Experimental investigation on the vascular thermal response to near-infrared laser pulses

Abstract

Port wine stains (PWS) are congenital vascular malformations that progressively darken and thicken with age. To improve the effect of laser therapy in clinical practice, thermal response of blood vessel to a 1064 nm Nd:YAG laser with controlled energy doses and pulse durations was evaluated using the dorsal skin chamber model. A total of 137 vessels with 30–300 μm diameters were selected from the dorsal skin of the mouse to match those capillaries in port wine stains. Experimental results showed that the thermal response of blood vessels to 1064 nm laser irradiation can be classified as follows: vessel dilation, coagulation, constriction with decreased diameter, complete constriction, hemorrhage, and collagen damage with increasing laser radiant exposure. In most cases, that is, 83 of 137 blood vessels (60.6%), Nd:YAG laser irradiation was characterized by complete constriction (immediate blood vessel disappearance). To reveal the possible damage mechanisms and evaluate blood vessel photocoagulation patterns, theoretical investigation using bioheat transfer equation was conducted in mouse skin with a depth of 1000 μm. Complete constriction as the dominant thermal response as evidenced by uniform blood heating within the vessel lumen was noted in both experimental observation and theoretical investigation. To achieve the ideal clinical effect using the Nd:YAG laser treatment, the radiant exposure should not only be high enough to induce complete constriction of the blood vessels but also controlled carefully to avoid surrounding collagen damage. The short pulse duration of 1–3 ms is better than long pulse durations because hemorrhaging of small capillaries is occasionally observed postirradiation with pulse durations longer than 10 ms.

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Examining colorectal cancer survivors’ surveillance patterns and experiences of care: a SEER-CAHPS study

Abstract

Purpose

We examined associations between experiences of care and adherence to surveillance guidelines among Medicare Fee-For-Service beneficiaries with colorectal cancer (CRC).

Methods

Using linked data from the National Cancer Institute's Surveillance, Epidemiology, and End results (SEER) cancer registry program and the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS^®) patient experience surveys (SEER-CAHPS), we identified local/regional CRC survivors diagnosed in 1999–2009 aged 65+, who underwent surgical resection and completed a CAHPS survey <36 months of diagnosis. Adherence for a 3-year observation period was defined as receiving a colonoscopy; ≥2 carcinoembryonic antigen (CEA) tests; and each year had ≥2 office visits and ≥1 computerized tomography test.

Results

Many of the 314 participants reported ratings of a 9 or 10 out of 10 for overall care (55.4%), personal doctor (58.6%), health plan (59.6%), and specialist doctor (47.0%). Adherence to post-resection surveillance was 76.1% for office visits, 36.9% for CEA testing, 48.1% for colonoscopy, and 10.3% for CT Imaging. Overall, 37.9% of the sample were categorized as non-adherent (adhering to ≤1 surveillance guideline). In multivariable models, ratings of personal doctor and specialist doctor were positively associated with adherence to office visits, and ratings of personal doctor were associated with adherence overall.

Conclusions

Findings point to the potentially important role of patient-provider relationships in adherence to office visits for CRC surveillance. As adherence may increase survival among CRC survivors, further investigation is needed to identify specific components of this relationship that impact office visit adherence, and other potentially modifiable drivers of surveillance guidelines.

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Rituximab Monotherapy Is Effective in Treating Orbital Necrobiotic Xanthogranuloma.

The authors report a case of a patient with bilateral orbital necrobiotic xanthogranuloma and no associated systemic paraproteinemia. Orbital biopsy showed strong expression of CD20-positive cells. The patient was treated with systemic rituximab monotherapy, with excellent clinical response and marked regression of the orbital lesions on imaging. At the time of writing, the patient has been treated with bimonthly rituximab maintenance therapy for 22 months and has stable clinical and imaging findings with sustained response to treatment and no reported side effects. To the authors' knowledge, this is the first reported case of orbital necrobiotic xanthogranuloma successfully treated with rituximab monotherapy. They hope that this well-documented case will encourage clinicians to consider rituximab monotherapy as a possible treatment option, albeit one entailing an off-label use of this drug, for patients with necrobiotic xanthogranuloma of the orbit. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Peri-Punctal Lymphangioma Treated With Bleomycin.

No abstract available

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Effect of Optic Nerve Disinsertion During Evisceration on Nonporous Implant Migration: A Comparative Case Series and a Review of Literature.

Aim: To determine whether evisceration with optic nerve disinsertion and nonporous implant placement increases the risk of implant migration. Methods: This was a single-center, retrospective consecutive comparative interventional case series including patients undergoing evisceration with nonporous implant between January and December 2014. Patients were grouped into 2 groups: group I where the optic nerve was not disinserted (n = 37) and group II with optic nerve disinsertion (n = 50). Implant migration was assessed clinically and on patient photographs. Migration was subclassified as decentration that did not affect the prosthetic outcome and displacement that affected the prosthetic outcome. The secondary outcome measures were the mean implant diameter, volume of the custom ocular prosthesis, and implant-related complications like exposure and extrusion between the 2 groups. Results: At a mean follow up of 12.5 months, none of the sockets in group I and 3 (6%) sockets in group II (p = 0.35) had evidence of implant decentration. There were no cases of implant displacement in both groups. The mean implant diameter in group I was 16.97 mm +/- 0.65 mm and in group II 19.2 mm +/- 0.83 mm (p = 0.0001). Implant extrusion was not different between the 2 groups. The mean custom ocular prosthesis volume in group I was 3.86 ml +/- 0.52 ml and in group II 2.50 ml +/- 0.68 ml (p

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Assessing the Accuracy of Eyelid Measurements Utilizing the Volk Eye Check System and Clinical Measurements.

Purpose: The purpose of this study was to validate the accuracy of marginal reflex distance 1 (MRD1) measurements obtained by the Volk Eye Check system, a modified smartphone that measures MRD1 automatically, relative to clinical and digital measurements. Methods: In this prospective observational study of adults with normal eyelids and ptosis, MRD1 was measured clinically, digitally, and automatically with the Volk device. Eyes were divided into successful versus unsuccessful Volk trial groups; successful eyes were then subdivided into control and ptosis subgroups. The primary outcome measures were mean MRD1 obtained by the 3 modalities. Secondary outcome measures included the success rate of the device and the prevalence of ptosis within the successful and unsuccessful groups. Results: In the overall sample of 88 eyes, clinical and digital MRD1 were not significantly different. Among eyes with successful Volk trials, significant differences in MRD1 measured by the 3 modalities were as follows: in the successful group, Volk MRD1 (3.05 mm) was significantly (p

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Haberland Syndrome Associated With Calvarial Exostosis.

No abstract available

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An Aesthetic Orbicularis Oculi Myectomy Technique for Blepharospasm: Use of Topical 5-Fluorouracil and Fibrin Sealant.

Purpose: To describe a modified technique of orbicularis oculi myectomy for refractory blepharospasm. This technique includes removal of orbicularis muscle, reformation of the eyelid crease and pretarsal platform using fibrin sealant (Tisseel), and topical 5-fluorouracil to reduce scar formation and improve aesthetic outcome. Methods: Retrospective chart review of 7 patients who underwent bilateral orbicularis oculi myectomy with our technique from 2013 to 2016. Outcome measures were postoperative botulinum toxin dose, frequency, duration between treatments, the amount of lagophthalmos, severity of dry eye, and patient satisfaction with aesthetic and functional outcome. Results: Patients who underwent the aesthetic myectomy technique had significantly decreased botulinum toxin use with relief of symptoms postoperatively. Only 1 of 7 patients experienced mild dry eye symptoms postoperatively, managed with artificial tears. All patients were satisfied with the aesthetic and functional outcome. Conclusions: The aesthetic myectomy technique provides effective treatment for blepharospasm with good functional and aesthetic outcome. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Common Versus Unique Findings on Processing-Based Task Performance in Korean Speaking Children With Cochlear Implants.

Hypothesis: To better understand individual variability by examining overall neurocognitive underlying features in children with cochlear implants (CIs), and to investigate whether previous findings hold constant in Asian-language users. Background: Studies have tried to explain the individual variability in children with CIs. However, performance on experience-dependent tasks does not seem to be sensitive enough to explain the underlying reason why children have language difficulties even after the surgical procedure. Thus, this current research has focused on underlying neurocognitive functions to better explain the reason for the wide variability in this population. Methods: Using a separate univariate analysis paradigm, performance on processing-based tasks was compared between children with CIs and children with normal hearing. A total of 34 children ranging from 10 to 12 years old participated in the study. There were two different categories of processing-based tasks tapping processing capacity and processing speed. This study used nonword repetition (NWR), competing language processing task (CLPT), and counting span (CS) for examining processing capacity, while rapid naming (RAN) in color, shape, and color shape were used to investigate processing speed. Results: Children with NH outperformed children with CIs on all processing-capacity tasks, except CS. Children with CIs performed similarly to children with NH on processing speed tasks. Conclusions: We found children with CIs still experienced difficulties with processing capacity. Due to cross-linguistic features, we also discovered some interesting findings that differed from previous studies. Lastly, we found processing speed was fairly intact in children with CIs, which is a new finding. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Olfactory Dysfunction Associated With Neuro-Behcet Disease.

Introduction: Neurologic involvement associated with Behcet disease (BD) is defined as a different entity: Neuro-Behcet disease (NBD). Behcet disease presents with olfactory dysfunction. It is not known whether this is the consequence of mucosal involvement or neurologic involvement. Objective: The aim of this study was to investigate whether olfactory dysfunction was further aggravated as the result of neurologic involvement. Methods: Sixteen patients diagnosed with NBD and 16 healthy control patients with similar demographic characteristics were recruited as the healthy control group. Expanded Disability Status Scale (EDSS) scoring was used for quantification of neurological disability. All diagnoses were confirmed and categorized with magnetic resonance imaging studies in all patients individually: parenchymal or nonparenchymal. A well-established test of orthonasal olfaction developed at the CCCRC was used. Correlation analysis was carried out. Results: The mean CCCRC score of NBD patients was 4.60 out of 7, and this group was diagnosed to be moderately hyposmic, whereas the average score of the control group was 6.5; the difference was significant (P

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Intraoperative Neurophysiologic Monitoring for Prediction of Postoperative Neurological Improvement in a Child With Chiari Type I Malformation.

