Cytotoxicity, genotoxicity and antibacterial activity of poly(vinyl alcohol)-coated silver nanoparticles and farnesol as irrigating solutions

Publication date: December 2017
Source:Archives of Oral Biology, Volume 84
Author(s): Gisselle M. Chávez-Andrade, Mário Tanomaru-Filho, Elisandra M. Rodrigues, Ana Lívia Gomes-Cornélio, Gisele Faria, Maria Inês B. Bernardi, Juliane M. Guerreiro-Tanomaru
ObjectiveTo evaluate the cytotoxicity, genotoxicity and antibacterial activity of poly(vinyl alcohol)-coated silver nanoparticles (AgNPs-PVA) and farnesol (FAR).DesignThe cytotoxicity (% of cell viability) was evaluated by MTT assay and the genotoxicity (% of DNA in the tail) was evaluated by Comet assay. Root canal disinfection with different irrigating protocols was evaluated ex vivo in human teeth contaminated with Enterococcus faecalis for 21days. Three microbiological samples were collected: initial (after contamination); post-irrigation (after irrigation); and final (after 7days). After each sample, the number of log 10 CFU mL⁻¹ was determined. Statistical analyses was performed using two-way ANOVA and Bonferroni post-hoc tests for MTT assay, Kruskal-Wallis and Dunn post-hoc tests for Cometa and antibacterial assays (α=0.05).ResultsThe MTT assay showed that AgNPs and FAR were less cytotoxic that sodium hypochlorite (NaOCl) and showed a lower% of DNA in the tail, in comparison with H2O2 (positive control − C+). In the post-irrigation microbiological sample, all the irrigating protocols were more effective than C+ (without irrigation). NaOCl/saline, NaOCl/saline/AgNPs-PVA and NaOCl/saline/FAR led to complete bacterial elimination (p >0.05). In comparison with the initial sample, both the post-irrigation and the final samples showed microbial reduction (p < 0.05).ConclusionsAgNPs-PVA and FAR showed low cytotoxicity and genotoxicity, and exhibit potential for use as a final endodontic irrigation protocols.



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Reply

Publication date: Available online 28 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Guus A. Westerhof, Elisabeth H. Bel




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Changing trends and challenges in the management of asthma in Asia

Publication date: Available online 28 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Woo-Jung Song, Gary WK. Wong




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Th17 cells mediate inflammation in a novel model of spontaneous experimental autoimmune lacrimal keratoconjunctivitis with neural damage

Publication date: Available online 27 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Kyoung Yul Seo, Kazuya Kitamura, Soo Jung Han, Brian Kelsall
BackgroundDry eye disease (DED) affects one third of population worldwide. In prior studies, experimental autoimmune lacrimal keratoconjunctivitis (EALK) induced by desiccating stress in mice has been used as a model of DED. This model is complicated by a requirement for exogenous epithelial cell injury and the administration of anticholinergic agents that have broad immunological effects.ObjectiveWe sought to develop a novel mouse model of EALK, and to demonstrate the responsible immunological pathogenic mechanisms.MethodsCD4+CD45RB^high naïve T cells with and without CD4+CD45RB^loCD25+ regulatory T cells were adoptively transferred to C57BL/10 RAG2^-/- mice. The eyes, draining lymph nodes, lacrimal glands and surrounding tissues of mice that spontaneously developed keratoconjuctivitis were evaluated for histopathological changes, cellular infiltration, and cytokine production in tissues and by isolated cells. Furthermore, the integrity of corneal nerves was evaluated by whole tissue immunofluorescence imaging. Gene-deficient naïve T cells or RAG2-hosts were evaluated to assess the roles of IFN-γ, IL-17A and IL-23 in disease pathogenesis. Finally, cytokine levels were determined in the tears of patients with DED.ResultsEALK spontaneously developed in C57BL/10 RAG2^-/- mice following adoptive of CD4+CD45RB^high naïve T cells characterized by the infiltration of CD4⁺ T cells, macrophages, and neutrophils. In addition to lacrimal keratoconjunctivitis, mice also developed damage to the corneal nerve, which connects components of lacrimal functional unit (LFU). Pathogenic T cell differentiation was dependent on IL-23p40 and controlled by co-transferred CD4+CD45RB^loCD25⁺ regulatory T cells (Tregs). Th17 rather than Th1 CD4+ cells were primarily responsible for EALK even though both IL-17 and IFN-γ were increased in inflammatory tissues likely due to their ability to drive the expression of CXC chemokines within the cornea, and the subsequent influx of myeloid cells. Consistent with the findings of this model, the tears of patients with DED had increased levels of inflammatory cytokines including IL-17A and TNFα.ConclusionWe describe a novel model of spontaneous EALK that supports a role for Th17 cells in disease pathogenesis, and that will contribute to our understanding of autoimmune lacrimal keratoconjunctivitis in many human eye diseases, including DED.

Graphical abstract

Teaser

Demonstrated is a novel spontaneous mouse model of experimental autoimmune lacrimal keratoconjunctivitis that results from Th17 cell activation, and will be important for understanding the contribution of environmental or microbial antigens to disease pathogenesis.


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ATF6α regulates airway hyperreactivity, smooth muscle proliferation, and contractility

Publication date: Available online 27 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Hirotoshi Unno, Marina Miller, Peter Rosenthal, Andrew Beppu, Sudipta Das, David H. Broide

Teaser

ORMDL3 on chromosome 17q21 is highly linked to asthma and regulates several downstream pathways including ATF6α. We demonstrated that ATF6α in airway smooth muscle (ASM) plays an important role in ASM contractility, proliferation, and AHR.


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Allergy and immunology in Africa: Challenges and unmet needs

Publication date: Available online 27 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Yehia M. El-Gamal, Elham M. Hossny, Zeinab A. El-Sayed, Shereen M. Reda
The tremendous increase in allergy in the African continent cannot simply be explained by the change in public hygiene. There are many "prehygiene" communities with sewage-contaminated water supplies, helminth infestations, bare footedness, and poor housing, and still there is a high prevalence of allergic disease. Africans can be exposed to many risk factors facilitating severe asthma and wheezing, including airborne viruses, smoke, indoor dampness, cockroaches, and poor access to health care. Although the reporting on food allergy is inadequate to perform systematic reviews or meta-analyses, the available data suggest that food allergy is underdiagnosed. The rate of new HIV infections in high-prevalence settings in Africa remains unacceptably high. Although the annual number of new HIV infections in Sub-Saharan Africa has decreased lately, new HIV infections in the Middle East and North Africa region have increased; however, the current prevalence of 0.1% is still among the lowest globally. Africa is densely populated, and consanguineous mating is high in some areas of North and Sub-Saharan Africa. This allows for emergence of many autosomal recessive primary immunodeficiency diseases. There is urgent need for the establishment of primary immunodeficiency disease registries, stem cell transplantation facilities, and neonatal screening programs. To address these expanding problems and perform local cutting-edge research, Africans need to be empowered by motivated governments, dedicated funds, and compassionate scientific partnership.



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Comments on clinical predictors of remission and persistence of adult-onset asthma

Publication date: Available online 28 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Erfan Ayubi, Saeid Safiri




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Succinate dehydrogenase B-deficient renal cell carcinoma: A case report with novel germline mutation

Succinate dehydrogenase-deficient renal cell carcinoma (SDH-deficient RCC) is a newly introduced histological type of RCC, which is caused by loss of subunit genes of SDH. It is known to frequently demonstrate familial occurrence and be frequently associated with gastrointestinal stromal tumors and paraganglioma. To date, only 53 cases have been reported. Here, we present an additional case of SDH-deficient RCC occurring in a 40-year-old female. The tumor was histologically biphasic, consisting of tubular and solid architectures. The tumor cells possessed oval nuclei with small nucleoli, and an eosinophilic granular cytoplasm with occasional vacuoles. These cells completely lost the immunohistochemical expression of B subunit of SDH (SDHB). Consequently, the tumor was diagnosed as SDHB-deficient RCC. We identified a novel germ line mutation of the SDHB gene, and also confirmed a hemizygous deletion of the wild-type allele in the tumor cells. To define the pathological characteristics of SDH-deficient RCC, precise diagnosis and accumulation of more cases are required.

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Treatment of acne scarring with a novel fractionated, dual-wavelength, picosecond-domain laser incorporating a novel holographic beam-splitter

Background and Objectives

Fractional treatment with a dual wavelength 1,064 and 532 nm picosecond-domain laser, delivering a 10 × 10 array of highly focused beamlets via a holographic optic, was investigated for the treatment of acne scars.

Study

Twenty-seven of 31 subjects completed the study, 19 were treated using 1,064 nm and 8 were treated at 532 nm, all having four-monthly treatments. Blinded evaluation of digital images by three physician evaluators comparing pre- and 3-month post-treatment images measured efficacy using a 10-point scale. Subject self-assessment of treatment effects were also recorded. Safety was measured by recording subject discomfort scores and adverse effects.

Results

Blinded reviewers correctly identified the baseline image in 61 of the 81 image sets (75%), and baseline acne scar scores were 1.8 ± 0.7 and 1.8 ± 0.5 for the 1,064 and 532 nm cohorts, and decreased to 1.1 ± 0.5 (P < 0.001) and 1.1 ± 0.0 (P < 0.005), respectively. Post-treatment erythema, mild edema, and petechiae were the only side effects noted.

