Levamisole-Induced Vasculitis

What is levamisole-induced vasculitis? Learn more about this condition and find out how it's best diagnosed and treated.
ePlasty, Open Access Journal of Plastic Surgery

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Down-Regulated miR-125a-5p Promotes the Reprogramming of Glucose Metabolism and Cell Malignancy by Increasing Levels of CD147 in Thyroid Cancer

Thyroid, Ahead of Print.


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Mild Blast Injury Produces Acute Changes in Basal Intracellular Calcium Levels and Activity Patterns in Mouse Hippocampal Neurons

Journal of Neurotrauma, Ahead of Print.


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Disruption of NSD1 in head and neck cancer promotes favorable chemotherapeutic responses linked to hypomethylation

Human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC) represents a distinct classification of cancer with poor expected outcomes. Of the 11 genes recurrently mutated in HNSCC, we identify a singular and substantial survival advantage for mutations in the gene encoding Nuclear Set Domain Containing Protein 1 (NSD1), a histone methyltransferase altered in approximately 10% of patients. This effect, a 55% decrease in risk of death in NSD1-mutated versus non-mutated patients, can be validated in an independent cohort. NSD1 alterations are strongly associated with widespread genome hypomethylation in the same tumors, to a degree not observed for any other mutated gene. To address whether NSD1 plays a causal role in these associations, we use CRISPR-Cas9 to disrupt NSD1 in HNSCC cell lines and find that this leads to substantial CpG hypomethylation and sensitivity to cisplatin, a standard chemotherapy in head and neck cancer, with a 40 - 50% decrease in IC50. Such results are reinforced by a survey of 1,001 cancer cell lines, in which loss-of-function NSD1 mutations have an average 23% decrease in cisplatin IC50 compared to cell lines with wild type NSD1. This study identifies a favorable subtype of head and neck cancer linked to NSD1 mutation, hypomethylation and cisplatin sensitivity.

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Editorial Board

Publication date: 1 April 2018
Source:Journal of Neuroscience Methods, Volume 299





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Targeting NAD+/PARP DNA repair pathway as a novel therapeutic approach to SDHB-mutated cluster I pheochromocytoma and paraganglioma

Purpose: Cluster I pheochromocytomas and paragangliomas (PCPGs) tend to develop malignant transformation, tumor recurrence, and multiplicity. Transcriptomic profiling suggests that cluster I PCPGs and other related tumors exhibit distinctive changes in the tricarboxylic acid (TCA) cycle, the hypoxia signaling pathway, mitochondrial electron transport chain, and methylation status, suggesting that therapeutic regimen might be optimized by targeting these signature molecular pathways. Experimental Design: In the present study, we investigated the molecular signatures in clinical specimens from cluster I PCPGs in comparison to cluster II PCPGs that are related to kinase signaling and often present as benign tumors. Results: We found that cluster I PCPGs develop dependency to mitochondrial complex I, evidenced by the upregulation of complex I components and enhanced NADH dehydrogenation. Alteration in mitochondrial function resulted in strengthened NAD+ metabolism, here considered as a key mechanism of chemoresistance, particularly, of succinate dehydrogenase subunit B (SDHB)-mutated cluster I PCPGs via the PARP1/BER DNA repair pathway. Combining a PARP inhibitor with temozolomide, a conventional chemotherapeutic agent, not only improved cytotoxicity but also reduced metastatic lesions, with prolonged overall survival of mice with SDHB knockdown PCPG allograft. Conclusions: In summary, our findings provide novel insights into an effective strategy for targeting cluster I PCPGs, especially those with SDHB mutations.

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Discovery of a glucocorticoid receptor (GR) activity signature using selective GR antagonism in ER-negative breast cancer

Purpose: Although high glucocorticoid receptor (GR) expression in early-stage estrogen receptor (ER)-negative breast cancer (BC) is associated with shortened relapse-free survival (RFS), how associated GR transcriptional activity contributes to aggressive BC behavior is not well understood. Using potent GR antagonists and primary tumor gene expression data, we sought to identify a tumor-relevant gene signature based on GR activity that would be more predictive than GR expression alone. Experimental Design: Global gene expression and GR ChIP-sequencing were performed to identify GR-regulated genes inhibited by two chemically distinct GR antagonists, mifepristone and CORT108297. Differentially expressed genes from MDA-MB-231 cells were cross-evaluated with significantly expressed genes in GR-high versus GR-low ER-negative primary BCs. The resulting subset of GR targeted genes was analyzed in two independent ER-negative BC cohorts to derive and then validate the GR activity signature (GRsig). Results: Gene expression pathway analysis of glucocorticoid-regulated genes (inhibited by GR antagonism) revealed cell survival and invasion functions. GR ChIP-seq analysis demonstrated that GR antagonists decreased GR chromatin association for a subset of genes. A GRsig comprised of n=74 GR activation-associated genes (also reversed by GR antagonists) was derived from an adjuvant chemotherapy-treated Discovery cohort and found to predicted probability of relapse in a separate Validation cohort (HR=1.9; p= 0.012). Conclusions: The GRsig discovered herein identifies high-risk ER-negative/GR-positive BCs most likely to relapse despite administration of adjuvant chemotherapy. Because GR antagonism can reverse expression of these genes, we propose that addition of a GR antagonist to chemotherapy may improve outcome of these high-risk patients.

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Resistance mechanisms to targeted therapies in ROS1+ and ALK+ non-small cell lung cancer

Purpose: Experimental Design: Results: Conclusions:

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A First-in-Human Phase 1 Study of LY3023414, an Oral PI3K/mTOR Dual Inhibitor, in Patients with Advanced Cancer

Purpose: The phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is frequently aberrated in cancer. LY3023414 is a potent and selective ATP competitive inhibitor of class I PI3K isoforms, mTOR, and DNA-PK. Here we report the dose escalation results of the first-in-human phase I study of LY3023414.  Experimental Design: A 3+3 dose escalation for QD and BID oral dosing of LY3023414 was followed by an expansion cohort for CYP3A4 drug-drug interaction (DDI) assessment. The primary objective was to determine the recommended phase 2 dose (RP2D). Additional objectives included safety, pharmacokinetics (PK)/pharmacodynamics, and antitumor activity. Results: Forty-seven patients with solid tumors received LY3023414 at QD (20-450 mg) or BID dosing (150-250 mg). Dose-limiting toxicities were observed at 450 mg QD (thrombocytopenia, hypotension, hyperkalemia) in 3/3 patients, 250 mg BID dosing (hypophosphatemia, fatigue, mucositis) in 3/4 patients, and in 1/15 patients at 200 BID mg (nausea). Common related AEs included nausea (38%), fatigue (34%), and vomiting (32%) and were mostly mild or moderate. LY3023414 pharmacokinetics demonstrated dose-dependent increase in exposure with ≥ 90% target inhibition at doses ≥150 mg. DDI analysis demonstrated LY3023414 to be a weak inhibitor of CYP3A4. Durable partial response was observed in an endometrial cancer patient harboring PIK3R1 and PTEN truncating mutations and 13 additional patients (28%) had decrease in their target lesions by up to 30%.  Conclusions: LY3023414 has a tolerable safety profile and single agent activity in patients with advanced cancers. The RP2D of LY3023414 monotherapy is 200 mg BID based on safety, tolerability, and PK/Pharmacodynamic data.

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Patterns of Care of Breast Cancer Patients in a Rural Cancer Center in Western India

Abstract

Breast cancer is an emerging public health problem in low- and middle-income countries. The main objective is to describe the clinical characteristics and patterns of care of breast cancer patients diagnosed and treated in a rural cancer hospital in Barshi, Western India. The results from a cross-sectional study of 99 consecutive breast cancer patients diagnosed and treated between February 2012 and November 2014 in Nargis Dutt Memorial Cancer Hospital is reported. The case records of the patients were scrutinized and reviewed to abstract data on their clinical characteristics, diagnostic, and treatment details. The mean age at diagnosis of the patients was 52.8 ± 11.6 years; 83.5% of women were married, and 60.6% were illiterate. Sixty percent of patients had tumors measuring 5 cm or less. Almost half of the patients (46.4%) had stage I or II A disease and a third (36.0%) had axillary lymph node metastasis. Estrogen, progesterone, and human epidermal growth factor receptor2 receptor status were investigated in 41 (41.4%) of patients only. The median interval between diagnosis and initiation of treatment was 11 days. Modified radical mastectomy was done in 91% of patients, and nearly a third of patients who were prescribed chemotherapy did not complete treatment. The rural-based tertiary cancer care center has made treatment more accessible to breast cancer patients and has reduced the interval between diagnosis and treatment initiation. However, there are still many challenges like non-compliance to and incomplete treatments and poor follow-up that need to be addressed.

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Enhanced lymphodepletion is insufficient to replace exogenous IL-2 or IL-15 therapy in augmenting the efficacy of adoptively transferred effector CD8+ T cells

Effector CD8+ T cells conditioned with IL-12 during activation mediate enhanced antitumor efficacy after adoptive transfer into lymphodepleted hosts; this is due in part to improved IL-7 responsiveness. Therefore, we hypothesized that increasing the intensity or type of lymphodepletion would deplete more IL-7-consuming host cells and improve the persistence and antitumor activity of IL-12-conditioned CD8+ T cells. Using cyclophosphamide (CTX), fludarabine (FLU), and total body irradiation (TBI, 6 Gy) either individually or in combination, we found that combined lymphodepletion best enhanced T cell engraftment in mice. This improvement was strongly related to the extent of leukopenia, as post-transfer levels of donor T cells inversely correlated to host cell counts after lymphodepletion. Despite the improvement in engraftment seen with combination lymphodepletion, dual-agent lymphodepletion did not augment the antitumor efficacy of donor T cells compared to TBI alone. Similarly, IL-7 supplementation after TBI and transfer of tumor-reactive T cells failed to improve persistence or anti-tumor immunity. However, IL-15 or IL-2 supplementation greatly augmented the persistence and antitumor efficacy of donor tumor-reactive T cells. Our results indicate that the amount of host IL-7 induced after single agent lymphodepletion is sufficient to potentiate the expansion and antitumor activity of donor T cells, and that the efficacy of future regimens may be improved by providing post-transfer support with IL-2 or IL-15.