Introduction: Although many surgical treatment strategies for Chiari malformation type I (CM-I) have been reported, the most appropriate surgical technique remains controversial. It is wholly ascribable to the complicacy of pathological condition in CM-I. Recently, intraoperative neurophysiologic monitoring (INM) is becoming prevalent in spinal surgery. Indeed, motor-evoked potentials (MEPs) monitoring and somatosensory-evoked potentials (SSEPs) monitoring are standard tools to minimize the risk of neurologic injury and postoperative deficits. The most recent study suggested that multimodality INM can be beneficial in foramen magnum decompression surgery for CM-I patients for surgical positioning and planning. Various authors have investigated the consistency of intraoperative evoked potential changes that might aid the surgeon to determine the appropriate extent of decompression required for an individual patient. Patient Description: The authors report the case of a 7-year-old boy who had the signs of medullary and cerebellar dysfunction, clumsy hands, and ataxic gait. He underwent a surgery of foramen magnum decompression with tonsillectomy and duraplasty for CM-I with cervicomedullary compression. His intraoperative MEPs improved (indicated increased-amplitude and shortened-latency) both after craniotomy and durotomy, whereas SSEPs improved only after durotomy. Those results were correlated well with a functional improvement that was apparent in the immediate postoperative hospitalization. Conclusions: The authors' data provides 1 possible interpretation of INM for safety aspect, but also which degree of decompression in each patient will require. The improvement in MEPs and SSEPs observed during decompression procedure may be a good indicator for the prediction of the clinical improvement seen postoperatively. (C) 2017 by Mutaz B. Habal, MD.

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Contextual Facilitators and Barriers of Community Reintegration among Injured Female Military Veterans: A Qualitative Study

Publication date: Available online 1 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Brent L. Hawkins, Brandi M. Crowe
ObjectiveTo understand the facilitators and barriers to community reintegration (CR) among injured female veterans.DesignPhenomenological qualitative designSettingCommunityParticipantsCommunity-dwelling female veterans with physical and/or psychological injury (N=13).InterventionsNoneMain Outcome MeasuresNoneResultsConventional content analysis revealed three types of facilitators, including: (a) strong social supports; (b) impactful programs; and (c) protective personal beliefs. Six types of barriers included: (a) inadequate services; (b) lack of access to services; (c) poor social support; (d) difficulty trusting others; (e) non-supportive personal beliefs; and (f) injury factors.DiscussionMultiple environmental and personal factors acted as facilitators and barriers to CR. Findings are relatively consistent with previous veteran and civilian community reintegration research that indicates the importance of health-related services, attitudes of others, and social support. However, females in this study reported being impacted by many of these facilitators and barriers because of their gender.ConclusionsThis study supports the need to foster social support among injured female veterans throughout the rehabilitation process to promote CR. Long-term social support can be gained by incorporating services such as adjunctive therapies, recreation, and other social programming into the rehabilitation repertoire to help with CR for all veterans, particularly females.



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What is the longitudinal profile of impairments and can we predict difficulty caring for the profoundly-affected arm in the first year post-stroke?

Publication date: Available online 1 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Rhoda Allison, Cherry Kilbride, Jade Chynoweth, Siobhan Creanor, Ian Frampton, Jonathon Marsden
ObjectiveTo establish the longitudinal profile of impairments of body functions and activity limitations of the arm, and evaluate potential predictors of difficulty caring for the profoundly-affected arm post-stroke.DesignProspective cohort study.SettingThree UK stroke services.ParticipantsPeople unlikely to regain functional use of the arm (N=155) were recruited at 2-4 weeks post-stroke, and followed up at 3, 6 and 12 months. Potential predictors at baseline were hypertonicity, pain, motor control, mood, sensation/perception, age and stroke severity.InterventionsNAMain Outcome MeasuresDifficulty caring for the arm (LASIS), pain, hypertonicity, range of movement, arm function and skin integrity. Multi-variable linear regression identified the best fitting model for predicting LASIS at 12 months.ResultsOne hundred and ten participants (71%) were reviewed at one year. There was a large variation in the profile of arm functions and activity limitations. Inability or severe difficulty caring for the arm affected 29% of participants. Hypertonicity developed in 77%, with severe hypertonicity present in 25%. Pain was reported by 65%, 94% developed shoulder contracture and 6% had macerated skin. Difficulty caring for the arm increased with age, greater level of hypertonicity and stroke classification; collectively these factors accounted for 33% of the variance in LASIS.ConclusionsAt one year post-stroke, there was a high incidence of impairments of body functions and activity limitations in people with a profoundly-affected arm. Individual profiles were very variable and although some pre-disposing factors have been identified, it remains difficult to predict who is at greatest risk.



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Development of a Computerized Adaptive Test of Children’s Gross Motor Skills

Publication date: Available online 1 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Chien-Yu Huang, Li-Chen Tung, Yeh-Tai Chou, Hing-Man Wu, Kuan-Lin Chen, Ching-Lin Hsieh
ObjectiveThis study aimed to develop a computerized adaptive test (CAT) for gross motor skills (GM-CAT) as a diagnostic test and an outcome measure, using the gross motor subtest of the Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT-GM) as the candidate item bank. Moreover, we examined the psychometric properties and the efficiency of the GM-CAT.SettingA developmental center of a medical centerDesignRetrospective study.ParticipantsChildren with and without developmental delay (N=1,738)InterventionsNot Applicable.Main Outcome MeasuresThe CDIIT-GM contains 56 universal items on gross motor skills assessing children's antigravity control, locomotion, and body movement coordination.ResultsThe item bank of the GM-CAT had 44 items that met the dichotomous Rasch model's assumptions. High Rasch person reliabilities were found for each estimated gross motor skill for the GM-CAT (Rasch person reliabilities = 0.940 ∼ 0.995, standard error = 0.68∼2.43). For children of 6 ∼ 71 months, the GM-CAT had good concurrent validity (rs = 0.97 ∼ 0.98), adequate to excellent diagnostic accuracy (area under receiver operating characteristics curve = 0.80 ∼ 0.98), and moderate to large responsiveness (effect size =0.65 ∼ 5.82). The averages of items administered for the GM-CAT were 7 to 11, depending on the age group.ConclusionsThe results of this study support the use of the GM-CAT as a diagnostic and outcome measure to estimate children's gross motor skills in both research and clinical settings.



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Long-Term Functional Outcomes in Military Service Members and Veterans after Traumatic Brain Injury/Polytrauma Inpatient Rehabilitation

Publication date: Available online 1 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Max Gray, Joyce Chung, Fatima Aguila, T. Gavin Williams, Jeffrey K. Teraoka, Odette A. Harris
ObjectiveTo determine the impact of the established Polytrauma/TBI infrastructure on immediate post-treatment functional gains, the long-term sustainability of any gains and participation-related community reintegration outcomes in a baseline cohort of patients eight years post-admission.DesignRetrospective review and prospective repeated measures of an inception cohort.SettingVeterans Affairs Palo Alto, Polytrauma Rehabilitation Center (PRC)Participants44 patients consecutively admitted to the PRC inpatient rehabilitation unit during its first full Fiscal Year, 2006.InterventionsThe PRC infrastructure and the formalized rehabilitation for Polytrauma/TBI.Main Outcome MeasuresFunctional Independence Measure scores at admission, discharge, 3 months and 8 years post discharge; participation-related socioeconomic factors reflecting community reintegration eight years after admission.ResultsFunctional gains were statistically significantly increased from admission to discharge. Improvements were maintained at both 3 months post-discharge and 8 years post-discharge. The socio-economic data collected at 8 year follow-up showed greater than 50% either competitively employed or continuing their education and 100% living in a non-institutionalized setting.ConclusionsThis study addresses a concern regarding the long-term functional outcomes of rehabilitation patients treated by the established infrastructure of the Polytrauma System of Care inpatient rehabilitation centers. The results suggest that Polytrauma/TBI rehabilitation care utilizing a comprehensive, integrated approach is effective and durable in achieving functional gains and successful community reintegration within our initial PRC cohort. Follow-up of subsequent FY cohorts would add to the validity of these outcome findings.



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Common Versus Unique Findings on Processing-Based Task Performance in Korean Speaking Children With Cochlear Implants.

Hypothesis: To better understand individual variability by examining overall neurocognitive underlying features in children with cochlear implants (CIs), and to investigate whether previous findings hold constant in Asian-language users. Background: Studies have tried to explain the individual variability in children with CIs. However, performance on experience-dependent tasks does not seem to be sensitive enough to explain the underlying reason why children have language difficulties even after the surgical procedure. Thus, this current research has focused on underlying neurocognitive functions to better explain the reason for the wide variability in this population. Methods: Using a separate univariate analysis paradigm, performance on processing-based tasks was compared between children with CIs and children with normal hearing. A total of 34 children ranging from 10 to 12 years old participated in the study. There were two different categories of processing-based tasks tapping processing capacity and processing speed. This study used nonword repetition (NWR), competing language processing task (CLPT), and counting span (CS) for examining processing capacity, while rapid naming (RAN) in color, shape, and color shape were used to investigate processing speed. Results: Children with NH outperformed children with CIs on all processing-capacity tasks, except CS. Children with CIs performed similarly to children with NH on processing speed tasks. Conclusions: We found children with CIs still experienced difficulties with processing capacity. Due to cross-linguistic features, we also discovered some interesting findings that differed from previous studies. Lastly, we found processing speed was fairly intact in children with CIs, which is a new finding. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Rituximab Monotherapy Is Effective in Treating Orbital Necrobiotic Xanthogranuloma.