Conclusion

The 1,064 and 532 nm picosecond-domain laser incorporating a 10 × 10 holographic beam-splitting handpiece was found to be safe and effective for the treatment of facial acne scars. The treatments were well tolerated and the subjects experienced little to no downtime. Lasers Surg. Med. © 2017 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

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Introducing a simple method of maxillary sinus volume assessment based on linear dimensions

Publication date: Available online 28 September 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Przystańska Agnieszka, Kulczyk Tomasz, Rewekant Artur, Sroka Alicja, Jończyk-Potoczna Katarzyna, Lorkiewicz-Muszyńska Dorota, Gawriołek Krzysztof, Czajka-Jakubowska Agata
Measuring sinus volume in a general practice clinic is a complex and time-consuming procedure, requiring experience in the use of radiological methods In the presented research, the automatically estimated maxillary sinus volume was compared with maxillary sinus volume assessed with mathematical formulas used to calculate the volume of spheres and pyramids. The starting point for the statistical analysis were specific measurements of the sinuses. We wanted to discover which geometric shape has the volume that is nearest to the automatically estimated volume.The study was performed using samples of CT scans of pediatric patients age 1 to 17. The dimensions (maximal width, maximal height, maximal length) were used for manual calculations. For the automatic volume calculation, the CT Image Segmentation algorithm (Syngo Via for Oncology, Siemens) was used. Pearson's correlation coefficient was applied to analyse the interrelationship between automatically and manually calculated volume of maxillary sinus. It was statistically established that the "sphere", "pyramid" and "mean" manually calculated maxillary sinus volume were accurate and strongly correlated with the automatically estimated maxillary sinus volume. The volume of the sphere corresponds better with the automatic measurements than the volume of the pyramid. The variations are significant and they were made reliable with the application of a statistical test. It is quick and easy to calculate the maxillary sinus volume based on its linear dimensions instead of applying advanced software. The manual method for maxillary sinus volume calculation requires three linear measurements of the sinus (length, width, and height) and can be recommended if the automatically estimated volume cannot be obtained.



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Bodies of children in the Institute of Anatomy in Halle (Saale), Germany, between 1920 and 1945

Publication date: Available online 27 September 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): F. Winter, D. Stoevesandt, R. Schultka, M. Viebig, K. Moeller, F. Steger, H. Kielstein
At the Institute of Anatomy and Cell Biology in Halle (Saale) 74 children's bodies of unknown historical provenance are being held in storage. The aim of this study was the evaluation of their identities, the circumstances of their acquisition, as well as the documentation of their individual characteristics. For these purposes, all bodies were comprehensively examined and photo-documented. Furthermore, CT-scans of 29 bodies were performed and information was collected from various local and national archives. Although most of the bodies were found to be those of stillborn children and infants, five children were between two and twelve years old, according to an age estimate by body-length and carpal bone analysis. The CT-scans revealed the cause of death for some of the children. The embalming method indicates that the bodies date from the first decades of the 20th century, and archival sources containing documents from 1920 to 1960 strongly suggest that these children's bodies were acquired by Institute of Anatomy between 1920 and 1942. During that period, a total of 2,602 children's bodies were delivered to the Institute of Anatomy and registered in the communal burial records. At this point, there is no evidence that these children might have been victims of National Socialist crimes. It is planned to give them a dignified burial.



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Assessment of facial asymmetry before and after the surgical repair of cleft lip in unilateral cleft lip and palate cases

Publication date: Available online 28 September 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): D. Al-Rudainy, X. Ju, F. Mehendale, A. Ayoub
This study was performed to assess facial asymmetry in patients with unilateral cleft lip and palate (UCLP) before and after primary lip repair. Three-dimensional facial images of 30 UCLP cases (mean age 3.7±0.8months) captured 1–2days before surgery and 4 months after surgery using stereophotogrammetry were analysed. A generic mesh – a mathematical facial mask consisting of thousands of points (vertices) – was conformed on the three-dimensional images. Average preoperative and postoperative conformed facial meshes were obtained and mirrored by reflecting on the lateral plane. Facial asymmetry was assessed by measuring the distances between the corresponding vertices of the superimposed facial meshes. Asymmetries were further examined in three directions: horizontal, vertical, and anteroposterior. Preoperatively, the philtrum and bridge of the nose were deviated towards the non-cleft side. The maximum vertical asymmetry was at the upper lip. The greatest anteroposterior asymmetry was at the alar base and in the paranasal area. The overall facial asymmetry improved markedly after surgery. Residual anteroposterior asymmetry was noted at the alar base, upper lip, and cheek on the cleft slide. In conclusion, dense correspondence analysis provided an insight into the anatomical reasons for the residual dysmorphology following the surgical repair of cleft lip for future surgical consideration.



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Outcomes of septorhinoplasty: a new approach comparing functional and aesthetic results

Publication date: Available online 28 September 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): T. Radulesco, M. Penicaud, L. Santini, J.-M. Thomassin, P. Dessi, J. Michel
The aim of this study was to compare objective and subjective functional results of septorhinoplasty with subjective aesthetic results. A prospective study was performed including global and subgroup analyses (primary versus secondary septorhinoplasty). Three instruments were used to evaluate pre- and postoperative results: rhinomanometry for the objective functional analysis, the Nasal Symptom Obstruction Evaluation (NOSE) scale for the subjective functional analysis, and the Rhinoplasty Outcome Evaluation (ROE) scale for the subjective aesthetic analysis. A septorhinoplasty was performed in all cases. Thirty-five patients were included (22 female), of whom 74% underwent primary septorhinoplasty. The correlation between rhinomanometry, NOSE and ROE scores was analysed. Mean resistance of the two nasal cavities was 4.9 (standard deviation (SD) 8.35) sPa/ml before surgery and 0.8 (SD 0.7) sPa/ml after surgery. NOSE and ROE scores were, respectively, 72.5/100 (SD 21.7) and 7.5/24 (SD 11.3) before surgery and 22/100 (SD 20.6) and 18/24 (SD 17.3) after surgery. Patients complaining of postoperative nasal obstruction had a worse aesthetic evaluation. Correction of the functional disease appears to be as important as aesthetic correction. This study comparing functional and aesthetic results after septorhinoplasty could provide a basis for future studies.



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The Canadian Otolaryngology-Head and Neck Surgery Workforce in the Urban-Rural Continuum: Longitudinal Data from 2002 to 2013.

Related Articles

The Canadian Otolaryngology-Head and Neck Surgery Workforce in the Urban-Rural Continuum: Longitudinal Data from 2002 to 2013.

Otolaryngol Head Neck Surg. 2017 Sep 01;:194599817733688

Authors: Crowson MG, Lin V

Abstract
Objectives To evaluate the proportion of otolaryngology-head and neck surgery (OHNS) providers who are rural versus urban based from 2002 to 2013. Secondary objective was to present perspectives of rural primary care providers on unmet needs for OHNS services. Study Design Mixed methods database analysis and prospective survey. Setting National administrative database. Subjects and Methods The Canadian Medical Association OHNS provider Masterfile and the Statistics Canada postal code file were used to determine provincial, urban, rural, and Aboriginal group care coverage. The Society of Rural Physicians of Canada was surveyed to explore care delivery and unmet needs for OHNS and audiology. Descriptive statistics and linear regression were used to describe results. Results Ontario and Quebec had the largest annual OHNS physician growth (6.38 providers/year; r(2) = 0.94) versus stagnant growth in the territories. The clear majority of OHNS providers are in urban centers, and rural OHNS coverage is decreasing annually (-0.33 providers/year, r(2) = 0.28). There are no OHNS providers in 485 population centers where Aboriginal groups are located. A survey of 40 rural primary care providers reported that OHNS care is most commonly delivered through seasonal visits to a local facility, with otology (hearing loss, chronic ear disease) and rhinology (nonmalignant nasal or sinus conditions) as the most frequently reported unmet needs. Conclusion From 2002 to 2013, OHNS coverage showed a trend for urban consolidation. Most Aboriginal groups may have decreased access to care, as there are no OHNS providers in 485 population centers where reserves are located. There is an unmet need for specialized OHNS services reported by rural primary care physicians, especially otology and rhinology.

PMID: 28949835 [PubMed - as supplied by publisher]

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Accuracy of the ETDQ-7 for Identifying Persons with Eustachian Tube Dysfunction.

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Accuracy of the ETDQ-7 for Identifying Persons with Eustachian Tube Dysfunction.

Otolaryngol Head Neck Surg. 2017 Sep 01;:194599817731729

Authors: Teixeira MS, Swarts JD, Alper CM

Abstract
Objective To compare the accuracy of the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) in identifying people with eustachian tube (ET) dysfunction based on symptoms and an objective ET function test. Study Design Cross-sectional study. ObjSettingective Tertiary referral center. Subjects and Methods Fifty-five subjects with and without symptoms suggestive of ET dysfunction completed the ETDQ-7 and had their ET function evaluated by the percentage of middle ear pressure equilibrated after 5 swallows (PEq5) either during a pressure chamber test (intact tympanic membranes) or by the inflation-deflation test (nonintact tympanic membranes). ETDQ-7 score ≥14.5 and PEq5 <60% were used to define ET dysfunction, and sensitivity, specificity, and receiver operating characteristic curves were used to assess the level of association between ETDQ-7 scores and PEq5. Results Twenty-five asymptomatic subjects (group 1 = 15 females, 15 white; mean ± SD age, 32 ± 12.8 years) and 30 subjects with ET dysfunction symptoms (group 2 = 17 females, 25 white; age, 27 ± 16.3 years) were included in the analysis. ETDQ-7 sensitivity and specificity regarding correct group assignment were 70% and 100%, respectively, and with respect to predicting PEq5<60%, 54% and 78%. An area under the curve (AUC) of 0.68 (95% CI, 0.53-0.83) at the participant level and 0.64 (95% CI, 0.50-0.77) at the ear level indicated a moderate level of association that was lower, though not statistically significant, for nonintact tympanic membranes (AUC = 0.63 at the participant level and AUC = 0.49 at the ear level). Conclusion The ETDQ-7 score had a higher correlation with the ET dysfunction symptoms than with an objective measure of ET function.

