Intra- and interpersonal effects of coping on the psychological well-being of adults with sensory loss and their spouses.

Intra- and interpersonal effects of coping on the psychological well-being of adults with sensory loss and their spouses.

Disabil Rehabil. 2017 Nov 30;:1-12

Authors: Lehane CM, Dammeyer J, Wittich W

Abstract
PURPOSE: The aim of the current study was to examine the associations between coping and psychological well-being among adults with sensory loss and their spouses.
METHODS: A total of 183 adults with sensory loss and 133 spouses participated in an online survey and were followed up six months later. Coping and well-being were measured using the Brief Coping Orientation to Problems Experienced Scale (Brief COPE) and the five-item World Health Organization Well-Being Index (WHO-5), respectively. Cross-sectional and longitudinal intra- and interpersonal effects of coping on psychological well-being were analyzed using a structural equation modeling approach.
RESULTS: Results showed that a significant portion of adults with sensory loss (32.4%) and spouses (23.8%) had poor well-being, and this remained stable over the six-month period. Coping styles associated with the well-being of adults with sensory loss included active coping, avoidance, distraction, venting and spouse support seeking. Coping styles associated with the well-being of spouses included support seeking, distraction, venting, avoidance (by partner) and humor (by partner).
CONCLUSION: The results highlight the need to support the well-being of adults with sensory loss and their spouses in rehabilitation, and the importance of both intra- and interpersonal coping in the adjustment process. Implications for rehabilitation Rehabilitation specialists and social workers working with adults with sensory loss should, where possible, incorporate family members into support plans. Rehabilitation specialists and social workers working in sensory rehabilitation should be mindful of how the coping styles of one partner can impact the well-being of their significant other. In addition to promoting positive coping behaviors, such as planning and support seeking, rehabilitation specialists and social workers should also take care to identify and reduce maladaptive coping behaviors such as avoidance and distraction. Online and print information for spouses on how to cope with a partner's sensory loss should be available and accessible for couples attending sensory rehabilitation clinics.

PMID: 29189088 [PubMed - as supplied by publisher]

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[A case of hereditary sensory and autonomic neuropathy type 1E with frontal lobe dysfunction as an initial symptom].

[A case of hereditary sensory and autonomic neuropathy type 1E with frontal lobe dysfunction as an initial symptom].

Rinsho Shinkeigaku. 2017 Nov 28;:

Authors: Watanabe M, Matsumoto Y, Okamoto K, Okuda B, Mizuta I, Mizuno T

Abstract
A 49-year-old man had developed gradually personality change, gait disturbance, and hearing loss for five years. On admission, he presented with frontal release signs, stuttering, vertical gaze palsy, sensorineural deafness, muscle rigidity, ataxia, and sensory disturbance with areflexia in the lower extremities. Brain MRI demonstrated atrophy in the cerebellum and midbrain tegmentum as well as cerebral atrophy, predominantly in the frontal lobe. He was tentatively diagnosed as progressive supranuclear palsy on the basis of clinical features and imagings. On nerve conduction study, no sensory nerve action potentials were elicited in the upper and lower extremities. Details of family history revealed a hereditary sensory neuropathy with autosomal dominant inheritance in his relatives. Because genetic analysis showed a rare missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene, we diagnosed him as having hereditary sensory and autonomic neuropathy type 1E (HSAN1E). In addition, p.M232R mutation in prion protein gene was detected. It should be kept in mind that there are some patients with HSAN1E presenting with frontal lobe dysfunction as an initial symptom and with clinical features mimicking progressive supranuclear palsy.

PMID: 29187684 [PubMed - as supplied by publisher]

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2nd Symposium on Advances in Cancer Immunology and Immunotherapy, December 15–17, 2016, Athens, Greece

Abstract

This is the 2nd Symposium of a series organized annually. It aims to integrate tumor immunology basic research with results from most recent clinical trials based on the use of anti-cancer agents targeting immune system components.

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[Microvascular reconstruction of the larynx following total laryngectomy].

[Microvascular reconstruction of the larynx following total laryngectomy].

Laryngorhinootologie. 2017 Nov 29;:

Authors: Hackenberg S, Kleinsasser N, Scherzad A, Kraus F, Hagen R

Abstract
Total laryngectomy still is a standard procedure for the treatment of advanced laryngeal or hypopharyngeal carcinoma. The unavoidable loss of voice may lead to serious impairments in quality of life. The most common technique of voice restoration is the tracheal-esophageal puncture combined with the application of a voice prosthesis. Laryngeal reconstruction with a radial forearm flap represents a possible surgical method of voice restoration. This study is a mono-center retrospective analysis of patients receiving a so-called laryngoplasty after total laryngectomy between 2006 and 2015, focusing on long-term functional outcome and complications. 39 patients were included. Sufficient phonation was possible in 77 %, finger-free speaking was achieved in 62 %. Exclusion of irradiated patients revealed a rehabilitation rate of 91 %. The most common early complication was cervical hematoma in 15 %, whereas no loss of flap was assessed. Stenosis of the laryngoplasty was seen in 7 cases, mainly post-irradiation. The rate of successful voice restoration is equal in both, laryngoplasty and voice prosthesis patients. However, voice quality is better after surgical reconstruction. Complications induced by the voice prosthesis, which may be severe in some cases, were not seen in the study group. Furthermore, life-long support by an ENT specialist regarding voice prosthesis exchange is not necessary. Assuming correct choice of candidates, laryngoplasty is a sufficient method for voice restoration after laryngectomy.

PMID: 29186749 [PubMed - as supplied by publisher]

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[Impact of microphone position on sound localization in cochlear implant users].

[Impact of microphone position on sound localization in cochlear implant users].

Laryngorhinootologie. 2017 Nov 29;:

Authors: Bandeira M, Baumann U, Weißgerber T

Abstract
Objective The delivery of directional cues of a hearing device microphone are highly dependent on the position of the microphones. The aim of this work was the evaluation of different microphone positions with regard to the transmission of interaural time and level differences as well as the spectral characteristics and its impact on the localization abilities. Methods Head-related transfer functions of 30 subjects were measured with three different omnidirectional microphones at different positions: in the pinna (ITP), behind the ear (BTE), at the entrance of the ear canal (EEC). Sound localization abilities of 12 bilateral CI users was assessed for the microphone positions ITP and BTE. Results Only the microphone positions in the ear (ITP, EEC) could sample the spectral cues of the pinna. However, the positioning of the microphone inside of the pinna did not significantly improve sound localization abilities compared to BTE microphones. For sound incidence from rear significantly less front-back confusions were achieved with the microphone inside of the pinna. Conclusion The microphone position in the pinna showed only a slight improvement in sound localization compared with BTE microphones in CI users. A precondition for better sound localization abilities is the improvement of the delivery of temporal and spectral fine structure cues in CI systems.

PMID: 29186748 [PubMed - as supplied by publisher]

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Globus symptoms in patients undergoing thyroidectomy: Relationships with psychogenic factors, thyroid disease, and surgical procedure.

Globus symptoms in patients undergoing thyroidectomy: Relationships with psychogenic factors, thyroid disease, and surgical procedure.

Thyroid. 2017 Nov 28;:

Authors: Tomoda C, Sugino K, Tanaka T, Ogimi Y, Masaki C, Akaishi J, Hames KY, Suzuki A, Matsuzu K, Uruno T, Ohkuwa K, Kitagawa W, Nagahama M, Ito K

Abstract
INTRODUCTION: The number of patients who need thyroid surgery has increased worldwide in recent decades. Patients with thyroid disease experience globus pharyngeus as a result of direct compression and edema of surrounding organs. Thyroid surgery is needed to improve these symptoms or as treatment for thyroid cancer. After thyroid surgery, globus symptoms may become worse and may affect the daily life of the patient for a long time. Psychogenic problems have also been thought to cause the globus sensation. A prospective analysis of globus symptoms and psychogenic factors following thyroidectomy was performed.
MATERIAL AND METHODS: Patients scheduled to undergo thyroid surgery between February and September 2016 completed the foreign-body sensation in the throat score (FBST, range 0-8.2) and the self-rating depression scale (SDS, range 0-100) preoperatively and 3 days, 1 month, 3 months, 6 months, and 12 months postoperatively.
RESULTS: Long-term follow-up was completed in 616 patients (491 females, 125 males). A total of 365 patients had malignant thyroid cancer, 169 patients had benign tumors, and 82 patients had diffuse goiters with Graves' disease. The percentage of patients who complained about neck discomfort (FBST > 2) was 29.4% before surgery. A preoperative high FBST showed a significant direct correlation with a high SDS, but thyroid volume did not. A postoperative high FBST was seen in 75.3% of patients at 2 days and 78.9% at 1 month after surgery, and it then gradually decreased to 49.3% at 12 months after surgery. At 3 days after the operation, the median FBST was significantly higher in patients who had total thyroidectomy (TT) with lateral neck dissection or TT only compared with those who had lobectomy only (all p < 0.05). These differences were still present 12 months after surgery. A higher preoperative SDS was also identified as an independent predictor for a high FBST at 12 months after surgery, but not at 1 month or 3 months postoperatively, on multivariate analyses.
CONCLUSION: Preoperative globus symptoms appear directly related to psychological factors. The area of the surgical procedure and preoperative psychological factors were related to persistent neck discomfort.

PMID: 29183262 [PubMed - as supplied by publisher]

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Relationship Between Frequency of Spontaneous Swallowing and Salivary Substance P Level in Patients with Acute Stroke.

Relationship Between Frequency of Spontaneous Swallowing and Salivary Substance P Level in Patients with Acute Stroke.