The authors report a case of a patient with bilateral orbital necrobiotic xanthogranuloma and no associated systemic paraproteinemia. Orbital biopsy showed strong expression of CD20-positive cells. The patient was treated with systemic rituximab monotherapy, with excellent clinical response and marked regression of the orbital lesions on imaging. At the time of writing, the patient has been treated with bimonthly rituximab maintenance therapy for 22 months and has stable clinical and imaging findings with sustained response to treatment and no reported side effects. To the authors' knowledge, this is the first reported case of orbital necrobiotic xanthogranuloma successfully treated with rituximab monotherapy. They hope that this well-documented case will encourage clinicians to consider rituximab monotherapy as a possible treatment option, albeit one entailing an off-label use of this drug, for patients with necrobiotic xanthogranuloma of the orbit. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Peri-Punctal Lymphangioma Treated With Bleomycin.

No abstract available

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Effect of Optic Nerve Disinsertion During Evisceration on Nonporous Implant Migration: A Comparative Case Series and a Review of Literature.

Aim: To determine whether evisceration with optic nerve disinsertion and nonporous implant placement increases the risk of implant migration. Methods: This was a single-center, retrospective consecutive comparative interventional case series including patients undergoing evisceration with nonporous implant between January and December 2014. Patients were grouped into 2 groups: group I where the optic nerve was not disinserted (n = 37) and group II with optic nerve disinsertion (n = 50). Implant migration was assessed clinically and on patient photographs. Migration was subclassified as decentration that did not affect the prosthetic outcome and displacement that affected the prosthetic outcome. The secondary outcome measures were the mean implant diameter, volume of the custom ocular prosthesis, and implant-related complications like exposure and extrusion between the 2 groups. Results: At a mean follow up of 12.5 months, none of the sockets in group I and 3 (6%) sockets in group II (p = 0.35) had evidence of implant decentration. There were no cases of implant displacement in both groups. The mean implant diameter in group I was 16.97 mm +/- 0.65 mm and in group II 19.2 mm +/- 0.83 mm (p = 0.0001). Implant extrusion was not different between the 2 groups. The mean custom ocular prosthesis volume in group I was 3.86 ml +/- 0.52 ml and in group II 2.50 ml +/- 0.68 ml (p

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Assessing the Accuracy of Eyelid Measurements Utilizing the Volk Eye Check System and Clinical Measurements.

Purpose: The purpose of this study was to validate the accuracy of marginal reflex distance 1 (MRD1) measurements obtained by the Volk Eye Check system, a modified smartphone that measures MRD1 automatically, relative to clinical and digital measurements. Methods: In this prospective observational study of adults with normal eyelids and ptosis, MRD1 was measured clinically, digitally, and automatically with the Volk device. Eyes were divided into successful versus unsuccessful Volk trial groups; successful eyes were then subdivided into control and ptosis subgroups. The primary outcome measures were mean MRD1 obtained by the 3 modalities. Secondary outcome measures included the success rate of the device and the prevalence of ptosis within the successful and unsuccessful groups. Results: In the overall sample of 88 eyes, clinical and digital MRD1 were not significantly different. Among eyes with successful Volk trials, significant differences in MRD1 measured by the 3 modalities were as follows: in the successful group, Volk MRD1 (3.05 mm) was significantly (p

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Haberland Syndrome Associated With Calvarial Exostosis.

No abstract available

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An Aesthetic Orbicularis Oculi Myectomy Technique for Blepharospasm: Use of Topical 5-Fluorouracil and Fibrin Sealant.

Purpose: To describe a modified technique of orbicularis oculi myectomy for refractory blepharospasm. This technique includes removal of orbicularis muscle, reformation of the eyelid crease and pretarsal platform using fibrin sealant (Tisseel), and topical 5-fluorouracil to reduce scar formation and improve aesthetic outcome. Methods: Retrospective chart review of 7 patients who underwent bilateral orbicularis oculi myectomy with our technique from 2013 to 2016. Outcome measures were postoperative botulinum toxin dose, frequency, duration between treatments, the amount of lagophthalmos, severity of dry eye, and patient satisfaction with aesthetic and functional outcome. Results: Patients who underwent the aesthetic myectomy technique had significantly decreased botulinum toxin use with relief of symptoms postoperatively. Only 1 of 7 patients experienced mild dry eye symptoms postoperatively, managed with artificial tears. All patients were satisfied with the aesthetic and functional outcome. Conclusions: The aesthetic myectomy technique provides effective treatment for blepharospasm with good functional and aesthetic outcome. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Current insight in the localized insulin-derived amyloidosis (LIDA): clinico-pathological characteristics and differential diagnosis

Publication date: Available online 1 September 2017
Source:Pathology - Research and Practice
Author(s): Amir Mehdi Ansari, Lais Osmani, Aerielle E. Matsangos, Qing K. Li
BackgroundIn diabetic patients, subcutaneous insulin injection may cause several types of injection site-related lesions, such as lipoatrophy, insulin-induced cutaneous lipohypertrophy (IICL), allergic reaction, and iatrogenic localized insulin-derived amyloidosis (LIDA). Among these complications, both IICL and LIDA present as tumor-like and slow growing lesions; and they may be confused with one another. The clinical implication and management of IICL and LIDA are different. LIDA causes poor blood glycemic controls due to inadequate absorption of the insulin. Thus, accurate diagnosis of the lesion is critical in diabetic patients.Review of literatureLIDA is an extremely rare complication and often overlooked, it is managed by a surgical intervention. Whereas, IICL is a common side effect and can be managed by a non-surgical approach. Furthermore, in long-standing diabetics, patients may develop hypertrophic cardiomyopathy, proteinuria, peripheral, and autonomic neuropathy; these symptoms can be mistaken for a systemic amyloidosis. It is also necessary to distinguish LIDA from the systemic amyloidosis, which requires a more aggressive systemic therapy. LIDA should also be distinguished from primary cutaneous amyloidosis, with high risk of progression to a systemic amyloidosis. In this effort we reviewed 25 published manuscripts, including case reports and case series studies. We also summarized the literature and discussed differential diagnosis, including the approach to diagnose LIDA.ConclusionThe identification of amyloid material and immunoreactivity with anti-insulin antibodies are key diagnostic features of LIDA. Although several clinical and animal studies were made in recent years, the lesion is still under-diagnosed and underreported. The clinical suspicion and knowledge of the lesion play a crucial role for the accurate diagnosis of LIDA. Surgical excision of the lesion can dramatically decrease insulin requirement and improve glycemic control.



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Bugging allergy; role of pre-, pro- and synbiotics in allergy prevention

Publication date: Available online 1 September 2017
Source:Allergology International
Author(s): Christina E. West, Majda Dzidic, Susan L. Prescott, Maria C. Jenmalm
Large-scale biodiversity loss and complex changes in social behaviors are altering human microbial ecology. This is increasingly implicated in the global rise in inflammatory diseases, most notably the "allergy epidemic" in very early life. Colonization of human ecological niches, particularly the gastrointestinal tract, is critical for normal local and systemic immune development and regulation. Disturbances in composition, diversity and timing of microbial colonization have been associated with increased allergy risk, indicating the importance of strategies to restore a dysbiotic gut microbiota in the primary prevention of allergic diseases, including the administration of probiotics, prebiotics and synbiotics. Here, we summarize and discuss findings of randomized clinical trials that have examined the effects of these microbiome-related strategies on short and long-term allergy preventative effects – including new guidelines from the World Allergy Organization which now recommend probiotics and prebiotics for allergy prevention under certain conditions. The relatively low quality evidence, limited comparative studies and large heterogeneity between studies, have collectively hampered recommendations on specific probiotic strains, specific timing and specific conditions for the most effective preventive management. At the same time the risk of using available products is low. While further research is needed before specific practice guidelines on supplement probiotics and prebiotics, it is equally important that the underlying dietary and lifestyle factors of dysbiosis are addressed at both the individual and societal levels.



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Development of a questionnaire to evaluate asthma control in Japanese asthma patients

Publication date: Available online 1 September 2017
Source:Allergology International
Author(s): Yuji Tohda, Soichiro Hozawa, Hiroshi Tanaka
BackgroundThe asthma control questionnaires used in Japan are Japanese translations of those developed outside Japan, and have some limitations; a questionnaire designed to optimally evaluate asthma control levels for Japanese may be necessary. The present study was conducted to validate the Japan Asthma Control Survey (JACS) questionnaire in Japanese asthma patients.MethodsA total of 226 adult patients with mild to severe persistent asthma were enrolled and responded to the JACS questionnaire, asthma control questionnaire (ACQ), and Mini asthma quality of life questionnaire (Mini AQLQ) at Weeks 0 and 4. The reliability, validity, and sensitivity/responsiveness of the JACS questionnaire were evaluated.ResultsThe intra-class correlation coefficients (ICCs) were within the range of 0.55–0.75 for all JACS scores, indicating moderate/substantial reproducibility. For internal consistency, Cronbach's alpha coefficients ranged from 0.76 to 0.92 in total and subscale scores, which were greater than the lower limit of internal consistency. As for factor validity, the cumulative contribution ratio of four main factors was 0.66. For criterion-related validity, the correlation coefficients between the JACS total score and ACQ5, ACQ6, and Mini AQLQ scores were −0.78, −0.78, and 0.77, respectively, showing a significant correlation (p < 0.0001).ConclusionsThe JACS questionnaire was validated in terms of reliability and validity. It will be necessary to evaluate the therapeutic efficacy measured by the JACS questionnaire and calculate cutoff values for the asthma control status in a higher number of patients.Clinical Trial registrationUMIN000016589



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Phase II basket trial of perifosine monotherapy for recurrent gynecologic cancer with or without PIK3CA mutations

Summary

Objective Perifosine exhibits anti-tumor activity by inhibiting AKT phosphorylation. The purpose of this phase II basket trial was to evaluate the efficacy and safety of perifosine monotherapy for ovarian, endometrial, and cervical cancers. Methods Recurrent or persistent ovarian, endometrial, or cervical cancer patients were assigned to PIK3CA wild-type or mutant groups. Each patient received 600 mg oral perifosine on day 1 followed by a maintenance dose of 100 mg daily. The primary endpoint was disease control rate; secondary endpoints included response rate, progression-free survival, overall survival, and safety. Immunohistochemical staining and targeted sequencing were used to explore new biomarkers in such patients. Results Sixteen and 5 ovarian, 17 and 7 endometrial, and 18 and 8 cervical cancer patients with PIK3CA wild-type and mutant, respectively, were enrolled. Disease control rates (wild-type/mutant) were 12.5/40.0%, 47.1/14.3%, and 11.1/25.0% in ovarian, endometrial, and cervical cancer, respectively. The most common grade 3/4 toxicities were anemia (22.5%) and anorexia (11.3%). Immunohistochemical staining revealed that the disease control rate in patients with negative phosphatase and tensin homolog (PTEN) expression was 50.0%, and the odds ratio of positive to negative patients was 0.24 in all patients. Conclusions Perifosine monotherapy showed good tolerability but expected efficacy was not achieved. Modest efficacy was demonstrated in ovarian cancer patients with PIK3CA mutations and endometrial cancer patients with PIK3CA wild-type; no difference was observed between PIK3CA wild-type and mutant in cervical cancer. Absence of PTEN expression may be predictive of clinical efficacy with perifosine monotherapy.