PMID: 28949806 [PubMed - as supplied by publisher]

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Can Dexmedetomidine Influence Recovery Profiles from General Anesthesia in Nasal Surgery?

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Can Dexmedetomidine Influence Recovery Profiles from General Anesthesia in Nasal Surgery?

Otolaryngol Head Neck Surg. 2017 Sep 01;:194599817733735

Authors: Lee HS, Yoon HY, Jin HJ, Hwang SH

Abstract
Objectives Dexmedetomidine has sympatholytic, sedative, anesthetic, and analgesic effects, as well as vasoconstrictive effects, which may help prevent hypotension under general anesthesia. This meta-analysis aimed to perform a systematic review of the literature and investigate the effect of dexmedetomidine on perioperative morbidity following nasal surgery and its adverse effects. Data Sources MEDLINE, SCOPUS, and the Cochrane database. Review Methods Two authors independently searched the databases from their inception to March 2017. Studies were selected that compared perioperative dexmedetomidine administration (dexmedetomidine groups) with a placebo or remifentanil (control groups) with regard to intraoperative morbidity, including surgical time, bleeding amount, hypotension, and bradycardia during operation, and postoperative morbidity, such as emergence agitation, nausea and vomiting, and sedation after operation. Results Surgical time, intraoperative blood loss, dose of inhaled anesthetic gas, dose of fentanyl, postoperative pain, and incidence of emergence agitation were significantly lower in the dexmedetomidine group versus the placebo group. In contrast, there were no significant differences in intraoperative hemodynamic stability and postoperative residual sedation and nausea and vomiting between groups. Additionally, compared with remifentanil (a currently widely used agent), dexmedetomidine was superior in view of postoperative pain and intraoperative blood pressure control. Conclusion This meta-analysis shows that the systemic administration of dexmedetomidine can decrease surgical time, intraoperative blood loss, and doses of intraoperative inhaled anesthetic gas and fentanyl as compared with placebo. It can also decrease postoperative pain and incidence of the emergence agitation. Due to the small number of studies, further clinical trials are needed to confirm these results.

PMID: 28949804 [PubMed - as supplied by publisher]

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An Algorithm to Evaluate Suspected Lung Metastases in Patients with HPV-Associated Oropharyngeal Cancer.

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An Algorithm to Evaluate Suspected Lung Metastases in Patients with HPV-Associated Oropharyngeal Cancer.

Otolaryngol Head Neck Surg. 2017 Sep 01;:194599817733677

Authors: VanKoevering KK, Marchiano E, Walline HM, Carey TE, McHugh JB, Brenner JC, Goudsmit CM, Belille E, Spector ME, Shuman AG, University of Michigan Head and Neck SPORE Team

Abstract
Distinguishing between distantly metastatic and metachronous lung primary carcinoma is challenging for patients with a history of head and neck cancer. There are implications for registry data, prognosis and related counseling, and management options, including eligibility for precision oncology trials. Patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma who were treated under a uniform clinical protocol and achieved a complete response were identified in a single-institution prospective head and neck cancer epidemiology database (n = 205). Fifteen patients presented with pulmonary nodule(s) after completion of therapy. We describe our algorithm for the evaluation of these patients, including histopathology, p16 immunohistochemistry, and HPV in situ hybridization.

PMID: 28949800 [PubMed - as supplied by publisher]

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Comparison between Awake Endoscopy and Computed Tomography to Define Lingual Tonsil Hypertrophy.

Related Articles

Comparison between Awake Endoscopy and Computed Tomography to Define Lingual Tonsil Hypertrophy.

Otolaryngol Head Neck Surg. 2017 Sep 01;:194599817731731

Authors: Tang JA, Gorelick G, Friedman M

Abstract
Objectives To analyze correlations between endoscopic lingual tonsil grade (LTG) by the Friedman Lingual Tonsil Hypertrophy grading system and computed tomography (CT) measurements of lingual tonsil thickness (LTT). Study Design Retrospective chart review. Setting Single-center database, September 2016 to April 2017. Subjects and Methods Patients who received CT covering base of tongue and endoscopic LTG were included. LTT was measured on axial and sagittal CT. LTT measurements were compared against endoscopic LTG. One-way analysis of variance with Tukey's post hoc adjustment for multiple comparisons was performed. Results Seventy-five charts were included for a total of 150 LTT measurements. Axial CT measurements of LTG 1 and LTG 2 were each significantly different from LTG 3 ( P < .001 for both), and LTG 1 and LTG 2 also differed significantly ( P = .010). Mean sagittal CT measurements were significantly different between LTG 1 and LTG 3 ( P < .001) and between LTG 2 and LTG 3 ( P = .002) but not between LTG 1 and LTG 2 ( P = .186). Those without lingual tonsil hypertrophy had a mean axial CT thickness of 6.45 ± 1.39 mm and mean sagittal CT thickness of 6.58 ± 1.53 mm, which was significantly different from both the mean axial CT thickness of 8.48 ± 1.52 mm and the mean sagittal CT thickness of 8.07 ± 1.16 mm in the LTG 3 group ( P < .001 for both). Threshold analysis showed a potential cutoff of approximately 7.5 mm on axial and sagittal CT for defining clinically significant lingual tonsil hypertrophy. Conclusion Awake endoscopy grading of lingual tonsil hypertrophy is a subjective measurement that seems to correlate with objective CT measurements. LTT measurements of LTG 1 and LTG 2 on awake endoscopy differed significantly from LTG 3.

PMID: 28949799 [PubMed - as supplied by publisher]

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Unplanned 30-Day Readmissions after Parathyroidectomy in Patients with Chronic Kidney Disease: A Nationwide Analysis.

Related Articles

Unplanned 30-Day Readmissions after Parathyroidectomy in Patients with Chronic Kidney Disease: A Nationwide Analysis.

Otolaryngol Head Neck Surg. 2017 Sep 01;:194599817721154

Authors: Ferrandino R, Roof S, Ma Y, Chan L, Poojary P, Saha A, Chauhan K, Coca SG, Nadkarni GN, Teng MS

Abstract
Objective To examine rates of readmission after parathyroidectomy in patients with chronic kidney disease and determine primary etiologies, timing, and risk factors for these unplanned readmissions. Study Design Retrospective cohort study. Setting Nationwide Readmissions Database. Subjects and Methods The Nationwide Readmissions Database was queried for parathyroidectomy procedures performed in patients with chronic kidney disease between January 2013 and November 2013. Patient-, admission-, and hospital-level characteristics were compared for patients with and without at least 1 unplanned 30-day readmission. Outcomes of interest included rates, etiology, and timing of readmission. Multivariate logistic regression was used to identify predictors of 30-day readmission. Results There were 2756 parathyroidectomies performed in patients with chronic kidney disease with an unplanned readmission rate of 17.2%. Hypocalcemia/hungry bone syndrome accounted for 40% of readmissions. Readmissions occurred uniformly throughout the 30 days after discharge, but readmissions for hypocalcemia/hungry bone syndrome peaked in the first 10 days and decreased over time. Weight loss/malnutrition at time of parathyroidectomy and length of stay of 5 to 6 days conferred increased risk of readmission with adjusted odds ratios (aOR) of 3.31 (95% confidence interval [CI], 1.55-7.05; P = .002) and 1.87 (95% CI, 1.10-3.19; P = .02), respectively. Relative to primary hyperparathyroidism, parathyroidectomies performed for secondary hyperparathyroidism (aOR, 2.53; 95% CI, 1.07-5.95; P = .03) were associated with higher risk of readmission. Conclusion Postparathyroidectomy readmission rates for patients with chronic kidney disease are nearly 5 times that of the general population. Careful consideration of postoperative care and electrolyte management is crucial to minimize preventable readmissions in this vulnerable population.

PMID: 28949797 [PubMed - as supplied by publisher]

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Endoscopically Assisted Drilling, Exposure of the Fundus through a Presigmoid Retrolabyrinthine Approach: A Cadaveric Feasibility Study.

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Endoscopically Assisted Drilling, Exposure of the Fundus through a Presigmoid Retrolabyrinthine Approach: A Cadaveric Feasibility Study.

Otolaryngol Head Neck Surg. 2017 Sep 01;:194599817733665

Authors: Muelleman T, Shew M, Alvi S, Shah K, Staecker H, Chamoun R, Lin J

Abstract
The presigmoid retrolabyrinthine approach to the cerebellopontine angle is traditionally described to not provide access to the internal auditory canal (IAC). We aimed to evaluate the extent of the IAC that could be exposed with endoscopically assisted drilling and to measure the percentage of the IAC that could be visualized with the microscope and various endoscopes after drilling had been completed. Presigmoid retrolabyrinthine approaches were performed bilaterally on 4 fresh cadaveric heads. We performed endoscopically assisted drilling to expose the fundus of the IAC, which resulted in exposure of the entire IAC in 8 of 8 temporal bone specimens. The microscope afforded a mean view of 83% (n = 8) of the IAC. The 0°, 30°, 45°, and 70° endoscope each afforded a view of 100% of the IAC in 8 of 8 temporal bone specimens. In conclusion, endoscopic drilling of the IAC of can provide an extradural means of exposing the entire length of the IAC while preserving the labyrinth.