Dysphagia. 2017 Nov 28;:

Authors: Niimi M, Hashimoto G, Hara T, Yamada N, Abo M, Fujigasaki H, Ide T

Abstract
The frequency of spontaneous swallowing is useful for screening of dysphagia in acute stroke. Low levels of substance P (SP) in saliva attenuate the swallowing reflex. The aim of this study was to determine the relationship between the frequency of spontaneous swallowing and salivary SP levels. In 40 subjects, saliva was collected within 72 h after stroke onset and salivary SP levels were measured using ELISA kit at a later date. The frequency of spontaneous swallowing was measured over 1 h using a microphone placed on the neck. Pneumonia was diagnosed by the presence of pyrexia and at least two respiratory problems of four categories (sputum, cough or breathing pattern, breath sound, and gas change). The presence of detectable levels of SP in the saliva was confirmed in 17 patients (high SP group), whereas the level was below the detection limit of the ELISA kit in 23 patients (low SP group). The frequency of spontaneous swallowing was significantly lower in low SP group (16.1 ± 11.6 per hour) than in the high SP group (30.4 ± 20.4, p = 0.016). As the result of multiple regression analysis, salivary SP levels were correlated with frequency of spontaneous swallowing independently of age, NIHSS, and GCS. The incidence of pneumonia was significantly higher in the low than high SP group (p < 0.001). In conclusion, the frequency of spontaneous swallowing was decreased in acute stroke patients with low salivary SP levels. Salivary SP levels can be potentially a useful biomarker of risk of stroke-associated pneumonia in the acute stage.

PMID: 29185035 [PubMed - as supplied by publisher]

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Effects of jaw opening exercise on aspiration in stroke patients with dysphagia: a pilot study.

Effects of jaw opening exercise on aspiration in stroke patients with dysphagia: a pilot study.

J Phys Ther Sci. 2017 Oct;29(10):1817-1818

Authors: Oh DH, Won JH, Kim YA, Kim WJ

Abstract
[Purpose] The purpose of this study was to investigate the effect of jaw opening exercise (JOE) on aspiration in patients with dysphagia after stroke. [Subjects and Methods] Three subjects were recruited. Isometric and isotonic JOE were performed using a rubber ball, 5 days a week for 4 weeks. Aspiration was evaluated using the penetration-a spiration scale (PAS) based on a videofluoroscopic swallowing study. [Results] All subjects showed a score reduction of at least 1 point and a maximum reduction of 2 points in the PAS in the liquid type. [Conclusion] This study confirmed that JOE can be used to reduce aspiration in patients with dysphagia after stroke.

PMID: 29184295 [PubMed]

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Effects of bedside self-exercise on oropharyngeal swallowing function in stroke patients with dysphagia: a pilot study.

Effects of bedside self-exercise on oropharyngeal swallowing function in stroke patients with dysphagia: a pilot study.

J Phys Ther Sci. 2017 Oct;29(10):1815-1816

Authors: Cho YS, Oh DH, Paik YR, Lee JH, Park JS

Abstract
[Purpose] The purpose of this study was to investigate the effect of self-exercise on oropharyngeal swallowing function in patients with dysphagia. [Subjects and Methods] Nine patients with dysphagia after stroke were recruited. Self-exercise including effortful swallowing, tongue strengthening, and shaker exercise was performed 5 times a week for 4 weeks. Swallowing function was evaluated using the videofluoroscopic dysphagia scale (VDS) based on a videofluoroscopic swallowing study. [Results] There were significant differences in both the oral and pharyngeal phases of the VDS before and after the intervention. [Conclusion] This study demonstrated that bedside self-exercise is a positive method to improve oropharyngeal swallowing function in patients with dysphagia after stroke.

PMID: 29184294 [PubMed]

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Relationship Between Frequency of Spontaneous Swallowing and Salivary Substance P Level in Patients with Acute Stroke.

Relationship Between Frequency of Spontaneous Swallowing and Salivary Substance P Level in Patients with Acute Stroke.

Dysphagia. 2017 Nov 28;:

Authors: Niimi M, Hashimoto G, Hara T, Yamada N, Abo M, Fujigasaki H, Ide T

Abstract
The frequency of spontaneous swallowing is useful for screening of dysphagia in acute stroke. Low levels of substance P (SP) in saliva attenuate the swallowing reflex. The aim of this study was to determine the relationship between the frequency of spontaneous swallowing and salivary SP levels. In 40 subjects, saliva was collected within 72 h after stroke onset and salivary SP levels were measured using ELISA kit at a later date. The frequency of spontaneous swallowing was measured over 1 h using a microphone placed on the neck. Pneumonia was diagnosed by the presence of pyrexia and at least two respiratory problems of four categories (sputum, cough or breathing pattern, breath sound, and gas change). The presence of detectable levels of SP in the saliva was confirmed in 17 patients (high SP group), whereas the level was below the detection limit of the ELISA kit in 23 patients (low SP group). The frequency of spontaneous swallowing was significantly lower in low SP group (16.1 ± 11.6 per hour) than in the high SP group (30.4 ± 20.4, p = 0.016). As the result of multiple regression analysis, salivary SP levels were correlated with frequency of spontaneous swallowing independently of age, NIHSS, and GCS. The incidence of pneumonia was significantly higher in the low than high SP group (p < 0.001). In conclusion, the frequency of spontaneous swallowing was decreased in acute stroke patients with low salivary SP levels. Salivary SP levels can be potentially a useful biomarker of risk of stroke-associated pneumonia in the acute stage.

PMID: 29185035 [PubMed - as supplied by publisher]

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Effects of jaw opening exercise on aspiration in stroke patients with dysphagia: a pilot study.

Effects of jaw opening exercise on aspiration in stroke patients with dysphagia: a pilot study.

J Phys Ther Sci. 2017 Oct;29(10):1817-1818

Authors: Oh DH, Won JH, Kim YA, Kim WJ

Abstract
[Purpose] The purpose of this study was to investigate the effect of jaw opening exercise (JOE) on aspiration in patients with dysphagia after stroke. [Subjects and Methods] Three subjects were recruited. Isometric and isotonic JOE were performed using a rubber ball, 5 days a week for 4 weeks. Aspiration was evaluated using the penetration-a spiration scale (PAS) based on a videofluoroscopic swallowing study. [Results] All subjects showed a score reduction of at least 1 point and a maximum reduction of 2 points in the PAS in the liquid type. [Conclusion] This study confirmed that JOE can be used to reduce aspiration in patients with dysphagia after stroke.

PMID: 29184295 [PubMed]

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Effects of bedside self-exercise on oropharyngeal swallowing function in stroke patients with dysphagia: a pilot study.

Effects of bedside self-exercise on oropharyngeal swallowing function in stroke patients with dysphagia: a pilot study.

J Phys Ther Sci. 2017 Oct;29(10):1815-1816

Authors: Cho YS, Oh DH, Paik YR, Lee JH, Park JS

Abstract
[Purpose] The purpose of this study was to investigate the effect of self-exercise on oropharyngeal swallowing function in patients with dysphagia. [Subjects and Methods] Nine patients with dysphagia after stroke were recruited. Self-exercise including effortful swallowing, tongue strengthening, and shaker exercise was performed 5 times a week for 4 weeks. Swallowing function was evaluated using the videofluoroscopic dysphagia scale (VDS) based on a videofluoroscopic swallowing study. [Results] There were significant differences in both the oral and pharyngeal phases of the VDS before and after the intervention. [Conclusion] This study demonstrated that bedside self-exercise is a positive method to improve oropharyngeal swallowing function in patients with dysphagia after stroke.

PMID: 29184294 [PubMed]

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Spinal movement and dural sac compression during airway management in a cadaveric model with atlanto-occipital instability

Abstract

Purpose

To analyze the compression of the dural sac and the cervical spinal movement during performing different airway interventions in case of atlanto-occipital dislocation.

Methods

In six fresh cadavers, atlanto-occipital dislocation was performed by distracting the opened atlanto-occipital joint capsule and sectioning the tectorial membrane. Airway management was done using three airway devices (direct laryngoscopy, video laryngoscopy, and insertion of a laryngeal tube). The change of dural sac's width and intervertebral angulation in stable and unstable atlanto-occipital conditions were recorded by video fluoroscopy with myelography. Three-dimensional overall movement of cervical spine was measured in a wireless human motion track system.

Results

Compared with a mean dural sac compression of − 0.5 mm (− 0.7 to − 0.3 mm) in stable condition, direct laryngoscopy caused an increased dural sac compression of − 1.6 mm (− 1.9 to − 0.6 mm, p = 0.028) in the unstable atlanto-occipital condition. No increased compression on dural sac was found using video laryngoscopy or the laryngeal tube. Moreover, direct laryngoscopy caused greater overall extension and rotation of cervical spine than laryngeal tube insertion in both stable and unstable conditions. Among three procedures, the insertion of a laryngeal tube took the shortest time.

Conclusion

In case of atlanto-occipital dislocation, intubation using direct laryngoscopy exacerbates dural sac compression and may cause damage to the spinal cord.

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Letter to the Editor concerning ‘‘Efficacy and safety of tranexamic acid in reducing blood loss in scoliosis surgery: a systematic review and meta-analysis.’’ by Yuan, QM. et al. (Eur Spine J; 2017. doi:10.1007/s00586-016-4899-0)

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Radiotherapy for locally advanced resectable T3-T4 laryngeal cancer-does laryngeal preservation strategy compromise survival?

Radiotherapy for locally advanced resectable T3-T4 laryngeal cancer-does laryngeal preservation strategy compromise survival?

J Radiat Res. 2017 Nov 28;:1-14

Authors: Yamazaki H, Suzuki G, Nakamura S, Hirano S, Yoshida K, Konishi K, Teshima T, Ogawa K

Abstract
With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP.

PMID: 29190391 [PubMed - as supplied by publisher]

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Adjusting Pediatric Endotracheal Tube Depths Relative to the Cricoid by Using Longitudinal Ultrasound Images of the Saline-Inflated Cuff in the Trachea: Two Case Reports.

Adjusting Pediatric Endotracheal Tube Depths Relative to the Cricoid by Using Longitudinal Ultrasound Images of the Saline-Inflated Cuff in the Trachea: Two Case Reports.

A A Case Rep. 2017 Nov 16;:

Authors: Kayashima K, Mizuyama H, Takesue M, Doi T, Imai K, Murashima K

Abstract
Cuff positions of endotracheal tubes should be confirmed to ensure safe anesthesia. However, determining the cuff positions relative to the cricoid by using chest radiography or fiberoptic bronchoscopy is difficult. We identified the cephalad edges of saline-inflated pediatric endotracheal tube cuffs relative to the cricoid on longitudinal ultrasound images over the larynx and trachea in 2 children. Thereafter, we adjusted the endotracheal tube depths and confirmed the cuff positions relative to the cricoid. Longitudinal ultrasound images over the larynx and trachea can help confirm the distance from the caudal edge of the cricoid to the saline-inflated cuff.

