Αρχειοθήκη ιστολογίου

Δευτέρα 21 Αυγούστου 2017

Issue Information - Masthead



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Annals of Neurology: Volume 82, Number 2, August 2017

ON THE COVER: A section through the brain of a patient with type-2 diabetes showing vascular deposition of amylin (brown) and astroglial reaction (green stain for glial fibrillary acidic protein). See Ly et al, pages 208–222, in this issue for details.



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A Single-Center Review of Palatal Fractures

Gain a better understanding of the presentation, concomitant injuries, and management of palatal fractures with data from a single center's experience.
ePlasty, Open Access Journal of Plastic Surgery

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The clinical impact of bedside fiberoptic laryngoscopic recording on a tertiary consult service

Objectives/Hypothesis

Fiberoptic laryngoscopy is dependent on accurate descriptions of examination findings. Traditional recording methods can be impractical for inpatient consults. Therefore, we aim to determine the utility of a smartphone-coupled portable recording system with flexible laryngoscopy for transmitting information between resident and attending physicians in a real-time setting.

Study Design

Pilot prospective study in a tertiary academic hospital.

Methods

This is a prospective study of inpatient consultations in a tertiary referral hospital over a 3-month period from April 2015 to June 2015. Flexible laryngoscopy was performed by a resident physician, and mobile recordings were relayed to an attending physician. Concordance of laryngoscopy interpretations between resident and attending physicians as well as changes in management were documented.

Results

Seventy-nine fiberoptic examinations were recorded and compared. Each consult was categorized as follows: airway evaluation (AE) (43%, 34/79), voice evaluation (VE) (3.7%, 3/79), dysphagia (D) (24%, 19/79), and aerodigestive tract mass/pathology (ADM) (29.1%, 23/79). Nine examinations showed discordance between resident and attending interpretations. Inter-rater agreement was good, with a kappa value of 0.747 (95% confidence interval: 0.643-0.851). The frequency of discordant exams within each group was as follows: AE (15%, 5/34), VE (33%, 1/3), D (11%, 2/19), and ADM (4.3%, 1/23). In five patients, changes in laryngoscopy interpretation changed clinical management. Seven nondiscordant exams had a change in management after attending review. Of the 79 exams, only one required repeat flexible laryngoscopy by the attending physician.

Conclusions

Portable recording of flexible laryngoscopy is an effective tool for timely management of inpatient consultations.

Level of Evidence

4. Laryngoscope, 2017



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Semicircular canal dehiscence among idiopathic intracranial hypertension patients

Objectives/Hypothesis

The cause of superior semicircular canal dehiscence (SSCD) is unknown. Because of a demonstrated association with tegmental defects and obesity, some have suggested idiopathic intracranial hypertension (IIH) could contribute by eroding the bone over the canal and resulting in SSCD. However, an association between IIH and SSCD has not previously been evaluated. Our objective was to evaluate an association between IIH and SSCD.

Study Design

Retrospective cohort.

Methods

A retrospective study was performed of opening pressures for consecutive patients presenting at a lumbar puncture clinic between August 2012 and October 2015. Imaging for patients who also had thin-sectioned computed tomography (CT) imaging was reviewed for the presence of radiographic SSCD. Association between IIH and SSCD was evaluated using the Student t test and multivariate logistic regression.

Results

One hundred twenty-one patients had both a lumbar puncture performed and thin-sectioned CT imaging available, of which 24 patients (19.8%) met the criteria for IIH with an opening pressure >25 cm H2O. The remaining 97 patients (80.2%) did not have elevated opening pressures and served as the control cohort. None of the 24 patients with IIH had radiographic SSCD, whereas eight of the 97 patients (8.2%) without IIH had radiographic SSCD. The average opening pressure in patients without radiographic SSCD was 20.2 cm H2O compared to 19.3 cm H2O in patients with radiographic SSCD (P = .521). In multivariate logistic regression controlling for age, body mass index, gender, and comorbidities (hypertension, diabetes, hyperlipidemia), opening pressure was not a significant predictor of radiographic SSCD.

Conclusions

The results of this retrospective pilot study do not suggest an association between IIH and SSCD.

Level of Evidence

3b Laryngoscope, 2017



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In response to “in reference to is esophagoscopy necessary during panendoscopy?”



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Sonographic differentiation between lymphatic and metastatic diseases in cervical lymphadenopathy

Objectives/Hypothesis

The spectrum of differential diagnosis in cervical lymphadenopathy is extremely broad. In lymphoma and inflammatory diseases, surgical approaches are restricted to diagnostic lymph extirpation, whereas metastatic outgrowth into regional lymph nodes usually requires neck dissection. Lymph node surgery has to manage the balancing act between sufficient radicality and preservation of functional structures. The current study, therefore, aimed to identify parameters to differentiate between lymph nodes of lymphatic and metastatic origin.

Study Design

Single-center, retrospective cohort study.

Methods

Clinical and sonographic parameters from all patients who underwent diagnostic cervical lymphadenectomy from 2010 to 2015 (N = 262) were included in this retrospective analysis. Parameters with significant differences between the two subgroups were utilized to create a clinical algorithm to distinguish between cervical lymphadenopathy of lymphatic and metastatic genesis.

Results

Statistically significant differences between the two subgroups could be shown for clinical (gender, age, nicotine/alcohol abuse, B symptoms, history of cutaneous melanoma, or lymphoma) and ultrasonographic parameters (string-of-beads confirmation, bilaterality, homogenous echostructure, localization in level I, long-to-short axis ratio, and hilar vascularity). The proposed algorithm yielded a sensitivity of 92.4% for metastatic disease.

Conclusions

The implemented algorithm based on ultrasonographic and clinical criteria contributes to one-step surgical approaches that guarantee a sufficient radicality with a minimum of functional loss.

Level of Evidence

4. Laryngoscope, 2017



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Intraosseous mucoepidermoid carcinoma: Outcome review

Objective

Identify the effect of patient characteristics, disease traits, and treatment modality on patient outcomes in the rare disease process of intraosseous mucoepidermoid carcinoma.

Study Design

Retrospective review of institutional case records and literature.

Methods

This study includes one case report, a literature review of the MEDLINE database from 1950 through June 2017 using keywords "intraosseous" and "mucoepidermoid," and a query of the University of California, Los Angeles, Department of Pathology database for all documented cases of intraosseous mucoepidermoid carcinoma of the head and neck.

Results

Indicators of poorer prognosis were male gender (P = 0.0071) and higher histological grade (P = 0.0095). Lesion site, size, association with odontogenic cyst, and treatment type did not have a statistically significant correlation with patient outcomes. There also was no statistically significant correlation observed between treatment modality and recurrent or progressive disease when stratified by histological grade of the cancer.

Conclusion

This study identified male gender and high histological tumor grade as poor prognostic indicators; however, it did not reveal a statistically significant relationship between treatment modality and patient outcomes. Data regarding patient outcomes following treatment was limited due to loss to follow-up, suggesting that further investigation is required. Based on this review, decisions regarding treatment should be clinically guided and individually tailored to the patient's baseline health, disease severity, and the patient's treatment goals. A multi-disciplinary conference, as was utilized in the presented case report, may be the best approach to treatment planning for these patients at this time.

Level of Evidence

4. Laryngoscope, 2017



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Gastrostomy in the era of minimally invasive head and neck cancer surgery

Objective

Minimally invasive transoral robotic surgery (TORS) is less likely to necessitate gastrostomy tube (GT) following resection of head and neck lesions versus conventional open procedures. However, the incidence of and indications for GT after TORS have not been reported in detail. This study defines the incidence of intra- and postoperative gastrostomy following robotic resection of advanced head and neck disease. It seeks to clarify the relevance of GT after TORS.

Study Design

Adult patients undergoing TORS and neck dissection from 2008 to 2014 were identified in the New York Statewide Planning and Research Cooperative System all-payer administrative database.

Methods

Demographic data and timing of GT in relation to surgery were recorded. Emergency department (ED) visits and inpatient readmissions were compared with multivariable logistic analysis.

Results

Of the 441 included patients, immediate, delayed, and total GT incidence within the first postoperative year was 9.5%, 11.6%, and 21.1%, respectively. Gastrostomy tube complications resulted in 4.5% of 30-day ED visits, 3.3% of 30-day readmissions, and 3.5% of 90-day readmissions. Thirty-nine percent of 90-day readmissions were linked to poor postoperative oral intake. Delayed GT status was associated with an increase in 30-day ED visits, and 30- or 90-day readmissions attributable to poor oral intake (P = 0.10, P < 0.0001, 0.002, respectively).

Conclusion

Even in the era of minimally invasive TORS, impaired oral intake is a significant postoperative burden to head and neck cancer patients with advanced disease. Attention to patient risk factors combined with a complicated hospital course may identify patients benefiting from early GT.

Level of Evidence

2c. Laryngoscope, 2017



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A case-control evaluation of fungiform papillae density in burning mouth syndrome

Hypothesis

It has been hypothesized that high fungiform papillae density may be a risk factor for developing the taste and pain alterations characteristic of burning mouth syndrome.

Objective

Evaluate whether fungiform papillae density, taste sensitivity, and mechanical pain sensitivity differ between burning mouth syndrome cases and controls.

Study Design

This case-control study compared cases diagnosed with primary burning mouth syndrome with pain-free controls.

Methods

Participants (17 female cases and 23 female controls) rated the intensity of sucrose, sodium chloride, citric acid, and quinine applied separately to each side of the anterior tongue and sampled whole mouth. Mechanical pain sensitivity was assessed separately for each side of the tongue using weighted pins. Digital photographs of participants' tongues were used to count fungiform papillae.

Results

Burning mouth syndrome cases had increased whole mouth taste intensity. Cases also had increased sensitivity to quinine on the anterior tongue, as well as increased mechanical pain sensitivity on the anterior tongue. Fungiform papillae density did not differ significantly between cases and controls. Fungiform papillae density on the left and right sides of the tongue were correlated in controls; however, there was no left/right side correlation in cases.