PMID: 28948858 [PubMed - as supplied by publisher]

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An investigation of operative outcomes: Pediatric invasive fungal sinusitis

Publication date: November 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): Curtis Hanba, Peter F. Svider, Wanda Lai, Syed Naweed Raza, Anthony Sheyn, Jean Anderson Eloy, Adam J. Folbe
Objectives/HypothesisInvasive fungal sinusitis is an uncommon entity among children. Early recognition is crucial for facilitating successful treatment with minimal morbidity. The goal of this analysis was to identify patient characteristics associated with high-risk surgical disease through a population-based examination into this rare and deadly disease process.MethodsA retrospective chart review of the 2009 and 2012 Kids' Inpatient Database (KID) was conducted. A series of queries (Fungal infection→immunocompromised diagnosis→sinus procedure) identified 102 patients with likely invasive fungal sinusitis. Outcomes included: species, invasive extension, death, and other clinical characteristics.ResultsPatients with leukemia/lymphoma constituted 90.2% of individuals evaluated in this analysis. Nearly a quarter of pediatric patients receiving surgical treatment for invasive fungal sinusitis died during their hospital stay –24.9%. Aspergillus was the most commonly recorded mycotic species. Average hospital stay was 59.3 days, and associated hospital costs averaged $746,299 per stay. Patients 0–5 years old were more likely to have orbital involvement –56.3%. Brain extension was noted in 33.7% of this cohort as well. Mucormycosis was an independent predictor of death (p = 0.03), with an odds ratio of 3.835.ConclusionTo the best of our knowledge, this is the largest pediatric cohort with invasive fungal sinusitis in the literature. Patient demographics, cytology, and disease extension offer predictive information regarding patient outcomes for invasive fungal sinusitis. A high clinical suspicion and early treatment may decrease the lengthy and costly hospitalizations in this population.



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Editorial Board

Publication date: October 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 101





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Clinical variables determining the success of adenotonsillectomy in children with Down syndromed

Publication date: November 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): Maíra da Rocha, Renata Caroline Monteiro Ferraz, Vitor Guo Chen, Gustavo Antonio Moreira, Reginaldo Raimundo Fujita
ObjectivesTo evaluate the evolution of polysomnographic parameters of children with Down syndrome and obstructive sleep apnea syndrome submitted to adenotonsillectomy and the interaction of comorbidities on therapeutic outcome.MethodsNinety patients with Down syndrome and habitual snoring were identified between 2005 and 2015 in a Pediatric Otorhinolaryngology Clinic. Parent's complaints were evaluated by the test of equality of two proportions. Wilcoxon test was used to examine pre- and post-operative polysomnographic differences. Mann-Whitney test evaluated the influence of comorbidities. A p < 0.05 was considered significant.ResultsA total of 27 patients met the inclusion criteria (55.6% patients were males; mean (SD) age were 6.7 (3.6) years (range, 1.5–16 years). Significant improvement of parent's complaints (p < 0.001), arousal index (p = 0.045), and minimum oxygen saturation were observed post-adenotonsillectomy (p = 0.034). Adenotonsillectomy was able to resolve obstructive sleep apnea syndrome in 29.6% of children with Down syndrome. Nineteen patients (70.4%) remained with obstructive sleep apnea syndrome and 44.4% showed a reduction of at least 50% of obstructive apnea-hypopnea index. Central apnea index post-adenotonsillectomy was worse in patients with heart disease (p = 0.022). Sleep efficiency (p = 0.031), N1 sleep stage (p = 0.001), apnea-hypopnea index (p = 0.023), and central apnea index (p = 0.008) were worse after surgery in patients with hypothyroidism. Patients with severe OSAS showed significant improvement in polysomnographic parameters after surgery.ConclusionAlthough adenotonsillectomy improved symptoms and objective sleep data in children with Down syndrome, it was not able to resolve obstructive sleep apnea syndrome in most patients. Congenital heart diseases and hypothyroidism may affect the outcome.



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Mentees

Publication date: October 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 101





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Both Earlier Times and the Future Are “Front”: The Distinction Between Time- and Ego-Reference-Points in Mandarin Speakers’ Temporal Representation

Abstract

Mandarin speakers, like most other language speakers around the world, use spatial terms to talk about time. However, the direction of their mental temporal representation along the front-back axis remains controversial because they use the spatial term "front" to refer to both earlier times (e.g., front-year means "the year before last") and the future (e.g., front-road means "prospect"). Although the linguistic distinction between time- and ego-reference-point spatiotemporal metaphors in Mandarin suggests a promising clarification of the above controversy, there is little empirical evidence verifying this distinction. In this study, Mandarin speakers' time- and ego-reference-point temporal representations on three axes (i.e., sagittal, lateral, and vertical) were separately examined through two tasks. In a time-reference-point task, Mandarin speakers judged whether the time point of the second picture was earlier or later than the time point of the first picture, while in an ego-reference-point task, they judged whether an event or phase had happened in the past or would happen in the future. The results indicate that Mandarin speakers construe an earlier-times-in-front-of-later-times temporal sequence and adopt the front-to-the-future orientation.

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Developmental Differences Between Children and Adults in the Use of Visual Cues for Segmentation

Abstract

Recent work asked if visual cues facilitate word segmentation in adults and infants (Thiessen, 2010). While adults showed better word segmentation when presented with a regular visual cue (consistent mapping between words and objects), infants did not. This difference was attributed to infants' lack of understanding that objects have labels. Alternatively, infants' performance could reflect their difficulty with tracking and integrating multiple multimodal cues. We contrasted these two accounts by looking at the effect of visual cues on word segmentation in adults and across childhood (6–12 years). We found that older children (M_age 10;7) benefitted from the regular visual cues, but younger children (M_age 7;10), who already knew that objects have labels, did not. Knowing that objects have labels was not enough to use visual cues as an aid for segmentation. These findings show that the ability to integrate multimodal cues develops during childhood, and it is not yet adult-like in children.

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The person-centered acne severity scale study

Abstract

Acne is one of the most common skin conditions seen by dermatologists. As with many other cutaneous diseases, due to its visibility, acne often produces a large psychosocial impact on patients who suffer from the disease. Such psychosocial burdens are exacerbated by the variation in acne presentation that can lead to the usage of multiple different treatments before visible improvements are appreciated. Although many scales have been established to determine severity from the clinician standpoint, patient-oriented scales are lacking. Clinicians use these severity tools to guide management and judge patient improvement from visit to visit. Creation of such a severity scale from a patient's perspective would allow patients to not only assess their perception of their acne independent of a physician but could also be used to determine patient satisfaction with treatment that would then help to more effectively guide management. Therefore the goal of this study is to create and validate a patient-centered acne severity scale using a visual analogue scale format.

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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci

Abstract

Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer, but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 colorectal cancer cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism rs992157 (2q35) and colorectal cancer was independently replicated (p=2.08x10⁻⁴; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50x10⁻⁹; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3, and 20q13.33 were associated with colorectal cancer in the Finnish population (false discovery rate <0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of colorectal cancer and identify shared risk alleles between the Finnish population isolate and outbred populations. This article is protected by copyright. All rights reserved.

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Gougerot-Sjogren-like syndrome under PD-1 inhibitor treatment.

pembrolizumabgougerot-sjrokentoxicityimmune related adverse events

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Bevacizumab + chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial - PRODIGE 20 study results

Abstract

BACKGROUND

Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific endpoints in this population.

PATIENTS AND METHODS

Patients aged 75 and over were randomly assigned to bevacizumab + chemotherapy (BEV) versus chemotherapy (CT). LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary endpoint, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.

RESULTS

102 pts were randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary endpoint was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival (OS) was 21.7 months in BEV and 19.8 months in CT. The 36-months OS rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non hematologic toxicities (80.4% in BEV, 63.3% in CT).

CONCLUSION

Bevacizumab combined with chemotherapy was safe and efficient. Both arms met the primary safety and efficacy criteria.

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Cancers, Vol. 9, Pages 132: Regulation of mTOR, Metabolic Fitness, and Effector Functions by Cytokines in Natural Killer Cells

Cancers, Vol. 9, Pages 132: Regulation of mTOR, Metabolic Fitness, and Effector Functions by Cytokines in Natural Killer Cells

Cancers doi: 10.3390/cancers9100132

Authors: Sébastien Viel Laurie Besson Marie Marotel Thierry Walzer Antoine Marçais

The control of cellular metabolism is now recognized as key to regulate functional properties of immune effectors such as T or Natural Killer (NK) cells. During persistent infections or in the tumor microenvironment, multiple metabolic changes have been highlighted in T cells that contribute to their dysfunctional state or exhaustion. NK cells may also undergo major phenotypic and functional modifications when infiltrating tumors that could be linked to metabolic alterations. The mammalian target of rapamycin (mTOR) kinase is a central regulator of cellular metabolism. mTOR integrates various extrinsic growth or immune signals and modulates metabolic pathways to fulfill cellular bioenergetics needs. mTOR also regulates transcription and translation thereby adapting cellular pathways to the growth or activation signals that are received. Here, we review the role and regulation of mTOR in NK cells, with a special focus on cytokines that target mTOR such as IL-15 and TGF-β. We also discuss how NK cell metabolic activity could be enhanced or modulated to improve their effector anti-tumor functions in clinical settings.