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An improved method for identifying SUMOylation sites of viral proteins

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DC-SIGN promotes Japanese encephalitis virus transmission from dendritic cells to T cells via virological synapses

Abstract

Skin-resident dendritic cells (DCs) likely encounter incoming viruses in the first place, and their migration to lymph nodes following virus capture may promote viral replication. However, the molecular mechanisms underlying these processes remain unclear. In the present study, we found that compared to cell-free viruses, DC-bound viruses showed enhanced capture of JEV by T cells. Additionally, JEV infection was increased by co-culturing DCs and T cells. Blocking the C-type lectin receptor DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) with neutralizing antibodies or antagonists blocked JEV transmission to T cells. Live-cell imaging revealed that DCs captured and transferred JEV viral particles to T cells via virological synapses formed at DC-T cell junctions. These findings indicate that DC-SIGN plays an important role in JEV transmission from DCs to T cells and provide insight into how JEV exploits the migratory and antigen-presenting capabilities of DCs to gain access to lymph nodes for dissemination and persistence in the host.

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Evaluation of carbon dioxide laser therapy for benign tumors of the eyelid margin

Abstract

Eyelid margin tumors require special attention based on both anatomical and histological perspectives. Our aim in this study was to evaluate carbon dioxide (CO₂) laser therapy for the treatment of eyelid margin tumors. Fifty-two patients with 55 eyelid margin tumors were included in this study. All tumors were removed with a CO₂ laser, and histopathological evaluation was obtained in 52 cases. All patients were followed up for a mean period of 8.5 months (range 6 to 14 months). There were no bleedings in the intra- and postoperative period; the wounds were dry and reepithelized after 10–14 days and no recurrence occurred during follow-up period. Compared to the surrounding tissue, the treated area was hypopigmented and maximum five eyelashes (average 2.5) were wasted during the procedure. We achieved complete patient and surgeon satisfaction with cosmetic and therapeutic results. CO₂ laser treatment of eyelid margin is a safe and effective procedure; its cosmetic result is beneficial as it does not cause malposition of the eyelid or damage to the lacrimal drainage system if the tumor is located in its proximity.

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mTOR kinase inhibition effectively decreases progression of a subset of neuroendocrine tumors that progress on rapalog therapy and delays cardiac impairment

Inhibition of mTOR signaling using the rapalog everolimus is an FDA-approved targeted therapy for patients with lung and gastroenteropancreatic neuroendocrine tumors (NETs). However, patients eventually progress on treatment, highlighting the need for additional therapies. We focused on pancreatic NETs (pNETs) and reasoned that treatment of these tumors upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi) such as CC-223 could overcome a number of resistance mechanisms in tumors and delay cardiac carcinoid disease. We performed preclinical studies using human pNET cells in vitro and injected them subcutaneously or orthotopically to determine tumor progression and cardiac function in mice treated with either rapamycin alone or switched to CC-223 upon progression. Detailed signaling and RNA sequencing analyses were performed on tumors that were sensitive or progressed on mTOR treatment. Approximately 57% of mice bearing pNET tumors which progressed on rapalog therapy showed a significant decrease in tumor volume upon a switch to CC-223. Moreover, mice treated with an mTORKi exhibited decreased cardiac dilation and thickening of heart valves than those treated with placebo or rapamycin alone. In conclusion, in the majority of pNETs that progress on rapalogs, it is possible to reduce disease progression using an mTORKi, such as CC-223. Moreover, CC-223 had an additional transient cardiac benefit on valvular fibrosis compared to placebo- or rapalog-treated mice. These results provide the preclinical rationale to further develop mTORKi clinically upon progression on rapalog therapy and to further test their long term cardioprotective benefit in those NET patients prone to carcinoid syndrome.

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Inhibition of discoidin domain receptor 1 reduces collagen-mediated tumorigenicity in pancreatic ductal adenocarcinoma

The extracellular matrix (ECM), a principal component of pancreatic ductal adenocarcinoma (PDA), is rich in fibrillar collagens that facilitate tumor cell survival and chemoresistance. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that specifically binds fibrillar collagens and has been implicated in promoting cell proliferation, migration, adhesion, ECM remodeling, and response to growth factors. We found that collagen-induced activation of DDR1 stimulated pro-tumorigenic signaling through protein tyrosine kinase 2 (PYK2) and pseudopodium-enriched atypical kinase 1 (PEAK1) in pancreatic cancer cells. Pharmacologic inhibition of DDR1 with an ATP competitive orally available small molecule kinase inhibitor (7rh) abrogated collagen-induced DDR1 signaling in pancreatic tumor cells and consequently reduced colony formation and migration. Furthermore, the inhibition of DDR1 with 7rh showed striking efficacy in combination with chemotherapy in orthotopic xenografts and autochthonous pancreatic tumors where it significantly reduced DDR1 activation and downstream signaling, reduced primary tumor burden, and improved chemoresponse. These data demonstrate that targeting collagen-signaling in conjunction with conventional cytotoxic chemotherapy has the potential to improve outcome for pancreatic cancer patients.

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Dual inhibition of Hedgehog and c-Met pathways for pancreatic cancer treatment

Pancreatic adenocarcinoma (PDA) is one of the most chemotherapy and radiotherapy resistant tumors. The c-Met and Hedgehog (Hh) pathways have been shown previously by our group to be key regulatory pathways in the primary tumor growth and metastases formation. Targeting both the HGF/c-Met and Hh pathways has shown promising results in pre-clinical studies; however, the benefits were not readily translated into to clinical trials with PDA patients. In this study, utilizing mouse models of PDA, we showed that inhibition of either HGF/c-Met or Hh pathways sensitize the PDA tumors to gemcitabine resulting in decreased primary tumor volume as well as significant reduction of metastatic tumor burden. However, prolonged treatment of single HGF/c-Met or Hh inhibitor leads to the resistance to these single inhibitors, likely because the single c-Met treatment leads to the enhanced expression of Shh, and vice versa. Targeting both the HGF/c-Met and Hh pathways simultaneously overcame the resistance to the single inhibitor treatment and led to a more potent anti-tumor effect in combination with the chemotherapy treatment.

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A CRISPR/Cas9-based screening for non-homologous end joining inhibitors reveals ouabain and penfluridol as radiosensitizers

Non-homologous end joining (NHEJ) is the major pathway responsible for the repair of ionizing radiation (IR)-induced DNA double-strand breaks (DSBs), and correspondingly regulates the cellular response to IR. Identification of NHEJ inhibitors could substantially enhance the tumor radiosensitivity and improve the therapeutic efficiency of radiotherapy. In present study, we demonstrated a screening for NHEJ inhibitors by using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and high-resolution melting (HRM) analysis. Since NHEJ is regarded as an error-prone mechanism, the NHEJ-mediated ligation of the site-specific DSB induced by Cas9 nuclease would eventually cause the mutation of the targeted sequence. Then, HRM analysis, a reliable and rapid assay for detecting sequence variation, was performed to evaluate the mutation efficiency of the targeted site. Validating analysis confirmed the NHEJ activities was positively correlated with the mutation frequencies. Next, an approved drug library containing 1540 compounds was interrogated by using this screening strategy. Our results identified ouabain, a cardiotonic agent, and penfluridol, an antipsychotic agent, have the capacity to restrain NHEJ activity. Further experiments in vitro revealed the radiosensitizing effects of these compounds. Overall, we presented a cell-based screening for NHEJ inhibitors which could promote the discovery of novel radiosensitizers.

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Total reference air kerma can accurately predict isodose surface volumes in cervix cancer brachytherapy. A multicenter study

Publication date: Available online 1 September 2017
Source:Brachytherapy
Author(s): Karen S. Nkiwane, Else Andersen, Jerome Champoudry, Astrid de Leeuw, Jamema Swamidas, Jacob Lindegaard, Richard Pötter, Christian Kirisits, Kari Tanderup
PurposeTo demonstrate that V60 Gy, V75 Gy, and V85 Gy isodose surface volumes can be accurately estimated from total reference air kerma (TRAK) in cervix cancer MRI-guided brachytherapy (BT).Methods and Materials60 Gy, 75 Gy, and 85 Gy isodose surface volumes levels were obtained from treatment planning systems (VTPS) for 239 EMBRACE study patients from five institutions treated with various dose rates, fractionation schedules and applicators. An equation for estimating VTPS from TRAK was derived. Furthermore, a surrogate Point A dose (Point A*) was proposed and tested for correlation with V75 Gy.ResultsPredicted volumes Vpred = 4965 (TRAK/dref) 3/2 + 170 (TRAK/dref) − 1.5 gave the best fit to VTPS. The difference between VTPS and predicted volumes was 0.0% ± 2.3%. All volumes were predicted within 10%. The prediction was valid for (1) high-dose rate and pulsed dose rate, (2) intracavitary vs. intracavitary/interstitial applicators, and (3) tandem-ring, tandem-ovoid, and mold. Point A* = 14 TRAK was converted to total EQD2 and showed high correlation with V75 Gy.ConclusionsTRAK derived Isodose surface volumes may become a tool for assessment of treatment intensity. Furthermore, surrogate Point A^∗ doses can be applied for both intracavitary and intracavitary/interstitial BT and can be used to compare treatments across fractionation schedules.