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Commentary on: Thoughts on the American Board of Radiology Examinations and the Resident Experience in Radiation Oncology

Publication date: Available online 10 April 2018
Source:Practical Radiation Oncology
Author(s): Paul E. Wallner, Lisa A. Kachnic, Anthony M. Gerdeman




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Local Control for Clinical Stage I Non-small Cell Lung Cancer Treated with Five Fraction Stereotactic Body Radiation Therapy is Not Associated with Treatment Schedule

Publication date: Available online 10 April 2018
Source:Practical Radiation Oncology
Author(s): Pamela Samson, Sana Rehman, Aditya Juloori, Todd DeWees, Michael Roach, Jeffrey Bradley, Gregory M.M. Videtic, Kevin Stephans, Clifford Robinson
PurposeClinical concern remains regarding the relationship between consecutive (QD) versus non-consecutive (QoD) lung SBRT treatment schedules and outcomes for clinical Stage I NSCLC. We examined a multi-institutional series of patients receiving five fraction lung SBRT to compare the local failure rates and overall survival between patients receiving QD versus QoD treatment.Methods and MaterialsLung SBRT databases from two high-volume institutions were combined, and patients receiving five fraction SBRT for a solitary Stage I NSCLC were identified. QD treatment was defined as completing SBRT in ≤7days, while QoD treatment was defined as completing treatment in >7days. To control for patient characteristics between the two institutions, a 1:1 propensity matched analysis was performed. Multivariable logistic regression was performed to identify variables independently associated with local failure, and Cox proportional hazards modeling to identify variables independently associated with increased mortality.ResultsFrom 2005–2016, 245 clinical Stage I NSCLC patients receiving five fraction SBRT were identified. 117 (47.8%) patients received QD treatment and 128 (52.2%) patients received QoD treatment. On propensity matched analysis, no association was seen between QD treatment and local failure (Odds Ratio for QD treatment 0.48, 95% CI 0.12–1.99, p=0.5). On multivariable logistic regression central tumors were independently associated with increased likelihood of local recurrence (OR 5.2, 95% CI 1.11–24.2, p=0.04). Kaplan–Meier analysis identified no difference in median overall survival between QD versus QoD treatments (38.0months versus 38.0months, log-rank p=0.7), respectively. QD treatment was not associated with an increased mortality hazard (HR 1.08, 95% CI 0.67–1.75, p=0.75).ConclusionsThis analysis demonstrated no association between QD versus QoD treatment scheduling and local control or overall survival for early stage NSCLC.



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The long-term sequelae of palliative radiotherapy to Lumbo-sacral spine using conventional PA-single portal technique

Publication date: Available online 10 April 2018
Source:Practical Radiation Oncology
Author(s): Kuan-Yin Hsiao, Hui-Chuan Wang, Steve H Fung, Waqar Haque, E Brian Butler, Bin S Teh




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Long‐term outcomes in oral cavity squamous cell carcinoma with adjuvant and salvage radiotherapy after surgery

The Laryngoscope, EarlyView.


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Retronasal olfaction in chronic rhinosinusitis

The Laryngoscope, EarlyView.


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Current trends in the medical management of osteoradionecrosis using triple therapy

Publication date: Available online 9 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): J. Dhanda, L. Rennie, R. Shaw
Recent guidelines from the National Institute for Health and Care Excellence (NICE) have suggested that the medical management of osteoradionecrosis (ORN) of the jaws should be used in clinical trials only, and some drugs and therapeutics committees have withdrawn funds for such prescriptions. With increased scrutiny on the use of these agents, the aims of this study were to ascertain current trends in the presentation and management of ORN, with particular focus on which agents are being used.



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Re: re: Retroseptal transconjunctival approach for fractures of the zygomaticomaxillary complex: a retrospective study

Publication date: Available online 9 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): R. Sharma




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Tetanus after a penetrating injury to the right globe: a case report

Publication date: Available online 9 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): B. Rushworth, L. Carter
A 24-year-old man attended the emergency department with a penetrating injury to the right globe after a road traffic accident. He later contracted tetanus for which he was given human tetanus immunoglobulin. Although it is rare, tetanus is life-threatening and a thorough immunisation history should be obtained before treatment of tetanus-prone injuries.



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Use of patient-reported outcome measures in oral and maxillofacial trauma surgery: a review

Publication date: Available online 9 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): R. Ologunde, N.M.H. McLeod
In the UK, about one person/100/year sustains a facial injury, so trauma surgery accounts for a considerable part of the caseload in oral and maxillofacial surgery (OMFS). Patient-reported outcome measures (PROM) allow for patient-centred assessment of postoperative outcomes, but to our knowledge, most research in OMFS trauma does not currently include them. To investigate their use, we searched Medline to find relevant studies that reported outcomes from inception in January 1879 to August 2016. Those not in the English language and those that did not report operations were excluded. We retrieved 416 articles, of which 21 met the inclusion criteria (five randomised controlled trials and 16 cohort studies) yielding 16 outcome measures. Most of these had been devised by authors (eight studies), four studies reported use of the Geriatric Oral Health Assessment Index, and three the Nasal Obstruction Symptom Evaluation. Most were used in studies on mandibular surgery (n=13), followed by those on nasal and facial surgery (n=3 each). There is a great heterogeneity in the use of these assessments in OMF trauma. In view of their increasing importance compared with simpler objective measures that may not be relevant to the patients' own perception, more research is needed to establish which of them can be used to measure the QoL of patients treated for OMF trauma.



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Dentin dysplasia type I—A dental disease with genetic heterogeneity

Oral Diseases, EarlyView.


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Preliminary study on the treatment of vitiligo with carbon dioxide fractional laser together with tacrolimus

Lasers in Surgery and Medicine, EarlyView.


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Pulsed dye laser treatment of rosacea using a novel 15 mm diameter treatment beam

Lasers in Surgery and Medicine, EarlyView.


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Validierung der deutschen Version des Eating Assessment Tool bei Kopf-Hals-Tumor-Patienten

Laryngo-Rhino-Otol
DOI: 10.1055/a-0596-7780

Hintergrund Die Erfassung von subjektiv empfundenen Schluckbeschwerden bildet ein wichtiges Element in einem multidimensionalen und damit modernen Management von schluckgestörten Patienten infolge eines Kopf-Hals-Tumors. Zur Verfügung steht hier der international anerkannte und validierte 10-Item-Fragebogen EAT-10, der 2008 von Belafsky et al. entwickelt und validiert wurde. Ziel der vorliegenden Studie ist die Übersetzung des EAT-10 in die deutsche Sprache und dessen Validierung für Patienten mit einem Kopf-Hals-Tumor. Material und Methoden Nach Übersetzung des EAT-10 ins Deutsche gemäß den Richtlinien zur Übersetzung fremdsprachlicher Messinstrumente erfolgte die Validierung des gEAT-10 anhand von 210 Kopf-Hals-Tumor-Patienten. Ermittelt wurden die Reliabilität anhand der internen Konsistenz (Cronbachs Alpha) und Eigentrennschärfe (Spearman-Korrelation). Die Konstruktvalidität wurde geprüft anhand der uni- und multivariaten Berechnung der Verteilung von gEAT-10-Gesamtscores abhängig von Geschlecht, Alter, BMI, Tumorstadium und -lokalisation sowie der Art der onkologischen Therapie. Ergebnisse Die interne Konsistenz betrug α = 0,94. Die Eigentrennschärfe variierte zwischen ρ = 0,59 und ρ = 0,85. Es ließ sich kein signifikanter Zusammenhang zwischen gEAT-10-Gesamtscore und Geschlecht bzw. Alter univariat erkennen, jedoch einer für BMI, Tumorstadium und -lokalisation sowie Art der onkologischen Therapie. In der Regression lieferte dagegen nur das Tumorstadium ein signifikantes Ergebnis. Schlussfolgerung Der gEAT-10 erwies sich als ein reliabler und konstruktvalider Fragebogen zur Erfassung subjektiver Schluckbeschwerden bei Patienten mit Kopf-Hals-Tumor.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Laryngopharyngealer Reflux

Laryngo-Rhino-Otol 2018; 97: 238-245
DOI: 10.1055/s-0044-100794

Die Prävalenz von laryngopharyngealem Reflux (LPR) wird in der Allgemeinbevölkerung mit bis zu 31 % angegeben. Bei Patienten mit Stimmproblemen bzw. Kehlkopferkrankungen tritt ein LPR bei ca. 50 % der Patienten als Begleiterscheinung auf. Typische refluxbedingte Erkrankungen am Larynx sind eine chronische Laryngitis und das Kontaktgranulom. Nicht abschließend geklärt ist die Rolle des LPR bei der Genese des Stimmlippenkarzinoms. Für die Diagnose des LPR gibt es noch keine evidenzbasierten Daten, er kann jedoch üblicherweise klinisch aus der Kombination typischer Symptome (Heiserkeit, chronischer Hustenreiz/Räuspern, Globusgefühl/Dysphagie) und dem charakteristischen laryngoskopischen Bild (ein Schleimhauterythem bzw. eine Schleimhauthyperplasie mit Fältelung der Interarytenoidregion und ein Stimmlippenödem) gestellt werden. Gelegentlich wird eine LPR zusätzlich durch eine pharyngeale 24h-pH-Metrie-Untersuchung gesichert. Die Therapie des LPR umfasst mehrere Bereiche, wie z.B. diätetische Maßnahmen, die medikamentöse Therapie mit Protonenpumpeninhibitoren (PPIs) und ggf. eine chirurgische Intervention. Bei symptomatischen Patienten erfolgt oft eine Therapie mit PPIs, bei der der HNO-Arzt im engen Dialog mit dem Gastroenterologen steht.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Zusammenhang zwischen Tinnituston und Frequenzbereich des Gehörverlusts