PMID: 29189285 [PubMed - as supplied by publisher]

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The role of laryngectomy in locally advanced thyroid carcinoma. Review of 16 cases.

The role of laryngectomy in locally advanced thyroid carcinoma. Review of 16 cases.

Acta Otorhinolaryngol Ital. 2017 Nov 30;:

Authors: Chala AI, Vélez S, Sanabria A

Abstract
Locally advanced disease with larynx invasion is a challenge to the surgeon, but laryngectomy is almost never necessary in thyroid carcinoma. The aim of this study was to review the clinical outcomes of patients with locally advanced thyroid carcinoma invading the larynx who underwent laryngectomy. A case series of patients treated in a tertiary care hospital was reviewed. Data about the type of operation, method of reconstruction, complications and overall survival of 16 patients operated on between 2002 and 2015 with larynx invasion is presented. There were 10 females. The mean age was 63 ± 8.8 years. Besides total thyroidectomy and neck dissection, four patients underwent total pharyngolaryngectomy, 11 total laryngectomy and one hemi-laryngectomy. Reconstruction was made with regional flaps in 10 patients (7 pectoral/Bakamjian flaps and 3 gastric pull-through procedures) and a jejunum free flap in one patient. Two patients needed carotid artery reconstruction. Five tumours were classic (conventional) papillary carcinoma variants, while the others were aggressive histological varieties (insular, tall cell, sclerosing). The mean tumour size was 4.3 ± 1.6 cm. All tumours had lymphovascular invasion and 12 had positive lymph nodes. Concomitantly, oesophageal/hypopharynx invasion was present in 7 cases and invasion of carotid vessels in 2 cases. There were two postoperative deaths and two anastomotic leaks that were treated conservatively. The mean overall survival was 31 ± 33 months (median 27.6 months, range 0-120). Laryngectomy is an alternative surgical procedure to control selected cases of advanced thyroid carcinoma that offers good local control and long term survival.

PMID: 29187757 [PubMed - as supplied by publisher]

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[Microvascular reconstruction of the larynx following total laryngectomy].

[Microvascular reconstruction of the larynx following total laryngectomy].

Laryngorhinootologie. 2017 Nov 29;:

Authors: Hackenberg S, Kleinsasser N, Scherzad A, Kraus F, Hagen R

Abstract
Total laryngectomy still is a standard procedure for the treatment of advanced laryngeal or hypopharyngeal carcinoma. The unavoidable loss of voice may lead to serious impairments in quality of life. The most common technique of voice restoration is the tracheal-esophageal puncture combined with the application of a voice prosthesis. Laryngeal reconstruction with a radial forearm flap represents a possible surgical method of voice restoration. This study is a mono-center retrospective analysis of patients receiving a so-called laryngoplasty after total laryngectomy between 2006 and 2015, focusing on long-term functional outcome and complications. 39 patients were included. Sufficient phonation was possible in 77 %, finger-free speaking was achieved in 62 %. Exclusion of irradiated patients revealed a rehabilitation rate of 91 %. The most common early complication was cervical hematoma in 15 %, whereas no loss of flap was assessed. Stenosis of the laryngoplasty was seen in 7 cases, mainly post-irradiation. The rate of successful voice restoration is equal in both, laryngoplasty and voice prosthesis patients. However, voice quality is better after surgical reconstruction. Complications induced by the voice prosthesis, which may be severe in some cases, were not seen in the study group. Furthermore, life-long support by an ENT specialist regarding voice prosthesis exchange is not necessary. Assuming correct choice of candidates, laryngoplasty is a sufficient method for voice restoration after laryngectomy.

PMID: 29186749 [PubMed - as supplied by publisher]

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Liver Transplantation From Donors With a History of Malignancy: A Single-Center Experience.

Liver Transplantation From Donors With a History of Malignancy: A Single-Center Experience.

Transplant Direct. 2017 Nov;3(11):e224

Authors: Benkö T, Hoyer DP, Saner FH, Treckmann JW, Paul A, Radunz S

Abstract
Background: The demand for transplantable organs exceeds donor organ supply. Transplantation of organs from donors with a history of malignancy remains controversial and the transmission of cancer in liver transplant recipients has not been sufficiently examined.
Methods: From 2002 until 2017, 83 livers from donors with a history of malignancy were transplanted at the University Hospital Essen, Germany. Donor and recipient data, type of malignancy, tumor-free interval at organ procurement, and follow-up data were analyzed.
Results: Nine different tumor sites (central nervous system [n = 27], genitourinary [n = 24], breast [n = 10], skin [n = 8], colorectal [n = 5], lung [n = 3], hemato-oncological [n = 3], thyroid [n = 2], and larynx [n = 1]) were detected in 83 donors. The majority (58%) of donors had tumor-free intervals of less than 5 years versus 19% of 6 to 10 years versus 23% over 10 years. The risk of tumor transmission from donors was assessed as low in 44 (53%), intermediate in 28 (34%), and high in 11 (13%) cases. During median follow-up of 19.9 (0-155) months, none of the recipients developed donor-transmitted malignancy.
Conclusions: Liver transplantation with organs from donors with a medical history of malignancy is feasible, and the risk of donor-transmitted malignancy appears to be low in this single-center analysis. A careful selection of donors remains mandatory and can expand the donor pool.

PMID: 29184912 [PubMed]

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Laryngomalacia: is there an evidence base for management?

Related Articles

Laryngomalacia: is there an evidence base for management?

J Laryngol Otol. 2017 Nov;131(11):946-954

Authors: McCaffer C, Blackmore K, Flood LM

Abstract
BACKGROUND: The advent of supraglottoplasty clearly has transformed the surgical management of severe laryngomalacia. The condition, however, generally runs a milder course, with spontaneous resolution the norm.
OBJECTIVES: To identify gaps in the knowledge and identify topics for future study.
METHOD: Systematic review of the literature.
RESULTS: The literature suggests that there is a range of abnormalities leading to the typical collapsing upper airway, and that neurological disease, other airway abnormalities, syndromes and gastroesophageal reflux all contribute to disease severity and influence outcomes. The procedures involved in supraglottoplasty are rarely specified, the indications for surgery are vaguely defined and the role of medical therapy is unclear.
CONCLUSION: Every review article or survey of opinion suggests that there is still a marked variation in individual practice and a lack of consensus.

PMID: 29067893 [PubMed - indexed for MEDLINE]

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MicroRNA let-7a up-regulates OPN expression in a mouse model of allergic rhinitis.

Related Articles

MicroRNA let-7a up-regulates OPN expression in a mouse model of allergic rhinitis.

J Laryngol Otol. 2017 Nov;131(11):955-960

Authors: Yu H, Sun H, Wang Z, Liu Y

Abstract
OBJECTIVE: To investigate the effect of microRNA let-7a on OPN expression in a mouse model of allergic rhinitis.
METHODS: Thirty-two mature female C57BL/6 mice were randomly divided into four groups, with eight mice in each group: microRNA let-7a, microRNA control, OVA and phosphate-buffered saline groups. The microRNA let-7a, microRNA control and OVA groups were sensitised with OVA to establish a mouse model of allergic rhinitis. Nose-scratching events were counted. Nasal mucosa was used to evaluate histological changes of goblet cell hyperplasia. Interleukins 5 and 13 were detected. Interferon-γ levels in the nasal lavage fluid were assayed with enzyme-linked immunosorbent assay. OPN expression was estimated with polymerase chain reaction.
RESULTS: Compared with microRNA control mice, microRNA let-7a treated mice had a significantly increased number of nose-scratching events, nasal mucosal eosinophilia and goblet cell hyperplasia (p 0.05). In addition, microRNA let-7a treated mice had significantly enhanced OPN expression in nasal mucosa (p < 0.05).
CONCLUSION: MicroRNA let-7a can promote allergic rhinitis development partly by regulating OPN expression.

PMID: 28807083 [PubMed - indexed for MEDLINE]

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[The possibilities for sex determination based on the specific anatomical features of the human thyroid cartilage].

Related Articles

[The possibilities for sex determination based on the specific anatomical features of the human thyroid cartilage].

Sud Med Ekspert. 2017;60(4):21-24

Authors: Poletaeva MP

Abstract
The objective of the present work was to study the specific morphological features in the structure of the human thyroid cartilage obtained from 35 men and 35 women. The analysis and evaluation of 31 characteristics of the thyroid cartilage have demonstrated that its size in the men was bigger than in the women with the exception of the angle between the plates that was of a larger size in the women than in the men and showed the closest correlation with the sex. The majority of other characteristics of the thyroid cartilage measured in the study either strongly or moderately correlated with the sex which makes it possible to use these measurements for the purpose of personality identification during forensic medical expertise.

PMID: 28766524 [PubMed - indexed for MEDLINE]

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The thumb sign.

Related Articles

The thumb sign.

N Z Med J. 2017 07 21;130(1459):71-72

Authors: Bakshi SS, Balpande G

PMID: 28727696 [PubMed - indexed for MEDLINE]

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Comparative proteomics of paired vocal fold and oral mucosa fibroblasts.

Related Articles

Comparative proteomics of paired vocal fold and oral mucosa fibroblasts.