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Giant Hepatic Adenoma in a 12-Year-Old Girl

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Cetuximab with radiotherapy as an alternative treatment for advanced squamous cell carcinoma of the temporal bone

Publication date: Available online 1 September 2017
Source:Auris Nasus Larynx
Author(s): Koji Ebisumoto, Kenji Okami, Masashi Hamada, Daisuke Maki, Akihiro Sakai, Kosuke Saito, Fukuko Shimizu, Shoji Kaneda, Masahiro Iida
The prognosis of advanced temporal bone cancer is poor, because complete surgical resection is difficult to achieve. Chemoradiotherapy is one of the available curative treatment options; however, its systemic effects on the patient restrict the use of this treatment. A 69-year-old female (who needed peritoneal dialysis) presented at our clinic with T4 left external auditory canal cancer and was treated with cetuximab plus radiotherapy (RT). The primary lesion showed complete response. The patient is currently alive with no evidence of disease two years after completion of the treatment and does not show any late toxicity. This is the first advanced temporal bone cancer patient treated with RT plus cetuximab. Cetuximab plus RT might be a treatment alternative for patients with advanced temporal bone cancer.



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Anatomia del nervo faciale

Publication date: September 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 3
Author(s): J. Barbut, F. Tankéré, I. Bernat
Il nervo faciale è al centro della pratica quotidiana in oto-rino-laringoiatria. La sua singolare fisiologia e la sua patologia fanno di questo paio di nervi cranici un soggetto appassionante in cui alcuni si sono specializzati. La precisa conoscenza della sua anatomia, il cui percorso è tortuoso e presenta molte relazioni con altri elementi nobili, è un prerequisito indispensabile per il suo approccio, sia in chirurgia cervicale che in quella otologica che in quella neuro-otologica. Gli autori cominciano con il discutere i principi fondamentali dell'embriologia del secondo arco branchiale per aiutare la comprensione dell'anatomia e delle possibili variazioni del tragitto e dei rapporti del nervo faciale. Di seguito è descritta dettagliatamente l'anatomia descrittiva del nervo faciale. Lo studio inizia con la genesi del messaggio nervoso a livello corticale con le afferenze per i nuclei centrali. Viene, poi, descritto il tragitto intracranico del nervo, dal suo prcorso intrapontino al suo tragitto intrapetroso, passando attraverso la sua porzione nell'angolo pontocerebellare. Infine, sono presentate le divisioni intraparotidee precisando i diversi muscoli che innervano. Un punto importante è costituito dai diversi rami nervosi collaterali intra- ed extrapetrosi. Viene spiegata anche l'anatomia funzionale descrivendo le funzioni e i tragitti dei diversi rami collaterali del nervo insieme alle origini e alle terminazioni dei componenti vegetativi, sensitivi e sensoriali del nervo. Infine, un capitolo è dedicato alle variazioni anatomiche del tragitto del nervo la cui conoscenza è indispensabile per limitare i rischi di paralisi facciale iatrogena durante la dissecazione del nervo.



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Poliposi nasosinusale. Rinosinusite cronica con polipi

Publication date: September 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 3
Author(s): P. Bonfils, P. Halimi, A.-L. Gaultier, Q. Lisan
La poliposi nasosinusale (chronic rhinosinusitis with polyps nella letteratura anglosassone) è una rinosinusite cronica bilaterale caratterizzata dallo sviluppo di polipi nelle cavità nasosinusali. La sua prevalenza è stimata, nella popolazione generale, pari a circa il 4%. La poliposi nasosinusale può essere associata ad alcune malattie come la fibrosi cistica, la discinesia ciliare, le immunodeficienze e l'intolleranza all'aspirina e ai farmaci antinfiammatori non steroidei (FANS). Deriva da un'infiammazione cronica della mucosa nasosinusale dove l'infiltrazione eosinofila è uno dei marker della malattia. Ma la sua fisiopatologia rimane ancora sconosciuta. Sono state sviluppate, nel corso degli ultimi trent'anni, numerose teorie che coinvolgono in particolare l'infezione micotica e il ruolo delloStaphylococcus aureus. La sintomatologia della poliposi è dominata dall'ostruzione nasale e dall'anosmia e da un minimo grado di rinorrea posteriore. È la forma di rinosinusite diffusa che compromette di più la qualità della vita. La triade di Widal (triade di Samter) associa tipicamente poliposi nasosinusale, asma e intolleranza all'aspirina e ai FANS. La prevalenza dell'asma è elevata nella poliposi nasosinusale; la ricerca di asma o di iperreattività bronchiale non specifica deve essere sistematica davanti ad ogni paziente con una poliposi. Il trattamento è sempre medico, eventualmente completato da un intervento chirurgico. I trattamenti medici si basano sui corticosteroidi, sia locali che sistemici. La chirurgia della poliposi si basa su una videochirurgia endonasale generalmente effettuata sotto controllo endoscopico. I criteri di selezione dei pazienti per la chirurgia sono dominati dall'importanza dei sintomi e dalla resistenza ai trattamenti medici.



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Actinomicosi cervicofacciale

Publication date: September 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 3
Author(s): A. Loth-Bouketala, J. Graziani, N. Fakhry
L'actinomicosi è una malattia rara causata da batteri anaerobi e filamentosi, gli Actinomyces, che si presenta sotto forma di tumefazione sottocutanea, infiammatoria e, il più delle volte, cronica. L'actinomicosi può avere diverse sedi, ma la regione cervicofacciale è quella il più delle volte colpita. Alcuni fattori favoriscono l'insorgenza di questa malattia (immunodepressione, trauma orale). La presentazione clinica è aspecifica e la diagnosi è spesso ritardata. Il quadro clinico può suggerire una patologia tumorale oppure una tubercolosi. L'evoluzione clinica può portare a una fistolizzazione cutanea della tumefazione. La valutazione tramite esami strumentali e del sangue è poco specifica. I campioni batteriologici e anatomopatologici (citopuntura, biopsie, evacuazione del pus) confermano la diagnosi. Per trattare l'actinomicosi è proposta un'antibioticoterapia, talvolta associata a un trattamento chirurgico.



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In memoriam: Dr. Robert William McCarley

Dr. Robert William McCarley, Professor of Psychiatry, was a world-renowned leader in the fields of sleep and schizophrenia research, and a past President of the Sleep Research Society. He passed away on May 27th, 2017 at the age of 79. Dr. McCarley's scientific pursuits and contributions have been recognized nationally and internationally. He was the recipient of many prestigious awards throughout his career including the Distinguished Scientist Award and the Mary A. Carskadon Outstanding Educator Award from the Sleep Research Society, the William C.

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Commentary to “Outcome After Turndown for Elective Abdominal Aortic Aneurysm Surgery”

Publication date: Available online 1 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Edward Choke




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Commentary on “Follow-up on Small Abdominal Aortic Aneurysms Using Three Dimensional Ultrasound: Volume Versus Diameter”

Publication date: Available online 1 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Regula S. von Allmen




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Collateral Circulation in Chronic Aortic Occlusive Disease

Publication date: Available online 1 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Zhongzhi Jia, Guomin Jiang




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Symmetrical Peripheral Gangrene

Publication date: Available online 1 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Ana Carina Ferreira, Vasco Fernandes




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Aortic Reconstruction in an Infected Field. Commentary on “Self-made Xeno-pericardial Aortic Tubes to Treat Native and Aortic Graft Infections”

Publication date: Available online 31 August 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Oliver Lyons




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Nasal interleukin 25 as a novel biomarker for patients with chronic rhinosinusitis with nasal polyps and airway hypersensitiveness

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airway and is tightly linked with airway hyperresponsiveness (AHR) and asthma. However, the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP remain elusive.

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Assessing hypoxia risk during air travel after a severe asthma exacerbation in children

Decreased atmospheric cabin pressure in commercial aircrafts (cruising altitude 9,000–13,000 m), requiring cabin pressurization from 1,530 to 2,440 m, is equivalent to breathing a fraction of inspired oxygen (FiO2) of 15.1% at sea level.

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Sponsoring Organizations and Liaisons

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





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Table of Contents

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





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Lay preferences for dentogingival esthetic parameters: A systematic review

Publication date: Available online 1 September 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Stefano Del Monte, Kelvin I. Afrashtehfar, Elham Emami, Samer Abi Nader, Faleh Tamimi
Statement of problemAn objective definition of the characteristics that render a smile esthetically acceptable in the eye of laypeople is lacking.PurposeThe purpose of this systematic review was to identify, appraise, and synthesize the available evidence on the opinion of laypeople regarding the dentogingival characteristics that render a smile esthetically acceptable. The evidence was collected by surveying with standardized digitally modified smile images.Material and methodsFour databases were used to search English language studies published between January 1996 and December 2015. This was complemented by a manual search of 8 dental journals. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, 2 independent reviewers extracted the relevant characteristics of lay evaluators, the images evaluated, and the outcomes measure. Included studies were assessed in agreement with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Outcomes were treated as a continuous variable, and when more than 1 article provided information on a parameter, the weighted arithmetic mean was calculated.ResultsAfter 8851 articles were screened, 20 studies were included. Those studies addressed 20 different dentogingival esthetic parameters. The total number of participants interviewed was 3107. According to the Olmos classification, 6 studies had a high level of quality, and 14 studies had a moderate level of quality. The 2 reviewers agreed on all the quality assessments. In the articles reviewed, central incisors clearly played a key role in smile esthetics. Almost all dental, gingival, and occlusal parameters are related to the proportion, shape, and position of central incisors and their relation to the adjacent dental structures.ConclusionsThe present review provides the estimated thresholds of tolerability and ideal values of smile parameters determined by laypeople. This may guide clinicians in evidence-based diagnosis and the planning of dental esthetic treatments.