Laryngo-Rhino-Otol 2018; 97: 230-231
DOI: 10.1055/s-0044-100277

Keppler H et al. The relationship between tinnitus pitch and parameters of audiometry and distortion product otoacoustic emissions. J Laryngol Otol 2017; 131: 1017–1025 Ein chronischer Tinnitus ist mit einem reduzierten akustischen Reiz assoziiert. Auf die Schädigung reagiert das zentrale Hörsystem mit Veränderungen. Den Zusammenhang zwischen Tinnituston und Parametern der Audiometrie sowie der distorsiv produzierten otoakustischen Emissionen (DPOAE) untersuchten Ärzte des Hör-Sprachzentrums der Universität der belgischen Stadt Gent.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Rhinoplastik

Laryngo-Rhino-Otol 2018; 97: 289-292
DOI: 10.1055/a-0549-3244

© Georg Thieme Verlag KG Stuttgart · New York

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Radiologisch basierte Therapie des Kehlkopfkrebses überprüft

Laryngo-Rhino-Otol 2018; 97: 231-232
DOI: 10.1055/s-0044-100272

Ko HC et al. Survival Outcomes for Patients With T3N0M0 Squamous Cell Carcinoma of the Glottic Larynx. JAMA Otolaryngol Head Neck Surg 2017; 143: 1126–1133 Wie ist das Überleben von Patienten mit Kehlkopfkrebs im Stadium T3N0M0, die operativ oder mittels Radiotherapie behandelt wurden? Zur Klärung dieser Frage verglichen chinesische Wissenschaftler die retrospektiven Daten dieser Patienten über einen langfristigen Nachbeobachtungszeitraum.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Endoskopische Frühdiagnostik von Karzinomen im oberen Aerodigestivtrakt

Laryngo-Rhino-Otol 2018; 97: 276-286
DOI: 10.1055/a-0575-3564

Der obere Aerodigestivtrakt ist mit endoskopischen Methoden gut zugänglich. Die Entwicklung moderner endoskopisch bildgebender Verfahren (EBV) hat dazu beigetragen, Tumorerkrankungen im oberen Aerodigestivtrakt frühzeitig zu entdecken und minimalinvasiv, onkologisch wirksam sowie funktionserhaltend zu behandeln. Damit wird ein gutes onkologisches Ergebnis bei Erhalt der Lebensqualität und Reduzierung der Mortalität und Komplikationsrate erreicht.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Was bestimmt die Prognose von Patienten mit Störungen des Schluckvorganges?

Laryngo-Rhino-Otol 2018; 97: 232-234
DOI: 10.1055/s-0044-100285

Bock JM et al. Evaluation of the natural history of patients who aspirate. Laryngoscope 2017; 127: S1–S10 Die klinische Progression der Aspiration bis zu eventuellen pulmonalen Störungen ist nicht vollständig verstanden. Empfehlungen zur Ernährungsumstellung, Schwere von Penetration und Aspiration gemäß PAS sowie die Ätiologie der Dysphagie beeinflussen möglicherweise die Zeitspanne bis zum Auftreten des ersten pulmonalen Ereignisses sowie das Gesamtüberleben von Patienten mit VFS-dokumentierter, asymptomatischer Penetration und Aspiration.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Techniken der Stapedotomie

Laryngo-Rhino-Otol 2018; 97: 236-237
DOI: 10.1055/s-0044-102148

© Georg Thieme Verlag KG Stuttgart · New York

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Versorgung mit Hörgeräten und Hörimplantaten

Laryngo-Rhino-Otol 2018; 97: 235-235
DOI: 10.1055/s-0043-125366

© Georg Thieme Verlag KG Stuttgart · New York

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Zum richtigen Umgang mit Bonusmeilen

Laryngo-Rhino-Otol 2018; 97: 274-275
DOI: 10.1055/s-0043-125169

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Basic Otorhinolaryngology. A Step-by-Step Learning Guide, Second Edition

Laryngo-Rhino-Otol 2018; 97: 235-235
DOI: 10.1055/s-0043-125367

© Georg Thieme Verlag KG Stuttgart · New York

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Fragen für die Facharztprüfung

Laryngo-Rhino-Otol 2018; 97: 287-288
DOI: 10.1055/a-0549-3200

© Georg Thieme Verlag KG Stuttgart · New York

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Aerobe Belastung verschlechtert die Wahrnehmungsschwelle kurzer H2S-Impulse

Laryngo-Rhino-Otol
DOI: 10.1055/a-0589-1158

Hintergrund Ob sich bei akuter aerober körperlicher Belastung das Riechvermögen verschlechtert, wird in der Literatur widersprüchlich beschrieben. Material und Methoden Zur Klärung dieser Fragestellung wurden die passiven Wahrnehmungsschwellen für kurze H2S-Stimuli mittels eines Fluss-Olfaktometers inspirationssynchron bei nasaler Atmung im staircase Verfahren während einer Ruhephase, einer anschließenden submaximalen Belastung auf einem Fahrradergometer und einer nachfolgenden Erholungsphase bei Gesunden bestimmt und mit einander verglichen. Parallel fanden Messungen von Herzfrequenz, Blutdruck, Blutlaktat und Körpertemperatur statt, um eine aerobe Belastung abzusichern. Ergebnisse Die Versuchsteilnehmer hatten ihre höchsten Werte für die Wahrnehmungsschwelle in der Belastungsphase. Mittels rm-ANOVA und post-hoc-Tests war ein signifikanter Unterschied der Mittelwerte der Wahrnehmungsschwellen zwischen den Messungen in Ruhe und während körperlicher Belastung sowie zwischen der Erholungs- und Belastungsphase zu verzeichnen. Die Mittelwerte der Wahrnehmungsschwellen zwischen der Ruhe- und Erholungsphase differierten hingegen nicht. Schlussfolgerung Die Verschlechterung der olfaktorischen Wahrnehmungsschwellen während einer akuten aeroben körperlichen Belastung und deren unverzügliche Verbesserung während der Erholungsphase auf Ruhewerte lassen auf eine Beeinflussung der Riechschwelle durch die körperliche Anstrengung schließen. Als wahrscheinlichste Ursache hierfür kommt ein bei forcierter Nasenatmung ausgelöster Verdünnungseffekt durch zusätzlich einströmende geruchsneutrale Umgebungsluft in Betracht.
[...]

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Unklare submuköse Raumforderung im supraglottischen Bereich: Erste Fallbeschreibung

Laryngo-Rhino-Otol
DOI: 10.1055/s-0044-100256

© Georg Thieme Verlag KG Stuttgart · New York

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Ossär destruierender, schmerzloser Tumor des Gesichtsschädels mit sekundärer Stirnhöhlenmukozele

Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-123653

© Georg Thieme Verlag KG Stuttgart · New York

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Kommentar der Schriftleitung

Laryngo-Rhino-Otol 2018; 97: 227-228
DOI: 10.1055/a-0549-3134

© Georg Thieme Verlag KG Stuttgart · New York

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Interne Validität des Acoustic Voice Quality Index Version 03.01 und des Acoustic Breathiness Index

Laryngo-Rhino-Otol
DOI: 10.1055/a-0596-7819

Hintergrund Akustische Messverfahren haben das Potential Heiserkeit und Behauchtheit objektiv zu messen und der Acoustic Voice Quality Index (AVQI) und der Acoustic Breathiness Index (ABI) zeigen gute Ergebnisse hinsichtlich Validität und Reliabilität. Das Ziel dieser Studie war die Überprüfung der internen Validität der aktuellen Version des AVQI 03.01 und des ABI im Deutschen. Hierzu wurde die Sensitivität gegenüber Stimmveränderungen im Heiserkeits- und Behauchtheitsgrad durch logopädische Stimmtherapie untersucht. Material und Methoden Insgesamt wurden 84 Stimmaufzeichnungen von fortlaufender Sprache und dem Vokal [a:] vor und nach einer Stimmtherapie verwendet. Alle Aufnahmen der 42 Probanden stammten von Stimmpatienten mit unterschiedlichen Schweregraden einer Dysphonie vor und nach einer konservativen Therapie. Alle Stimmen wurden von drei Stimmexperten nach dem RBH-System beurteilt. Ergebnisse Die Intra- Beurteiler Reliabilität ergab insgesamt eine hohe Reliabilität für Heiserkeit (Kappa Mittelwert = 0,76) und Behauchtheit (Kappa Mittelwert = 0,69). Die Inter- Beurteiler Reliabilität erreichte hingegen eine niedrigere Reliabilität für beide Stimmqualitätsaspekte, die zwischen Kappa = 0,27 und 0,29 lag. Für beide Messverfahren, AVQI und ABI, zeigte sich ein deutlicher Zusammenhang zwischen der Perzeption von Veränderungen der Stimmqualität vor und nach der Therapie und dem Messergebnis (Heiserkeit vs. AVQI: r = 0,715, p < 0,01 und Behauchtheit vs. ABI: r = 0,712, p < 0,01). Die Unterschiede waren auch nicht signifikant. Schlussfolgerung Die Resultate zeigten, dass AVQI Version 03.01 und ABI eine hohe interne Validität haben, um Stimmveränderungen nach Intervention zu erfassen. AVQI und ABI sind zwei valide und robuste Messinstrumente, die Heiserkeit und Behauchtheit objektiv messen können.
[...]