J Proteomics. 2017 Feb 23;155:11-21

Authors: Karbiener M, Darnhofer B, Frisch MT, Rinner B, Birner-Gruenberger R, Gugatschka M

Abstract
Injuries of the vocal folds frequently heal with scar formation, which can have lifelong detrimental impact on voice quality. Current treatments to prevent or resolve scars of the vocal fold mucosa are highly unsatisfactory. In contrast, the adjacent oral mucosa is mostly resistant to scarring. These differences in healing tendency might relate to distinct properties of the fibroblasts populating oral and vocal fold mucosae. We thus established the in vitro cultivation of paired, near-primary vocal fold fibroblasts (VFF) and oral mucosa fibroblasts (OMF) to perform a basic cellular characterization and comparative cellular proteomics. VFF were significantly larger than OMF, proliferated more slowly, and exhibited a sustained TGF-β1-induced elevation of pro-fibrotic interleukin 6. Cluster analysis of the proteomic data revealed distinct protein repertoires specific for VFF and OMF. Further, VFF displayed a broader protein spectrum, particularly a more sophisticated array of factors constituting and modifying the extracellular matrix. Conversely, subsets of OMF-enriched proteins were linked to cellular proliferation, nuclear events, and protection against oxidative stress. Altogether, this study supports the notion that fibroblasts sensitively adapt to the functional peculiarities of their respective anatomical location and presents several molecular targets for further investigation in the context of vocal fold wound healing.
BIOLOGICAL SIGNIFICANCE: Mammalian vocal folds are a unique but delicate tissue. A considerable fraction of people is affected by voice problems, yet many of the underlying vocal fold pathologies are sparsely understood at the molecular level. One such pathology is vocal fold scarring - the tendency of vocal fold injuries to heal with scar formation -, which represents a clinical problem with highly suboptimal treatment modalities. This study employed proteomics to obtain comprehensive insight into the protein repertoire of vocal fold fibroblasts, which are the cells that predominantly synthesize the extracellular matrix in both physiological and pathophysiological conditions. Protein profiles were compared to paired fibroblasts from the oral mucosa, a neighboring tissue that is remarkably resistant to scarring. Bioinformatic analyses of the data revealed a number of pathways as well as single proteins (e.g. ECM-remodeling factors, transcription factors, enzymes) that were significantly different between the two fibroblast types. Thereby, this study has revealed novel interesting molecular targets which can be analyzed in the future for their impact on vocal fold wound healing.

PMID: 28099887 [PubMed - indexed for MEDLINE]

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Pre-operative language ability in patients with presumed low-grade glioma

Abstract

In patients with low-grade glioma (LGG), language deficits are usually only found and investigated after surgery. Deficits may be present before surgery but to date, studies have yielded varying results regarding the extent of this problem and in what language domains deficits may occur. This study therefore aims to explore the language ability of patients who have recently received a presumptive diagnosis of low-grade glioma, and also to see whether they reported any changes in their language ability before receiving treatment. Twenty-three patients were tested using a comprehensive test battery that consisted of standard aphasia tests and tests of lexical retrieval and high-level language functions. The patients were also asked whether they had noticed any change in their use of language or ability to communicate. The test scores were compared to a matched reference group and to clinical norms. The presumed LGG group performed significantly worse than the reference group on two tests of lexical retrieval. Since five patients after surgery were discovered to have a high-grade glioma, a separate analysis excluding them were performed. These analyses revealed comparable results; however one test of word fluency was no longer significant. Individually, the majority exhibited normal or nearly normal language ability and only a few reported subjective changes in language or ability to communicate. This study shows that patients who have been diagnosed with LGG generally show mild or no language deficits on either objective or subjective assessment.

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2nd Symposium on Advances in Cancer Immunology and Immunotherapy, December 15–17, 2016, Athens, Greece

Abstract

This is the 2nd Symposium of a series organized annually. It aims to integrate tumor immunology basic research with results from most recent clinical trials based on the use of anti-cancer agents targeting immune system components.

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Surgical complications and their management in cochlear implantees less than 5 years of age: The KEMH Pune experience.

Surgical complications and their management in cochlear implantees less than 5 years of age: The KEMH Pune experience.

Cochlear Implants Int. 2017 Nov 30;:1-5

Authors: Shiras S, Vaid N, Vaid S, Kothadiya A

Abstract
OBJECTIVE: To evaluate the incidence of surgical complications of cochlear implantation and their management at K.E.M. hospital Pune.
METHODS: It was a retrospective and prospective observational study conducted from February 2006 to December 2015 in the paediatric age group of 12 months to 5 years (213 cases). The complications were divided into major and minor groups based on the classification proposed by Cohen and Hoffman.
RESULTS: The mean age of implantation was 3.03 years (ranged from 1 to 4.11 years). Sixteen patients had complications. The overall incidence of complications was 7.51% which comprised of major (2.34%) and minor (5.16%) complications. The commonest major complications were flap-related issues and the commonest minor complication was facial paresis.
DISCUSSION: The results of our study were compared with similar studies conducted in the past. All surgical complications were treated conservatively or surgically with success.
CONCLUSIONS: Cochlear implantation is the safe procedure in children between the age group of 12 months and less than 5 years.

PMID: 29188760 [PubMed - as supplied by publisher]

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Utility of intraoperative computed tomography for cochlear implantation in patients with difficult anatomy.

Utility of intraoperative computed tomography for cochlear implantation in patients with difficult anatomy.

Cochlear Implants Int. 2017 Nov 30;:1-10

Authors: Kim CS, Maxfield AZ, Foyt D, Rapoport RJ

Abstract
OBJECTIVE AND IMPORTANCE: To describe cases that illustrate the utility of intraoperative computed tomography (CT) in cochlear implantation of patients with difficult temporal bone anatomy.
CLINICAL PRESENTATION: A 2-year-old male with congenital X-linked stapes gusher syndrome and a 2-year-old female with enlarged vestibular aqueduct underwent successful cochlear implantation with the help of intraoperative CT. In the latter case, the initial intraoperative C-arm fluoroscopy suggested malposition of the electrode, however, was not able to provide details for adjustments. In both cases, intraoperative CT changed the insertion technique of the operating surgeon and allowed for improved electrode positioning. A 47-year-old female with polyostotic fibrous dysplasia and a 55-year-old male with post-meningitis near-total cochlear obliteration underwent successful cochlear implantation with confirmation of electrode position with intraoperative CT. In the former case, the image-guided navigation system was also implemented. Finally, a 72-year-old female underwent cochlear implantation during which intraoperative C-arm fluoroscopy suggested intra-cochlear insertion. However, postoperative CT showed the electrode extending into the internal auditory canal (IAC), illustrating the limitations of C-arm fluoroscopy.
INTERVENTION: Intraoperative CT imaging and image-guided navigation system.
CONCLUSION: When faced with challenging temporal bone anatomy, intraoperative CT can provide critical details of the patient's microanatomy that allows for improved localization of the electrode and adjustments in operative techniques for successful cochlear implantation.

PMID: 29188758 [PubMed - as supplied by publisher]

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2nd Symposium on Advances in Cancer Immunology and Immunotherapy, December 15–17, 2016, Athens, Greece

Abstract

This is the 2nd Symposium of a series organized annually. It aims to integrate tumor immunology basic research with results from most recent clinical trials based on the use of anti-cancer agents targeting immune system components.

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Minimally conscious state or cortically mediated state?

Abstract

Durable impairments of consciousness are currently classified in three main neurological categories: comatose state, vegetative state (also recently coined unresponsive wakefulness syndrome) and minimally conscious state. While the introduction of minimally conscious state, in 2002, was a major progress to help clinicians recognize complex non-reflexive behaviours in the absence of functional communication, it raises several problems. The most important issue related to minimally conscious state lies in its criteria: while behavioural definition of minimally conscious state lacks any direct evidence of patient's conscious content or conscious state, it includes the adjective 'conscious'. I discuss this major problem in this review and propose a novel interpretation of minimally conscious state: its criteria do not inform us about the potential residual consciousness of patients, but they do inform us with certainty about the presence of a cortically mediated state. Based on this constructive criticism review, I suggest three proposals aiming at improving the way we describe the subjective and cognitive state of non-communicating patients. In particular, I present a tentative new classification of impairments of consciousness that combines behavioural evidence with functional brain imaging data, in order to probe directly and univocally residual conscious processes.

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Update on pediatric sinus surgery: indications and outcomes

Purpose of review To review the recent literature of pediatric endoscopic sinus surgery (ESS). Recent findings Sinus balloon catheter dilation is an important addition to the surgical treatment tools for pediatric chronic rhinosinusitis (PCRS). ESS is a safe and effective therapeutic modality for uncomplicated PCRS. For PCRS complicated by comorbidities including cystic fibrosis and primary ciliary dyskinesia, ESS and adjuvant medical therapy confers significant sinus, pulmonary, and quality of life benefits to pediatric patients. Summary ESS is a safe and effective treatment modality in the management of pediatric acute and chronic sinus disorders.

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Role of reinnervation in the management of recurrent laryngeal nerve injury: current state and advances

Purpose of review To present the current state of knowledge concerning different laryngeal reinnervation procedures for unilateral and bilateral vocal palsy. Recent findings Recent reports show positive outcomes on both unilateral and bilateral reinnervations. The phrenic nerve is the most commonly used donor for bilateral vocal palsy, but use of the superior laryngeal nerve has also been suggested. Summary Reinnervation of the larynx is a complex undertaking that can be performed by ENT surgeons with skills in microsurgery. Advances in this this field represent a paradigm shift in laryngeal rehabilitation and a prerequisite for laryngeal transplantation. Advances in basic understanding of nerve regeneration and in particular the need to surgically manage competitive reinnervation make the results of laryngeal reinnervation more predictable.

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Management of Type I and Type II laryngeal clefts: controversies and evidence

Purpose of review To summarize the pediatric Type I and Type II laryngeal cleft literature, paying special attention to recent trends, including evolution of surgical techniques, standardization of outcome assessments, and utilization of management algorithms. Recent findings There are a variety of options to choose from whenever considering Type I and Type II cleft repair, including endoscopic repair, transoral robotic surgery, and injection laryngoplasty. Conservative management including feeding therapy and treatment of comorbid medical conditions is recommended prior to repair. Validated outcome measures have arisen for swallow study interpretation and timing, as well as caregiver quality-of-life assessment. In addition, a series of medical algorithms have been proposed, which provide specific recommendations for diagnosis, treatment, and follow-up. Summary For clefts that fail conservative management, endoscopic repair has become the gold standard. In addition, injection laryngoplasty appears to provide both a diagnostic and therapeutic option in the management of these patients. Transoral robotic-assisted endoscopic repair appears well tolerated and feasible, although broader implementation of this technology remains limited. The development and refinement of best practice algorithms can help standardize management and improve decision-making. Furthermore, incorporating validated outcome measures, recorded and followed over time, will improve both patient care and research efforts moving forward.

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Vocal tremor: where are we at?

