy subjects were studied. Hydrogen levels were similar pre- and post-probiotic across the 3-h study (p = 0.768). In contrast, methane levels were significantly higher with probiotic administration (p = 0.012). A rise in methane > 20 ppm was seen in three subjects pre-probiotic but six post-probiotic. Of the 19 subjects, an "abnormal" LBT pre-probiotic was present in ten subjects and during the probiotic, 13 were abnormal.

Conclusions

This study found that 2 weeks of B. infantis 35624 (Align) supplementation affects LBT assessment for SIBO by significantly increasing methane, but not hydrogen, excretion after lactulose administration. Methane levels reached values that would be considered positive for SIBO patients. This study suggests that patients undergoing LBT should discontinue probiotics prior to the test as these supplements may alter the test results.

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Crohn’s Disease in Niemann–Pick Disease Type C1: Caught in the Cross-Fire of Host-Microbial Interactions

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Concise Commentary: Presurgical Evaluation of IPMNs—Eight Is Enough

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Acetarsol Suppositories: Effective Treatment for Refractory Proctitis in a Cohort of Patients with Inflammatory Bowel Disease

Abstract

Background

Management of proctitis refractory to conventional therapies presents a common clinical problem. The use of acetarsol suppositories, which are derived from organic arsenic, was first described in 1965. Data concerning clinical efficacy and tolerability are very limited.

Aim

To examine the efficacy of acetarsol suppositories for the treatment of refractory proctitis.

Methods

A retrospective analysis was performed on patients with inflammatory bowel disease treated with acetarsol suppositories between 2008 and 2014 at Addenbrooke's Hospital, Cambridge, United Kingdom. Clinical response was defined as resolution of symptoms back to baseline at the time of next clinic review.

Results

Thirty-nine patients were prescribed acetarsol suppositories between March 2008 and July 2014 (29 patients with ulcerative colitis, nine with Crohn's disease, and one with indeterminate colitis). Thirty-eight were included for analysis. The standard dose of acetarsol was 250 mg twice daily per rectum for 4 weeks. Clinical response was observed in 26 patients (68%). Of the 11 patients who had endoscopic assessment before and after treatment, nine (82%) showed endoscopic improvement and five (45%) were in complete remission (Wilcoxon signed-rank test p = 0.006). One patient developed a macular skin rash 1 week after commencing acetarsol, which resolved within 4 weeks of drug cessation.

Conclusion

Acetarsol was effective for two out of every three patients with refractory proctitis. This cohort had failed a broad range of topical and systemic treatments, including anti-TNFα therapy. Clinical efficacy was reflected in significant endoscopic improvement. Adverse effects of acetarsol were rare.

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Gastric Acid and Enteric Infections: Souring on the Use of PPIs

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A 19-Gauge Histology Needle Versus a 19-Gauge Standard Needle in Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Solid Lesions: A Multicenter Randomized Comparison Study (GREATER Study)

Abstract

Background

The necessity of histological analysis is increasing. A 19-gauge histology needle (PC19) in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has recently been developed and has shown high yields of tissue acquisition and histological diagnosis.

Aims

To compare the histological diagnostic yield in single-pass EUS-FNA for solid lesions using PC19 and a standard 19-gauge needle (EC19).

Patients and Methods

Consecutive patients with solid lesions were enrolled and underwent one pass with each of PC19 and EC19 for EUS-FNA with the randomized order of the needles. The primary endpoint was the histological diagnostic accuracy. The secondary endpoints were the feasibility, yield of histological core, cytological and overall diagnostic accuracies, and adverse events. Subgroup analysis was performed for the optimal situation with PC19.

Results

Of the 115 patients, 110 underwent EUS-FNA and five were excluded. EUS-FNA was performed from the esophagus in four, stomach in 80, or duodenum in 26. The final diagnosis was malignancy in 100 and benign in 10. The feasibility was 98.2 and 97.3% with PC19 and EC19, respectively (p = 1.00). The rate of presence of a histological core and the histological, cytological, and overall diagnostic accuracies for PC19 versus EC19 were 84.6 versus 80.9% (p = 0.593), 83.6 versus 73.6% (p = 0.099), 63.6 versus 56.4% (p = 0.335), and 90.0 versus 79.1% (p = 0.039), respectively. PC19 was favored in the trans-esophageal/gastric approaches to obtain a histological diagnosis (p = 0.013). Adverse events were observed in four patients.

Conclusion

Single-pass EUS-FNA with PC19 was feasible and showed significantly higher overall diagnostic accuracy and an increased tendency towards histological diagnostic accuracy, especially with trans-esophageal/gastric FNA.

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Profiles: Benjamin Lebwohl, MD, MS

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Plastic Surgery: Cholangioscopic Intra-stent Balloon Retrieval of a Proximally Migrated Biliary Stent

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Novel Albumin–Bilirubin Grade-Based Risk Prediction Model for Patients with Hepatocellular Carcinoma Undergoing Chemoembolization

Abstract

Background

Recently, albumin–bilirubin (ALBI) grade has been suggested as a better surrogate for hepatic functional reserve for patients with hepatocellular carcinoma (HCC).

Aims

We developed and validated a novel prediction model to predict outcome for HCC patients who underwent transcatheter arterial chemoembolization (TACE) as a first-line therapy.

Methods

From a multivariate Cox regression model for overall survival, five objective variables (ALBI grade), the Barcelona clinic liver cancer (BCLC) stage, response after the first TACE session, Alpha-fetoprotein level, and sex were chosen and the ABRAS score was developed from the derivation cohort (n = 476) and scored to generate an 8-point risk prediction model. The model's prognostic performance was assessed in the randomly assigned internal validation set (n = 475) and external validation set (n = 243).

Results

The ALBI grade was able to stratify patient survival within the same Child–Pugh class. The time-dependent area under receiver operating characteristics curves (AUROCs) for overall survival at 1 and 3 years were 0.78 and 0.73 in the training set, 0.78 and 0.71 in the internal validation set, and 0.70 and 0.65 in the external validation set, respectively. When stratified by BCLC stage, ABRAS score at a cutoff point of more than 3, 4, and 5 for BCLC stage 0/A, B, and C could identify subset of patients with dismal prognosis.

Conclusion

ABRAS score was useful in estimating prognosis for patients who underwent TACE as a first-line therapy. This score can be useful in planning and guiding treatment strategies with TACE, which warrants prospective validation.

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