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Veränderte Indikation zur Parotidektomie im nordwestlichen Brandenburg:Eine Longitudinaluntersuchung

Laryngo-Rhino-Otol
DOI: 10.1055/a-0596-7714

Hintergrund Kenntnisse über die Indikationen zu einer Parotidektomie basieren auf den Mitteilungen einzelner Kliniken, Tumor- und Krankenhausdatenbanken. Die Studie prüft die Hypothese, dass sich die Operationsindikation während der vergangenen Jahre verändert hat. Material und Methoden Wir führten eine retrospektive Beobachtungsstudie der Patienten durch, die zwischen 1975 und 2016 (Einteilung in 4 Quartilen) in einem Ausbildungskranken haus einer Medizinischen Hochschule mit Schwerpunktversorgung eine Parotidektomie erhielten. Ergebnisse 405 Männer und 366 Frauen wurden wegen eines benignen (600/78 %) oder malignen (116/15 %) Tumors oder einer Parotitis (55/7 %) operiert. Der Anteil der benignen Tumore blieb weitgehend konstant (78 %), der der malignen Tumore stieg (7 %–23 %) bei gleichzeitigem Abfall der Parotitiden (17 % – < 1 %). Bei den benignen Tumoren fiel der Anteil der pleomorphen Adenome (60 % –24 %), während Warthin Tumore häufiger auftraten (23 % –58 %). Unter den malignen Tumoren stieg der Anteil der Metastasen von 2/13 auf 31/49 (insbes. Plattenepithelkarzinomen der Haut). Diskussion Die vorliegende Studie zeigt die sinkende Bedeutung der Parotitis als Indikation für eine Parotidektomie bedingt durch verbesserte nicht-chirurgische Verfahren. Die ansteigende Prävalenz von Warthin-Tumoren in der aktuellen Arbeit war mit einem steigenden Anteil der Raucher assoziiert. Der Anstieg der Malignome war auf die steigende Prävalenz von intraparotidealen Matastasen der Plattenepithelkarzinome der Haut zurückzuführen. Die Ergebnisse der histologischen Diagnosen basieren auf der Auswertung von Krankenakten und können bisher nicht durch die Auswertungen überregionaler Tumordatenbanken oder Krankenhausstatistiken (ICD- oder DRG-Bezug) generiert werden. Hierzu befürworten die Autoren die Einrichtung eines speziellen Speicheldrüsenregisters.
[...]

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Vorhersage von modalitätsspezifischen Arbeitsgedächtnisleistungen im Kindergartenalter

Laryngo-Rhino-Otol
DOI: 10.1055/a-0594-0244

Hintergrund Das Arbeitsgedächtnis (AG) als ein zentrales kognitives Konstrukt ist eine fundamentale Voraussetzung für Lernen und gilt als Marker für Entwicklungsstörungen. In den letzten Jahren hat es beachtliche Aufmerksamkeit in der Forschung gewonnen. Um Prädiktoren für phonologische und visuelle AG-Leistungen zu bestimmen, wurden hier multivariate Regressionsanalysen mittels generalisierter linearer Modelle gerechnet. Material und Methoden Das phonologische AG wurde durch das Nachsprechen von Nichtwörtern (SETK 3–5-Subtest PGN) und von Zahlenfolgen (K-ABC-Subtest), das visuell-räumliche durch die Imitation von Handbewegungen (K-ABC-Subtest) untersucht. Eine Intelligenzschätzung wurde durch das Ergebnis in der K-ABC-Skala „Ganzheitliches Denken" vorgenommen. Stichprobe: 169 Kindergartenkinder (49 % Jungen; 51 % Mädchen), überwiegend mit Migrationshintergrund und Deutsch als Zweitsprache, im mittleren Alter von 45,9 (SD 6,2; Min 36; Max 61) Monaten; zum Zeitpunkt der Untersuchung im Durchschnitt seit 9,9 (SD 6,9) Monaten im Kindergarten und durchschnittlich intelligent. Als Faktoren wurden Geschlecht und Migrationshintergrund festgelegt, als Kovariaten Lebensalter, Dauer des Kindergartenbesuchs bis zur Testung sowie ganzheitliches Denken in die Modelle aufgenommen. Ergebnisse Alle mittleren AG-Leistungen waren durchschnittlich. Nur das Alter zum Untersuchungszeitpunkt sowie das ganzheitliche Denken hatte einen signifikanten Einfluss auf die AG-Leistungen. Schlussfolgerung Im Alter von 36–61 Monaten lassen sich die beiden o. g. Arbeitsgedächtnissysteme als ein anlagebedingter, reifungsabhängiger und eher geschlechtsunspezifischer Mechanismus beschreiben.
[...]

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Impact of acute administration of sodium oxybate on heart rate variability in children with type 1 narcolepsy

Cardiovascular measurements in children affected with type 1 narcolepsy (NT1) have never been investigated, neither have their modulation by the administration of sodium oxybate (SO).

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Association between UCP polymorphisms and adipokines with obesity in Mexican adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Fatigue Related to Speech Processing in Children With Hearing Loss: Behavioral, Subjective, and Electrophysiological Measures

Purpose

The purpose of this study was to examine fatigue associated with sustained and effortful speech-processing in children with mild to moderately severe hearing loss.

Method

We used auditory P300 responses, subjective reports, and behavioral indices (response time, lapses of attention) to measure fatigue resulting from sustained speech-processing demands in 34 children with mild to moderately severe hearing loss (M = 10.03 years, SD = 1.93).

Results

Compared to baseline values, children with hearing loss showed increased lapses in attention, longer reaction times, reduced P300 amplitudes, and greater reports of fatigue following the completion of the demanding speech-processing tasks.

Conclusions

Similar to children with normal hearing, children with hearing loss demonstrate reductions in attentional processing of speech in noise following sustained speech-processing tasks—a finding consistent with the development of fatigue.

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Lexical and Grammatical Factors in Sentence Production in Semantic Dementia: Insights From Greek

Purpose

Language production in semantic dementia (SD) is characterized by a lexical–semantic deficit and largely preserved argument structure and inflection production. This study investigates (a) the effect of argument structure on verb retrieval and (b) the interrelation between inflection marking and verb retrieval in SD.

Method

Seven individuals with SD and 7 healthy controls performed 2 sentence elicitation tasks. In Experiment 1, participants described the action taking place in a video. In Experiment 2, they watched the same videos preceded by a phrase prompting the production of past tense. Three verb classes were tested: (a) unergative (e.g., to walk), (b) unaccusative (e.g., to fall), and (c) transitive with 1 object (e.g., to read a book).

Results

There was not any quantitative difference among the verb classes in Experiment 1, but error analysis hinted at difficulties related with argument structure complexity. The findings of Experiment 2 suggest no general effect of inflection on verb retrieval; nevertheless, inflection marking impeded the retrieval of verbs with complex argument structure. Large individual variation was established.

Conclusions

Argument structure complexity may challenge speakers with SD. Verb retrieval and inflection marking seem to interrelate at the expense of the former. Inflection production may be affected at severe stages of the disease.

Supplemental Material

https://doi.org/10.23641/asha.6030779

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Does the Visual Channel Improve the Perception of Consonants Produced by Speakers of French With Down Syndrome?

Purpose

This work evaluates whether seeing the speaker's face could improve the speech intelligibility of adults with Down syndrome (DS). This is not straightforward because DS induces a number of anatomical and motor anomalies affecting the orofacial zone.

Method

A speech-in-noise perception test was used to evaluate the intelligibility of 16 consonants (Cs) produced in a vowel–consonant–vowel context (Vo = /a/) by 4 speakers with DS and 4 control speakers. Forty-eight naïve participants were asked to identify the stimuli in 3 modalities: auditory (A), visual (V), and auditory–visual (AV). The probability of correct responses was analyzed, as well as AV gain, confusions, and transmitted information as a function of modality and phonetic features.

Results

The probability of correct response follows the trend AV > A > V, with smaller values for the DS than the control speakers in A and AV but not in V. This trend depended on the C: the V information particularly improved the transmission of place of articulation and to a lesser extent of manner, whereas voicing remained specifically altered in DS.

Conclusions

The results suggest that the V information is intact in the speech of people with DS and improves the perception of some phonetic features in Cs in a similar way as for control speakers. This result has implications for further studies, rehabilitation protocols, and specific training of caregivers.

Supplemental Material

https://doi.org/10.23641/asha.6002267

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Direct estimation of human trabecular bone stiffness using cone-beam computed tomography

Publication date: Available online 10 April 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Eva Klintström, Benjamin Klintström, Dieter Pahr, Torkel Brismar, Örjan Smedby, Rodrigo Moreno
ObjectivesThe aim of this study was to evaluate the possibility of estimating biomechanical properties of trabecular bone through finite element (FE) simulations using dental cone beam computed tomography (CBCT) data.Study designFourteen human radius specimens were scanned in three CBCT devices: 3D Accuitomo 80, NewTom 5G, and Verity. The imaging data was segmented using two different methods. Stiffness (Young's modulus), shear moduli, and the size and shape of the stiffness tensor were studied. Corresponding evaluations using micro-CT were regarded as the reference standard.ResultsThe 3D Accuitomo 80 showed good performance in estimating stiffness and shear moduli, but was sensitive to the choice of segmentation method. NewTom 5G and Verity yielded good correlations, but they were not as strong as the Accuitomo. The CBCT devices overestimated both stiffness and shear compared to the micro-CT estimations.ConclusionsFE-based calculations of biomechanics from CBCT data are feasible, with strong correlations for the Accuitomo 80 scanner combined with an appropriate segmentation method. Such measurements might be useful for predicting implant survival by in vivo estimations of bone properties.



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Does volumetric measurement of cervical lymph nodes serve as an imaging biomarker for locoregional recurrence of oral squamous cell carcinoma?