Conclusion

Cases had increased pain and taste perception on the anterior tongue. The lack of correlation between left and right fungiform papillae density in cases may be an indication of asymmetrical lingual innervation in these patients.

Level of Evidence

3b. Laryngoscope, 2017



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The effect of inferior turbinate surgery on ear symptoms

Objective

The aim of this placebo-controlled study was to evaluate the effect of various inferior turbinate surgery techniques on Eustachian tube dysfunction-related symptoms.

Study Design

Outcomes were evaluated using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and tympanometry results.

Methods

A total of 72 consecutively blinded and randomized adult patients with enlarged inferior turbinates due to persistent year-round rhinitis underwent either a radiofrequency ablation, diode laser, microdebrider-assisted inferior turbinoplasty, or sham surgery procedure. Assessments were conducted prior to surgery and 3 months subsequent to the surgery.

Results

In the evaluation of all patients, radiofrequency ablation, microdebrider-assisted inferior turbinoplasty, and sham surgery procedures decreased the ETDQ-7 total score significantly. In a three-way analysis of covariance, there were no significant differences in the results between sham surgery and any of the active treatment procedures. Allergic sensitization, sex, and age also had no effect on the results. There were no significant changes in the pre- and postoperative amounts of abnormal tympanometry curves or in the pre- and postoperative tympanometric peak pressure values in the actively treated patients or in the sham surgery group.

Conclusion

The improvement of Eustachian tube dysfunction-related symptoms due to surgery of the anterior half of the inferior turbinate was found to be equal to placebo. The findings of this study do not support the use of reduction of the anterior half of the inferior turbinate as a sole procedure intended to treat the ear symptoms assessed by the ETDQ-7 questionnaire.

Level of Evidence

1b. Laryngoscope, 2017



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Persistent respiratory effort after adenotonsillectomy in children with sleep-disordered breathing

Objectives

Adenotonsillectomy (AT) markedly improves but does not necessarily normalize polysomnographic findings in children with adenotonsillar hypertrophy and related sleep-disordered breathing (SDB). Adenotonsillectomy efficacy should be evaluated by follow-up polysomnography (PSG), but this method may underestimate persistent respiratory effort (RE). Mandibular movement (MMas) monitoring is an innovative measurement that readily identifies RE during upper airway obstruction. We hypothesized that MMas indices would decrease in parallel of PSG indices and that children with persistent RE more reliably could be identified with MMas.

Methods

Twenty-five children (3–12 years of age) with SDB were enrolled in this individual prospective-cohort study. Polysomnography was supplemented with a midsagittal movement magnetic sensor that measured MMas during each respiratory cycle before and > 3 months after AT.

Results

Adenotonsillectomy significantly improved PSG indices, except for RE-related arousals (RERA). Mandibular movement index changes after AT significantly were correlated with corresponding decreases in sleep apnea–hypopnea index (AHI) and O2 desaturation index (ODI) (Spearman's rho = 0.978 and 0.922, respectively), whereas changes in MMas duration significantly were associated with both RERA duration (rho = 0.475, P = 0.017) and index (rho = 0.564, P = 0.003). Conditional multivariate analysis showed that both AHI and RERA significantly contributed to the variance of MMas index after AT (P = 0.0003 and 0.0005, respectively), whereas MMas duration consistently was related to the duration of RERA regardless of AT.

Conclusion

Adenotonsillectomy significantly reduced AHI. However, persistent RERA were apparent in a significant proportion of children, and this was reflected by the remaining abnormal MMas pattern. Follow-up of children after AT can be recommended and readily achieved by monitoring MMas to identify persistent RE.

Level of Evidence

4. Laryngoscope, 2017



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What is the role of imaging in the evaluation of the patient presenting with unilateral facial paralysis?



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Is acupuncture an effective complementary tool within otolaryngological perioperative care?



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Effect of postoperative radiotherapy in pT1pN1cM0 and pT2p/cN0cM0 oropharyngeal squamous cell carcinoma

Objectives/Hypothesis

Consulting of patients with oropharyngeal carcinoma, classified as pT1pN1cM0 and pT2p/cN0cM0, about postoperative radiotherapy is a precarious task as data are lacking. The aim of this study was to evaluate the effects of postoperative radiotherapy for patients with intermediate-stage oropharyngeal carcinoma.

Study Design

Multicentric retrospective study.

Methods

This analysis was conducted at seven Austrian institutions and included data of patients treated between 2000 and 2012. A total of 81 patients with oropharyngeal squamous cell carcinoma were included, of whom 33 patients received postoperative radiotherapy. p16 status determined by immunohistochemistry was available in 68 patients.

Results

Median follow-up was 47.9 months. Postoperative radiotherapy showed no benefits in regard to overall survival (P = .701). In contrast, disease-free survival was significantly shortened in all patients without postoperative radiotherapy (P = .001). When dividing the cohort in dependence of p16, p16-positive patients did not benefit from postoperative radiotherapy regarding overall and disease-free survival (P = .934 and P = .102), whereas p16-negative patients showed improved disease-free survival after postoperative radiotherapy (P = .007). Multivariate analysis showed that outcome of postoperative radiotherapy is dependent on p16 status.

Conclusions

In terms of disease-free survival, patients with p16-negative tumors may benefit from postoperative radiotherapy, whereas survival of p16-positive patients is good regardless of additional treatment.

Level of Evidence

4 Laryngoscope, 2017



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Expiratory muscle strength training for radiation-associated aspiration after head and neck cancer: A case series

Objective/Hypothesis

Expiratory muscle strength training (EMST) is a simple, inexpensive, device-driven exercise therapy. Therapeutic potential of EMST was examined among head and neck cancer survivors with chronic radiation-associated aspiration.

Study Design

Retrospective case series.

Methods

Maximum expiratory pressures (MEPs) were examined among n = 64 radiation-associated aspirators (per penetration–aspiration scale score ≥ 6 on modified barium swallow). Pre–post EMST outcomes were examined in a nested subgroup of patients (n = 26) who enrolled in 8 weeks of EMST (25 repetitions, 5 days/week, 75% load). Nonparametric analyses examined effects of EMST on the primary endpoint MEPs. Secondary measures included swallowing safety (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]), perceived dysphagia (M.D. Anderson Dysphagia Inventory [MDADI]), and diet (performance status scale for head and neck cancer patients [PSSHN]).

Results

Compared to sex-matched published normative data, MEPs were reduced in 91% (58 of 64) of aspirators (mean ± standard deviation: 89 ± 37). Twenty-six patients enrolled in EMST and three patients withdrew. MEPs improved on average 57% (87 ± 29 to 137 ± 44 cm H2O, P < 0.001) among 23 who completed EMST. Swallowing safety (per DIGEST) improved significantly (P = 0.03). Composite MDADI scores improved post-EMST (pre-EMST: 59.9 ± 17.1, post-EMST: 62.7 ± 13.9, P = 0.13). PSSHN diet scores did not significantly change.

Conclusion

MEPs were reduced in chronic radiation-associated aspirators relative to normative data, suggesting that expiratory strengthening could be a novel therapeutic target to improve airway protection in this population. Similar to findings in neurogenic populations, these data also suggest improved expiratory pressure-generating capabilities after EMST and translation to functional improvements in swallowing safety in chronic radiation-associated aspirators.

Level of Evidence

4. Laryngoscope, 2017



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Volumetric analysis of olfactory neuroblastoma skull base laterality and implications on neck disease

Objective

To determine if the laterality of primary tumors in patients with olfactory neuroblastoma (ONB) influenced the pattern and development of neck disease.

Methods

Using a retrospective cohort study design from 1994 to 2015, the primary tumors of patients who either presented with or developed neck disease were volumetrically analyzed using iPlan software (version 3.0.0, BrainLAB, Feldkirchen, Germany) by two independent observers. Agreement of volume-derived sidedness was assessed with a kappa statistic, whereas agreement in volume-derived degree of tumor laterality was evaluated with an intraclass correlation coefficient. A one-sample t test was used to assess the difference in dominant percentage between the two observers.

Results

Sixty-one patients with histological diagnosis and treatment of ONB at our institution were identified. Twenty-four patients exhibited neck involvement, 13 of whom could be volumetrically analyzed. Tumors that were greater than 75% eccentric to one side all exhibited contralateral disease, whereas the majority of unilateral neck disease was associated with relatively midline masses. Within the entire cohort, ipsilateral level 2 lymph nodes displayed the highest involvement (83%, 20 of 24), followed by ipsilateral level 1 (54%, 13 of 24), contralateral level 2 (46%, 11 of 24), contralateral level 1 (21%, 5 of 24), and ipsilateral level 3 (21%, 5 of 24).

Conclusion

Ipsilateral neck involvement frequently was observed; however, the degree of ONB primary site laterality did not appear to have implications on the development of contralateral neck disease. Therefore, when considering elective therapy to the neck, ONB laterality should not be used to justify unilateral neck treatment.

Level of Evidence

4. Laryngoscope, 2017



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In response to letter to the editor to Does mutational analysis influence the management of differentiated thyroid cancers? - Molecular markers for thyroid nodules



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How Cross-Linguistic Differences in the Grammaticalization of Future Time Reference Influence Intertemporal Choices

Abstract

According to Chen's (2013) Linguistic Savings Hypothesis (LSH), our native language affects our economic behavior. We present three studies investigating how cross-linguistic differences in the grammaticalization of future-time reference (FTR) affect intertemporal choices. In a series of decision scenarios about finance and health issues, we let speakers of altogether five languages that represent FTR with increasing strength, that is, Chinese, German, Danish, Spanish, and English, choose between hypothetical sooner-smaller and later-larger reward options. While the LSH predicts a present-bias that increases with FTR-strength, our decision makers preferred later-larger options and this future-bias increased with FTR-strength. In multiple regressions, the FTR-strength effect persisted when controlled for socioeconomic and cultural differences. We discuss why our findings deviate from the LSH and ask in how far the FTR-strength effect represents a habitual constitution of linguistic relativity or an instance of online decision framing.