Purpose of review Vocal tremor in movement disorders is often overlooked, although it has a significant impact on quality of life. Careful observation of tremor phenomenology allows for accurate diagnosis and tailored treatment. Recent findings The central pathways associated with various vocal tremor-associated diseases have been further elucidated. Summary Patients are likely to benefit from a combination of medical and interventional treatments delivered within a multidisciplinary setting

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Editorial

No abstract available

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Epidemiology of Vestibular Disorders in the Otoneurology Unit

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Gloria Guerra-Jiménez, Alejandra Arenas Rodríguez, Juan Carlos Falcón González, Daniel Pérez Plasencia, Ángel Ramos Macías
Introduction and objectivesThe set of symptoms relating to disorders of the balance system are common in the general population. However, there are few studies quantifying the frequency of onset of the various vestibular disorders that present in specialist otoneurology units in the Spanish population. The aim of this study is to establish the epidemiology of vestibular disorders, their form of presentation, and the expected care burden in a specialist otoneurology clinic.Material and methodsA retrospective, descriptive, observational study of patients referred to the otoneurology unit of a third level hospital between 1/1/2015 and 31/12/2015.ResultsOne hundred and seventy-four patients were assessed (121 women and 53 men) with a mean age of 53±17 years. Forty-three individuals per 100,000 inhabitants were assessed over the study period. The patients were referred in the majority from external ENT (36.8%) and primary care (28.7%) clinics. The most frequent reason for consultation was dizziness (40.2%) followed by vertigo (31%). The most frequent diagnoses were benign paroxysmal positional vertigo (28.2%) and vestibular migraine (28.2%) –defined (59%) or probable (41%)–, followed by Ménière's disease (13.8%), vascular disorders (5.7%), chronic subjective dizziness (4.6%) and vestibular neuritis (4%).ConclusionsThe availability of precise information on the prevalence and impact of vestibular disorders is important to enable the health services to plan an appropriate response to the expected care demand in the community. Benign paroxysmal positional vertigo and vestibular migraine are the most commonly diagnosed disorders in otoneurology clinics. Systematic terminology is essential for the comparison of results.



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Does calcemia influence the onset of myringosclerosis after myringotomy with the insertion of ventilation tubes?

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Carla Branco, João Paço
IntroductionMyringosclerosis is one of the most frequent late complications of the insertion of ventilation tubes, and its aetiopathogenesis remains unknown. The calcification that occurs in the formation of myringosclerosis plaque raises the hypothesis of the presence of a calcium metabolism disorder. The objective is to determine whether calcemia contributes to the development of myringoscelerosis after insertion of ventilation tubes.Material and methodsA longitudinal, prospective, analytical cohort study was conducted in patients undergoing myringotomy with the insertion of ventilation tubes due to otitis media with effusion. Calcemia was evaluated pre-operatively and in the follow-up the appearance of myringosclerosis and the percentage of the tympanum involved were evaluated.ResultsThe study included 156 patients (297 ears), with calcemia values ranging from 7.6 to 10.2mg/dl. Myringosclerosis was identified in 35.4% of the operated ears. No relationship was found between the appearance of myringosclerosis and calcemia (p=.596). It was found, however, that the greater the percentage of the tympanum affected by myringosclerosis, the lower the calcemia values (p=.014).ConclusionThe population studied had calcemia values within the normal range, which allows us to infer that no changes in calcium metabolism are required for the development of myringosclerosis. Moreover, unlike in previous studies, higher calcium levels are not associated with more myringosclerosis. Calcemia did not influence the appearance of myringosclerosis after myringotomy with the insertion of ventilation tubes.



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Results of Total Laryngectomy as Treatment for Locally Advanced Hypopharyngeal Cancer

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Patricia García-Cabo Herrero, Laura Fernández-Vañes, Fernando López Álvarez, César Álvarez Marcos, José Luis Llorente, Juan Pablo Rodrigo
Introduction and objectivesTotal laryngectomy (TL), with eventual postoperative radiotherapy, has proven to be effective in treating cases of locally advanced hypopharyngeal cancer. The aim of this study was to analyse the oncological outcomes of this procedure in patients with hypopharyngeal cancer classified T3 and T4.MethodsWe studied 59 patients (33 T3 and 26 T4a) with primary squamous cell carcinoma of the hypopharynx treated with TL from 1998 to 2012.ResultsMean age was 61 years with a male predominance (96.6%). All the patients were smokers and 96% consumed alcohol. Unilateral selective neck dissection (ND) was performed in 12 patients, unilateral radical ND in 11 patients, bilateral selective ND in 20 patients and radical ND plus selective ND in 14 patients. Sixty-six percentage of the patients received postoperative radiotherapy. Lymph node metastases occurred in 81% of the patients and extranodal invasion in 56% of them. Twenty-nine percentage of the patients had loco-regional recurrence, 17% developed distant metastases, and 25% a second primary tumour. The 5-year disease-specific survival was 46%.ConclusionsTL extended to pharynx (with eventual postoperative radiotherapy) offers good oncological results in terms of loco-regional control and survival in locally advanced hypopharyngeal cancer, so organ preservation protocols should achieve similar oncological results to those shown by TL.



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Lessons from Healthcare Utilization in Children With Obstructive Sleep Apnoea Syndrome

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Paz Martinez-Beneyto, Cristina E. Soria Checa, Paloma Botella-Rocamora, Inés Rincon-Piedrahita, Francisco J. Garcia Callejo, Jaime Marco Algarra
Introduction and objectivesPaediatric Obstructive Sleep Apnoea-Hypopnoea Syndrome (OSAS) is a multisystemic condition affecting child's health status that may be investigated analyzing demand for healthcare. Objective: to quantify the frequency of medical consultations in children with OSAS over a 5-year period, compared to a healthy population.MethodsA longitudinal, case–control, ambispective study was conducted at a hospital pertaining to the national public health system. 69 consecutive children referred for OSAS were recruited with no diseases other than OSAS so that healthcare demand was purely attributed to this condition. Matched healthy control children were selected to compare these data. Data regarding frequency of the medical consultations were obtained over 5 years: the year of the treatment ("Year 0"), 1 and 2 years before ("Year −1" and "Year −2" respectively), and 1 and 2 years after treatment ("Year +1" and "Year +2").ResultsFrequentation index (FI), as ratio between the use of health services by OSAS children and healthy controls was 1.89 during Year −2, and 2.15 during Year −1 (P<.05). Treatment diminishes utilisation, with FI of 159 during Year +1 and 1.72 during Year +2 (P<.05). The main causes of attendance were otolaryngological and pneumological diseases, improving after treatment.ConclusionsChildren suffering from OSAS demand more healthcare services, at least 2 years before treatment, implying that the disease could be present years before we manage it. Therapeutic actions improve healthcare services utilisation, although remain higher than for controls, which suggests OSAS sequelae or residual disease.



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Audiologic and Subjective Evaluation of Baha® Attract Device

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Tomàs Pérez-Carbonell, Ignacio Pla-Gil, Jaume Redondo-Martínez, Antonio Morant-Ventura, Francisco Javier García-Callejo, Jaime Marco-Algarra
We included 9 patients implanted with Baha^® Attract. All our patients were evaluated by free field tonal audiometry, free field verbal audiometry and free field verbal audiometry with background noise, all the tests were performed with and without the device. To evaluate the subjective component of the implantation, we used the Glasgow Benefit Inventory (GBI) and Abbreviated Profile of Hearing Aid Benefit (APHAB).The auditive assessment with the device showed average auditive thresholds of 35.8dB with improvements of 25.8dB over the previous situation. Speech reception thresholds were 37dB with Baha^® Attract, showing improvements of 23dB. Maximum discrimination thresholds showed an average gain of 60dB with the device.Baha^® Attract achieves auditive improvements in patients for whom it is correctly indicated, with a consequent positive subjective evaluation. This study shows the attenuation effect in transcutaneous transmission, that prevents the device achieving greater improvements.



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Findings from the experience with the punch technique for auditory osseointegrated implants: A retrospective single center comparative study

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Alfonso Bonilla, Carlos Magri, Eulalia Juan
ObjectiveTo compare the punch technique and linear incision with soft tissue reduction for the placement of auditory osseointegrated implants (AOI) and analyze results of osseointegration obtained with the punch technique as measured with the Implant Stability Quotient (ISQ).MethodsCase review of 34 patients who received auditory osseointegrated implants between January 2010 and July 2015 and were divided into two groups according to the surgical technique: 18 with the punch technique (PT) and 16 with the linear incision technique (LI). Minimum follow-up was four months (mean: 24 months; range 4–64 months). Included in the analysis were patient profiles and records of the demographic data, surgical indications, surgical technique, implant placement, surgical time, intraoperative complications, as well as postsurgical complications (Holgers classification) and implant stability quotients (ISQ).ResultsUse of larger abutments was significantly greater in the PT group (PT, 10mm; LI, 6mm, p<0.001). The PT technique resulted in a shorter procedure than the LI (PT, 20min; LI, 45min, p<0.001). Holgers classification scores identified significantly fewer skin complications one week after surgery for the PT group; however, only small differences were seen between the two groups at the one- and three-month control visits.ConclusionsAs shown for our cohort, the punch technique for surgical placement of AOI is faster and presents fewer immediate postoperative complications when compared to the linear incision technique. The clinical application of the ISQ is a useful, easy method to demonstrate the status of osseointegration and, thus, the stability of the device.



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Spontaneous Resolution of Chronic Maxillary Atelectasis in a Paediatric Patient: An Exceptional Case

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Claudia González, Karen M. García, Soledad Palma, Claudio A. Callejas




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Nasal Osteoma and Inhaled Salmon Calcitonin: Coincidence or Consequence?