Publication date: Available online 10 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Ali-Farid Safi, Martin Kauke, Hendrik Jung, Marco Timmer, Jan Borggrefe, Thorsten Persigehl, Hans-Joachim Nickenig, Max Zinser, David Maintz, Matthias Kreppel, Joachim Zöller




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The effect of DLC-coating deposition method on the reliability and mechanical properties of abutment’s screws

Publication date: Available online 10 April 2018
Source:Dental Materials
Author(s): Dimorvan Bordin, Paulo G. Coelho, Edmara T.P. Bergamo, Estevam A. Bonfante, Lukasz Witek, Altair A. Del Bel Cury
ObjectiveTo characterize the mechanical properties of different coating methods of DLC (diamond-like carbon) onto dental implant abutment screws, and their effect on the probability of survival (reliability).MethodsSeventy-five abutment screws were allocated into three groups according to the coating method: control (no coating); UMS – DLC applied through unbalanced magnetron sputtering; RFPA-DLC applied through radio frequency plasma-activated (n=25/group). Twelve screws (n=4) were used to determine the hardness and Young's modulus (YM). A 3D finite element model composed of titanium substrate, DLC-layer and a counterpart were constructed. The deformation (μm) and shear stress (MPa) were calculated. The remaining screws of each group were torqued into external hexagon abutments and subjected to step-stress accelerated life-testing (SSALT) (n=21/group). The probability Weibull curves and reliability (probability survival) were calculated considering the mission of 100, 150 and 200N at 50,000 and 100,000 cycles.ResultsDLC-coated experimental groups evidenced higher hardness than control (p<0.05). In silico analysis depicted that the higher the surface Young's modulus, the higher the shear stress. Control and RFPA showed β<1, indicating that failures were attributed to materials strength; UMS showed β>1 indicating that fatigue contributed to failure. High reliability was depicted at a mission of 100N. At 200N a significant decrease in reliability was detected for all groups (ranging from 39% to 66%). No significant difference was observed among groups regardless of mission. Screw fracture was the chief failure mode.SignificanceDLC-coating have been used to improve titanium's mechanical properties and increase the reliability of dental implant-supported restorations.

Graphical abstract

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Thermo-setting glass ionomer cements promote variable biological responses of human dental pulp stem cells

Publication date: Available online 9 April 2018
Source:Dental Materials
Author(s): Mar Collado-González, Miguel R. Pecci-Lloret, Christopher J. Tomás-Catalá, David García-Bernal, Ricardo E. Oñate-Sánchez, Carmen Llena, Leopoldo Forner, Vinicius Rosa, Francisco J. Rodríguez-Lozano
ObjectiveTo evaluate the in vitro cytotoxicity of Equia Forte (GC, Tokyo, Japan) and Ionostar Molar (Voco, Cuxhaven, Germany) on human dental pulp stem cells (hDPSCs).MethodshDPSCs isolated from third molars were exposed to several dilutions of Equia Forte and Ionostar Molar eluates (1/1, 1/2 and 1/4). These eluates were obtained by storing material samples in respective cell culture medium for 24h (n=40). hDPSCs in basal growth culture medium were the control. Cell viability and cell migration assays were performed using the MTT and wound-healing assays, respectively. Also, induction of apoptosis and changes in cell phenotype were evaluated by flow cytometry. Changes in cell morphology were analysed by immunocytofluorescence staining. To evaluate cell attachment to the different materials, hDPSCs were directly seeded onto the material surfaces and analyzed by scanning electron microscopy (SEM). The chemical composition of the materials was determined by energy dispersive X-ray (EDX) and eluates were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Statistical analysis was performed with analysis of variance (ANOVA) and Student's t-test (α<0.05).ResultsUndiluted Equia Forte extracts led to a similar cell proliferation rates than the control group from 72h onwards. There were no significance differences between Equia Forte and Ionostar Molar in terms of cell apoptosis and phenotype. However, in presence of Equia extracts the migration capacity of hDPSCs was higher than in presence of Ionostar Molar (p<0.05). Also, SEM studies showed a higher degree of cell attachment when Equia Forte extracts were used. Finally, EDX analysis pointed to different weight percentages of C, O and Ca ions in glass ionomer cements, while other elements such as La, Al, Si, W, Mo and F were also detected.SignificanceIn summary, Equia Forte promoted better biological responses in hDPSCs than Ionostar Molar.



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Numerical fatigue analysis of premolars restored by CAD/CAM ceramic crowns

Publication date: Available online 10 April 2018
Source:Dental Materials
Author(s): Ehsan Homaei, Xiao-Zhuang Jin, Edmond Ho Nang Pow, Jukka Pekka Matinlinna, James Kit-Hon Tsoi, Khalil Farhangdoost
ObjectivesThe purpose of this study was to estimate the fatigue life of premolars restored with two dental ceramics, lithium disilicate (LD) and polymer infiltrated ceramic (PIC) using the numerical method and compare it with the published in vitro data.MethodsA premolar restored with full-coverage crown was digitized. The volumetric shape of tooth tissues and crowns were created in Mimics^®. They were transferred to IA-FEMesh for mesh generation and the model was analyzed with Abaqus. By combining the stress distribution results with fatigue stress–life (S–N) approach, the lifetime of restored premolars was predicted.ResultsThe predicted lifetime was 1,231,318 cycles for LD with fatigue load of 1400N, while the one for PIC was 475,063 cycles with the load of 870N. The peak value of maximum principal stress occurred at the contact area (LD: 172MPa and PIC: 96MPa) and central fossa (LD: 100MPa and PIC: 64MPa) for both ceramics which were the most seen failure areas in the experiment. In the adhesive layer, the maximum shear stress was observed at the shoulder area (LD: 53.6MPa and PIC: 29MPa).SignificanceThe fatigue life and failure modes of all-ceramic crown determined by the numerical method seem to correlate well with the previous experimental study.



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Does volumetric measurement of cervical lymph nodes serve as an imaging biomarker for locoregional recurrence of oral squamous cell carcinoma?

Publication date: Available online 10 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Ali-Farid Safi, Martin Kauke, Hendrik Jung, Marco Timmer, Jan Borggrefe, Thorsten Persigehl, Hans-Joachim Nickenig, Max Zinser, David Maintz, Matthias Kreppel, Joachim Zöller




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Adenoid cystic carcinoma of head and neck: A retrospective clinical analysis of a single institution

Adenoid cystic carcinoma (ACC), first described by Billroth in 1856, was originally called cylindroma because of its histologic appearance [1]. ACC is a rare tumor, accounting for about 1% of head and neck tumors, but it is the most common malignancy of the minor salivary glands [2]. Characteristically, ACC progresses slowly, with wide perineural invasion; lymphatic spread to the neck is rare. Histologically, adenoid cystic carcinomas also arise in other sites in the head and neck field, such as the major salivary glands, the tracheobronchial tree, the esophagus, the lacrimal gland, and even sites outside the head and neck.

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Cycle length identifies obstructive sleep apnea and central sleep apnea in heart failure with reduced ejection fraction

Abstract

Aim

To clarify whether unmasking of central sleep apnea during continuous positive airway pressure (CPAP) initiation can be identified from initial diagnostic polysomnography (PSG) in patients with heart failure with reduced ejection fraction (HFREF) and obstructive sleep apnea (OSA)

Materials and methods

Forty-three consecutive patients with obstructive sleep apnea and central sleep apnea (OSA/CSA) in HFREF were matched with 43 HFREF patients with OSA and successful CPAP initiation. Obstructive apneas during diagnostic PSG were then analyzed for cycle length (CL), ventilation length (VL), apnea length (AL), time to peak ventilation (TTPV), and circulatory delay (CD). We calculated duty ratio (DR) as the ratio of VL/CL and mathematic loop gain (LG).

Results

While AL was similar, CL, VL, TTPV, CD, and DR was significantly longer in patients with OSA/CSA compared to those with OSA, and LG was significantly higher. Receiver operator curves identified optimal cutoff values of 50.2 s for CL (area under the curve (AUC) 0.85, 29.2 s for VL (AUC 0.92), 11.5 s for TTPV (AUC 0.82), 26.4 s for CD (AUC 0.79), and 3.96 (AUC 0.78)) respectively for LG to identify OSA/CSA.

Conclusion

OSA/CSA in HFREF can be identified by longer CL, VL, TTPV, and CD from obstructive events in initial diagnostic PSG. The underlying mechanisms seem to be the presence of an increased LG.

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Cycle length identifies obstructive sleep apnea and central sleep apnea in heart failure with reduced ejection fraction

Abstract

Aim

To clarify whether unmasking of central sleep apnea during continuous positive airway pressure (CPAP) initiation can be identified from initial diagnostic polysomnography (PSG) in patients with heart failure with reduced ejection fraction (HFREF) and obstructive sleep apnea (OSA)

Materials and methods

Forty-three consecutive patients with obstructive sleep apnea and central sleep apnea (OSA/CSA) in HFREF were matched with 43 HFREF patients with OSA and successful CPAP initiation. Obstructive apneas during diagnostic PSG were then analyzed for cycle length (CL), ventilation length (VL), apnea length (AL), time to peak ventilation (TTPV), and circulatory delay (CD). We calculated duty ratio (DR) as the ratio of VL/CL and mathematic loop gain (LG).

Results

While AL was similar, CL, VL, TTPV, CD, and DR was significantly longer in patients with OSA/CSA compared to those with OSA, and LG was significantly higher. Receiver operator curves identified optimal cutoff values of 50.2 s for CL (area under the curve (AUC) 0.85, 29.2 s for VL (AUC 0.92), 11.5 s for TTPV (AUC 0.82), 26.4 s for CD (AUC 0.79), and 3.96 (AUC 0.78)) respectively for LG to identify OSA/CSA.