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Exploring Furnas-McGregor paradox: describing normal distribution in central limb stereometric gain in 60° Z-plasty



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Reconstruction of full-thickness cheek defect with a folded cervico-pectoral cutaneous flap following ablation of advanced oral cancer in elderly patient

Abstract

Background

Reconstruction of full-thickness cheek defects involving both the oral lining and the external facial skin following ablative surgery remains a difficult task. Free flap reconstruction is the main modality of treatment, but sometimes there is a reluctance to use it in elderly patients with several comorbidities for an increased risk of non-cancer-related cause of death.

Methods

This article describes a folded cervico-pectoral fasciocutaneous flap that has been used to reconstruct a full-thickness cheek defect in elderly patients. Moreover, surgical technique and aesthetic results 2 years after surgery are discussed in this article.

Results

Currently, after 2 years, the patient is free of disease and enjoys good health.

Conclusions

In conclusion, folded cervico-pectoral fasciocutaneous flap is a fast and practical technique for reconstructing full-thickness cheek defects after tumor excision. The flap was straightforward to perform and reliable in both blood supply and cosmetic outcome, and it provides a good alternative to free flaps for cheek and upper neck reconstruction of elderly patients.

Level of Evidence: Level V, therapeutic study.



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Clinical description of skin lesions in pathology requisition forms completed by plastic surgeons is lacking: a retrospective study of 499 lesions



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Anatomy of superficial inferior epigastric vessels: revival of superficial inferior epigastric (SIEA) flap

Abstract

Background

Development of perforator flaps evolves the perspective of reconstructive surgery to another level due to many of their advantages over the pedicled flaps, particularly lower donor-site morbidity and versatility in flap design. Superficial inferior epigastric artery (SIEA) flap offers this significant advantage over other lower abdominal flaps, as dissection of the rectus abdominis muscle is not required. However, both vascular agenesis and inappropriate vessel size for anastomosis are the major limitations. This study was therefore aimed to investigate these aspects of this flap.

Methods

Twenty cadavers were dissected bilaterally to demonstrate vascular anatomy of these vessels. The SIEA of each cadaver was dissected and traced from the origin (femoral arteries) to their presence in the subcutaneous layer. Originating patterns of these vessels, whether sharing a common trunk with other vessels such as superficial circumflex iliac (SCI) or superficial external pudendal (SEP) arteries, was determined and their diameters measured.

Results

SIEA agenesis rate was found to be 7.5% (3/40). The diameters greater than 1 and 1.5 mm were found in 86% (32/37) and 30% (11/37), respectively. The distance between its origin and point of entering Scarpa's fascia varies from 10.29 to 62.62 mm (mean 37.48 mm). As opposed to the artery, the superficial inferior epigastric vein was found to be present in all dissections with a diameter ranging from 2.12 to 5 mm (mean 3.09 mm) and the distance, as measured in SIEA, ranging from 20.1 to 74.28 mm (mean 41.24 mm). SIEA usually crosses the inguinal ligament within area between mid-inguinal point and 3 cm medially. Correlations were found (1) between SIEA diameter and pedicle length and (2) between bilateral pedicle lengths of both artery and vein.

Conclusions

The high prevalence of both SIEA presence and appropriate diameter for anastomosis, and thus flap success, makes the SIEA perforator flap an appropriate option for reconstructive treatment.

Level of Evidence: not ratable.



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Exploring Furnas-McGregor paradox: describing normal distribution in central limb stereometric gain in 60° Z-plasty



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Reconstruction of full-thickness cheek defect with a folded cervico-pectoral cutaneous flap following ablation of advanced oral cancer in elderly patient

Abstract

Background

Reconstruction of full-thickness cheek defects involving both the oral lining and the external facial skin following ablative surgery remains a difficult task. Free flap reconstruction is the main modality of treatment, but sometimes there is a reluctance to use it in elderly patients with several comorbidities for an increased risk of non-cancer-related cause of death.

Methods

This article describes a folded cervico-pectoral fasciocutaneous flap that has been used to reconstruct a full-thickness cheek defect in elderly patients. Moreover, surgical technique and aesthetic results 2 years after surgery are discussed in this article.

Results

Currently, after 2 years, the patient is free of disease and enjoys good health.

Conclusions

In conclusion, folded cervico-pectoral fasciocutaneous flap is a fast and practical technique for reconstructing full-thickness cheek defects after tumor excision. The flap was straightforward to perform and reliable in both blood supply and cosmetic outcome, and it provides a good alternative to free flaps for cheek and upper neck reconstruction of elderly patients.

Level of Evidence: Level V, therapeutic study.



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Clinical description of skin lesions in pathology requisition forms completed by plastic surgeons is lacking: a retrospective study of 499 lesions



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2g1tSh1

Anatomy of superficial inferior epigastric vessels: revival of superficial inferior epigastric (SIEA) flap

Abstract

Background

Development of perforator flaps evolves the perspective of reconstructive surgery to another level due to many of their advantages over the pedicled flaps, particularly lower donor-site morbidity and versatility in flap design. Superficial inferior epigastric artery (SIEA) flap offers this significant advantage over other lower abdominal flaps, as dissection of the rectus abdominis muscle is not required. However, both vascular agenesis and inappropriate vessel size for anastomosis are the major limitations. This study was therefore aimed to investigate these aspects of this flap.

Methods

Twenty cadavers were dissected bilaterally to demonstrate vascular anatomy of these vessels. The SIEA of each cadaver was dissected and traced from the origin (femoral arteries) to their presence in the subcutaneous layer. Originating patterns of these vessels, whether sharing a common trunk with other vessels such as superficial circumflex iliac (SCI) or superficial external pudendal (SEP) arteries, was determined and their diameters measured.

Results

SIEA agenesis rate was found to be 7.5% (3/40). The diameters greater than 1 and 1.5 mm were found in 86% (32/37) and 30% (11/37), respectively. The distance between its origin and point of entering Scarpa's fascia varies from 10.29 to 62.62 mm (mean 37.48 mm). As opposed to the artery, the superficial inferior epigastric vein was found to be present in all dissections with a diameter ranging from 2.12 to 5 mm (mean 3.09 mm) and the distance, as measured in SIEA, ranging from 20.1 to 74.28 mm (mean 41.24 mm). SIEA usually crosses the inguinal ligament within area between mid-inguinal point and 3 cm medially. Correlations were found (1) between SIEA diameter and pedicle length and (2) between bilateral pedicle lengths of both artery and vein.

Conclusions

The high prevalence of both SIEA presence and appropriate diameter for anastomosis, and thus flap success, makes the SIEA perforator flap an appropriate option for reconstructive treatment.

Level of Evidence: not ratable.



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Positive influence of partial resection on overall survival of patients with overlapping glioblastomas

Publication date: October 2017
Source:Clinical Neurology and Neurosurgery, Volume 161
Author(s): Johanna Quick-Weller, Stephanie Tritt, Peter Baumgarten, Jürgen Konczalla, Sepide Kashefiolasl, Anika Noack, Julia Tichy, Volker Seifert, Gerhard Marquardt
ObjectivesPatients with overlapping glioblastomas (former known as gliomatosis cerebri according to the 2007 WHO classification) have a poor prognosis. Most of the patients undergo biopsy to confirm histopathological diagnosis. Treatment comprises chemotherapy, radiation and combination of both. We determined whether resection of the contrast enhancing tumor parts leads to a prolonged survival.Patients and methodsWe performed a retrospective analysis and included 31 patients with overlapping glioblastomas (OG) who showed WHO IV in the initial histopathological examination. All patients fulfilled criteria of overlapping glioblastomas in the MRI according to WHO criteria (3 or more lobes were affected).We evaluated Karnofsky performance score (KPS), gender, age, IDH-1_R132H status, MGMT promotor methylation status, proliferation index, postoperative therapy, biopsy vs. partial resection and extent of resection as possible factors affecting overall survival (OAS).A matched pair analysis was performed between the biopsy and resection group on basis of age, KPS and combined radio-chemotherapy.Results10 Patients underwent resection of the contrast enhancing tumor parts, 21 patients underwent stereotactic biopsy. All included patients showed contrast enhancing lesions in the MRI.Median age was 61 years in the biopsy-group and 53 in the partial resection (PR) group. We found a significant correlation between OAS and age <50 (p=0.02). Median KPS was 80 in the STX group vs. 100 in the PR group. KPS above 80 was significantly associated with longer OAS (p=0.02). Median survival was 174days in the STX group compared to 446days in the PR group (p=0.05). Also the matched pair analysis showed significant p-values for resection.ConclusionPartial resection might have a positive impact on overall survival of patients with overlapping glioblastomas (former known as gliomatosis cerebri), although the prognosis remains limited.



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Nocturnal blood pressure fluctuations measured by using pulse transit time in patients with severe obstructive sleep apnea syndrome

Abstract

Background

Obstructive sleep apnea syndrome (OSAS) is related to arterial hypertension. In the present study, we test the hypothesis that patients with severe OSAS have excessive apnea induced blood pressure (BP).

Methods

We investigated 97 patients with an apnea/hypopnea index (AHI) greater than 30. Systolic BP (SBP) was continuously determined by using the pulse transit time (PTT). Apnea/hypopnea induced nocturnal BP fluctuations (NBPFs) were detected and showed phenomena of continuous increases of the SBP baseline. Such periods of SBP baseline elevations ≥ 10 mmHg were called superposition. Respiratory and cardiac parameters were obtained from the polysomnographic investigation.

Results

Eighty-four periods of superposition were detected in 48 patients. They occurred mainly during REM sleep (76%). Apnea duration was increased and the time in respiration was reduced in periods of superposition compared to non-superposition periods. In superposition periods mean oxygen saturation (SpO2) and the minimal SpO2 were lower, desaturations were more pronounced, and the mean heart rate (HR) was increased. The maximum SBP during superposition was significantly increased (204 ± 32 vs.171 ± 28 mmHg). The clinic BP was higher in patients with superposition (SBP 149.2 ± 17.5 vs. 140 ± 19.1, DBP 91.5 ± 11.5 vs. 86.3 ± 11.8).