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Zoila A. Peña-Rodríguez, Matilde Haro-García, Juan R. Benito-Navarro




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Epithelioid haemangioendothelioma of the nasal cavity in a woman

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Emili Navalón-Ramon, Tomàs Pérez-Garrigues, Pascual Meseguer-Garcia, Tomàs Pérez-Carbonell




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Obstructive ectopic intratracheal thyroid

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Miguel Mayo Yáñez, Gonzalo Nemecio Esquía Medina, Juan Carlos Vázquez Barro




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Black hairy tongue

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): Kenta Watanabe




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Comments on the Finding of Right Non Recurrent Laryngeal Nerve During Thyroidectomy

Publication date: November–December 2017
Source:Acta Otorrinolaringologica (English Edition), Volume 68, Issue 6
Author(s): José Luis Pardal-Refoyo




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Durable Resolution of Severe Psoriasis in a Patient Treated with Pentostatin for Hairy Cell Leukemia: A Case Report

Abstract

Introduction

Pentostatin (2′-deoxycoformycin) and cladribine (2-chlorodeoxyadenosine) are adenosine analogues widely used to treat lymphoid malignancies, mainly hairy cell leukemia (HCL). Oral or parenteral adenosine analogues have been also used as immunomodulatory agents in multiple sclerosis and in acute graft-versus-host disease.

Case Report

Here, we report the case of a 43-year-old patient with a history of extensive psoriasis who later developed HCL.

Results

The patient had achieved complete remission of both psoriasis and HCL after receiving intravenous infusions of pentostatin. It is worth noting that cladribine has already been reported to treat plaque psoriasis lesions in two patients with HCL and in a third patient with gastric marginal zone B cell lymphoma [1].

Conclusion

We believe that adenosine analogues constitute a promising therapeutic option for moderate to severe psoriasis, especially for severe and refractory psoriasis, as well as for patients with adjacent lymphoid malignancies.

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Cochlear Implant Electrode Choice in Challenging Surgical Cases: Malformation, Residual Hearing, Ossification, or Reimplantation

Abstract

Purpose of Review

The limits of cochlear implantation candidacy have been expanding over the last decade and recent studies show that patients with inner ear anomalies, significant residual hearing, ossified cochlea, or far advanced otosclerosis can benefit from implant. The cochlear implant companies are coming up with various electrode designs. The purpose of this study is to review the factors that can affect the choice of electrode array in the expanding indications of cochlear implantation and suggest some surgical tips.

Recent Findings

A comprehensive preoperative evaluation is crucial. Detailed audiologic examination and radiologic assessment of inner ear structures with high-resolution computed tomography and/or magnetic resonance imaging is necessary. The choice of electrode array should be made regarding the type of cochlea in the presence of inner ear anomalies. If the patient has residual hearing in low-frequencies, electrode array and surgical insertion technique should be as atraumatic as possible to protect apical part of the cochlea. Appropriate selection of electrodes and surgical techniques are necessary if the cochlea is obstructed by fibrosis or ossified. The surgeon also should consider the possibility of reimplantation in the future and select the initial electrode after comprehensive evaluation.

Summary

There is a diversity of electrode arrays for different indications. The selection of the most accurate electrode depends on the audiological tests, etiology of hearing loss, and cochlear anatomy. Surgeon must be prepared preoperatively for various clinical situations and unexpected surgical circumstances. One should keep in mind that making the right electrode choice will impact the outcomes of unusual or challenging cases.

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Influence of Soil Parameters on the Efficiency of the Attrition Process to Remove Metals, PCP, Dioxins and Furans from Contaminated Soils

Abstract

The objective of this study was to evaluate the influence of the soil parameters (particle size, initial contamination level, etc.) on the performances of an attrition process to remove As, Cr, Cu, pentachlorophenol (PCP) and dioxins and furans (PCDD/F). Five different contaminated soils were wet-sieved to isolate five soil fractions (< 0.250, 0.250–1, 1–4, 4–12 and > 12 mm). Five attrition steps of 20 min each, carried out in the presence of a biodegradable surfactant ([BW] = 2%, w w⁻¹) at room temperature with a pulp density fixed at 40% (w w⁻¹), were applied to the coarse soil fractions (> 0.250 mm) of different soils. The results showed good performances of the attrition process to simultaneously remove PCP and PCDD/F from contaminated soil fractions initially containing between 1.1 and 13 mg of PCP kg⁻¹ (dry basis) and between 1795 and 5720 ng TEQ of PCDD/F kg⁻¹. It appeared that the amounts of contaminants removed were significantly correlated (p value < 0.05, R ² = 0.96) with the initial amounts of PCP and PCDD/F, regardless of the particle size of the soils studied. The nature of the soil (granulometric distribution, pH, total organic carbon (TOC) (organic matter) and diverse industrial origin) slightly and negatively influenced the efficiency of organic contaminants removals using attrition. However, the attrition treatment allowed an efficient removal of both PCP and PCDD/F from the coarse fraction of contaminated soil, despite the nature of the soil.

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Plasma IL-8 signature correlates with pain and depressive symptomatology in patients with Burning Mouth Syndrome: results from a pilot study

Abstract

Background

Burning mouth syndrome (BMS) is a neuropathic orofacial pain condition of unknown aetiology that encompasses intra-oral burning pain without abnormal clinical findings. Psychological, neural and inflammatory processes are associated with BMS pathogenesis. Currently, studies characterising plasma cytokine/chemokine profiles with pain and depression in BMS patients are lacking. Considering that inflammation is associated with the pathophysiology of BMS, and that inflammation is closely associated with pain and depression, we aimed to correlate depressive symptomatology and oral cavity pain with plasma cytokine/chemokine signatures in a cohort of patients with BMS.

Methods

In the present study, plasma protein levels of Th1 cytokines (IFN-γ, IL-2, IL-12p70, TNF-α), Th2 cytokines (IL-4, IL-10, IL-6, IL-13), and the chemokine IL-8, were assessed in BMS patients (n = 10) and healthy volunteers (n = 10), using pro-inflammatory-10-plex assays. Clinical histories, alongside self-rated oral cavity pain intensities and depressive symptomatology were assessed using a visual analogue scale (VAS) and the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR₁₆) questionnaires, respectively.

Results

We present evidence that BMS is associated with increased depressive symptomatology and enhanced oral cavity pain. Plasma isolated from BMS patients display enhanced expression of the pro-inflammatory chemokine IL-8, when compared to plasma from healthy individuals. Plasma IL-8 signature correlates with pain and depressive symptomatology in the study cohort.

Conclusions

Overall, these findings indicate that plasma IL-8 profiles are dysregulated in BMS and that modulation of IL-8 production in the disorder may be a tool in the management of BMS symptomatology.

This article is protected by copyright. All rights reserved.

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Serum lipid and bone metabolism effects of Toremifene vs. Letrozole as adjuvant therapy for postmenopausal early breast cancer patients: results of a multicenter open randomized study

Abstract

A prospective randomized phase II trial was conducted to evaluate the time course effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive, postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer patients [ER positive, HER2 negative, T1–2, node metastases (n = 0–3), M0] who had undergone curative resection were enrolled. They were randomized to receive either TOR 40 mg/day or LET 2.5 mg/day as adjuvant hormone therapy. Serum lipids and bone markers were measured prior to, and again at 6, 12, and 24 months after initiation of treatment. Changes in serum lipids and bone markers were compared. Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were decreased compared with the baseline values at 6 months in 6.5 and 14.0% of patients, respectively, receiving TOR. Lipid levels did not change in patients administered LET. Significant differences were observed in TC and LDL-C between the two groups at 12 and 24 months. In the TOR group, serum bone-specific alkaline phosphatase (BAP) was decreased by 25.0% at 12 months, and serum cross-linked N-telopeptide of type-I collagen (NTx) was decreased by 13.6% at 6 months, and these reductions were maintained for at least 24 months. In contrast, in the LET group, serum BAP did not change and NTx was increased by 16.0% at 6 months and by 18.6% at 24 months, as compared with the baseline.TOR and LET exert different effects on serum lipid profiles and bone metabolism markers. The effects of TOR, as adjuvant hormone therapy, on both lipids and bone metabolism in postmenopausal breast cancer patients are superior to those of LET.

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Metastatic serous carcinoma presenting as inflammatory carcinoma over the breast – report of two cases and literature review

Abstract

Non-mammary metastases involving breast are rare and most commonly involve the breast parenchyma. Infrequently, metastasis from an extramammary primary site presents as inflammatory carcinoma over the breast. Diagnosis of such lesions can be challenging, especially in patients with co-existing primary breast carcinoma. Few such cases have been described in literature; however, none of the previously reported cases had a prior history of primary breast carcinoma.

We present two patients with history of breast carcinoma and serous carcinoma of ovarian/peritoneal origin that presented with inflammatory carcinoma over the breast. Biopsies from breast tissue showed atypical cells in the dermis forming cords and papillary structures. Histopathologic differential diagnosis included infiltrating ductal carcinoma of breast origin and metastatic serous carcinoma. Immunohistochemical studies showed that the tumor cells were positive for markers of ovarian origin such as PAX-8 and CA125 and negative for breast markers such as GATA-3, thus supporting the diagnosis.

In summary, we describe the unusual presentation of metastatic serous carcinoma as inflammatory carcinoma over breast and discuss the diagnostic challenges in patients with co-existing primary breast and ovarian malignancies. We also review the morphologic features of tumors of breast and ovarian origin and the immunohistochemical stains to differentiate these two entities.

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Metastatic Laryngeal Large Cell Neuroendocrine Carcinoma: A Rare Case of Presentation and Extreme Tumor Burden

ABSTRACT

Large cell neuroendocrine carcinoma (LCNEC) of the larynx is an aggressive form of neuroendocrine carcinoma that affects smokers at an average age of 60 years. LCNEC is characterized by large cells with round to ovoid nuclei distributed in a trabecular or nested growth pattern. Previously, laryngeal LCNEC and atypical carcinoid tumors were considered synonymous; however, laryngeal LCNEC has been shown to have higher mitotic rates and worse prognosis, which has led to laryngeal LCNEC to be separated from atypical carcinoid and classified as a poorly differentiated neuroendocrine carcinoma in the most recent World Health Organization classification. We present a case of a 56-year-old female who presented with painful subcutaneous skin lesions that were diagnosed as metastatic carcinoma at an outside facility. Subsequent workup revealed a primary epiglottic lesion. Over the next 4 years, she continued to develop over 100 similar subcutaneous nodules. Additional workup confirmed neuroendocrine differentiation, thus clarifying the diagnosis of metastatic large cell neuroendocrine carcinoma. Review of literature has only revealed one reported case of LCNEC with skin metastasis. This is the first reported case whereby skin metastasis was the initial presenting symptom; moreover, our case is unique with regard to the heavy metastatic burden to the skin.