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Multimodal molecular analysis of astroblastoma enables reclassification of most cases into more specific molecular entities

Abstract

Astroblastoma is a rare and controversial glioma with variable clinical behavior. The diagnosis currently rests on histologic findings of a circumscribed glioma with astroblastomatous pseudorosettes and vascular hyalinization. Immunohistochemical studies have suggested different oncogenic drivers, such as BRAF p.V600E, but very few cases have been studied using genome-wide methodologies. Recent genomic profiling identified a subset of CNS embryonal tumors with astroblastoma-like morphology that harbored MN1 gene fusions, termed "CNS high-grade neuroepithelial tumors with MN1 alteration" (CNS-HGNET-MN1). To further characterize the genetic alterations that drive astroblastomas, we performed targeted next-generation sequencing (NGS) of 500 cancer-associated genes in a series of 8 cases. We correlated these findings with breakapart FISH analysis of the MN1 locus and genome-wide DNA methylation profiling. Four cases showed MN1 alteration by FISH, including two pediatric cases that lacked other pathogenic alterations, and two adult cases that harbored other cancer associated gene mutations or copy number alterations (e.g. CDKN2A/B homozygous deletion, TP53, ATM, and TERT promoter mutations). Three of these cases grouped with the CNS-HGNET-MN1 entity by methylation profiling. Two of four MN1 intact cases by FISH showed genetic features of either anaplastic pleomorphic xanthoastrocytoma (BRAF p.V600E mutation, CDKN2A/B homozygous deletion, and TERT promoter mutation) or IDH-wildtype glioblastoma (trisomy 7, monosomy 10, CDK4 amplification, and TP53, NRAS, and TERT promoter mutations) and these cases had an aggressive clinical course. Two clinically indolent cases remained unclassifiable despite multimodal molecular analysis. We conclude that astroblastoma histology is not specific for any entity including CNS-HGNET-MN1, and that additional genetic characterization should be considered for astroblastomas, as a number of these tumors likely contain a methylation profile or genetic alterations that suggest classification as other tumor entities. Our heterogeneous molecular findings help to explain the clinical unpredictability of astroblastoma. This article is protected by copyright. All rights reserved.

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The value of intramural vascular invasion in colorectal cancer – a systematic review and meta-analysis

Abstract

Extramural venous invasion (EMVI) is a well-known prognostic factor in colorectal cancer (CRC). Vascular invasion within the bowel wall, intramural vascular invasion (IMVI), has received less attention and its incidence and prognostic importance in CRC is not completely known. A systematic literature search was performed focusing on the impact of IMVI in CRC. Data were analysed using Review Manager 5.3 on incidence and clinical endpoints local recurrence, five year cancer specific survival (CSS) and five year overall survival (OS). Meta-analysis was performed in terms of risk ratios (RR) and hazard ratios (HR) with 95% confidence interval (95%CI).

Of the initial 1199 articles identified by our search strategy, 20 were included in this meta-analysis. Of the 8078 included patients, 1008 patients had IMVI (12.5%). Studies that re-examined histological slides showed a higher incidence of IMVI compared to studies extracting IMVI from pathology reports (17.6% vs. 7.7%, p<0.001). Detection of IMVI increased significantly with the use of additional staining (22.9% vs. 12.3%, p<0.001). IMVI was associated with a decreased CSS (HR 1.6, 95%CI 1.2-2.2 in multivariate analysis). A borderline significant effect was observed for IMVI on local recurrence (RR 1.5, 95%CI 0.98-2.3) and OS (RR 1.2, 95%CI 1.0-1.4).

In conclusion, despite the limited number of studies, there is a clear association with outcome in the presence of IMVI. This warrants more attention to this underreported prognostic factor.

This article is protected by copyright. All rights reserved.

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Neuronal Rho GTPase Rac1 Elimination Confers Neuroprotection in a Mice Model of Permanent Ischemic Stroke

ABSTRACT

The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our results show that pMCAO significantly increased total Rac1 levels in wild type mice, mainly through rising nuclear Rac1, while a reduction in Rac1 activation was observed. Such changes preceded cell death induced by excitotoxic stress. Pharmacological inhibition of Rac1 in primary neuronal cortical cells prevented the increase in oxidative stress induced after overactivation of glutamate receptors. However, this was not sufficient to prevent the associated neuronal cell death. In contrast, RNAi-mediated knock down of Rac1 in primary cortical neurons prevented cell death elicited by glutamate excitotoxicity and decreased the activity of NADPH oxidase. To test whether in vivo down regulation of neuronal Rac1 was neuroprotective after pMCAO, we used tamoxifen-inducible neuron-specific conditional Rac1-knockout mice. We observed a significant 50% decrease in brain infarct volume of knockout mice and a concomitant increase in HIF-1α expression compared to littermate control mice, demonstrating that ablation of Rac1 in neurons is neuroprotective. Transmission electron microscopy performed in the ischemic brain showed that lysosomes in the infarct of Rac1- knockout mice were preserved at similar levels to those of non-infarcted tissue, while littermate mice displayed a decrease in the number of lysosomes, further corroborating the notion that Rac1 ablation in neurons is neuroprotective.

Our results demonstrate that Rac1 plays important roles in the ischemic pathological cascade and that modulation of its levels is of therapeutic interest. This article is protected by copyright. All rights reserved.

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Spinal Lewy Body Pathology in Older Adults without an Antemortem Diagnosis of Parkinson's Disease

ABSTRACT

Objective: To test the hypothesis that Lewy body pathology (LBs) is present in the spinal cord of older community-dwelling adults without a clinical diagnosis of Parkinson's disease (PD).

Methods: We studied 162 prospective autopsies from older adults with PD (N=6) and without PD (N=156). We documented the presence of LBs in cerebrum and brainstem structures from each of the 6 regions used for Braak PD staging and 4 spinal cord levels (C5/6, T7, L4/5 and S4/5). Parkinsonism proximate to death was based on a previously validated measure present if 2 or more of the 4 signs of parkinsonism were present based on a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS).

Results: Fifty-three of 156 individuals without PD (34%) had LBs in a least one site within the CNS. About half of cases with LBs in the cerebrum or brainstem, (25/53, 47%) also had spinal LBs. Almost 90% (22/25 88%) of cases with spinal LBs had LBs in the cerebrum (Braak stages 4-6) and about 10% (3/25, 12%) had only brainstem LBs (Braak stages 1-3). Four of 6 cases with PD showed LBs in cerebrum, brainstem and spinal cord. Individuals with LBs in the spinal cord were more likely to have clinical parkinsonism proximate to death compared to individuals with LBs in brainstem and cerebrum alone (52% vs 32%; Chi-Square х² = 5.368, df = 1, p = 0.0.021) and more severe nigral neuronal loss (48%% vs 11%; Chi-Square х² = 9.049, df = 1, p = 0.003). These findings were unchanged when we included cases with a history of PD.

Conclusion: Older community-dwelling adults without a clinical diagnosis of PD have evidence of LBs throughout the CNS including the spinal cord which is associated with parkinsonism and more severe nigral neuronal loss. This article is protected by copyright. All rights reserved.

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Targeted Therapy and Local Control: The Dynamic Duo

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Usefulness of Mapping Biopsy in the Treatment of Penoscrotal Extramammary Paget’s Disease

Abstract

Background

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy; however, the standard treatment of EMPD has not been established. In this study, we applied mapping biopsy to penoscrotal EMPD and evaluated its effects.

Methods

A retrospective chart review was performed to determine the outcomes of patients with primary penoscrotal EMPD who underwent surgery at our institution between 2007 and 2014. Patients were divided into two groups (one group underwent mapping biopsy, while the other group did not), and the difference between the two groups was analyzed. The 5-year tumor-free rate was estimated using the Kaplan–Meier method, and the risk factors for local recurrence were also estimated.

Results

A total of 44 patients were analyzed, and the mean follow-up of patients was 50.27 months. Patients who underwent mapping biopsy showed significantly lower tumor involvement at permanent and frozen biopsies and a lower local recurrence rate than those who did not undergo mapping biopsy. The 5-year tumor-free rate was significantly higher in the mapping biopsy group than in the non-mapping biopsy group. Multivariable analysis demonstrated that age at operation, mapping biopsy, and false-negative results at frozen biopsy were associated with local recurrence.

Conclusions

Mapping biopsy is beneficial to reduce local recurrence in penoscrotal EMPD.

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A 10-Year Experience with Mastectomy and Tissue Expander Placement to Facilitate Subsequent Radiation and Reconstruction

Abstract

Background

An integrated approach to skin sparing mastectomy with tissue expander placement followed by radiotherapy and delayed reconstruction was initiated in our institution in 2002. The purpose of this study was to assess the surgical outcomes of this strategy.

Methods

Between September 2002 and August 2013, a total of 384 reconstructions had a tissue expander placed at the time of mastectomy and subsequently underwent radiotherapy. Rates and causes of tissue expander explantation before, during, and after radiotherapy, as well as tumor specific outcomes and reconstruction approaches, were collected.