Conclusions

The study reveals that patients with severe OSAS can have periods of BP superposition during night with extremely high SBP and very low oxygen saturation, which may add to a high risk for cardiovascular events during the night.



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Nocturnal blood pressure fluctuations measured by using pulse transit time in patients with severe obstructive sleep apnea syndrome

Abstract

Background

Obstructive sleep apnea syndrome (OSAS) is related to arterial hypertension. In the present study, we test the hypothesis that patients with severe OSAS have excessive apnea induced blood pressure (BP).

Methods

We investigated 97 patients with an apnea/hypopnea index (AHI) greater than 30. Systolic BP (SBP) was continuously determined by using the pulse transit time (PTT). Apnea/hypopnea induced nocturnal BP fluctuations (NBPFs) were detected and showed phenomena of continuous increases of the SBP baseline. Such periods of SBP baseline elevations ≥ 10 mmHg were called superposition. Respiratory and cardiac parameters were obtained from the polysomnographic investigation.

Results

Eighty-four periods of superposition were detected in 48 patients. They occurred mainly during REM sleep (76%). Apnea duration was increased and the time in respiration was reduced in periods of superposition compared to non-superposition periods. In superposition periods mean oxygen saturation (SpO2) and the minimal SpO2 were lower, desaturations were more pronounced, and the mean heart rate (HR) was increased. The maximum SBP during superposition was significantly increased (204 ± 32 vs.171 ± 28 mmHg). The clinic BP was higher in patients with superposition (SBP 149.2 ± 17.5 vs. 140 ± 19.1, DBP 91.5 ± 11.5 vs. 86.3 ± 11.8).

Conclusions

The study reveals that patients with severe OSAS can have periods of BP superposition during night with extremely high SBP and very low oxygen saturation, which may add to a high risk for cardiovascular events during the night.



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Therapeutic Strategies of Clustered Regularly Interspaced Palindromic Repeats-Cas Systems for Different Viral Infections

Viral Immunology , Vol. 0, No. 0.


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Effects of Autologous Cytokine-Induced Killer Cells Infusion in Colorectal Cancer Patients: A Prospective Study

Cancer Biotherapy & Radiopharmaceuticals Aug 2017, Vol. 32, No. 6: 221-226.


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In Vivo and In Vitro Effects of ATM/ATR Signaling Pathway on Proliferation, Apoptosis, and Radiosensitivity of Nasopharyngeal Carcinoma Cells

Cancer Biotherapy & Radiopharmaceuticals Aug 2017, Vol. 32, No. 6: 193-203.


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Clinical Effects of CpG-Based Treatment on the Efficacy of Hepatocellular Carcinoma by Skewing Polarization Toward M1 Macrophage from M2

Cancer Biotherapy & Radiopharmaceuticals Aug 2017, Vol. 32, No. 6: 215-219.


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Selected Literature Watch

Cancer Biotherapy & Radiopharmaceuticals Aug 2017, Vol. 32, No. 6: 227-228.


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A Comprehensive Review on Pharmacotherapeutics of Three Phytochemicals, Curcumin, Quercetin, and Allicin, in the Treatment of Gastric Cancer

Abstract

Objective

Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer.

Methods

Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were "curcumin," "quercetin," "allicin," and "gastric cancer" or "cancer."

Results

Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability.

Conclusions

Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents.

Mini-Abstract

Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.



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Surgical approaches in neck dissection: Comparing functional, oncologic and aesthetic aspects of transverse cervicotomy to Paul André’s approach

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Publication date: Available online 21 August 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): D. Guillier, V. Moris, A.A. Al Hindi, K. Rem, H. Chatel, L.-A. See, M. Revol, S. Mazouz Dorval
BackgroundSurgical approaches in neck dissection: comparing functional, oncologic and aesthetic aspects of transverse cervicotomy to Paul André's approach.MethodsThis single-center retrospective study compares a new transverse incision for cervicotomy to the classical approach described by Paul André in neck dissections. The evaluation criteria were: number of lymph nodes analyzed, operative time, complications, patient satisfaction and aesthetic aspects of the scar.ResultsA total of 34 patients were included in this study, from September 2009 until January 2015. The number of lymph nodes analyzed is not affected by this new approach compared to the classical one (P=0.9). The scar has a significantly more discreet appearance in the transverse cervicotomy group (P=0.023) likewise; patient satisfaction is higher in this group (P=0.006).ConclusionsAesthetic and functional impairment can be reduced using this new transverse cervical approach hidden in the natural creases of the neck described by Langer.



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Conclusions : le lifting cervico-facial “up-to-date” ?

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Publication date: Available online 21 August 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): E. Delay




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Postnatal hypoxia evokes persistent changes within the male rat’s dopaminergic system

Abstract

Purpose

Hypoxic insults occurring during the perinatal period remain the leading cause of permanent brain impairment. Severe cognitive and motor dysfunction, as seen in cerebral palsy, will occur in 4–10% of post-hypoxic newborns. Subtle cognitive impairment, apparent in disorders of minimal brain dysfunction will occur in > 3 million post-hypoxic newborns. Analyses of post-hypoxic rodent brains reveal reduced extracellular levels of dopamine, a key neurotransmitter of vigilance, execute function, and behavior. The purpose of this study was to assess whether synaptic levels of dopamine could be enhanced in post-hypoxic, hypodopaminergic rats.

Methods

Newborn male rats were exposed to subtle, repetitive hypoxic insults for 4–6 h per day, during postnatal days 7–11. During adolescence, we quantified dopamine content within the caudate nuclei. We then determined whether extracellular dopamine levels could be increased by injecting the psychostimulant d-amphetamine. We next assessed whether the post-hypoxic rat's response to d-amphetamine would differentially impact place preference behavior when compared with littermate controls.

Results

Total tissue content of dopamine was significantly higher in post-hypoxic rats. Injection of d-amphetamine liberated that dopamine which subsequently enhanced extracellular levels. Post-hypoxic rats acquired conditioned place preference for d-amphetamine during the training days. During the testing day, total time spent in the amphetamine-pairing box did not differ between post-hypoxic and control littermates.

Conclusion

Postnatally occurring hypoxic insults promote remodeling of the dopaminergic system resulting in increased intracellular sequestering of this monoamine. That sequestered dopamine can be released using the psychostimulant d-amphetamine, which did not promote a conditioned place preference any greater than was observed in non-hypoxic littermate controls.



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Activity of anthracycline- and ifosfamide-based chemotherapy in a series of patients affected by advanced myxofibrosarcoma

Abstract

Background

We report on the activity of anthracycline-based and high-dose prolonged-infusion ifosfamide chemotherapy in a retrospective series of patients affected by advanced myxofibrosarcoma treated at Istituto Nazionale Tumori in Milan, Italy, and within the Italian Rare Cancer Network (RTR).

Methods

Advanced myxofibrosarcoma patients treated with anthracycline + ifosfamide and high-dose prolonged-infusion ifosfamide as a single agent from November 2001 to December 2016 were retrospectively reviewed. All pathological diagnosis were centrally reviewed by at least two expert pathologists. Response was evaluated by RECIST, and survival functions were computed.

Results

Among 34 advanced myxofibrosarcoma patients, 13 were treated with front-line anthracycline + ifosfamide chemotherapy (male/female = 6/7, median age 54 years, range 33–72). Overall best response was: 4 partial responses, 3 stable diseases and 6 progressive diseases, with a median progression-free survival of 4 months. Twenty-eight patients received second/further line high-dose prolonged-infusion ifosfamide (male/female = 17/11, median age 55 years, range 27–75 years). We observed 10 partial responses, 4 stable diseases and 14 progressive diseases, with a median progression-free survival of 4 months. Median overall survival was 12 months.

Conclusions

This retrospective analysis suggests that the combination of anthracyclines and ifosfamide is active in myxofibrosarcoma. In patients already treated with a combination of anthracyclines and ifosfamide, high-dose prolonged-infusion ifosfamide showed activity as well.



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PI-273, a substrate-competitive, specific small molecule inhibitor of PI4KII{alpha}, inhibits the growth of breast cancer cells

While phosphatidylinositol 4-kinase PI4KIIα has been identified as a potential target for antitumor therapy, the clinical applications of PI4KIIα are limited by a lack of specific inhibitors. Here we report the first small-molecule inhibitor (SMI) of human PI4KIIα. Docking-based and ligand-based virtual screening strategies were first employed to identify promising hits, followed by two rounds of kinase activity inhibition validation. 2-(3-(4-Chlorobenzoyl)thioureido)-4-ethyl-5-methylthiophene-3-carboxamide (PI-273) exhibited the greatest inhibitory effect on PI4KIIα kinase activity (IC50 = 0.47 μM) and suppressed cell proliferation. Surface plasmon resonance (SPR) and thermal shift assays indicated that PI-273 interacted directly with PI4KIIα. Kinetic analysis identified PI-273 as a reversible competitive inhibitor with respect to the substrate phosphatidylinositol (PI), which contrasted with most other PI kinase inhibitors that bind the ATP binding site. PI-273 reduced PI4P content, cell viability, and AKT signaling in wild-type MCF-7 cells but not in PI4KIIα knockout MCF-7 cells, indicating that PI-273 is highly selective for PI4KIIα. Mutant analysis revealed a role of palmitoylation insertion in the selectivity of PI-273 for PI4KIIα. Additionally, PI-273 treatment retarded cell proliferation by blocking cells in G2/M, inducing cell apoptosis and suppressing colony-forming ability. Importantly, PI-273 significantly inhibited MCF-7 cell-induced breast tumor growth without toxicity. PI-273 is the first substrate-competitive, subtype-specific inhibitor of PI4KIIα, the use of which will facilitate evaluations of PI4KIIα as a cancer therapeutic target.