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Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma

Publication date: Available online 30 November 2017
Source:Cancer Cell
Author(s): Érika Cosset, Sten Ilmjärv, Valérie Dutoit, Kathryn Elliott, Tami von Schalscha, Maria F. Camargo, Alexander Reiss, Toshiro Moroishi, Laetitia Seguin, German Gomez, Jung-Soon Moo, Olivier Preynat-Seauve, Karl-Heinz Krause, Hervé Chneiweiss, Jann N. Sarkaria, Kun-Liang Guan, Pierre-Yves Dietrich, Sara M. Weis, Paul S. Mischel, David A. Cheresh
While molecular subtypes of glioblastoma (GBM) are defined using gene expression and mutation profiles, we identify a unique subpopulation based on addiction to the high-affinity glucose transporter, Glut3. Although Glut3 is a known driver of a cancer stem cell phenotype, direct targeting is complicated by its expression in neurons. Using established GBM lines and patient-derived stem cells, we identify a subset of tumors within the "proneural" and "classical" subtypes that are addicted to aberrant signaling from integrin αvβ3, which activates a PAK4-YAP/TAZ signaling axis to enhance Glut3 expression. This defined subpopulation of GBM is highly sensitive to agents that disrupt this pathway, including the integrin antagonist cilengitide, providing a targeted therapeutic strategy for this unique subset of GBM tumors.

Graphical abstract

Teaser

Cosset et al. identify a subset of glioblastoma within the proneural and the classical subtypes that are addicted to aberrant signaling from integrin αvβ3, which activates a PAK4-YAP/TAZ signaling axis to enhance Glut3 expression, and are sensitive to agents disrupting the pathway such as cilengitide.


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Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment

Publication date: Available online 30 November 2017
Source:Cancer Cell
Author(s): Anna H. Turaj, Khiyam Hussain, Kerry L. Cox, Matthew J.J. Rose-Zerilli, James Testa, Lekh N. Dahal, H.T. Claude Chan, Sonya James, Vikki L. Field, Matthew J. Carter, Hyung J. Kim, Jonathan J. West, Lawrence J. Thomas, Li-Zhen He, Tibor Keler, Peter W.M. Johnson, Aymen Al-Shamkhani, Stephen M. Thirdborough, Stephen A. Beers, Mark S. Cragg, Martin J. Glennie, Sean H. Lim
Monoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T cell responses. Here, we examined the therapeutic potential of combining a direct tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs. Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple lymphoma models, including huCD27 transgenic mice using the anti-huCD27, varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing demonstrated that anti-CD27 stimulated CD8⁺ T and natural killer cells to release myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration and macrophage activation. This study demonstrates the therapeutic advantage of using an immunomodulatory mAb to regulate lymphoid cells, which then recruit and activate myeloid cells for enhanced killing of mAb-opsonized tumors.

Graphical abstract

Teaser

Turaj et al. test anti-tumor efficacy of immunomodulatory antibodies combined with anti-CD20 and find that anti-CD27/CD20 has a strong benefit in several tumor models. Anti-CD27 induces IFNγ and chemokines in CD8⁺ T and NK cells, enhancing macrophage infiltration and activation to promote anti-CD20 activity.


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Truncated isoform Vav3.1 is highly expressed in ovarian cancer stem cells and clinically relevant in predicting prognosis and platinum-response

Abstract

Vav3 is a key modulator of GTP-hydrolases of the Rho/Rac family, which are crucially involved in cell proliferation. Vav3 is alternatively spliced in full-length Vav3-alpha and N-terminal truncated Vav3.1 lacking its self-regulatory domains. The aim of this study was to estimate the clinical impact of Vav3 and all other Vav family members in ovarian cancer. Purification of a stem-cell like side-population (SP) from ovarian cancer cell lines was performed by flow cytometry/FACS. Differences in gene expression between SP and NSP were assessed by Gene Array analysis and confirmed by RT-PCR and immunoblot. In addition, Vav mRNA expression was determined in 150 epithelial ovarian cancers. Clinicopathological parameters, platinum-sensitivity and survival were analyzed and associated to Vav expression. SP fractions of ovarian cancer cell lines exhibited marked overexpression of Vav3.1 (P < 0.001). Vav1 and Vav2 did not prove to be of clinicopathologic relevance in ovarian cancer. High Vav3.1 expression correlated with higher FIGO stage and residual disease. Furthermore, Vav3.1 overexpression was associated with poor progression-free (HR = 2.820, P = 0.0001) and overall survival (HR = 2.842, P = 0.0001). Subgroup analyses revealed an impact of Vav3.1 on survival in type-II but not in type-I cancers. Notably, platinum-refractory cancers showed marked overexpression of Vav3.1 compared to other subsets of platinum-sensitivity (15.848 vs. 6.653, P = 0.0001). In conclusion, Vav3.1 is over-expressed in stem-cell like SP fractions and is clinically relevant in the pathophysiology of ovarian cancer. The N-terminal truncated Vav3.1 may be decisively involved in mechanisms causing genuine multi-drug resistance. This article is protected by copyright. All rights reserved.

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Letter to the Editor: Re: The Impact of Overdiagnosis on the Selection of Efficient Lung Cancer Screening Strategies

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Re: Think Before You Leap

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How to Analyse The Spatiotemporal Tumour Samples Needed To Investigate Cancer Evolution: A Case Study using Paired Primary and Recurrent Glioblastoma

Abstract

Many traits of cancer progression (e.g. development of metastases or resistance to therapy) are facilitated by tumour evolution: Darwinian selection of subclones with distinct genotypes or phenotypes that enable such progression. Characterising these subclones provides an opportunity to develop drugs to better target their specific properties but requires the accurate identification of somatic mutations shared across multiple spatiotemporal tumours from the same patient. Current best practices for calling somatic mutations are optimised for single samples, and risk being too conservative to identify shared mutations with low prevalence in some samples. We reasoned that datasets from multiple matched tumours can be used for mutual validation and thus propose an adapted two-stage approach: 1) low-stringency mutation calling to identify mutations shared across samples irrespective of the weight of evidence in a single sample; 2) high-stringency mutation calling to further characterise mutations present in a single sample. We applied our approach to three independent cohorts of paired primary and recurrent glioblastoma tumours, two of which have previously been analysed using existing approaches, and found that it significantly increased the amount of biologically-relevant shared somatic mutations identified. We also found that duplicate removal was detrimental when identifying shared somatic mutations. Our approach is also applicable when multiple datasets e.g. DNA and RNA are available for the same tumour. This article is protected by copyright. All rights reserved.

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Letter to the Editor regarding the paper by F. Cardoso et al. ‘European Breast Cancer Conference manifesto on breast centres/units’

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Gianni Saguatti, Carlo Naldoni, Eva Benelli, Chiara Fedato, Alfonso Frigerio, Vania Galli, Livia Giordano, Paola Golinelli, Doralba Morrone, Adriana Paduos, Fiammetta Querci, Antonio Rizzo, Lauro Bucchi




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Immune checkpoint inhibitor–associated CNS autoimmune disorder (ICICAD) following nivolumab treatment: A new entity of drug-induced autoimmune encephalitis?

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Herwig Strik, Ursula Keber, Wasim Alhaj Hammoud, Jorge Riera-Knorrenschild, Barbara Carl, Richard Dodel, Axel Pagenstecher, Andreas Neubauer




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Re: Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Peter C. Albertsen




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Reply to letter from Suguatti et al.

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Luigi Cataliotti, Lorenza Marotti, Marc Beishon, Alberto Costa, Susan Knox, Emiel Rutgers, Fatima Cardoso




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Response to letter – Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Lucie-Marie Scailteux




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European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results from the treatment of mucosal cancers

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Christina Caroline Plaschke, Giulia Bertino, James A. McCaul, Juan J. Grau, Remco de Bree, Gregor Sersa, Antonio Occhini, Ales Groselj, Cristobal Langdon, Derrek A. Heuveling, Maja Cemazar, Primoz Strojan, C. Rene Leemans, Marco Benazzo, Francesca De Terlizzi, Irene Wessel, Julie Gehl
AimElectrochemotherapy is an effective local treatment for cutaneous tumours and metastases. In this prospective trial, six European institutions investigated electrochemotherapy in recurrent, mucosal head and neck tumours.Patient and methodsForty-three patients with recurrent mucosal head and neck tumours and no further curative or reasonably effective palliative treatment options were enrolled and treated with electrochemotherapy. Patients were treated in general anaesthesia using intravenous or local injection of bleomycin followed by delivery of electric pulses to the tumour area. Primary end-point was local tumour response. Secondary end-points were safety and toxicity, overall and progression free survival, and quality-of-life.ResultsThirty-seven patients were evaluable for tumour response, pain score, side-effects and quality of life questionnaires. Six patients were not evaluable due to lost follow-up, disease progression or death before evaluation. Intention to treat analysis revealed an objective response of 56% (complete response 8 (19%), partial response 16 (37%), stable disease 10 (23%), progressive disease 3 (7%), and not evaluable 6 (14%)). Three patients (7%) remained in complete response at 30, 34, and 84 months post-treatment. The treatment procedure was generally well tolerated. Swelling of the mucosa was observed in the first days after treatment. Pain and use of pain medication rose temporarily; fatigue and dysphagia were also noted in the quality of life assessment.ConclusionElectrochemotherapy can be applied to mucosal head and neck recurrent tumours accessible to the procedure with promising objective response, survival and toxicity profile. Attention should be paid to post-treatment swelling and planning of pain medication. These favourable results indicate that electrochemotherapy could play a role in patients with recurrent head and neck cancer.



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Characterization of CD45RO+ Memory T Lymphocytes in Keloid Disease

Abstract

Background

Memory T cells, a highly effective subset of T lymphocytes, have been reported to be involved in many inflammatory skin disorders. However, the potential role of memory T cells in keloid disease (KD) remains unclear.

Objectives

Due to their important role in regulating inflammation, we investigated the characteristics of CD45RO⁺ memory T cells (mT) in KD.

Methods

Primary cutaneous cells were isolated from keloid scars and normal skin by enzymic digestion. Combined with peripheral blood mononuclear cells (PBMCs) isolated from a related blood sample, flow cytometry was applied to identify the phenotypic and functional abnormalities of memory T cells in KD.