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The Essentials

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





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Editorial Board

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





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News and Notes

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





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Growth curves for intracranial volume in normal Asian children fortify management of craniosynostosis

Craniosynostosis alters the morphology of cranial vault, prevents normal cranial growth, and can elevate intracranial pressure over time. Surgical goals in the event of craniosynostosis are to reduce intracranial pressure and to achieve aesthetic cranial contours, but the timing of such surgery is open to debate. Although excess intracranial pressure must be avoided, premature surgical interventions may necessitate secondary revisions. Also, direct attempts to measure intracranial pressure are invasive by design and thus may not be feasible in every case.

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Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia

Publication date: Available online 1 September 2017
Source:Cancer Cell
Author(s): Diana Passaro, Alessandro Di Tullio, Ander Abarrategi, Kevin Rouault-Pierre, Katie Foster, Linda Ariza-McNaughton, Beatriz Montaner, Probir Chakravarty, Leena Bhaw, Giovanni Diana, François Lassailly, John Gribben, Dominique Bonnet
The biological and clinical behaviors of hematological malignancies can be influenced by the active crosstalk with an altered bone marrow (BM) microenvironment. In the present study, we provide a detailed picture of the BM vasculature in acute myeloid leukemia using intravital two-photon microscopy. We found several abnormalities in the vascular architecture and function in patient-derived xenografts (PDX), such as vascular leakiness and increased hypoxia. Transcriptomic analysis in endothelial cells identified nitric oxide (NO) as major mediator of this phenotype in PDX and in patient-derived biopsies. Moreover, induction chemotherapy failing to restore normal vasculature was associated with a poor prognosis. Inhibition of NO production reduced vascular permeability, preserved normal hematopoietic stem cell function, and improved treatment response in PDX.

Graphical abstract

Teaser

Passaro et al. show that acute myeloid leukemia, mainly via nitric oxide (NO), causes bone marrow vascular abnormalities and that failure to restore normal vasculature after induction chemotherapy is associated with a poor prognosis. Importantly, inhibition of NO production improves treatment response in vivo.


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Focal necrotizing myopathy with ‘dropped-head syndrome’ induced by cobimetinib in metastatic melanoma

Therapeutic advances derived from targeted therapy and immune checkpoint inhibitors can improve melanoma prognosis. Since 2015, cobimetinib has been approved in combination with vemurafenib in the first-line treatment for BRAF-mutated melanoma. For NRAS-mutated melanomas, MEK inhibition seems to be a therapeutic target, and association with checkpoint inhibitor provides a further therapeutic perspective. Infraclinical creatine phosphokinase (CPK) elevation is an MEK inhibitor side effect. We describe a case of focal necrotizing myopathy with 'dropped-head syndrome' induced by cobimetinib, 1 month after its introduction. The clinical presentation comprised interscapular pain, axial fatigue with cervical hypotonia, CPK elevation, intense fluorine-18-fluorodeoxyglucose uptake in cervical muscles, and necrotizing myopathy was confirmed by muscle biopsy. Cobimetinib was temporarily discontinued, resulting in CPK normalization. Re-evaluation showed partial response, motivating continuation of combination therapy with a reduced dose of cobimetinib (40 mg/day). Because prescription of targeted therapies is likely to increase, this adverse event should be known.

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Cyclic AMP-Epac signaling pathway contributes to repression of PUMA transcription in melanoma cells

The universal second messenger cAMP regulates numerous cellular processes. Although the cAMP-signaling pathway leads to induction of gene transcription, it remains unknown whether this pathway contributes toward suppression of transcription. Here, we show that blockade of cAMP signaling using MDL12330A led to an increase in PUMA transcript levels, but not p21 in melanoma cells. cAMP downstream component Epac activation was essential for suppression of PUMA transcription as an Epac agonist reversed the effects of MDL12330A. These results suggest that transcriptional repression is one of the functions of the cAMP-Epac signaling pathway.

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Characteristics of melanoma in Japan: a nationwide registry analysis 2011–2013

The distribution and incidence of melanoma vary among different races and ethnic groups. This study aimed to investigate the characteristics of cutaneous melanoma, mucosal melanoma, uveal melanoma, and melanoma of unknown primary (MUP) origin in a Japanese population. We studied these four types of melanoma in patients registered in Hospital Based Cancer Registries in Japan from 2011 to 2013. A total of 5566 patients with melanoma were identified. The distribution of sex, age, primary site, and clinical stage was analyzed. The number of patients, proportion in comparison with all melanoma cases, and crude incidence rate per 100 000 person-year of each melanoma type were 4481, 80.5%, and 1.24 in invasive cutaneous; 821, 14.8%, and 0.32 in mucosal; 163, 2.9%, and 0.064 in uveal; and 101, 1.8%, and 0.039 in MUP origin, respectively. Including the patients with in-situ cutaneous melanoma and stage unknown cutaneous melanoma, the crude incidence rate of cutaneous melanoma increased at 1.75. Almost half of the cutaneous melanomas were located in the lower limb. Cutaneous melanoma was the most common, but less frequent than that in western countries. Mucosal melanoma was quite rare, but its proportion and crude incidence rate were higher than those in western countries. Uveal melanoma was particularly rare, and its crude incidence rate was lower than that in western countries. MUP origin was also particularly rare, but it had almost the same incidence rate as that in other countries. Melanoma in Japan was heterogeneous among the four melanoma types and shares some attributes with that in western countries.

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Quantification of microRNA-21 and microRNA-125b in melanoma tissue

Although microRNAs (miRNAs) have emerged as potent mediators of melanoma development and progression, a precise understanding of their oncogenic role remains unclear. In this study, we analysed formalin-fixed and paraffin-embedded tissues from two separate melanoma cohorts and from a series of benign melanocytic nevi. Using three different quantification methods [array analysis, quantitative PCR (qPCR) and in-situ hybridization (ISH) quantified by digital image analysis], we found considerable miRNA dysregulation in tumours. Using array analysis, samples mainly clustered according to their biological group (benign vs. malignant) and 77 miRNAs differed significantly between nevi and melanoma samples. Increase of miR-21 and miR-142, and decrease of miR-125b, miR-211, miR-101 and miR-513c in the melanomas were verified in both cohorts using qPCR, whereas the decrease of miR-205 observed with array analysis could not be confirmed using qPCR. ISH with digital quantification showed expression of miR-21 and miR-125b in the melanocytic lesions. miR-21 ISH was increased in melanomas, whereas quantification of miR-125b showed uniform ISH expression across nevi and melanomas. Our results support the important involvement of different miRNAs in melanoma biology and may serve as solid basics for further miRNA investigations in melanoma formalin-fixed and paraffin-embedded tissue. In particular, there is increased expression of miR-21 in melanomas compared with benign nevi.

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Current status and future direction in the management of malignant melanoma

The incidence of malignant melanoma is increasing rapidly on a global scale. Although some types of melanoma, for example primary cutaneous melanoma, can be managed by surgery, metastatic melanoma cannot and it has a high mortality rate. Both oncogene and immune-targeted strategies have shown marked efficacy in some patients, but their effect on overall survival is still variable. Therefore, newer therapeutic approaches are needed. Fortunately, new advances in molecular medicine have led to an understanding of an individual patient's cancer at the genomic level. This information is now being used in all stages of cancer treatment including diagnosis, treatment selection, and treatment monitoring. This new strategy of personalized medicine may lead to marked shifts in immunotherapeutic treatment approaches such as individualized cancer vaccines and adoptive transfer of genetically modified T cells. This review provides an overview of recent approaches in cancer research and expected impact on the future of treatment for metastatic melanoma.

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MGMT methylation correlates with melphalan pelvic perfusion survival in stage III melanoma patients: a pilot study

Approximately 25% of melanoma patients with locoregional metastases are nonresponsive to new molecular target therapy and immunotherapy. When metastases are located in the pelvis, melphalan hypoxic perfusion can be an optional treatment. Because methylation of MGMT promoter increases the efficacy of alkylating agents, studies on melanoma outcome of patients treated with melphalan regional chemotherapy should consider this epigenetic change. This study aims to evaluate whether the survival of stage III melanoma patients treated with melphalan regional chemotherapy may be correlated with MGMT methylation status. The metastatic tissues of 27 stage III melanoma patients with locoregional metastases located in the pelvis subjected to melphalan hypoxic pelvic perfusion were examined. The methylation status of the MGMT promoter was investigated by MS-MLPA probes analysis and the presence of the BRAF V600E mutation was analyzed by CAST-PCR. The median survival times were estimated using the Kaplan–Meier curves and were stratified according to the clinicopathological characteristics of patients and lesions. The overall median survival time was 17 months. The 1-year, 3-year, and 5-year survival rates were 66.7, 18.5, and 7.4%, respectively. Disease stage, burden, and percentage of MGMT methylation significantly affected survival. We estimated an MGMT promoter methylation cut-off of at least 14%, which was significantly associated with a longer survival after melphalan regional chemotherapy. Our data suggest that MGMT promoter methylation could be an important factor in determining which melanoma patients should receive melphalan regional chemotherapy, but its prognostic significance in the routine clinical setting needs to be clarified in a larger study.

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A unique gene expression signature is significantly differentially expressed in tumor-positive or tumor-negative sentinel lymph nodes in patients with melanoma

The purpose of this study was to learn whether molecular characterization through gene expression profiling of node-positive and node-negative sentinel lymph nodes (SLNs) in patients with clinical stage I and II melanoma may improve the understanding of mechanisms of metastasis and identify gene signatures for SLNs+/SLNs− that correlate with diagnosis or clinical outcome. Gene expression profiling was performed on SLN biopsies of 48 (24 SLN+ and 24 SLN−) patients (T3a/b–T4a/b) who underwent staging of SLNs using transcriptome profiling analysis on 5 μm sections of fresh SLNs. U133A 2.0 Affymetrix gene chips were used. Significance analysis of microarrays was used to test the association between gene expression level and SLN status. Genes with fold change more than 1.5 and q value less than 0.05 were considered differentially expressed. Pathway analysis was performed using Ingenuity Pathway Analysis. The Benjamini and Hochberg method was used to adjust for multiple testing in pathway analysis. We identified 89 probe sets that were significantly differentially expressed (1.5–27-fold; q

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Meningeal melanomatosis following discontinuation of dabrafenib: implications for the maintenance of long-term complete remission

A subset of 10–20% of patients under continuous BRAF inhibitor monotherapy achieve long-term progression-free and overall survival. Definitive criteria for the safe cessation of BRAF inhibitor monotherapy in treatment-responsive melanoma patients are lacking. We report a patient who remained in complete remission (CR) for 5 years under dabrafenib. The treatment was withdrawn because of concerns about cardiac toxicity. Four months thereafter the patient developed neurological symptoms, including diplopia and bilateral visual loss. Meningeal melanomatosis and parenchymal brain metastases were diagnosed. Extracerebral metastases were excluded. Reinduction of dabrafenib, combined with trametinib, led to the rapid relief of the neurological symptoms, and a partial remission was confirmed radiologically. Unfortunately, the response was not maintained and the patient died 9 months later. This observation demonstrates that discontinuation of BRAF inhibition can result in loss of disease control. On the basis of this observation, we suggest that BRAF-targeted therapy should be withdrawn only when the risks of continued treatment exceed the risk for disease relapse. However, future studies are urgently required to confirm and quantify the risk for rapid disease relapse following withdrawal of BRAF inhibitor monotherapy.