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Monocarboxylate transporter MCT1 promotes tumor metastasis independently of its activity as a lactate transporter

Extracellular acidosis resulting from intense metabolic activities in tumors promotes cancer cell migration, invasion and metastasis. While host cells die at low extracellular pH, cancer cells resist, as they are well equipped with transporters and enzymes to regulate intracellular pH homeostasis. A low extracellular pH further activates proteolytic enzymes that remodel the extracellular matrix to facilitate cell migration and invasion. Monocarboxylate transporter MCT1 is a passive transporter of lactic acid that has attracted interest as a target for small molecule drugs to prevent metastasis. In this study, we present evidence of a function for MCT1 in metastasis beyond its role as a transporter of lactic acid. MCT1 activated transcription factor NF-κB to promote cancer cell migration independently of MCT1 transporter activity. While pharmacological MCT1 inhibition did not modulate MCT1-dependent cancer cell migration, silencing or genetic deletion of MCT1 in vivo inhibited migration, invasion and spontaneous metastasis. Our findings raise the possibility that pharmacological inhibitors of MCT1-mediated lactic acid transport may not effectively prevent metastatic dissemination of cancer cells.

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STRAP promotes stemness of human colorectal cancer via epigenetic regulation of the NOTCH pathway

NOTCH signaling exerts essential roles in normal and malignant intestinal physiology and the homeostasis of cancer stem-like cells (CSC), but the basis for this latter role remains obscure. The signaling scaffold protein STRAP is upregulated in several cancers where it promotes tumorigenicity and metastasis. Here we report a novel oncogenic function for STRAP in maintaining CSC subpopulations in a heterogeneous mixture by antagonizing formation of the chromatin modifier PRC2 and by epigenetically activating NOTCH signals in human colorectal cancer (CRC). Silencing STRAP sensitized CRC cells to chemotherapeutic drugs in vitro and in vivo. STRAP depletion also contributed to a reduced stem-like phenotype of CRC cells, as indicated by reduced expression of the CSC signature and NOTCH signaling regulators in vitro and by diminished tumorigenesis in vivo. Genes encoding some upstream activators of NOTCH were highly enriched for H3K27me3, which form repressive chromatin domains upon STRAP silencing. Mechanistically, STRAP competitively disrupted association of the PRC2 subunits EZH2 and SUZ12, thereby inhibiting PRC2 assembly. Restoring the NOTCH pathway by lentiviral expression of NICD1 or HES1 in STRAP-depleted tumor cells reversed the CSC phenotype. In 90 CRC clinical specimens, a significant positive correlation was documented between the expression of STRAP and HES1. Overall, our findings illuminated a novel STRAP-NOTCH1-HES1 molecular axis as a CSC regulator in CRC, with potential implications to improve treatment of this disease.

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Different engagement of TLR2 and TLR4 in Porphyromonas gingivalis vs. ligature-induced periodontal bone loss

Abstract This study was conducted to investigate the roles of different Toll-like receptor (TLR) signaling in Porphyromonas gingivalis (P. gingivalis)-induced and ligature-induced experimental periodontal bone resorption in mice. Wild-type (WT), TLR2 knockout (KO), TLR4KO, and TLR2&4 KO mice with C57/BL6 background were divided into three groups: control, P. gingivalis infection, and ligation. Live P. gingivalis or silk ligatures were placed in the sulcus around maxillary second molars over a 2-week period. Images were captured by digital stereomicroscopy, and the bone resorption area was measured with ImageJ software. The protein expression level of gingival RANKL was measured by ELISA. The gingival mRNA levels of RANKL, IL-1β, TNF-α, and IL-10 were detected by RT-qPCR. The results showed that P. gingivalis induced significant periodontal bone resorption in WT mice and TLR2 KO mice but not in TLR4 KO mice or TLR2&4 KO mice. For all four types of mice, ligation induced significant bone loss compared with that in control groups, and this bone loss was significantly higher than that in the P. gingivalis infection group. RANKL protein expression was significantly increased in the ligation group compared with that in the control group for all four types of mice, and in the P. gingivalis infection group of WT, TLR2 KO, and TLR4 KO mice. Expression patterns of RANKL, IL-1β, TNF-α, and IL-10 mRNA were different in the P. gingivalis infection group and the ligation group in different types of mice. In summary, P. gingivalis-induced periodontal bone resorption is TLR4-dependent, whereas ligation-induced periodontal bone resorption is neither TLR2- nor TLR4-dependent.

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Comparing depth-dependent curing radiant exposure and time of curing of regular and flow bulk-fill composites

Abstract The effect of restoration depth on the curing time of a conventional and two bulk-fill composite resins by measuring microhardness and the respective radiosity of the bottom surface of the specimen was investigated. 1-, 3- and 5-mm thick washers were filled with Surefil SDR Flow–U (SDR), Tetric EvoCeram Bulk Fill-IVA (TEC) or Esthet-X HD–B1 (EHD), and cured with Bluephase® G2 for 40s. Additional 1-mm washers were filled with SDR, TEC or EHD, placed above the light sensor of MARC®, stacked with pre-cured 1-, 3- or 5-mm washer of respective material, and cured for 2.5~60s to mimic 2-, 4- and 6-mm thick composite curing. The sensor measured the radiosity (EB) at the bottom of specimen stacks. Vickers hardness (VH) was measured immediately at 5 locations with triplicate specimens. Nonlinear regression of VH vs EB by VH=α[1-exp(-EB/β)] with all thickness shows that the values of α, maximum hardness, are 21.6±1.0 kg/mm2 for SDR, 38.3±0.6 kg/mm2 for TEC and 45.3±2.6 kg/mm2 for EHD, and the values of β, rate parameter, are 0.40±0.06 J/cm2 for SDR, 0.77±0.04 J/cm2 for TEC and 0.58±0.09 J/cm2 for EHD. The radiosity of the bottom surface was calculated when the bottom surface of each material attained 80% of α of each material. The curing times for each material are in agreement with manufacturer recommendation for thickness. It is possible to estimate time needed to cure composite resin of known depth adequately by the radiosity and microhardness of the bottom surface.

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Ki-67 protein predicts survival in oral squamous carcinoma cells: an immunohistochemical study

Abstract The aim of this study was to identify the expression of Ki-67 and MCM3 in oral squamous cell carcinoma (OSCC) as well as to address the correlation with patient survival and clinical features. Samples were collected from 51 patients with OSCC who presented for follow-up. Immunohistochemical expression of Ki-67 and MCM3 in all groups was performed. The scoring system was previous published by Tsurutani in 2005. We used Kappa index to evaluate observers agreement degree. The associations between protein expression and clinical variables were examined for statistical significance using the chi-squared test. The overall survival rates were estimated by the Kaplan-Meier method and the relationship between protein expression and survival was compared using the log-rank test (p < 0.05). The overall survival time for a patient with positive immunostaining for Ki-67 is shorter than for a patient with negative immunostaining, (log-rank test, p = 0.00882). Patients with tumor size T3 and T4 showed a statistically significant relationship with Ki-67 immunoexpression (log-rank test, p = 0.0174). The relationship between Ki-67 expression and the relation between age, gender, smoking, tumor site, lymph node metastasis and disease stage was not significant. The examiners agreement degree by Kappa presented p value < 0.05. There was not a significant correlation when we evaluated MCM3 expression regarding clinical characteristics and survival rate. From these results, the present study suggests that positive Ki-67 expression found in OSCC patients may contribute to predict the survival in OSCC samples, as well as the relation between the protein and the tumor size.

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Characterization and coating stability evaluation of nickel-titanium orthodontic esthetic wires: an in vivo study

1807-3107-bor-31-1807-3107BOR-2017vol310

Abstract The objective of this study was to compare coating dimensions and surface characteristics of two different esthetic covered nickel-titanium orthodontic rectangular archwires, as-received from the manufacturer and after oral exposure. The study was designed for comparative purposes. Both archwires, as-received from the manufacturer, were observed using a stereomicroscope to measure coating thickness and inner metallic dimensions. The wires were also exposed to oral environment in 11 orthodontic active patients for 21 days. After removing the samples, stereomicroscopy images were captured, coating loss was measured and its percentage was calculated. Three segments of each wire (one as-received and two after oral exposure) were observed using scanning electron microscopy for a qualitative analysis of the labial surface of the wires. The Lilliefors test and independent t-test were applied to verify normality of data and statistical differences between wires, respectively. The significance level adopted was 0.05. The results showed that the differences between the wires while comparing inner height and thickness were statistically significant (p < 0.0001). In average, the most recently launched wire presented a coating thickness twice that of the control wire, which was also a statistically significant difference. The coating loss percentage was also statistically different (p = 0.0346) when the latest launched wire (13.27%) was compared to the control (29.63%). In conclusion, the coating of the most recent wire was thicker and more uniform, whereas the control had a thinner coating on the edges. After oral exposure, both tested wires presented coating loss, but the most recently launched wire exhibited better results.

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Risk factors for implant failure: a retrospective study in an educational institution using GEE analyses

Abstract This study aimed to evaluate dental implant outcomes and to identify risk factors associated with implant failure over 12 years via dental records of patients attending an educational institution. Dental records of 202 patients receiving 774 dental implants from 2002 to 2014 were analyzed by adopting a more reliable statistical method to evaluate risk factors with patients as the unit [generalized estimating equation (GEE)]. Information regarding patient age at implantation, sex, use of tobacco, and history of systemic diseases was collected. Information about implant location in the arch region and implant length, diameter, and placement in a grafted area was evaluated after 2 years under load. Systemic and local risk factors for early and late implant failure were studied. A total of 18 patients experienced 25 implant failures, resulting in an overall survival rate of 96.8% (2.84% and 0.38% early and late implant failures, respectively). The patient-based survival rate was 91.8%. GEE univariate and multivariate analyses revealed that a significant risk factor for implant failure was the maxillary implant (p = 0.006 and p = 0.014, respectively). Bone grafting appeared to be a risk factor for implant failure (p = 0.054). According to GEE analyses, maxillary implants had significantly worse outcomes in this population and were considered to be a risk factor for implant failure. Our results suggested that implants placed in a bone augmentation area had a tendency to fail.