Results

Median follow-up after diagnosis was 5.6 (range 1.3–13.4) years. In the study cohort, 364 patients (94.8%) had stage II–III breast cancer, and 7 patients (1.8%) had locally recurrent disease. The 5-year rates of actuarial locoregional control, disease-free survival, and overall survival were 99.2, 86.1, and 92.4%, respectively. The intended delayed-immediate reconstruction was subsequently completed in 325 of 384 mastectomies (84.6% of the study cohort). Of the remaining 59 tissue expanders, 1 was explanted before radiotherapy, 1 during radiotherapy, and 7 patients (1.8%) were lost to follow-up. Fifty patients (13.0%) required tissue expander explantation after radiation and before their planned final reconstruction, primarily due to cellulitis. Nonetheless, the cumulative rate of completed reconstructions was 89.6%. The median time from placement of the tissue expander until reconstruction was 12 (interquartile range 9–15) months.

Conclusions

Tissue expander placement at skin-sparing mastectomy in patients who require radiotherapy appears to be a viable strategy for combining reconstruction and radiotherapy.

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Impact of Sustained Virological Response to Interferon Therapy on Recurrence of Hepatitis C Virus-Related Hepatocellular Carcinoma

Abstract

Background

Although achieving a sustained virological response (SVR) in hepatitis C virus (HCV) infection is recognized as improving liver function and reducing hepatocellular carcinoma (HCC) development, its impact on HCC recurrence is unclear. This study investigated how preoperative SVR achievement by interferon treatment affects HCC recurrence in patients undergoing hepatic resection.

Methods

The study subjects were 521 patients with HCV infection who underwent initial and curative hepatic resection for HCC. To adjust for confounding factors between the SVR and non-SVR groups, propensity score-matching analysis was performed.

Results

After propensity score matching, 45 of the 49 patients in the SVR group, and an equal number of the 472 patients in the non-SVR group, were matched. The two groups had similar distributions of clinicopathological characteristics. In the matched cohort, the 3-, 5-, and 7-year recurrence-free survival rates after surgery were 56, 45, and 37%, respectively, in the SVR group, and 34, 23, and 7.2%, respectively, in the non-SVR group (p = 0.033). Additionally, the 3-, 5-, and 7-year overall survival rates after surgery were 82, 80, and 75%, respectively, in the SVR group, and 78, 64, and 44%, respectively, in the non-SVR group (p = 0.065). The 1- and 2-year cumulative recurrence rates in the early phase showed no significant difference between the SVR and non-SVR groups (p = 0.27). however, the 3-, 5-, and 7-year cumulative recurrence rates in the late phase were 14, 32, and 43%, respectively, in the SVR group, and 33, 55, and 86%, respectively, in the non-SVR group (p = 0.037).

Conclusion

Achievement of SVR may reduce postoperative recurrence after hepatic resection.

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Impact of Patient Age on the Postoperative Survival in Pancreatic Head Cancer

Abstract

Background

Some reports have stated that pancreatoduodenectomy for elderly patients have comparable morbidity and mortality to that of young patients. However, the long-term outcomes of these patients have not been fully evaluated, especially for pancreatic head cancer.

Methods

A total of 227 patients who underwent pancreatoduodenectomy for pancreatic head cancer between 2007 and 2014 were included. They were stratified according to age: young (<70 years), elderly (70 to <80 years), and very elderly (≥80 years). The short- and long-term outcomes were evaluated.

Results

There were no significant differences in terms of morbidity among the three groups. The median disease-free survival times were 15 months in the young, 11 months in the elderly, and 7 months in the very elderly. The disease-free survival of the young patients was significantly better than that in both the elderly and the very elderly (p = 0.012 and p = 0.016). The median overall survival times were 30 months in the young, 20 months in the elderly, and 14 months in the very elderly. The overall survival of the young patients was significantly better than that in both the elderly and the very elderly (p = 0.007 and p < 0.001). The difference was marginal between the elderly and the very elderly (p = 0.053). Multivariate analysis revealed that lymph node metastasis (p < 0.001), age ≥80 years (p = 0.013), lack of adjuvant chemotherapy (p = 0.003), blood transfusion (p = 0.015), and CA 19-9 ≥300 U/ml (p = 0.040) were significant prognostic factors.

Conclusions

Patient age influenced the survival after pancreatoduodenectomy for pancreatic cancer.

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2017 Update on the Querleu–Morrow Classification of Radical Hysterectomy

Abstract

Background

One of the most important principles in modern cervical cancer surgery is the concept of tailoring surgical radicality. In practice, this means abandoning the "one-fits-all" concept in favor of tailored operations. The term "radical hysterectomy" is used to describe many different procedures, each with a different degree of radicality. Anatomic structures are subjected to artificial dissection artifacts, as well as different interpretations and nomenclatures. This study aimed to refine and standardize the principles and descriptions of the different classes of radical hysterectomy as defined in the Querleu–Morrow classification and to propose its universal applicability.

Methods

All three authors independently examined the current literature and undertook a critical assessment of the original classification. Images and pathologic slides demonstrating different types of radical hysterectomy were examined to document a consensual vision of the anatomy. The Cibula 3-D concept also was included in this update.

Results

The Querleu–Morrow classification is based on the lateral extent of resection. Four types of radical hysterectomy are described, including a limited number of subtypes when necessary. Two major objectives remain constant: excision of central tumor with clear margins and removal of any potential sites of nodal metastasis.

Conclusion

Studies evaluating radicality in the surgical management of cervical cancer should be based on precise, universally accepted descriptions. The authors' updated classification presents standardized, universally applicable descriptions of different types of hysterectomies performed worldwide, categorized according to degree of radicality, independently of theoretical considerations.

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Sustained Growth of a University-Based Endocrine Surgery Program Over 10 Years

Abstract

Background

Endocrine surgery continues to mature as a subspecialty field. We describe the clinical performance of an academic endocrine surgery program (ESP) over its first 10 years.

Methods

We examined all endocrine procedures performed during the 10-year period (2006–2015) following the inception of the ESP. Institutional and state-level data on case volume, patient geographic origin, and hospital-side costs were obtained.

Results

Endocrine case volume increased by approximately ninefold over the study period (from 102 cases in 2006 to 919 cases in 2015). The rate of growth remained approximately linear, and was driven by geographic expansion of referral regions coupled with transitioning low- to moderate-acuity operations to venues outside of the main tertiary care hospital. Market share across the eight-county Southern California region grew by more than twofold over the study period. Increased utilization of outpatient surgery led to cost reductions, averaging 11.1% per case by 2015.

Conclusions

Establishment of an academic ESP can lead to sustained clinical growth and a fundamental shift in regional referral patterns. The nation's continued need for skilled high-volume endocrine surgeons represents opportunities for medical centers to institute their own dedicated endocrine surgery programs.

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Selective Use of Sentinel Lymph Node Surgery in Patients Undergoing Prophylactic Mastectomy Using Intraoperative Pathology

Abstract

Background

Routine sentinel lymph node (SLN) surgery during prophylactic mastectomy (PM) is unnecessary, because most PMs do not contain cancer. Our institution utilizes intraoperative pathology to guide the surgical decision for resection of SLNs in PM. The purpose of this study was to review the effectiveness of this approach.

Methods

We identified all women aged ≥18 years who underwent bilateral PM (BPM) or contralateral PM (CPM) at our institution from January 2008 to July 2016. We evaluated the frequency of SLN resection and rate of occult breast cancer (DCIS or invasive disease) in the PM. We used the following definitions: over-treatment—SLN surgery in patients without cancer; under-treatment—no SLN surgery in patients with cancer; appropriate treatment—no SLN in patients without cancer or SLN surgery in patients with cancer.

Results

PM was performed on 1900 breasts: 1410 (74.2%) CPMs and 490 (25.8%) BPMs. Cancer was identified in 58 (3.0%) cases (32 invasive disease and 26 DCIS) and concurrent SLN surgery was performed in 44 (75.9%) of those cases. Overall, SLN surgery guided by intraoperative pathology resulted in appropriate treatment of 1787 (94.1%) cases: 1319 (93.5%) CPMs and 468 (95.5%) BPMs, by avoiding SLN in 1743/1842 cases without cancer (94.6%), and performing SLN surgery in 44/58 cases with cancer (75.9%).

Conclusions

Use of intraoperative pathology to direct SLN surgery in patients undergoing PM minimizes over-treatment from routine SLN in PM and minimizes under-treatment from avoiding SLN in PM, demonstrating the value of intraoperative pathology in this era of focus on appropriateness of care.

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Presidential Address: The Road Ahead—Challenges and Opportunities

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Usefulness of Mapping Biopsy in the Treatment of Penoscrotal Extramammary Paget’s Disease

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Expanded Gene Panel Use for Women With Breast Cancer: Identification and Intervention Beyond Breast Cancer Risk

Abstract

Background

Clinicians ordering multi-gene next-generation sequencing panels for hereditary breast cancer risk have a variety of test panel options. Many panels include lesser known breast cancer genes or genes associated with other cancers. The authors hypothesized that using broader gene panels increases the identification of clinically significant findings, some relevant and others incidental to the testing indication. They examined clinician ordering patterns and compared the yield of pathogenic or likely pathogenic (P/LP) variants in non-BRCA genes of female breast cancer patients.

Methods

This study analyzed de-identified personal and family histories in 1085 breast cancer cases with P/LP multi-gene panel findings in non-BRCA cancer genes and sorted them into three groups by the panel used for testing: group A (breast cancer genes only), group B (commonly assessed cancers: breast, gynecologic, and gastrointestinal), and group C (a more expanded set of tumors). The frequency of P/LP variants in genes with established management guidelines was compared and evaluated for consistency with personal and family histories.

Results

This study identified 1131 P/LP variants and compared variants in clinically actionable genes for breast and non-breast cancers. Overall, 91.5% of these variants were in genes with management guidelines. Nearly 12% were unrelated to personal or family history.