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The safety of pembrolizumab in metastatic melanoma and rheumatoid arthritis

Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies. Here, we report on the safety and efficacy of pembrolizumab in a melanoma patient with multiple medical problems including poorly controlled rheumatoid arthritis and we review the available literature on the use of immunotherapy and autoimmune diseases. The weight of evidence suggests that these patients should be offered the opportunity to benefit from immune check point inhibitors, with drugs targeting programmed cell death-1 being preferred. More research is required to study the long-term effects of immunotherapy on patients with autoimmune diseases.

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Prognostic significance of cyclooxygenase 2 and phosphorylated Akt1 overexpression in primary nonmetastatic and metastatic cutaneous melanomas

Cyclooxygenase 2 (COX-2) and phosphorylated Akt1 (p-Akt1) are associated with tumor spreading, cell proliferation, high metabolism, and angiogenesis in solid tumors. This study aimed to investigate COX-2 and p-Akt1 expression in primary and metastatic melanomas by correlating with the cellular proliferation index (as revealed by minichromosome maintenance 2 expression) and the outcome of patients with malignant melanomas. Seventy-seven biopsies of malignant melanomas, including 42 primary nonmetastatic melanomas (PNMMs), 12 primary metastatic melanomas (PMMs), and 23 metastatic melanomas (MMs), were retrospectively selected. Tissue microarrays were developed and submitted for immunohistochemical staining for COX-2, p-Akt1, and minichromosome maintenance 2. Increased COX-2 cytoplasmic staining patterns were observed in PMM and MM when compared with PNMM (P=0.0011). Higher nuclear and cytoplasmic expression of p-Akt1 was more closely associated with PMM than with MM and PNMM (P

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Concurrent radiotherapy for patients with metastatic melanoma and receiving anti-programmed-death 1 therapy: a safe and effective combination

A combination of immune-checkpoint inhibitors and radiation therapy (RT) represents a promising therapeutic strategy in part mediated by the abscopal effect, but clinical experience related to this combination remains scarce. Clinical data and patterns of treatment were retrospectively collected from all consecutive patients with metastatic melanoma and receiving programmed-death 1 (PD-1) immune-checkpoint inhibitors. Survival data, best overall response, and acute and delayed toxicities (graded according to Common Terminology Criteria for Adverse Events, v 4.3) were compared between patients receiving concurrent RT (IR) or no irradiation (NIR). Fifty-nine patients received anti-PD-1 immunotherapy [pembrolizumab (n=28) or nivolumab (n=31)] between August 2014 and December 2015 at our institution. Among these, 29% (n=17) received palliative RT for a total of 21 sites, with a mean dose of 30 Gy delivered in 10 fractions. Acute and late toxicity profiles were similar in the two groups. After a 10-month median follow-up, the objective response rate (complete or partial response) was significantly higher in the IR group versus the NIR group (64.7 vs. 33.3%, P=0.02) and one complete responder after RT was compatible with an abscopal effect. The 6-month disease-free survival and overall survival rates for the NIR group versus the IR group were 49.7 versus 64.7% (P=0.32) and 58.8 versus 76.4% (P=0.42), respectively. We report here that the combination of RT and anti-PD-1 immunotherapy is well tolerated and leads to a significant higher tumor response rate within and outside the irradiated field, which is emphasized by the first reported case of an abscopal effect in solid tumors.

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Futility of imaging to stage melanoma patients with a positive sentinel lymph node

The use of staging imaging in melanoma patients with a positive sentinel lymph node (SLN) has been reported to be of limited value. Improved accuracy resulting from the development of time-of-flight positron emission tomography (PET) and ongoing image quality improvement of computed tomography (CT) may challenge this statement. Our retrospective study assessed the clinical value of routine staging CT and PET/CT imaging in a recent cohort of asymptomatic SLN-positive patients. Between January 2011 and April 2014, 143 patients with a positive SLN were routinely staged using CT of various parts of the body or whole-body PET/CT. Scores were assigned for level of certainty for regional or distant metastases and incidental second primary malignancies. Diagnostic test performance was assessed, as well as the number and nature of ensuing additional diagnostic actions. CT was performed in 102 of 143 (71%) patients and PET/CT in 41 (29%) patients. The use of PET/CT increased over the study period. Metastases were found in two of the 143 patients (true-positive yield 1.4%). Sensitivity, specificity and positive predictive value were 11, 73 and 4% for CT and 17, 57 and 6%, respectively, for PET/CT. None of the 143 patients had a change in AJCC stage. Two other primary malignancies were found. Twenty-one (15%) patients were subjected to 37 additional investigations, referrals or procedures. Routine staging imaging with CT or PET/CT in SLN-positive patients is not useful. The yield is low and the results are often false positive, leading to unnecessary additional tests, most of which are costly and some potentially morbid.

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Malignant melanoma incidence trends in a Mediterranean population following socioeconomic transition and war: results of age–period–cohort analysis in Croatia, 1989–2013

The aim of this study was to analyse trends of malignant melanoma incidence in Croatia for men and women of different age groups by birth cohorts and time periods, and to interpret them in the context of national socioeconomic changes over time and the possible implications for future prevention in South-Eastern European postcommunist countries with high mortality rates. We used the Croatian National Cancer Registry data to analyse incidence trends of malignant melanoma of the skin (ICD-9 code 172 and ICD-10 code C43) in men and women aged 25–79 years by age–period–cohort modelling. Over the 25-year period, the incidence was increasing by 5.0% annually in men and 4.6% in women. The age–period model provided the best fit for data in both sexes, with steeply increasing incidence rates, followed by a stabilization after the 2000s. On the cohort scale, incidence rates increased in successive generations of men, whereas in women, the risk of malignant melanoma attenuated in recent cohorts. Even if some progress has been achieved in recent years, the increasing melanoma incidence without concomitant declines in mortality would indicate a need to rekindle prevention efforts in the country taking the specific socioeconomic context into account.

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Clinical experience of stereotactic radiosurgery at a linear accelerator for intraocular melanoma

Long-term results with linear accelerator LINAC-based stereotactic radiosurgery for intraocular uveal malignant melanoma were assessed. A retrospective study was carried out of patients with uveal melanoma after a 1-day session stereotactic radiosurgery at LINAC in Slovakia. In the period 2001–2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma) was treated. The median tumor volume at baseline was 0.5 cm3 (with range from 0.2 to 1.6 cm3). Tumors ranged in size from 2.4 to 20.8 mm in basal diameter and from 2.0 to 18.3 mm in thickness. The therapeutic dose was 35.0 Gy by 99% of dose volume histogram. Older age at treatment was correlated with the largest basal tumor diameter, tumor thickness, and TNM stage. The survival after stereotactic irradiation was 96% in 1 year, 93% in 2 years, 84% in 5 years, 80% in 7 years, and 53% in 11 years. In 20 (13.3%) patients, secondary enucleation was necessary because of complications (secondary glaucoma). Enucleation-free interval ranged from 1 to 6 years. The median age at death was lower (65.7 years) for patients who died from metastatic disease than for those who died from any other cause (75.0 years). Survival rates at 5-year intervals and the need for secondary enucleation because of complications after linear accelerator irradiation are comparable to other techniques.

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Response to targeted therapy in two patients with metastatic melanoma carrying rare BRAF exon 15 mutations: A598_T599insV and V600_K601delinsE

Concurrent BRAF-MEK inhibition improves clinical outcomes in patients with advanced BRAF V600E/K-mutant melanoma. There is currently less evidence for the efficacy of this treatment in patients with rare BRAF non-V600E/K genotypes. We report on two patients with rare BRAF exon 15 mutations – BRAF A598_T599insV and V600_K601delinsE – obtaining clinical benefit and a radiological response to inhibitors directed against the mitogen-activated protein kinase pathway. This highlights the importance of using tests that detect both V600E/K and non-V600E/K BRAF mutations to keep open the possibility of treatment with targeted therapy in patients with uncommon, yet potentially actionable, BRAF exon 15 mutations.