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Longitudinal impact of clinical and socioenvironmental variables on oral health-related quality of life in adolescents

Abstract The aim of the present study was to investigate the impact of oral diseases, socioeconomic status, and family environmental factors on changes in the perception of oral health-related quality of life (OHRQoL) in adolescents. A prospective cohort study was conducted in Juiz de Fora, Minas Gerais, Brazil, with a sample of 286 twelve-year-old adolescents from public and private schools, selected by means of multistage random sampling. The adolescents were clinically examined for dental caries experience (number of decayed, missing, and filled teeth - DMFT index), presence of bleeding, and orthodontic treatment needs. They were asked to complete the Brazilian version of the Child Perceptions Questionnaire (CPQ11-14). In addition, parents answered a questionnaire about their socioeconomic status and family environmental characteristics. After 3 years, the adolescents were contacted again to participate in the research. Logistic regression models, with explanatory variables assessed both individually and jointly, were used to determine which independent variables impacted longitudinally on OHRQoL. The final result demonstrated that only DMFT explained part of the response variability in CPQ11-14 scores. In conclusion, caries experience was an important predictor of OHRQoL in adolescents followed up for 3 years.

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Evaluation of the physicochemical properties of silicone- and epoxy resin-based root canal sealers

Abstract To assess the physicochemical properties of AH Plus, GuttaFlow 2, GuttaFlow BioSeal, and MM Seal, five samples of each root canal sealer were evaluated to determine their setting time (ST), dimensional change (DC), solubility (SL), flow (FL), and radiopacity (RD) according to American National Standards Institute/American Dental Association (ANSI/ADA) Specification 57. The distilled and deionized water obtained from the SL test were subjected to atomic absorption spectrometry to observe the presence of Ca2+, K+, and Na+ ions. Statistical analysis was performed by using one-way ANOVA and Tukey–Kramer tests (p < 0.05). The following results were obtained: ST (min) (AH Plus 463.6 ± 13.22; GuttaFlow 2 24.35 ± 2.78; GuttaFlow Bioseal 17.4 ± 0.55; MM Seal 47.60 ± 4.39), DC (%) (AH Plus 0.06 ± 0.12; GuttaFlow 2 −26.06 ± 1.24; GuttaFlow Bioseal 2.10 ± 1.47; MM Seal 8.47 ± 2.41), SL (%) (AH Plus 0.41 ± 0.21; GuttaFlow 2 5.13 ± 4.11; GuttaFlow Bioseal 3.03 ± 1.05; MM Seal 0.94 ± 0.17), FL (mm) (AH Plus 36.42 ± 0.40; GuttaFlow 2 36.44 ± 0.05; GuttaFlow Bioseal 35.4 ± 0.03; MM Seal 52.75 ± 0.60), and RD (mmAl) (AH Plus 7.52 ± 1.59; GuttaFlow 2 6.85 ± 0.14; GuttaFlow Bioseal 7.02 ± 0.18; MM Seal 3.32 ± 0.90). ST, DC, SL, FL, and RD showed statistical differences among the root canal sealers (p < 0.05). As AH Plus showed the lowest DC and SL values (p < 0.05), the findings indicate that this sample is the only sealer conforming to ANSI/ADA standards.

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Postnatal hypoxia evokes persistent changes within the male rat’s dopaminergic system

Abstract

Purpose

Hypoxic insults occurring during the perinatal period remain the leading cause of permanent brain impairment. Severe cognitive and motor dysfunction, as seen in cerebral palsy, will occur in 4–10% of post-hypoxic newborns. Subtle cognitive impairment, apparent in disorders of minimal brain dysfunction will occur in > 3 million post-hypoxic newborns. Analyses of post-hypoxic rodent brains reveal reduced extracellular levels of dopamine, a key neurotransmitter of vigilance, execute function, and behavior. The purpose of this study was to assess whether synaptic levels of dopamine could be enhanced in post-hypoxic, hypodopaminergic rats.

Methods

Newborn male rats were exposed to subtle, repetitive hypoxic insults for 4–6 h per day, during postnatal days 7–11. During adolescence, we quantified dopamine content within the caudate nuclei. We then determined whether extracellular dopamine levels could be increased by injecting the psychostimulant d-amphetamine. We next assessed whether the post-hypoxic rat's response to d-amphetamine would differentially impact place preference behavior when compared with littermate controls.

Results

Total tissue content of dopamine was significantly higher in post-hypoxic rats. Injection of d-amphetamine liberated that dopamine which subsequently enhanced extracellular levels. Post-hypoxic rats acquired conditioned place preference for d-amphetamine during the training days. During the testing day, total time spent in the amphetamine-pairing box did not differ between post-hypoxic and control littermates.

Conclusion

Postnatally occurring hypoxic insults promote remodeling of the dopaminergic system resulting in increased intracellular sequestering of this monoamine. That sequestered dopamine can be released using the psychostimulant d-amphetamine, which did not promote a conditioned place preference any greater than was observed in non-hypoxic littermate controls.



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Association of increased gait variability while dual tasking and cognitive decline: results from a prospective longitudinal cohort pilot study

Abstract

Dual task-related changes in gait are considered as a sensitive and a specific marker of adverse effects of cognitive impairment on the highest levels of gait control. No study has examined the longitudinal association between gait performance while dual tasking and the occurrence of cognitive decline. This study aims to examine the association of stride time parameters (i.e., mean value and coefficient of variation (CoV)) during single and dual tasking with the occurrence of cognitive decline in non-demented older community dwellers. A total of 56 non-demented community dwellers were recruited in a longitudinal prospective cohort study. Mini-Mental Status Examination (MMSE) scores at baseline assessment and at 5-year follow-up assessment, and mean value and CoV of stride time at self-selected usual pace, while usual walking and dual tasking (i.e., counting backward and verbal fluency task) at baseline assessment were recorded. Variation (i.e., delta) of MMSE score from baseline to follow-up assessment as well as of stride time parameters from single to dual task was used as outcomes. Worse stride time values were reported while dual tasking compared to single tasking (P < 0.03). An increase of mean value, CoV, and delta of CoV of stride time was associated with an increased delta MMSE while performing verbal fluency task (P < 0.05). Worsening stride time parameters while performing a verbal fluency task at baseline assessment was associated with decline in MMSE score during the 5-year follow-up period in this sample of older community dwellers.



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Compression of environmental representations following interactions with objects

Abstract

Previous work reveals that interacting with all objects in an environment can compress spatial memory for the entire group of objects. To assess the scope and magnitude of this effect, we tested whether interacting with a subset of objects compresses spatial memory for all objects in an environment. Participants inspected objects in one or two unmarked regions of space, then recalled the distances between pairs of objects from memory. One group of participants picked up objects in both regions, a second group picked up objects in one region and passively viewed objects in the other region, and a third group passively viewed objects in both regions. When participants manually interacted with objects, they recalled shorter object-pair distances throughout the environment. The magnitude of this effect was the same, regardless of whether participants interacted with all objects in the environment or just a subset of them. Together, these findings suggest that interacting with objects can compress environmental representations in memory, even when observers interact with a relatively small subset of objects.



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ITIH4: Effective Serum Marker, Early Warning and Diagnosis, Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor evolved from cirrhosis. It is quite significant to seek accurate, easy markers for early warning and diagnosis of HCC. Through prospective cohort follow-up study and mass spectrometry, we discovered and verified a serum marker valuable for early warning and diagnosis. Follow-up observation was performed on cirrhosis patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was adopted to detect the serums of patients, and the serum polypeptides with a potential value in early HCC warning and diagnosis were screened. Electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF-MS/MS) was exploited to identify these screened polypeptides. Moreover, the serum marker concentration was determined by ELISA to validate the clinical value of the serum marker. Among 109 cirrhosis patients followed up for two years, 29 patients (26.6%) finally progressed into HCC. MALDI-TOF MS shows that the concentration of a 3155.66Da polypeptide was significantly different between the patients that progressed into HCC and those not. Through MS/MS identification, it is confirmed that the polypeptide is inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4). The serum ITIH4 concentrations in two groups were measured with ELISA and compared with Alpha-fetoprotein (AFP). Results show that serum ITIH4 and AFP concentrations were negatively correlated (r=−0.263, p=0.0006), and the ITIH4 concentration had a significant intergroup difference (p=0.000). Receiver operating characteristic (ROC) curve indicates that its predictive value (area under the curve, AUC) is 0.667, superior to AFP. For the patients progressing into HCC, serum samples were separately collected when they were recruited and diagnosed as cirrhosis. Measurement on these samples reveals that ITIH4 was declining during the progression of HCC (p=0.006). By virtue of mass spectrometry, we discovered and identified a biomarker valuable for early HCC warning and diagnosis. This marker overperforms the commonly used AFP, demonstrating a bright prospect.



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How Loud Is the Sun?

How loud would the sun be measured on Earth if its soundwaves could propagate through space? The answer might surprise you, as solar physicists estimate that the solar surface noise would be approximately 100dB by the time it reaches Earth! The enormity of the sun's surface paired with its capability of generating of tens of thousands of watts of sound energy per meter makes the sun astronomically loud.



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Medicare Telehealth Parity Act of 2017 Would Expand Role of Audiology

Much of the focus of the Over-the-Counter (OTC) Hearing Aid Act of 2017 (S.670 and H.R.1652) has been on improving accessibility and affordability to hearing aids by providing a "do-it-yourself" (DIY) distribution channel for patients who are comfortable with self-assessment and fitting of hearing aids.



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Let’s Take This Outside: Is There a Place for Outdoor Walking Meetings in Your Work Environment?