Conclusion

OSA/CSA in HFREF can be identified by longer CL, VL, TTPV, and CD from obstructive events in initial diagnostic PSG. The underlying mechanisms seem to be the presence of an increased LG.

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Covered versus uncovered self-conformable metal stent for palliation of primary malignant extrahepatic biliary strictures: a randomized multicenter study

Self-expandable metal stents (SEMSs) are used to relieve malignant biliary obstruction. We aimed to compare stent patency, adverse events rate and overall survival of covered (Niti-S Biliary ComVi) versus uncovered (Niti-s D type) self-conformable metal stents in patients with primary malignant extrahepatic biliary stricture, not eligible for surgery.

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Risk factors for postoperative delirium in patients undergoing free flap reconstruction for oral cancer

The aim of this study was to investigate risk factors for postoperative delirium in patients undergoing free flap reconstruction for defects after oral cancer resection. This was a non-randomized, retrospective cohort study involving 102 patients who underwent oral cancer resection and free flap reconstruction. Data were collected from the medical records. Postoperative delirium occurred in 34 patients (33.3%), of whom 27 were male and seven were female. High preoperative total protein and albumin, diabetes mellitus, history of smoking, use of hypnotics or antipsychotics, time until getting out of bed after surgery, and postoperative insomnia were significantly related to delirium in the univariate analysis (P<0.05).

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Identification of ‘Point A’ as the prevalent source of error in cephalometric analysis of lateral radiographs

Deviations in measuring dentofacial components in a lateral X-ray represent a major hurdle in the subsequent treatment of dysgnathic patients. In a retrospective study, we investigated the most prevalent source of error in the following commonly used cephalometric measurements: the angles Sella-Nasion-Point A (SNA), Sella-Nasion-Point B (SNB) and Point A-Nasion-Point B (ANB); the Wits appraisal; the anteroposterior dysplasia indicator (APDI); and the overbite depth indicator (ODI). Preoperative lateral radiographic images of patients with dentofacial deformities were collected and the landmarks digitally traced by three independent raters.

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Clinicopathological investigation of odontogenic fibroma in tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disease characterized by systemic hamartoma and diverse systemic features. TSC1 and TSC2 are the causative genes, and mental retardation, epileptic seizures, and facial angiofibroma develop in many patients with the disease. The case of a patient with TSC who developed a central odontogenic fibroma of the mandible is reported here. The patient was a 21-year-old woman who was referred with a swelling of the labial gingiva in the region of the right lower lateral incisor and canine.

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Palatal orthodontic miniscrew insertion using a CAD-CAM surgical guide: description of a technique

The aim of this report was to describe a new computer-guided technique for a controlled site preparation and palatal orthodontic miniscrew insertion using a dedicated software. A surgical guide was designed after planning the appropriate insertion sites on three-dimensional images created by the fusion of cone-beam computed tomography (CBCT) and digital dental model images. Pre- and postoperative CBCT images were compared and the angular, coronal, and apical deviations between the planned and the placed miniscrews were calculated.

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Assessing an oral surgery specific protocol for patients on direct oral anticoagulants: a retrospective controlled cohort study

Chronic therapy with the new direct oral anticoagulants (DOACs) poses new challenges for dental practitioners assessing the risk versus benefit of cessation versus non-cessation of anticoagulant therapy for dentoalveolar procedures. A retrospective controlled cohort study was designed to evaluate a non-cessation protocol for patients taking DOACs in the setting of dental extractions. A records review covering the period 1 January 2016 to 31 December 2016 identified 43 patients on DOAC therapy; 53 dentoalveolar procedures were performed under local anaesthesia, of which 15 included varying degrees of peri-procedural cessation.

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A prospective study examining the effects of treatment timing in the management of mandible fractures

The ideal timing for treatment of mandible fractures has not been well established. The objective of this study was to analyse the effects of treatment timing in the surgical management of mandible fractures. A prospective evaluation of 215 continuous patients with a total of 359 mandible fractures was undertaken. Nine outcome variables were analysed in relation to treatment delay by logistic regression modelling: wound dehiscence, hardware exposure, local postoperative infection, malocclusion, trismus, nerve damage, fracture non-union, return to theatre, and radiographic outcome.

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A prospective study examining the effects of treatment timing in the management of mandible fractures

Publication date: Available online 10 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): M.J.L. Hurrell, M.C. David, M.D. Batstone
The ideal timing for treatment of mandible fractures has not been well established. The objective of this study was to analyse the effects of treatment timing in the surgical management of mandible fractures. A prospective evaluation of 215 continuous patients with a total of 359 mandible fractures was undertaken. Nine outcome variables were analysed in relation to treatment delay by logistic regression modelling: wound dehiscence, hardware exposure, local postoperative infection, malocclusion, trismus, nerve damage, fracture non-union, return to theatre, and radiographic outcome. Nineteen additional variables were included in the analysis to adjust for potential confounding. Delay was measured in days and ranged from 0 to 41days, with a mean delay of 4.6days. The incidence of wound dehiscence, hardware exposure, local postoperative infection, trismus, nerve damage, fracture non-union and return to theatre was 6%, 4%, 11%, 8.5%, 47%, 2% and 8%, respectively. Objective malocclusion and poor radiographic outcomes were evident in 13% and 4.5% of cases, respectively.No statistically significant association was found between treatment delay and treatment outcomes.The findings of this study suggest it may be safe to delay the definitive treatment of mandible fractures. Treatment delay may allow for improved resource distribution and prioritization of more time-dependent interventions.



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Identification of ‘Point A’ as the prevalent source of error in cephalometric analysis of lateral radiographs

Publication date: Available online 10 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): P. Grogger, C. Sacher, S. Weber, G. Millesi, R. Seemann
Deviations in measuring dentofacial components in a lateral X-ray represent a major hurdle in the subsequent treatment of dysgnathic patients. In a retrospective study, we investigated the most prevalent source of error in the following commonly used cephalometric measurements: the angles Sella-Nasion-Point A (SNA), Sella-Nasion-Point B (SNB) and Point A-Nasion-Point B (ANB); the Wits appraisal; the anteroposterior dysplasia indicator (APDI); and the overbite depth indicator (ODI). Preoperative lateral radiographic images of patients with dentofacial deformities were collected and the landmarks digitally traced by three independent raters. Cephalometric analysis was automatically performed based on 1116 tracings. Error analysis identified the x-coordinate of Point A as the prevalent source of error in all investigated measurements, except SNB, in which it is not incorporated. In SNB, the y-coordinate of Nasion predominated error variance. SNB showed lowest inter-rater variation. In addition, our observations confirmed previous studies showing that landmark identification variance follows characteristic error envelopes in the highest number of tracings analysed up to now. Variance orthogonal to defining planes was of relevance, while variance parallel to planes was not. Taking these findings into account, orthognathic surgeons as well as orthodontists would be able to perform cephalometry more accurately and accomplish better therapeutic results.



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Risk factors for postoperative delirium in patients undergoing free flap reconstruction for oral cancer

Publication date: Available online 10 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): T. Makiguchi, S. Yokoo, J. Kurihara
The aim of this study was to investigate risk factors for postoperative delirium in patients undergoing free flap reconstruction for defects after oral cancer resection. This was a non-randomized, retrospective cohort study involving 102 patients who underwent oral cancer resection and free flap reconstruction. Data were collected from the medical records. Postoperative delirium occurred in 34 patients (33.3%), of whom 27 were male and seven were female. High preoperative total protein and albumin, diabetes mellitus, history of smoking, use of hypnotics or antipsychotics, time until getting out of bed after surgery, and postoperative insomnia were significantly related to delirium in the univariate analysis (P<0.05). In a multiple logistic regression model, high preoperative albumin (odds ratio 4.45), postoperative insomnia (odds ratio 10.72), and history of smoking (odds ratio 2.91) were significant risk factors for delirium (P<0.05). The analysis of laboratory data before and after surgery showed greater decreases in albumin, total protein, and haemoglobin after surgery in patients with postoperative delirium than in those without this condition. These results show that the perioperative maintenance of nutritional status and early postoperative management of the sleep cycle are important to prevent delirium after oral cancer resection and free flap reconstruction.



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Assessing an oral surgery specific protocol for patients on direct oral anticoagulants: a retrospective controlled cohort study

Publication date: Available online 10 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): E. Lababidi, O. Breik, J. Savage, H. Engelbrecht, R. Kumar, C.W. Crossley
Chronic therapy with the new direct oral anticoagulants (DOACs) poses new challenges for dental practitioners assessing the risk versus benefit of cessation versus non-cessation of anticoagulant therapy for dentoalveolar procedures. A retrospective controlled cohort study was designed to evaluate a non-cessation protocol for patients taking DOACs in the setting of dental extractions. A records review covering the period 1 January 2016 to 31 December 2016 identified 43 patients on DOAC therapy; 53 dentoalveolar procedures were performed under local anaesthesia, of which 15 included varying degrees of peri-procedural cessation. A control group of 50 patients on uninterrupted warfarin therapy undergoing 59 dentoalveolar procedures was identified. The incidence, severity, and timing of bleeding events were recorded for each group. Four (10.5%) minor bleeding events were recorded in the non-cessation DOAC group and nine (15.3%) minor bleeding events in the warfarin group. No bleeding events were recorded in the DOAC cessation group. Comparison of the incidence of bleeding events between the non-cessation DOAC group and the warfarin group showed no statistically significant difference (odds ratio 0.65, P=0.56). Within the limitations of this study, dental extractions in the context of continuing DOAC therapy can be performed safely provided extra local haemostatic measures are applied.



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Thyroid FNA biopsies comprised of abundant, mature squamous cells can be reported as benign: A cytologic study of 18 patients with clinical correlation

Cancer Cytopathology, EarlyView.