Conclusion

Broader panels were used for 85.6% of our cohort (groups B and C). Although pathogenic variants in non-BRCA genes are reportedly rare, the study found that most were in clinically actionable genes. Expanded panel testing improved the identification of hereditary cancer risk. Small, breast-limited panels may miss clinically relevant findings in genes associated with other heritable cancers.

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Influence of Distance to Hospital and Insurance Status on the Rates of Contralateral Prophylactic Mastectomy, a National Cancer Data Base study

Abstract

Introduction

We evaluated the impact of travel distance and insurance status on contralateral prophylactic mastectomy (CPM) rates in breast cancer.

Methods

We queried the National Cancer Data Base (NCDB) for women >18 years of age with a nonmetastatic primary breast cancer of ductal, lobular, or mixed histology. Patient- and facility-specific CPM rates were calculated based on insurance, race, and distance to treatment center. Standard univariable and multivariable regression analysis was performed.

Results

Overall, the CPM rate was 6.5% for the 864,105 patients identified. Most patients traveled <20 miles to a treatment center (79.5%) and had private insurance or Medicare (58.3 and 33.4%, respectively). In general, younger, White, non-Hispanic, and privately insured patients residing further from a treatment center was associated with increased rates of CPM. However, distance to the treatment center and insurance type had a greater absolute impact on rates of CPM for Black and Hispanic patients. Absolute CPM rate increases for patients >100 miles from a treatment center compared with those <20 miles from a treatment center were observed to be greater for Black and Hispanic patients (3.5 and 3.9%, respectively) compared with White and non-Hispanic patients (2.5 and 2.6%). Additionally, further patient travel distance was associated with higher treatment center-specific CPM rates.

Conclusion

Increased travel distance is independently associated with increased rates of CPM for all patients and increased facility-specific rates of CPM. Black and Hispanic patients were found to be more vulnerable to the impact of travel distance and insurance status on rates of CPM.

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Clinical Decision-Making in Patients with Variant of Uncertain Significance in BRCA1 or BRCA2 Genes

Abstract

Background

How diagnosis with a variant of uncertain significance (VUS) in a BRCA gene impacts clinical decision-making is not well known.

Methods

We queried for all patients attending Mayo Clinic Rochester from 2004 to 2016 who tested positive for BRCA1 or BRCA2 VUS and reviewed patient management choices. Groups were compared by using Wilcoxon rank-sum and Chi-square tests.

Results

We identified 97 patients (95 females, 2 males) with BRCA VUS. For patients without cancer history (n = 20), 80% had a mother or sister with breast cancer, and median Tyrer-Cuzick (IBIS) lifetime breast cancer risk score was 27% (range 16–62%). Management included bilateral prophylactic mastectomy (BPM) in 39%, where choice for BPM was significantly associated with IBIS score (median 32 vs. 24%, p = 0.02) and first-degree family history of breast cancer (100 vs. 64%, p = 0.03) but not Gail score or total number of family members with cancer. For patients with breast cancer who had known VUS status prior to surgery (n = 9), the rate of contralateral prophylactic mastectomy (CPM) was 22% compared with 25% without known VUS and 83% with known BRCA pathogenic mutation. In 21 of 97 (22%) patients, the BRCA VUS has been reclassified (95% benign, 5% deleterious).

Conclusions

BRCA VUS carriers with cancer elected surgical choices similar to average-risk breast cancer patients. However, VUS carriers without cancer had high rates of BPM, associated with first-degree family history and IBIS score. Over time, a significant proportion of BRCA VUS were reclassified, illustrating the importance of appropriate counseling regarding VUS.

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Intraoperative Radiation Using Low-Kilovoltage X-Rays for Early Breast Cancer: A Single Site Trial

Abstract

Introduction

Two prospective, randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy (IORT) to be a safe alternative to whole breast radiation therapy following breast-conserving surgery for selected low-risk patients. However, minimal data are available about the clinical effectiveness of this modality of treatment using the Xoft^® Axxent^® Electronic Brachytherapy (eBx^®) System^®.

Methods

A total of 201 patients with 204 early-stage breast cancers were enrolled in a prospective X-ray IORT trial from June 2010 to September 2013. All tumors were treated with breast-conserving surgery and IORT. Data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter.

Results

With a median follow-up of 50 months, there have been seven ipsilateral breast tumor events (IBTE), no regional or distant recurrences, and no breast cancer-related deaths. One IBTE was within the IORT field, four outside of the IORT field but within the same quadrant as the index cancer, and two were new biologically different cancers in different quadrants. Three events were in patients who deviated from the protocol criteria. Kaplan–Meier analysis projects that 2.9% of patients will recur locally at 4 years.

Conclusions

Recurrence rates observed in this trial were comparable to those of the TARGIT-A and ELIOT trials as well as the retrospective TARGIT-R trial. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of IORT in selected women with low-risk breast cancer.

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Evaluating the Risk of Upstaging HER2-Positive DCIS to Invasive Breast Cancer

Abstract

Background

Overexpression of human epidermal growth factor 2 (HER2) in invasive breast cancer (IBC) is an independent poor prognostic factor. However, the significance of HER2 overexpression in ductal carcinoma in situ (DCIS) is not well defined. The current study assessed the correlation of HER2⁺ DCIS with the rate of upstaging to IBC on the final pathology.

Methods

The study retrospectively analyzed patients with the diagnosis of DCIS on core needle biopsy (CNB) at the authors' institution from 2009 to 2016. Data were analyzed using two-sample t tests. Multivariate analysis was performed using logistic regression.

Results

The study found that HER2⁺ DCIS had significantly higher rates of upstaging to IBC than HER2⁻ DCIS (odds ratio [OR] 1.89; p = 0.012). In addition, triple-positive disease was more than two times more likely to be upstaged (OR 2.5; p = 0.01), whereas patients with estrogen (ER)-positive, progesterone (PR)-positive, and HER2⁻ diseases were half as likely to be upstaged (OR 0.5; p = 0.04). Upstaging did not differ for patients with triple-negative disease (OR 0.89; p = 0.8). Additionally, patients with HER2⁺ DCIS were significantly younger regardless of ER/PR status (p = 0.03). The overexpression of HER2 in patients with an initial diagnosis of DCIS on CNB were twice as likely to have IBC on the final pathology as those who did not.

Conclusion

The results suggest that overexpression of HER2 may serve as a biomarker for risk stratification of patients with DCIS and may help to guide treatment strategies in the future. For institutions in which HER2 testing may be performed on DCIS, patients should be counseled appropriately about the risk of upgrade to IBC.

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MACRA and the Changing Medicare Payment Landscape

Abstract

Background

The Medicare Access and CHIP Reauthorization Act (MACRA) is being implemented in 2017 by the Centers for Medicare and Medicaid Services (CMS) as the Quality Payment Program (QPP) and will have important and far reaching effects on how physicians are reimbursed and on how they practice. The QPP modifies the Medicare physician payment system by eliminating the Sustainable Growth Rate formula and incorporating the existing Physician Quality Reporting System, EHR Incentive Program, and the Value Modifier into a single new Merit-based Incentive Payment System (MIPS).

Methods

The authors reviewed the MACRA legislation as well as the CMS resources on the QPP and other sources to summarize the regulations pertaining to the new program, particularly for the first performance period.

Results

CMS has taken great care to create a smooth transition for Medicare physicians. Clinicians can avoid any penalty for performance in 2017 by submitting a minimal amount of quality data, attesting to a single improvement activity, or successfully attaining the base score for the advancing care information portion of MIPS. The reduced reporting period also makes it possible for participants to begin collecting data as late as October 2nd and still achieve the full possible score in the program.

Conclusions

Surgeons should be taking steps now to ensure that they are prepared to succeed in the QPP. The transition period creates a clear pathway for avoiding penalties while providing an opportunity to test one's ability to participate and improve performance.

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Lobular Neoplasia and Atypical Ductal Hyperplasia on Core Biopsy: Current Surgical Management Recommendations

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Reappraisal of Staging Laparoscopy for Patients with Pancreatic Adenocarcinoma: A Contemporary Analysis of 1001 Patients

Abstract

Background

Recent advances in imaging and the increasing use of neoadjuvant therapy puts the contemporary utility of staging laparoscopy for patients with pancreatic adenocarcinoma (PDAC) into question. This study aimed to develop a prognostic score to optimize prevention of an unnecessary laparotomy and minimize the rate for unnecessary laparoscopy.

Methods

Clinicopathologic data were evaluated for all patients undergoing surgical intervention for PDAC between 2001 and 2015, who were stratified into group 1 (2001–2008) and group 2 (2009–2014).

Results

The study identified 1001 patients eligible for analysis, 331 (33%) of whom underwent a staging laparoscopy before exploration. An unnecessary laparotomy was prevented for 44.4% of the patients in period 1 and for 24% of the patients in period 2 (p < 0.001). Male gender [odds ratio (OR), 1.8; p < 0.05], preoperative resectability (borderline resectable OR 2.1; p < 0.019; locally advanced OR 7.6; p < 0.001), CA 19-9 levels higher than 394 U/L (OR 3.1; p < 0.001), no neoadjuvant chemotherapy (OR 2.7; p = 0.012), and pancreatic body or tail lesions (OR 1.8; p = 0.063) were predictive of occult metastatic disease. The developed scoring index demonstrated a c-statistic of 0.729. The observed-to-expected ratio for the index at every score level validated the index's model. A score cutoff at 4 was able to detect 76.1% of radiographically occult metastatic disease.