Do you wish your work meetings were more productive? Maybe it is time to leave the confines of the traditional conference room behind and take the meeting outdoors? 

Angel Chelick's article on the American Council of Exercise's website suggests that outdoor walking meetings improve creativity and facilitate conversation between co-workers. As an added bonus, we all know walking has cardiovascular health benefits (not to mention the added steps you will get on your fitness tracker).  



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Brain Health and Hearing

A recent commission from "The Lancet"  focused on dementia. In this review, the authors outline nine potentially modifiable health and lifestyle factors from different phases of life that, if eliminated, might prevent or at least delay dementia. The authors stress that dementia, much like hearing loss, is not an inevitable consequence of aging, rather it is multifaceted and potentially 1/3 of cases preventable.



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Recovery from TBI

A recent study suggests that recovery from TBI (traumatic brain injury) may be different between males and female subjects. Historically, TBI studies have used predominately male subjects, whether they be mice or men. However, investigating the effects of injury, disease, and pharmacological treatments in both male and female subjects has led to significant changes to clinical practice across numerous disciplines.



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EHDI and Vocabulary

Until recently, no studies have examined vocabulary outcomes of children with hearing loss that have met all three components of the EHDI guidelines:



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Is It the Offer You Have Been Waiting For?

You've been on the hunt for a new job. You've gone on the interview and have been offered the job. Now what? Should you accept?

If you find yourself in this situation, you may want to check out Rebecca Knight's article, "How to Evaluate, Accept, Reject, or Negotiate a Job Offer," in Harvard Business Review. This article provides the reader with job-offer consideration, potential negotiation strategies, and, if appropriate, how to turn down the job offer. She even provides two case study examples.

Reference



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How Often Is Hearing Loss Considered?

As audiologists, we know firsthand the impact that hearing loss has on communication. Before we begin speaking, we look at our patients and provide an unobstructed view of our face. As soon as patients walk into our office, we adjust the volume, pitch, and tempo of our speech to ensure that they can hear and understand us. We hope that other health-care providers, including physicians, are also attuned to their patients' hearing needs particularly when helping older adults where a prevalence of hearing loss is high.



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Why Do So Many Preemies Have Hearing Loss?

It is so very interesting how one can know two different facts very well but not connect them. For example, I have known from the very first days of studying audiology that the peripheral auditory structure is mature in the human by the third trimester of prenatal life. I have also known for a while that the incidence of hearing loss is higher in babies born prematurely, compared to those delivered after a full-term pregnancy. And when I say higher, I mean alarmingly higher.



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Can Bugs Talk?

Jason Moon of the New Hampshire Public Radio, reports that researchers at the University of New Hampshire are studying communication strategies of American Burying Beetles.



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NPR: Music to Ease Hearing Loss

NPR featured a piece on  "All Things Considered," considering how to improve speech understanding in noisy environments. The segment focused on an ongoing study by Frank Russo, the director of the Science of Music, Auditory Research, and Technology Lab (SMART Lab) at Ryerson University in Toronto.



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Falls Risk Reduction and Robotics

Understanding and reducing falls in the elderly is an important cornerstone in vestibular and balance rehabilitation, and there may be a new tool on the horizon that could change the way our patients achieve this, namely, exoskeleton technology. Previously, the use of exoskeletons assistance has been limited. Initial prototypes were cumbersome and designed for those with significant motor-control impairment, which left most of the control to the device itself. 



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Whispering Whales

Imagine traveling thousands of miles with your newborn in search of food. Now imagine doing this in almost complete darkness. This is exactly what humpback whales and their newborns do as a matter of routine. The journey to the food-rich Antarctic or Arctic waters from their tropical breeding grounds can be thousands of miles. The mother and calf swim in deep ocean waters where light is scarce and therefore vision is not very useful. The pair has to depend on sound to keep track of each other. But broadcasting their presence to killer whales can be fatal.  



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Sound Art

Got plans to visit Canada anytime soon?  The Museum London in London, Ontario, will be hosting the exhibit "Sounds Assembling: Communication and the Art of Noise."  The artwork includes glass panels etched with waveforms corresponding to spoken word (Artist: James Joynes) and a hand-cranked musical device that plays notes corresponding to the noise of insects (Artist: Kevin Curtis Norcross). 



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Is Cost the Primary Factor for Hearing Aid Adoption?

In 2015, the President's Council on Advisors on Science and Technology (PCAST) issued recommendations intended to improve hearing health- care delivery. Subsequently, the FDA and other federal agencies and consumer advocacy groups sponsored a study published by the National Academies of Sciences, Engineering, and Medicine in June 2016. Further considerations have been discussed in an FDA (April 2016) and FTC (April 2017) workshops. A common issue discussed in each of these reports and workshops is the high cost of hearing aids as a primary factor in adoption rates.



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Brachytherapy attains abscopal effects when combined with immunostimulatory monoclonal antibodies

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Publication date: Available online 21 August 2017
Source:Brachytherapy
Author(s): María E. Rodriguez-Ruiz, Inmaculada Rodriguez, Benigno Barbes, Lina Mayorga, Alfonso Rodriguez Sanchez-Paulete, Mariano Ponz-Sarvise, José Luis Pérez-Gracia, Ignacio Melero
Purpose/ObjectivesPreclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory monoclonal antibodies (mAb) to act both on irradiated tumor lesions and on tumors at distant, nonirradiated sites. We have recently reported that external beam radiotherapy achieves abscopal effects when combined with antagonist anti-PD1 mAbs and agonist anti-CD137 (4-1BB) mAbs. The goal of this work is to study the abscopal effects of radiotherapy instigated by brachytherapy techniques.Methods and MaterialsMice bearing a subcutaneous colorectal carcinoma, MC38 (colorectal cancer), in both flanks were randomly assigned to receive brachytherapy or not (8 Gy × three fractions) to only one of the two grafted tumors, in combination with intraperitoneal immunostimulatory monoclonal antibodies (anti-PD1, anti-CD137, and/or their respective isotype controls). To study the abscopal effects of brachytherapy, we established an experimental set up that permits irradiation of mouse tumors sparing a distant site resembling metastasis. Such second nonirradiated tumor was used as indicator of abscopal effect. Tumor size was monitored every 2 days.ResultsAbscopal effects on distant nonirradiated subcutaneous tumor lesions of transplanted MC38-derived tumors only took place when brachytherapy was combined with immunostimulatory anti-PD1 and/or anti-CD137 mAbs.ConclusionsOur results demonstrate that immunotherapy-potentiated abscopal effects can be attained by brachytherapy. Accordingly, immunotherapy plus brachytherapy combinations are suitable for clinical translation.



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Salvage brachytherapy for recurrent prostate cancer after definitive radiation therapy: A comparison of low-dose-rate and high-dose-rate brachytherapy and the importance of prostate-specific antigen doubling time

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Publication date: Available online 21 August 2017
Source:Brachytherapy
Author(s): Marisa A. Kollmeier, Sean McBride, Amandeep Taggar, Erik Anderson, Mary Lin, Xin Pei, Shi Weiji, Laszlo Voros, Gilad Cohen, Yoshiya Yamada, Michael J. Zelefsky
BackgroundSalvage brachytherapy is a treatment option for patients with locally recurrent prostate cancer after primary radiation therapy. We reviewed our experience using low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy to compare the outcome and toxicity profiles of each approach in the salvage brachytherapy setting.Methods and MaterialsNinety-eight patients with biopsy-proven locally recurrent prostate cancer who underwent salvage brachytherapy (LDR = 37; HDR = 61) following an initial course of definitive radiotherapy between 4/2003 and 4/2015 were retrospectively reviewed. All patients underwent salvage brachytherapy using LDR or HDR. Androgen deprivation therapy was used in 45% of the patients. Prostate-specific antigen (PSA) failure was determined using the Phoenix (nadir+2) definition. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4 and patient-reported questionnaires.ResultsMedian followup was 31 months. The 3-year PSA relapse-free survival (RFS) was 60.1% (95% CI, 49.6–72.5%). There was no difference between LDR and HDR brachytherapy in terms of PSA RFS (p = 0.84 by log-rank test). On multivariate analysis, only prostate-specific antigen doubling time (PSADT) <12 months was significantly associated with PSA relapse. The 3-year PSA RFS for patients with a PSADT <12 months was 39% compared with 73% for PSADT ≥12 months (p = 0.002 by long-rank test). There were no statistically significant differences in toxicity between LDR and HDR brachytherapy. There was a higher peak in urinary symptoms in LDR patients; however by 24–36 months, most patients in both groups returned to baseline.ConclusionsBoth LDR and HDR salvage brachytherapy are an excellent treatment options for appropriately selected patients with comparable outcome and toxicity. Patients with a PSADT < 12 months seem to have worse outcomes.



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Performance of ovarian cyst fluid fine-needle aspiration cytology

BACKGROUND

Although ovarian fine-needle aspiration (FNA) cytology is not commonly used as a primary modality of diagnosis for patients with ovarian lesions, many ovarian cysts are aspirated intraoperatively and occasionally for diagnostic purposes. Therefore, the ability to interpret these specimens remains critical. Previous studies have suggested a high specificity but low sensitivity as a limitation. The objective of the current study was to further explore the use and performance of ovarian cyst FNA for diagnosing malignancy at the study institution.

METHODS

The electronic database was searched from 1998 through 2016 for ovarian cyst fluid cytology specimens; any concurrent or follow-up surgical pathology; and clinical information including patient age, radiology findings, and procedure type. Test performance was calculated using the surgical pathology diagnosis as the gold standard.

RESULTS

A total of 459 ovarian cyst FNA specimens had the following diagnoses: 416 (90.6%) were diagnosed as benign, 32 (7.0%) as atypical, 4 (0.9%) as suspicious, and 7 (1.5%) as malignant. Overall, 300 specimens (65.4%) had a corresponding surgical pathology specimen. On follow-up, the rate of malignancy (including borderline neoplasms) for benign FNA was 10 of 264 specimens (3.8%), that for atypical FNA was 0 of 24 specimens (0%), that for suspicious FNA was 5 of 5 specimens (100%), and that for malignant FNA was 7 of 7 specimens (100%). Test sensitivity was 54.0% and test specificity was 100%. The positive predictive value was 1.00 and the negative predictive value was 0.97, with a disease (malignancy) prevalence of 7.33%.