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Chromosome 1q23.3q31.1 deletion associated with decreased newborn screening of T cell receptor rearrangement circles (TRECs)

We report a female newborn with abnormal newborn screening (NBS) for severe combined immunodeficiency (SCID)/T cell lymphopenia and chromosome 1q23.3q31.1 deletion. The infant was born at 36-weeks gestation with a birthweight of 1160 grams. At 20-weeks gestation, intrauterine growth retardation, bilateral cleft-lip and cleft-palate, absent kidney, absent stomach bubble, and lateral ventriculomegaly were identified. At birth, she had microcephaly, hypertelorism, bilateral low-set ears with over-folded helices, bilateral complete cleft-lip and cleft-palate, holosystolic murmur and a split second heart sound with a loud P2, sacral dimple, small hands with brachydactyly, left hand with single transverse palmar crease, clinodactyly of 5th fingers bilaterally, small feet bilaterally, and overlapping 2nd and 3rd toe on the right foot.

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Mepolizumab use: post-approval academic practice experience

Severe asthma of the eosinophilic subtype is associated with significant morbidity and mortality and health-care costs due to recurrent asthma exacerbations and need for treatment with oral corticosteroids 1,2. Thus, steroid-sparing medications for eosinophilic asthma have been sought to improve outcomes in these patients.

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Oral corticosteroids should be available on-hand at home for the next asthma exacerbation!

Asthma is characterized in many patients by recurrent exacerbations. For those patients, it is not generally a question of whether an exacerbation will recur. Rather the question is when will the next exacerbation occur? Unfortunately, that is not readily predictable. Patients with sthma exacerbation fill emergency rooms and are a major cause of hospitalization. Children with asthma, particularly, are prone to recurrent exacerbations, and asthma is the most frequent medical indication for children to be hospitalized.

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Factors correlated with repeated aspirin dosing during aspirin desensitization

Aspirin desensitization is an appropriate procedure for many patients with aspirin-exacerbated respiratory disease (AERD). Patients can require aspirin re-dosing, which prolongs the desensitization process. The frequency of this is not widely reported, nor is it known which patients will require multiple re-dosing.

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The pediatric asthma yardstick: practical recommendations for a sustained step-up in asthma therapy for children with inadequately controlled asthma

Current asthma guidelines recommend a control-based approach to management involving assessment of impairment and risk followed by implementation of treatment strategies individualized according to the patient's needs and preferences. However, for children with asthma, achieving control can be elusive. While tools are available to help children (and families) track and manage day-to-day symptoms, when and how to implement a longer-term step-up in care is less clear. Furthermore, treatment is challenged by the three age groups of childhood – adolescence (12-18 years old), school age (6-11 years old), and young children (≤ 5 years old), and what works for one age group may not be the best approach for another.

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Probing the brain with molecular fMRI

Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
Author(s): Souparno Ghosh, Peter Harvey, Jacob C Simon, Alan Jasanoff
One of the greatest challenges of modern neuroscience is to incorporate our growing knowledge of molecular and cellular-scale physiology into integrated, organismic-scale models of brain function in behavior and cognition. Molecular-level functional magnetic resonance imaging (molecular fMRI) is a new technology that can help bridge these scales by mapping defined microscopic phenomena over large, optically inaccessible regions of the living brain. In this review, we explain how MRI-detectable imaging probes can be used to sensitize noninvasive imaging to mechanistically significant components of neural processing. We discuss how a combination of innovative probe design, advanced imaging methods, and strategies for brain delivery can make molecular fMRI an increasingly successful approach for spatiotemporally resolved studies of diverse neural phenomena, perhaps eventually in people.



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Collaborating with Adolescents and Young Adults with Cancer as Advisors

Journal of Adolescent and Young Adult Oncology, Ahead of Print.


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Sleep Quality, Fatigue, and Quality of Life Among Teenage and Young Adult Cancer Survivors

Journal of Adolescent and Young Adult Oncology, Ahead of Print.


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Germ Cell Tumor Ovary: an Institutional Experience of Treatment and Survival Outcomes

Abstract

Malignant germ cell tumors (GCT) of the ovary account for 2–3% of all ovarian neoplasms and occur mostly in the second and third decade of life. Over the past three decades, survival rates for germ cell tumors have dramatically improved, coincident with more aggressive surgical staging and combination chemotherapy. Although there are several studies describing ovarian GCT and fertility-preserving surgery in the western population, there is very little Indian data. We present our experience of germ cell tumor ovary in the Department of Surgical Oncology, King George's Medical University over the last 5 years with special emphasis on treatment outcome and role of fertility preservation surgery. A retrospective review of medical records of patients with ovarian germ cell tumors, treated at our center from January 2012 to December 2016, was performed. Epidemiological and clinical profile of patients was reviewed. Clinical stage of presentation, neoadjuvant treatment, surgical treatment, and adjuvant treatment data were analyzed, and treatment outcome data was recorded. Patient follow-up was done to ascertain disease-free interval, treatment outcome, ability to conceive following fertility-preserving surgery, and quality of life. A total of 39 patients with ovarian germ cell tumor were treated during this period. Their median age at diagnosis was 22 years (range 11–65 years) and most common mode of presentation was abdominal lump without ascites. Around 36.8% (n = 14) patients had conservative surgery with preservation of opposite ovary and uterus. Most patients (71.1% n = 27) received neoadjuvant chemotherapy due to advanced disease in form of ascites or large mass, and five of these patients were amenable to fertility-preserving surgery after chemotherapy. Nine out of the fourteen patients have had return of menstrual function after a mean period of 3.5 + 0.5 months. One patient who underwent fertility-preserving surgery has delivered healthy children after treatment. Stage distribution for stage I to IV was as follows: 15.4% (n = 6), 35.9% (n = 14), 46.2% (n = 18), and 2.6% (n = 1), respectively. Dysgerminoma was the commonest histology (37.1% n = 13) followed by teratoma (22.9% n = 8). 17.1% (n = 6) patients had recurrence, with a median time to recurrence 16 months (range 5.5 to 37 months) and they were treated with second-line chemotherapy. Germ cell tumor of the ovary is an eminently treatable disease and selected patients can be managed with fertility-preserving surgery. BEP is the most effective chemotherapy regimen. Disease-free survival rates in these patients are quite high and recurrences can be managed with second-line chemotherapy.

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Promising drug may deter hearing loss, study finds

A new drug has the potential to revolutionize the prevention and treatment of hearing loss resulting from noise, drug toxicity, and possibly aging, researchers at St. Jude Children's Research Hospital claims. The researchers discovered inhibitors of enzyme Cyclin-dependent kinase 2 (CDK2) that may protect people from developing hearing loss, including hearing impairment in the elderly population.

The study's lead author Jian Zuo, PhD told The Hearing Journal, "We have reported a genomic study that identified a predisposition to cisplatin-induced hearing loss (CIHL) among pediatric brain tumor patients (Xu et al., Nature Genetics 2015). While predicting which patients will develop CIHL is important, it is more imperative to develop drugs to prevent CIHL. There are no FDA-approved drugs for hearing loss. It is these thoughts that inspired us to screen for drugs against CIHL."

The researchers developed an approach to mimic mammalian cochlear cell death caused by antibiotics, noise, aging, and cisplatin to discover otoprotectants. Cisplatin is a chemotherapy agent, a treatment for an array of cancers, reported to cause permanent hearing loss in patients.

Examining a bioactive library of more than 4,000 unique compounds of an immortalized cell from a cochlear cell line of a neonatal mouse, study authors found ten compounds with protective effects against cisplatin ototoxicity. Among the top-hit compounds was kenpaullone, an inhibitor of CDK2 and other kinases, which are found in zebrafish, adult mice, and rats. Kenpaullone was found to deter cisplatin- and noise-induced damage.

"Our compounds are protective [not only] against CIHL but also noise-induced hearing loss (NIHL). It is also likely that it protects against age-related hearing loss (ARHL)," Zuo explained. "Both NIHL and ARHL affect a large fraction of the society. Based on our results in an identical assay, our compound exhibits better protection against cisplatin-induced cell loss than four benchmark compounds currently in clinical trials. Therefore we believe that our compound will eventually fare well in future clinical trials."

When asked if the CDK2 inhibitors can help patients with inborn hearing loss, Zuo explained, "Our compounds will protect HL but have not been shown to restore hearing among patients with congenital deafness."

The researchers have filed a patent on the methods and the compositions of the CDK2 inhibitors that are discovered to prevent cisplatin- and noise-induced hearing loss.

Published: 4/10/2018 1:27:00 PM

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Genomics and pharmacogenomics of Pediatric Acute Lymphoblastic Leukemia

Publication date: Available online 10 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Chuan Wu, Wei Li
Acute lymphoblastic leukaemia (ALL) is a prevalent form of pediatric cancer that accounts for 70-80% of all leukemias. Genome-based analysis, exome sequencing, transcriptomics and proteomics have provided insight into genetic classification of ALL and helped identify novel subtypes of the disease. B and T cell-based ALL are two well-characterized genomic subtypes, significantly marked by bone marrow disorders, along with mutations in trisomy 21 and T53. The other ALLs include Early T-cell precursor ALL, Philadelphia chromosome-like ALL, Down syndrome-associated ALL and Relapsed ALL. Chromosomal number forms a basis of classification, such as, hypodiploid ALL, near-haploid, low-hypodiploid, high-hypodiploid and hypodiploid-ALL. Advances in therapies targeting ALL have been noteworthy, with significant pre-clinical and clinical studies on drug pharmacokinetics and pharmacodynamics. Methotrexate and 6-mercaptopurine are leading drugs with best demonstrated efficacies against childhood ALL. The drugs in combination, following dose titration, have also been used for maintenance therapy. Methotrexate-polyglutamate is a key metabolite that specifically targets the disease pathogenesis, and 6-thioguanine nucleotides, derived from 6-mercaptopurine, impede replication and transcription processes, inducing cytotoxicity. Additionally, glucocorticoids, asparaginase, anthracycline, vincristine and cytarabine that trans-repress gene expression, deprives cells of asparagine, triggers cell cycle arrest, influences cytochrome-P450 polymorphism and inhibits DNA polymerase, respectively, have been used in chemotherapy in ALL patients. Overall, this review covers the progress in genome technology related to different sub-types of ALL and pharmacokinetics and pharmacodynamics of its medications. It also enlightens adverse effects of current drugs, and emphasizes the necessity of genome-wide association studies for restricting childhood ALL.