Results

We observed that the majority of T lymphocytes in keloid scars had the memory phenotype, and a greater number of the CD8⁺ mT in keloid scars produced lower levels of TNF-α. This abnormal cytokine production was even more distinct in FOXP3^-CD8^- mT, with lower TNF-α production and enhanced IFN-γ production. Furthermore, FOXP3⁺CD8^- mT in keloid scars were abnormal, including showing reduced CD25 and CTLA-4 expression and IL-10 production. In addition, a significant decrease in the number of CD4⁺CD25^highFOXP3⁺ regulatory T cells was identified in patients with multiple keloid scars. We also found that there was significantly increased infiltration of CD103⁺CD8⁺ mT in keloid scars.

Conclusions

Our findings preliminarily elucidate the abnormalities of CD45RO⁺ memory T cells in keloid scars and provide early evidence that a disrupted T cell response contributes to the progression of KD.

This article is protected by copyright. All rights reserved.

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Impaired Langerhans’ cell migration in psoriasis is due to an altered keratinocyte phenotype induced by interleukin-17

Abstract

Psoriasis is a common skin condition driven by increased expression of interleukin (IL)-17. Langerhans' cells (LC) are epidermal dendritic cells that regulate cutaneous immune responses. Within uninvolved skin of patients with psoriasis, LC display impaired migration from the epidermis. Here the role of keratinocytes (KC) in the regulation of LC function, and the response of KC to IL-17 has been investigated. Keratinocytes were cultured from the uninvolved skin of psoriasis patients and healthy individuals with or without IL-17 treatment and the conditioned medium examined for its ability to alter LC function in an ex vivo human skin explant model. Furthermore, we examined the effect of IL-17 on LC mobilisation in psoriasis by neutralising IL-17 in the same skin explant model. We found that conditioned medium from psoriasis KC inhibited LC migration in healthy skin. Moreover, conditioned medium from healthy KC treated with IL-17 also inhibited healthy LC migration. Finally, neutralising IL-17 in psoriasis skin resulted in enhanced LC migration. Collectively, these data suggest that an altered KC secretome, driven by increased expression of IL-17, is responsible for impaired LC migration in uninvolved skin of patients with psoriasis.

This article is protected by copyright. All rights reserved.

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Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients with advanced cancer

Summary

Background The signaling protein p38 mitogen-activated protein kinase (MAPK) regulates the tumor cell microenvironment, modulating cell survival, migration, and invasion. This phase 1 study evaluated the safety of p38 MAPK inhibitor LY3007113 in patients with advanced cancer to establish a recommended phase 2 dose. Methods In part A (dose escalation), LY3007113 was administered orally every 12 h (Q12H) at doses ranging from 20 mg to 200 mg daily on a 28-day cycle until the maximum tolerated dose (MTD) was reached. In part B (dose confirmation), patients received MTD. Safety, pharmacokinetics, pharmacodynamics, and tumor response data were evaluated. Results MTD was 30 mg Q12H. The most frequent treatment-related adverse events (>10%) were tremor, rash, stomatitis, increased blood creatine phosphokinase, and fatigue. Grade ≥ 3 treatment-related adverse events included upper gastrointestinal haemorrhage and increased hepatic enzyme, both occurring at 40 mg Q12H and considered dose-limiting toxicities. LY3007113 exhibited an approximately dose-proportional increase in exposure and time-independent pharmacokinetics after repeated dosing. Maximal inhibition (80%) of primary biomarker MAPK-activated protein kinase 2 in peripheral blood mononuclear cells was not reached, and sustained minimal inhibition (60%) was not maintained for 6 h after dosing to achieve a biologically effective dose (BED). The best overall response in part B was stable disease in 3 of 27 patients. Conclusions The recommended phase 2 dosage of LY3007113 was 30 mg Q12H. Three patients continued treatment after the first radiographic assessment, and the BED was not achieved. Further clinical development of this compound is not planned as toxicity precluded achieving a biologically effective dose.

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Low-grade Spindle Cell Proliferation in Clear Cell Renal Cell Carcinoma is Unlikely to be an Initial Step in Sarcomatoid Differentiation

Abstract

Spindle cell proliferation within clear cell renal cell carcinoma (ccRCC) is usually considered as sarcomatoid differentiation. Low-grade spindle cell proliferation (LG-SCP) in ccRCC was first described in 2001. This phenomenon is not common and can pose diagnostic challenges particularly in core biopsies. The aim of this study was to describe morphologic, immunohistochemical and molecular characteristics of ccRCCs with LG-SCP.

11 cases of ccRCC with LG-SCP were retrieved from approximately 21,000 renal tumors in our registry. 10 cases of conventional ccRCC and 10 cases of typical sarcomatoid ccRCC were included as control groups. Morphologic and immunohistochemical characteristics of epithelial mesenchymal transition (EMT) were analyzed. VHL gene abnormalities were also analyzed using molecular genetics.

Among ccRCC with LG-SCP cases, there were 5 males and 5 females (clinical information was not available in one case) with median age of 67 years (mean 68.5, range 60-81 years). Average tumor size was 7.1 cm (median 7.5, range 1.7-12 cm). Follow up data were available in 9 cases (mean 44.78 months), with no aggressive behavior seen. On average, LG-SCP areas constituted 5-80% of tumor volume (mean 32.3%). Necrotic/regressed areas were seen in all cases ranging 5-30%. LG-SCP was clearly epithelial with no mitoses or any evidence of mesenchymal differentiation.

Immunohistochemical profile of LG-SCP was consistent with "conventional" ccRCC. Compared with sarcomatoid ccRCC, some EMT markers showed alteration in LG-SCP, including lower expression of N-Cadherin and Zeb1 as well as higher expression of E-cadherin. However, there were no significant differences in EMT markers between LG-SCP and conventional ccRCC. Abnormalities in VHL gene (mutations, LOH3p) were found in 6/11 cases.

Conclusions

Our findings showed that LG-SCP in ccRCC have comparable immunohistochemical and molecular characteristics to those seen in "conventional" ccRCC. Further, immunohistochemical analysis of EMT markers showed that LG-SCP did not differ from "conventional" ccRCC. We believe that LG-SCP is a part of morphologic heterogeneity in ccRCCs and that they may not represent an initial stage of sarcomatoid differentiation. This is further supported by the fact that ccRCC with LG-SCP did not display more aggressive behavior than "conventional" ccRCC.

This article is protected by copyright. All rights reserved.

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Mitteilungen der GÄCD

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Analysis of the relationship between prescribed dose and dosimetric advantage of real-time intraoperatively built custom-linked seeds in iodine-125 prostate brachytherapy

The purpose of this study was to investigate the differences in the dosimetric advantage of using intraoperatively built custom-linked (IBCL) seeds between permanent iodine-125 (I-125) seed implantation (PI) a...

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Evidence of the efficacy and safety of house dust mite subcutaneous immunotherapy in elderly allergic rhinitis patients: a randomized, double-blind placebo-controlled trial

Allergen specific immunotherapy (AIT) in elderly patients is controversial, and there is still little evidence supporting the safety and efficacy of this treatment in this population. The study objective was t...

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Stereotype Threat Effects on Learning From a Cognitively Demanding Mathematics Lesson

Abstract

Stereotype threat—a situational context in which individuals are concerned about confirming a negative stereotype—is often shown to impact test performance, with one hypothesized mechanism being that cognitive resources are temporarily co-opted by intrusive thoughts and worries, leading individuals to underperform despite high content knowledge and ability (see Schmader & Beilock, ). We test here whether stereotype threat may also impact initial student learning and knowledge formation when experienced prior to instruction. Predominantly African American fifth-grade students provided either their race or the date before a videotaped, conceptually demanding mathematics lesson. Students who gave their race retained less learning over time, enjoyed the lesson less, reported a diminished desire to learn more, and were less likely to choose to engage in an optional math activity. The detrimental impact was greatest among students with high baseline cognitive resources. While stereotype threat has been well documented to harm test performance, the finding that effects extend to initial learning suggests that stereotype threat's contribution to achievement gaps may be greatly underestimated.

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Association of high cost sharing and targeted therapy initiation among elderly Medicare patients with metastatic renal cell carcinoma

Abstract

High out-of-pocket costs may limit access to oral therapies covered by patients' prescription drug benefits. We explored financial barriers to treatment initiation in patients newly diagnosed with metastatic renal cell carcinoma (mRCC) by comparing Medicare Part D patients with low out-of-pocket costs due to receipt of full low-income subsidies (LIS beneficiaries) to their counterparts who were responsible for more than 25% cost sharing during Medicare's initial coverage phase (non-LIS beneficiaries). We used 2011–2013 100% Medicare claims for non-LIS and LIS beneficiaries newly diagnosed with metastases in the liver, lung, or bone to examine targeted therapy treatment initiation rates and time to initiation for (1) oral medications (sorafenib, sunitinib, everolimus, pazopanib, or axitinib) covered under Medicare's prescription drug benefit (Part D); (2) injected or infused medications (temsirolimus or bevacizumab) covered by Medicare's medical benefit (Part B); and (3) any (Part D or Part B) targeted therapy. The final sample included 1721 patients. On average, non-LIS patients were responsible for out-of-pocket costs of ≥$2,800 for their initial oral prescription, as compared to ≤$6.60 for LIS patients. Compared to LIS patients, a lower percentage of non-LIS patients initiated oral therapies (risk-adjusted rates, 20.7% vs. 33.9%; odds ratio [OR] = 0.49, 95% CI: 0.36–0.67, P < 0.001) and any targeted therapies (26.7% vs. 40.4%, OR = 0.52, 95% CI: 0.38–0.71, P < 0.001). Non-LIS patients were also slower to access therapy. High cost sharing was associated with reduced and/or delayed access to targeted therapies under Medicare Part D, suggesting that financial barriers play a role in treatment decisions.

Medicare Part D beneficiaries newly diagnosed with metastatic renal cell carcinoma have significantly lower rates of oral and any targeted therapy initiation—and are slower to initiate treatment—when they are responsible for high out-of-pocket costs. Financial barriers may be factoring into treatment decisions; this warrants further investigation.

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