CONCLUSIONS

Ovarian cyst fluid cytology is highly specific and moderately sensitive for the detection of ovarian malignancies. A negative FNA is reassuring for patients with a low pretest probability of malignancy. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.



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Identification of distinct cytomorphologic features in the diagnosis of NIFTP at the time of preoperative FNA: Implications for patient management

BACKGROUND

A major reclassification occurred with the redesignation of noninvasive encapsulated follicular variant of papillary thyroid carcinoma as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its indolent nature. The aim of this study was to determine whether distinct cytomorphologic features could be identified on preoperative fine-needle aspiration (FNA) when NIFTP cases were compared with invasive follicular variant of papillary thyroid carcinoma (FVPTC) subtypes.

METHODS

Thyroid resection cases with the diagnosis of FVPTC from 2012 to 2016 were reclassified as NIFTP, invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC), and invasive FVPTC subtypes. Corresponding FNA specimens were retrieved and retrospectively reviewed. A univariate analysis using Fisher's exact test was performed to determine any differences in the frequencies of various cytomorphologic features among NIFTP, IEFVPTC, and FVPTC cases. A multivariate analysis was performed to identify any independent salient features that would be helpful in differentiating NIFTP from its invasive counterparts.

RESULTS

The study population consisted of 93 cases, including 51 cases of NIFTP, 21 cases of IEFVPTC, and 21 cases of infiltrative FVPTC. Demographics such as age, sex, and tumor size were comparable across the 3 groups. A predominantly microfollicular pattern, an absence of nuclear pseudo-inclusions, and less frequent nuclear elongations and grooves were significantly more likely to be associated with NIFTP versus its invasive counterparts. The absence of nuclear pseudo-inclusions and the presence of a microfollicular pattern were the only independent predictors of a NIFTP diagnosis.

CONCLUSIONS

This study demonstrates that NIFTP cases have distinguishing cytomorphologic characteristics in comparison with invasive FVPTC cases. Therefore, a preoperative cytologic evaluation provides clues that can aid in the distinction between NIFTP and its invasive counterparts. Cancer Cytopathol 2017. © 2017 American Cancer Society.



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A pattern-based risk-stratification scheme for salivary gland cytology: A multi-institutional, interobserver variability study to determine applicability

BACKGROUND

Salivary gland aspiration cytology is useful in the preoperative management of patients but remains challenging, because of the extensive morphologic overlap of some tumors limits the ability to always determine the presence of malignancy. In response to this challenge, there has been increasing drive to develop a risk-based categorization scheme for salivary gland aspirates. Herein, the authors examine the interobserver variability of 1 such pattern and risk-based system.

METHODS

Select smears and cell-block sections of 50 salivary gland aspirates from 2 large academic centers were digitally imaged. These scanned slides were independently and blindly reviewed by 4 cytopathologists, and each aspirate was assigned to 1 of the proposed pattern-based categories if it was considered neoplastic by the observer. Interobserver agreement was scored and aggregated risks of malignancy were calculated for cases with available surgical follow-up.

RESULTS

In total, 42 samples (84%) were considered neoplastic by at least 2 observers and were scored for interobserver agreement: 10 of 42 (23.8%) had uniform agreement, 14 of 42 (33.3%) had majority agreement, and 5 of 42 (11.9%) had divided agreement. Only 9 of 42 samples (21.4%) had minimal agreement, and 4 of 42 (9.5%) had no agreement. Condensation of similar categories was able to improve interobserver agreement and still maintain stratified risk of malignancy.

CONCLUSIONS

The proposed pattern-based risk-stratification scheme, which could be implemented with the forthcoming Milan System, has good overall interobserver agreement and successfully stratifies the risk of malignancy. Some simplification is possible to make the system easier to use and improve interobserver agreement while maintaining stratification of risk. Cancer Cytopathol 2017. © 2017 American Cancer Society.



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Association of IL-27 rs153109 and rs17855750 Polymorphisms with Risk and Response to Therapy in Acute Lymphoblastic Leukemia

Abstract

Interleukin (IL)-27 is a cytokine with important anti-cancer activity. This study has evaluated the effects of IL-27 rs153109 and rs17855750 single nucleotide polymorphisms (SNPs) on risk of acute lymphoblastic leukemia (ALL) development, as well as their impact on prognosis and patient survival. A total of 200 patients and 210 healthy subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. We observed a higher frequency of rs153109 AG and rs17855750 TG genotypes and allele G in patients compared to controls (p < 0.001). Combined G variant genotypes (AG + GG and TG + GG) also conferred significantly greater risk of ALL. There was a significant correlation between the genotypes of both SNPs with event-free survival (EFS). Patients with GG genotypes of both SNPs and those of rs153109 AG and rs17855750 TG had a shorter EFS than patients with rs153109 AA and rs17855750 TT genotypes (p ≤ 0.035). Combined G variant genotypes for both SNPs showed poorer response to therapy in all patients (p < 0.027) as well as B-ALL (rs153109, p < 0.001) and T-ALL (rs153109, p = 0.048) patients. In multivariate analysis, rs153109 combined G variant genotype was associated with shorter EFS (relative risk = 9.7, p = 0.026). Among those who relapsed, 87.1% had the rs153109 AG genotype and 77.4% had the rs17855750 TG genotype (p < 0.01). Patients had higher IL-27 serum levels compared to controls, but this did not differ between genotypes. In conclusion, the association of IL-27 rs153109 and rs17855750 polymorphisms with risk of ALL development and their impact on EFS suggested an important role for this cytokine in biology and response to ALL therapy.



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Lactation-Based Maternal Educational Immunity Crosses MHC Class I Barriers and Can Impart Th1 Immunity to Th2-Biased Recipients [IMMUNE SYSTEM DEVELOPMENT]

We have previously demonstrated lactational transfer of T cell–based immunity from dam to foster pup. In the short term, a significant part of transferred immunity is passive cellular immunity. However, as time progresses, this is replaced by what we have described as maternal educational immunity such that by young adulthood, all immune cells responding to a foster dam immunogen are the product of the foster pup's thymus. To reduce confounding factors, this original demonstration used congenic/syngeneic dam and foster pup pairs. In this study, we investigated lactational transfer of immunity to Mycobacterium tuberculosis in MHC class I–mismatched animals, as well as from Th1-biased dams to Th2-biased foster pups. Using immunized C57BL/6J dams, lactational transfer to nonimmunized BALB/cJ foster pups resulted in much greater immunity than direct immunization in 5-wk-old pups (ex vivo assay of pup splenocytes). At this age, 82% of immunogen-responding cells in the pup spleen were produced through maternal educational immunity. FVB/NJ nonimmunized foster recipients had a greater number of maternal cells in the spleen and thymus but a much larger percentage was Foxp3+, resulting in equivalent immunity to direct immunization. Depletion of maternal Foxp3+ cells from pup splenocytes illustrated a substantial role for lactationally transferred dam regulatory T cells in suppression of the ex vivo response in FVB/NJ, but not BALB/cJ, recipients. We conclude that lactational transfer of immunity can cross MHC class I barriers and that Th1 immunity can be imparted to Th2-biased offspring; in some instances, it can be greater than that achieved by direct immunization.



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Immune Protection by a Cytomegalovirus Vaccine Vector Expressing a Single Low-Avidity Epitope [IMMUNOTHERAPY AND VACCINES]

Experimental CMV-based vaccine vectors expressing a single MHC class I–restricted high-avidity epitope provided strong, T cell–dependent protection against viruses or tumors. In this study we tested the low-avidity epitope KCSRNRQYL, and show that a mouse CMV (MCMV) vector provides complete immune control of recombinant vaccinia virus expressing the same epitope if KCSRNRQYL is expressed within the immediate-early MCMV gene ie2. The same epitope expressed within the early M45 gene provided no protection, although MCMV vectors expressing the high-avidity epitope SSIEFARL induced protective immunity irrespective of gene expression context. Immune protection was matched by Ag-induced, long-term expansion of effector memory CD8 T cells, regardless of epitope avidity. We explained this pattern by observing regularities in Ag competition, where responses to high-avidity epitopes outcompeted weaker ones expressed later in the replicative cycle of the virus. Conversely, robust and early expression of a low-avidity epitope compensated its weak intrinsic antigenicity, resulting in strong and sustained immunity and immune protection.



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Correction: A CD80-Biased CTLA4-Ig Fusion Protein with Superior In Vivo Efficacy by Simultaneous Engineering of Affinity, Selectivity, Stability, and FcRn Binding [CORRECTIONS]



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Retraction: Hypoxia-Inducible Factor-1{alpha}-Dependent Protection from Intestinal Ischemia/Reperfusion Injury Involves Ecto-5'-Nucleotidase (CD73) and the A2B Adenosine Receptor [LETTERS OF RETRACTION]



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Correction: Macrophage Mitochondrial and Stress Response to Ingestion of Cryptococcus neoformans [CORRECTIONS]



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Modified Vaccinia Virus Ankara Vector Induces Specific Cellular and Humoral Responses in the Female Reproductive Tract, the Main HIV Portal of Entry [MUCOSAL IMMUNOLOGY]

The female reproductive tract (FRT) is one of the major mucosal invasion sites for HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the FRT after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the FRT of nonhuman primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas APCs and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes). This compartmentalization of immune cells in the FRT was supported by transcriptomic analyses and a correlation network. Polyfunctional MVA-specific CD8+ T cells were detected in the blood, lymph nodes, vagina, cervix, uterus, and fallopian tubes. Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine dose. Thus, systemic vaccination with an MVA vector elicits cellular and Ab responses in the FRT.



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