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A prognostic model for resectable acral melanoma patients on the basis of preoperative inflammatory markers

Acral melanoma is a rare disease, but is common in Asia. Knowledge of its prognostic indicators is limited. Growing evidence indicates that inflammation plays a critical role in the development and progression of acral melanoma. We developed a novel prognostic model on the basis of preoperative inflammatory markers and examined its prognostic value in a cohort of patients. This retrospective study included 232 acral melanoma patients who underwent radical surgical resection between 2000 and 2010 at the Sun Yat-sen University Cancer Center. Significant predictive factors were identified by multivariate Cox regression analyses, and a prognostic model on the basis of these variables was constructed to predict survival. Kaplan–Meier curves were plotted to estimate overall survival. Multivariate analyses showed that C-reactive protein, albumin/globulin ratio, age, lactic dehydrogenase, and lymph node positivity were related independently to survival. After analyzing these variables, we classified patients into three risk groups. The new prognostic model identified three categories of patients with different prognoses (P

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Type 1 diabetes mellitus caused by treatment with low-dose interferon-α in a melanoma patient

Interferon-α (INF-α) is used as an adjuvant treatment for high-risk cutaneous melanoma. It has a large variety of potentially severe and irreversible side effects and can contribute toward the development of autoimmune disease. We report a case of a 59-year-old woman who developed type 1 diabetes following the use of low-dose IFN-α for the adjuvant treatment of stage IIB melanoma. Fifteen months after initiating IFN-α, she presented with blood glucose of 1126 mg/dl, hyponatremia, and microalbuminuria. Antibodies to glutamic acid decarboxylase and islet antigen-2 were negative and C-peptide was markedly reduced. There was no personal or family history of any autoimmune conditions. Reinforced insulin treatment and volume substitution with saline and glucose as a counter-regulation was started. To the best of our knowledge, this is the first reported case of low-dose IFN-α-induced type 1 diabetes. Clinicians should closely evaluate the pros and cons of IFN-α treatment in an adjuvant setting and remain mindful of the possibility of drug-induced autoimmune disease.

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Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

Melanoma metastasis to the brain is associated with a poor prognosis. We sought to determine patient demographics and primary tumor factors associated with the development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. A database of melanoma patients seen from 1999 to 2015 at our institution was reviewed to identify patients who developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group. Patient demographics, primary tumor characteristics, and clinical outcomes were analyzed. A total of 123 patients with BM were matched by initial presenting stage to 237 patients without BM. The characteristics of the primary melanoma tumor associated with BM development included location on the scalp (P=0.030), nodular histologic type (P=0.020), and Breslow depth more than 4 mm (P=0.048), whereas location on the leg was associated with decreased BM risk (P=0.006). In patients with BM, time to first recurrence for melanomas of the scalp was significantly shorter (10.8 vs. 24.8 months, P=0.007) than nonscalp head and neck tumors. Patient stage, tumor depth, nodular type, and ulceration were also associated with worse clinical outcomes. There were no differences in the clinical outcomes between patients whose BM were detected upon routine screening versus those detected upon symptomatic presentation. In summary, factors predictive of development of BM included primary scalp location, nodular type, and depth. In BM patients, scalp location, stage, tumor depth, nodular type, and ulceration, but not detection setting, were associated with worse clinical outcomes.

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Fulminant type 1 diabetes after adjuvant ipilimumab therapy in cutaneous melanoma

No abstract available

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Human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma: Controversies and New Concepts

Publication date: Available online 1 September 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Nuzhat Husain, Azfar Neyaz
High-risk human papillomavirus (HR-HPV) is a causative agent for an increasing subset of oropharyngeal squamous cell carcinoma. HPV 16 accounts for 90% of cases. The chance for malignant transformation due to infection with high-risk HPV is proportional to the expression of the viral oncogene products E6 and E7, which inactivate p53 and retinoblastoma (Rb) tumor suppressor functions. P16 is a surrogate marker of HPV associated HNSCC and 2+/3+ expression in more than 75% cells is diagnostic. Molecular demonstration of integrated virus by in situ hybridization is specific but has low sensitivity. HPV associated oropharyngeal carcinomas classically arise in the tonsillar crypts and commonly have basaloid morphology with a prominent lymphocytic repsonse and minimal despmoplastic reaction. In situ vs invasive carcinomas may be difficult to distinguish in histology. The HPV postitivity overrides traditional prognostic indicators such as tumour grade and histological subtype. Small cell morphology carries a poorer prognosis as does marked tumour anaplasia and multinucleation. Lymph node metastasis is extensive and frequently cystic however extranodal extension, laterality or nodal sizes do not carry prognostic implications as in conventional OSCC and OPSCC. Stage IV is reserved for distant metastasis. HPV-16–positive patients had significantly reduced overall and disease-specific mortality rates and an improved 3-year overall survival (OS) and disease-free survival (DFS) compared to patients with HPV negative tumors. Surgical treatment is the main option for primary and secondary HNSCC. Targeted therapies including drugs targeting EGFR and PIK3CA and have shown some promising results. HPV pathway expressing tumors are less aggressive and may receive adequate curative intent therapy from a reduced radiation or chemotherapy dose revision. OSCC however fails to show a distinct difference between HPV associated and Tobaccco associated cancer and prognostic differences do not clearly exist.



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ROLE OF TURMERIC IN MANAGEMENT OF ALVEOLAR OSTEITIS (DRY SOCKET) A RANDOMISED CLINICAL STUDY

Publication date: Available online 1 September 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Parveen Akhter Lone, Syed wakeel Ahmed, Vivek Prasad, Bashir Ahmed
Plants & their extracts have immense potential for the management Treatment of the wounds. The pyhto medicines for the wound healing are not only cheap & affordable but are purportedly safe as hypersensitivity reactions are rarely encountered with the use of these agents, these natural agents induce healing & regeneration of the lost tissue by multiple mechanisms Turmeric commonly is called as Haldi in Hindi. C Longa has been reported to possess anti bacterial, anti fungal & anti inflammatory activities Turmeric is known as traditional herb to Asia & India also called as curcuma longa, with maximum healing properties & other great uses. It is widely used in India & China for traditional Chinese medicine. This act as anti inflammatory agent to treat different kind of diseases & health problems.Aims & objectivesThe aim of this study was to study the therapeutic, healing benefits of turmeric, an herb commonly used in AsiaMaterial & methodsThe study was conducted in department of oral & maxillofacial surgery of Indira Gandhi government dental college jammu.178 patients were selected from the outpatient department of oral & maxillofacial surgery .The diagnosis of dry socket was made clinically. Turmeric dressing with mustard oil was given in group A & in group B ZOE dressing was given.ResultsIn this study there was significant reduction in pain, inflammation & discomfort after turmeric and ZOE dressing. Wound healing was seen faster, than dressing with ZOE. There is no side effect of Turmeric. Statistical analysis was done p<0.05, was found statistically significant



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AMELOBLASTOMA: A RETROSPECTIVE ANALYSIS OF 31 CASES

Publication date: Available online 1 September 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Girish B. Giraddi, Kirti Arora, Aamir Malick Saifi
Aims and objectiveTo evaluate the surgical treatment given and do a regular follow up to study the recurrence rate and complications of ameloblastoma in our institution.Materials and methodsA total of 31 cases of various subtypes of ameloblastoma, treated with different modalities, in the Department of OMFS, were recalled for a follow up & radiographs were taken along with the clinical examination for any recurrence or complications such as fracture/exposure of the reconstruction plate, loosening of the screw, infection of the graft, any draining sinus/signs of infection.ResultsTwo of our patients had fractured reconstruction plate, one patient developed infection, one patient complained of screw exposure and two other patients had infection of the iliac graft.ConclusionWe conclude that an adequate resection with a safe margin could be a treatment option and can be undertaken depending on the extent, location of the lesion and histopathologic variant.



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Evaluation of fracture resistance and mode of failure of premolars restored with nanohybrid composite, ORMOCER and ceramic inlays

Publication date: Available online 1 September 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Mohit. K. Gunwal, Pratima R. Shenoi, Tanvee Paranjape, Sonal Dhote, Ravish Tongya, Magesh Kumar, Sanjay Rastogi
ObjectivesTo evaluate the fracture resistance and mode of failure of maxillary premolars restorations restored with nanohybrid Composite, ORMOCER and Ceramic Inlays.Materials and method100 extracted first maxillary premolar were collected. Samples were divided into five groups. Group I – Intact premolars, Group II –MOD cavities without restorations, Group III – MOD cavities restored with composite restoration, GROUP IV – MOD cavities restored with ORMOCER restoration and GROUP V – MOD cavities restored with ceramic inlays. All the samples were sent for the axial compression test under the universal testing machine. Fracture resistance and fracture modes were recorded.ResultHighest fracture resistance was achieved in Group V (1324.74±336.78) almost comparable to that of natural tooth (1381.07±259.36) (p<0.05), followed by Group IV (MOD cavities with ORMOCER restorations) (1082.27±351.27) (p<0.01) and least fracture resistance in Group III (MOD cavities with composite restorations) (778.35±100.25) (p<0.0001). Mode of fracture in Group IV and Group V are almost similar and In Group III 65% of the cases showed non-restorable fractures.ConclusionORMOCER fracture resistance along with other groups of clinically restorable fracture stand better than Nanohybrid composite.Clinical RelevanceBased on the present study, the dentist can utilize the ORMOCER material as a restoration material for the cavities of posterior teeth which is better in terms of fracture resistance and durability of the restoration when compare to nanohybrid composite.



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The Use of Synthes MatrixWAVE Bone Anchored Arch Bars for Closed Treatment of Multiple Concurrent Mandibular Fractures

Publication date: Available online 1 September 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Elizabeth Kiwanuka, Rajiv Iyengar, Charles Christopher Jehle, Raman Mehrzad, Daniel Kwan
BackgroundMaxillomandibular fixation (MMF) is an important tool in the treatment of facial fractures and bone-anchored arch bar systems have emerged as treatment options. This study illustrates our experience with the Synthes MatrixWAVE MMF system and the novel application in closed treatment of patients with multiple concurrent mandibular fractures.MethodsWe enrolled eight patients with concurrent mandibular fractures and treated them with the Matrix Wave MMF system. The malleable arch bars were fitted and then secured using 6 to 8mm screws. The arch bar was and either stretched or compressed to ensure optimal positioning. 24-gauge interdental fixation wiring was placed using the fish loop technique on either side of the fracture to achieve stabilization of the mandible fractures.ResultsAll eight patients were retained in MMF until stable occlusion was achieved with clinical evidence of healing, approximately 4 to 6 weeks. Post-operative Panorex scans did not reveal any evidence of damage to tooth roots. None of the screws became overly embedded in the mucosa secondary to overgrowth; the arch bars were successfully removed in an outpatient setting without local anesthesia.ConclusionsThe Synthes MatrixWAVE MMF system has unique features such as prominent screw anchor heads and horizontal malleability unique from other bone anchored arch bars. These features allow for completely closed treatment of patients with multiple concurrent mandible fractures.



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