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Organization, Quality and Cost of Oncological Home-Hospitalization: A Systematic Review

Publication date: Available online 10 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Lieselot Cool, Dominique Vandijck, Philip Debruyne, Melissa Desmedt, Tessa Lefebvre, Michelle Lycke, Pieter Jan De Jonghe, Hans Pottel, Veerle Foulon, Koen Van Eygen
BackgroundHome-hospitalization might be a patient-centred approach facing the increasing burden of cancer on societies. This systematic review assessed how oncological home-hospitalization has been organized and to what extend its quality and costs were evaluated.ResultsTwenty-four papers describing parenteral cancer drug administration to adult patients in their homes were included. Most papers concluded oncological home-hospitalization had no significant effect on patient-reported quality of life (7/8=88%), but large majority of patients were satisfied (12/13, 92%) and preferred home treatment (7/8, 88%). No safety risks were associated with home-hospitalization (10/10, 100%). The cost of home-hospitalization was found beneficial in five trials (5/9, 56%); others reported no financial impact (2/9, 22%) or additional costs (2/9, 22%).ConclusionDespite heterogeneity, majority of reported models for oncological home-hospitalisation demonstrated that this is a safe, equivalent and acceptable alternative to ambulatory hospital care. More well-designed trials are needed to evaluate its economic impact.



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Relations entre le caractère obstructif des amygdales palatines, le type de ventilation et la posture labiale.

Related Articles

Relations entre le caractère obstructif des amygdales palatines, le type de ventilation et la posture labiale.

Int Orthod. 2018 Apr 05;:

Authors: Diouf JS, Diallo BK, Diop-Ba K, Badiane A, Ngom PI, Sonko O, Diagne F

PMID: 29628430 [PubMed - as supplied by publisher]

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Integration of Motor Learning Principles Into Real-Time Ambulatory Voice Biofeedback and Example Implementation Via a Clinical Case Study With Vocal Fold Nodules.

Related Articles

Integration of Motor Learning Principles Into Real-Time Ambulatory Voice Biofeedback and Example Implementation Via a Clinical Case Study With Vocal Fold Nodules.

Am J Speech Lang Pathol. 2017 Feb 01;26(1):1-10

Authors: Van Stan JH, Mehta DD, Petit RJ, Sternad D, Muise J, Burns JA, Hillman RE

Abstract
Purpose: Ambulatory voice biofeedback (AVB) has the potential to significantly improve voice therapy effectiveness by targeting one of the most challenging aspects of rehabilitation: carryover of desired behaviors outside of the therapy session. Although initial evidence indicates that AVB can alter vocal behavior in daily life, retention of the new behavior after biofeedback has not been demonstrated. Motor learning studies repeatedly have shown retention-related benefits when reducing feedback frequency or providing summary statistics. Therefore, novel AVB settings that are based on these concepts are developed and implemented.
Method: The underlying theoretical framework and resultant implementation of innovative AVB settings on a smartphone-based voice monitor are described. A clinical case study demonstrates the functionality of the new relative frequency feedback capabilities.
Results: With new technical capabilities, 2 aspects of feedback are directly modifiable for AVB: relative frequency and summary feedback. Although reduced-frequency AVB was associated with improved carryover of a therapeutic vocal behavior (i.e., reduced vocal intensity) in a patient post-excision of vocal fold nodules, causation cannot be assumed.
Conclusions: Timing and frequency of AVB schedules can be manipulated to empirically assess generalization of motor learning principles to vocal behavior modification and test the clinical effectiveness of AVB with various feedback schedules.

PMID: 28124070 [PubMed - indexed for MEDLINE]

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Biomarqueurs inflammatoires et immunologiques de réponse à la radiothérapie

Publication date: Available online 10 April 2018
Source:Cancer/Radiothérapie
Author(s): J.P. Nesseler, D. Schaue, W.H. McBride, P. Nickers




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The impact of auditory white noise on semantic priming

Publication date: May–July 2018
Source:Brain and Language, Volumes 180–182
Author(s): Anthony J. Angwin, Wayne J. Wilson, David A. Copland, Robert J. Barry, Grace Myatt, Wendy L. Arnott
It has been proposed that white noise can improve cognitive performance for some individuals, particularly those with lower attention, and that this effect may be mediated by dopaminergic circuitry. Given existing evidence that semantic priming is modulated by dopamine, this study investigated whether white noise can facilitate semantic priming. Seventy-eight adults completed an auditory semantic priming task with and without white noise, at either a short or long inter-stimulus interval (ISI). Measures of both direct and indirect semantic priming were examined. Analysis of the results revealed significant direct and indirect priming effects at each ISI in noise and silence, however noise significantly reduced the magnitude of indirect priming. Analyses of subgroups with higher versus lower attention revealed a reduction to indirect priming in noise relative to silence for participants with lower executive and orienting attention. These findings suggest that white noise focuses automatic spreading activation, which may be driven by modulation of dopaminergic circuitry.



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Stacked generalization: an introduction to super learning

Abstract

Stacked generalization is an ensemble method that allows researchers to combine several different prediction algorithms into one. Since its introduction in the early 1990s, the method has evolved several times into a host of methods among which is the "Super Learner". Super Learner uses V-fold cross-validation to build the optimal weighted combination of predictions from a library of candidate algorithms. Optimality is defined by a user-specified objective function, such as minimizing mean squared error or maximizing the area under the receiver operating characteristic curve. Although relatively simple in nature, use of Super Learner by epidemiologists has been hampered by limitations in understanding conceptual and technical details. We work step-by-step through two examples to illustrate concepts and address common concerns.

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Mepolizumab use: post-approval academic practice experience

Publication date: Available online 10 April 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Mariel R. Benjamin, Bruce S. Bochner, Anju T. Peters




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Oral corticosteroids should be available on-hand at home for the next asthma exacerbation!

Publication date: Available online 10 April 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Miles Weinberger, Leslie Hendeles, Mutasim Abu-Hasan




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Factors correlated with repeated aspirin dosing during aspirin desensitization

Publication date: Available online 10 April 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Charles F. Schuler, James L. Baldwin, Alan P. Baptist
BackgroundAspirin desensitization is an appropriate procedure for many patients with aspirin-exacerbated respiratory disease (AERD). Patients can require aspirin re-dosing, which prolongs the desensitization process. The frequency of this is not widely reported, nor is it known which patients will require multiple re-dosing.ObjectiveTo determine the frequency of and factors associated with repeat aspirin re-dosing during desensitization.MethodsCharts of aspirin desensitization procedures from 2011-2016 at the University of Michigan Allergy/Immunology Clinic were reviewed. Reactions with provoking doses and number of dose repetitions were characterized. Prior AERD history, medical history, medications, and baseline spirometry were also recorded. Bivariate correlation and multivariate logistic regression were used to analyze associations between patient characteristics and need for repeated dosing of aspirin.ResultsA total of 84 positive reacting patients during desensitization were found. 33% of these patients required two or more aspirin dose repetitions during desensitization. Requiring two or more repeat doses during desensitization was associated with male gender (odds ratio = 6.194, p = 0.008), FEV1 decrease during desensitization (odds ratio = 1.075 per percent point drop, p = 0.021), and initial aspirin provoking dose during desensitization of 81 mg or lower (odds ratio = 11.111, p = 0.003). No association was found with pre-desensitization medications, asthma severity, AERD duration, or number/character of reported prior aspirin reactions.ConclusionDuring aspirin desensitization for AERD, approximately 1/3 of our patients require multiple repeat doses. Risk factors for multiple repeated doses include male gender, drop in FEV1, and lower aspirin provoking doses during desensitization. This information can help inform which patients might require multiple re-dosing for desensitization.



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The pediatric asthma yardstick: practical recommendations for a sustained step-up in asthma therapy for children with inadequately controlled asthma

Publication date: Available online 10 April 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Bradley E. Chipps, Leonard B. Bacharier, Judith R. Farrar, Daniel J. Jackson, Kevin R. Murphy, Wanda Phipatanakul, Stanley J. Szefler, W. Gerald Teague, Robert S. Zeiger
Current asthma guidelines recommend a control-based approach to management involving assessment of impairment and risk followed by implementation of treatment strategies individualized according to the patient's needs and preferences. However, for children with asthma, achieving control can be elusive. While tools are available to help children (and families) track and manage day-to-day symptoms, when and how to implement a longer-term step-up in care is less clear. Furthermore, treatment is challenged by the three age groups of childhood – adolescence (12-18 years old), school age (6-11 years old), and young children (≤ 5 years old), and what works for one age group may not be the best approach for another. The Pediatric Asthma Yardstick provides an in-depth assessment of when and how to step-up therapy for the child with not well or poorly controlled asthma. Development of this tool follows the others in the Yardstick series, presenting patient profiles and step-up strategies based on current guidance documents, but modified according to newer data and the authors' combined clinical experience. The objective is to provide clinicians who treat children with asthma practical and clinically relevant recommendations for each step-up and each intervention, with the intent of helping practitioners better treat their pediatric patients with asthma, particularly those who do not always respond to recommended therapies.



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