Conclusion

The rate for unnecessary laparotomy among patients with PDAC has decreased in contemporary times, but unnecessary laparotomy still occurs for 1 in 4 patients. Using our scoring system, a cutoff of 4 allows 76% of radiographically occult metastases to be predicted, thereby selecting high-risk patients for laparoscopic biopsy and potentially avoiding a non-therapeutic laparotomy.

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Optimal Lymphadenectomy for Duodenal Adenocarcinoma: Does the Number Alone Matter?

Abstract

Background

Duodenal adenocarcinoma (DA) is a rare disease, and the optimal extent of lymphadenectomy and the role of limited resection remain controversial.

Objective

The aim of our study was to assess the pattern of regional lymph node spread of DA and to determine the optimal extent of resection.

Methods

A total of 65 patients who underwent curative resection for DA at our institution from 1989 through 2015 were included in this study. Clinicopathologic factors associated with long-term outcomes and the patterns of regional node spread per primary tumor location were evaluated.

Results

Fifty-one patients (78%) underwent pancreaticoduodenectomy (PD), with the remainder undergoing limited resection. The median number of retrieved lymph nodes was 24 (range 1–63) and 48% of patients had regional node metastasis. The 5-year overall survival (OS) rate was 67%. In the multivariate analysis, regional node and para-aortic lymph node metastasis were risk factors associated with poorer OS (hazard ratio [HR] 12.1 [p = 0.025], and HR 3.2 [p = 0.045], respectively). While pancreaticoduodenal (#13) and superior mesenteric (#14) lymph node stations were commonly involved by both distal and proximal DA (33 vs. 39% for #13, p = 0.39; and 33 vs. 22% for #14, p = 0.27), the pyloric lymph node station was much less involved by distal DA than proximal DA (0 vs. 37%, p = 0.036).

Conclusion

The pancreaticoduodenal lymph node station was the most commonly involved lymph node in DA, and PD should be the standard operation for DA. Segmental resection should only be reserved for patients with distal DA who are physically unfit for PD.

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Survival Rates for Patients with Resected Gastric Adenocarcinoma Finally have Increased in the United States

Abstract

Background

In the United States, the overall survival rates for gastric adenocarcinoma have remained low, with surgical resection as the only therapy for many patients. Given the advances in multimodality treatment and the development of guidelines recommending adequate lymph node evaluation, the authors determined whether overall survival rates for patients with gastric adenocarcinoma have increased in the United States.

Methods

The study used the Surveillance Epidemiology and End Results (SEER) database to examine overall survival for patients with the diagnosis of gastric adenocarcinoma between 1988 and 2013. The study cohort was divided into five periods: 1988–1992, 1993–1997, 1998–2002, 2003–2007, and 2008–2013. Kaplan–Meier methods and Cox proportional hazards modeling were used to determine the effect that year of diagnosis had on overall survival.

Results

The diagnosis was determined for 13,470 patients between 1988 and 2013. The use of radiation therapy and the proportion of patients who had at least 15 lymph nodes evaluated significantly increased during the study period. Unadjusted Kaplan–Meier estimates demonstrated significantly better survival rates for the patients with a diagnosis of gastric cancer in the later periods (2003–2007 and 2008–2013) than for those in the three earlier periods. In our Cox proportional hazards model, recent period was associated with a significantly lower hazard of 5-year mortality.

Conclusion

This analysis demonstrated for the first time that gastric cancer survival rates have significantly improved in the United States during the past 2 decades. This observation likely reflects improved adherence to cancer treatment guidelines, including adequate lymph node evaluation and delivery of adjuvant treatment more consistently.

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Eagle’s Syndrome

Figure 1.

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Efficacy and safety of topical JTE-052, a Janus kinase inhibitor, in Japanese adult patients with moderate-to-severe atopic dermatitis: A phase 2, multi-centre, randomised, vehicle-controlled clinical study

Summary

Background

JTE-052 is a novel Janus kinase inhibitor presently under clinical development for the topical treatment of atopic dermatitis (AD).

Objectives

To evaluate the efficacy and safety of JTE-052 ointment in Japanese adult patients with AD.

Methods Patients with moderate-to-severe AD were randomised (2:2:2:2:1:1) to receive JTE-052 ointment at 0.25%, 0.5%, 1% or 3%, the vehicle ointment or 0.1% tacrolimus ointment (reference) twice daily for 4 weeks. The primary efficacy endpoint was the percent change in modified Eczema Area Severity Index (m-EASI) score from the baseline at the end of treatment (EOT). Secondary efficacy endpoints included change from baseline in the pruritus numeric rating scale (NRS) score.

Results

A total of 327 patients were enrolled. At EOT, the least-squares mean percent change from baseline in m-EASI score for JTE-052 0.25%, 0.5%, 1%, 3% and the vehicle ointment was –41.7%, –57.1%, –54.9%, –72.9% and –12.2%, respectively. All JTE-052 groups showed significant reductions of m-EASI score versus the vehicle group (p <0.001 for all). In the tacrolimus group, the mean percent change in m-EASI score was –62.0%. JTE-052 groups also showed significant improvement in other parameters; notably, the pruritus NRS score was reduced as early as Day 1 night-time. JTE-052 ointment at doses up to 3% was safe and well tolerated.

Conclusions

Topical JTE-052 markedly and rapidly improved clinical signs and symptoms in Japanese adult patients with moderate-to-severe AD with a favourable safety profile. The study results indicate that topical JTE-052 is a promising therapeutic option for AD.

This article is protected by copyright. All rights reserved.

Trial registration number: JapicCTI-152887

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52 words for snow: Dermatologists naming epidermal nevi

Abstract

In the April 2017 issue of BJD, Kuentz et al (1) report an FGFR2 mutation in a subtype of nevus sebaceus (NS). On review of the histopathology, we question the clinical diagnosis and feel that these cases may better fit with keratinocytic epidermal nevus (KEN) or remain unclassified "epidermal nevi". Both KEN and NS are papillomatous with epidermal hyperplasia (2), and while the authors note "small foci of sebaceous glands and immature hair follicle buds", they wisely observe that the early gestational age may have limited the full adnexal development and thus, it is possible these may have developed into other clinical subtypes of epidermal nevi.

This article is protected by copyright. All rights reserved.

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Resistance development to mycobacterum tuberculosis is manageable in hidradentis suppurativa. Response to Treatment of hidradenitis suppurativa with rifampicin: have we forgotten tuberculosis?

Abstract

We read the letter by Mendes-Bastos et al. with concern.¹ Simply testing patients for latent tuberculosis solves the problem, and the authors did not mention that rifampin is an acceptable monotherapy for latent tuberculosis.² Hidradentitis suppurativa has the highest impact on quality of life of all dermatological diseases,³ and clindamycin and rifampin are a cornerstones of frequently failing therapy regimes.³ At the same time drug-resistant tuberculosis is a tremendous public health problem, particularly in China, the former Soviet Union, and India.

This article is protected by copyright. All rights reserved.

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Comparative morphology of snake (Squamata) endocasts: evidence of phylogenetic and ecological signals

Abstract

Brain endocasts obtained from computed tomography (CT) are now widely used in the field of comparative neuroanatomy. They provide an overview of the morphology of the brain and associated tissues located in the cranial cavity. Through anatomical comparisons between species, insights on the senses, the behavior, and the lifestyle can be gained. Although there are many studies dealing with mammal and bird endocasts, those performed on the brain endocasts of squamates are comparatively rare, thus limiting our understanding of their morphological variability and interpretations. Here, we provide the first comparative study of snake brain endocasts in order to bring new information about the morphology of these structures. Additionally, we test if the snake brain endocast encompasses a phylogenetic and/or an ecological signal. For this purpose, the digital endocasts of 45 snake specimens, including a wide diversity in terms of phylogeny and ecology, were digitized using CT, and compared both qualitatively and quantitatively. Snake endocasts exhibit a great variability. The different methods performed from descriptive characters, linear measurements and the outline curves provided complementary information. All these methods have shown that the shape of the snake brain endocast contains, as in mammals and birds, a phylogenetic signal but also an ecological one. Although phylogenetically related taxa share several similarities between each other, the brain endocast morphology reflects some notable ecological trends: e.g. (i) fossorial species possess both reduced optic tectum and pituitary gland; (ii) both fossorial and marine species have cerebral hemispheres poorly developed laterally; (iii) cerebral hemispheres and optic tectum are more developed in arboreal and terrestrial species.

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Radiological anatomy assessment of the fissura pterygomaxillaris for a surgical approach to ganglion pterygopalatinum

Abstract

The ganglion pterygopalatinum has become a therapeutic target to treat various pain syndromes in recent years. It is located in the fossa pterygopalatina, and the fissura pterygomaxillaris is the main access to surgically approach this structure. Recently, the neuromodulation of the ganglion pterygopalatinum by microstimulator implantation has become the first therapeutic line in refractory cluster headache treatment. This invasive technique is performed transorally through the fissura pterygomaxillaris, and is limited by the size of the implantation device, which requires an opening of at least 2 mm. Therefore, extensive knowledge about the anatomy of the fissura pterygomaxillaris prior to surgery is necessary to predict the success of both the approach and intervention. Likewise, establishing a morphological typology of the different fissura pterygomaxillaris variations would be a valuable predictive tool in the clinical practice. In this work, an anatomical analysis was performed of the morphological characteristics of the 242 fissurae pterygomaxillares, which corresponded to 121 adult patients, 58 males and 63 females, aged between 18 and 87 years. For each subject, right and left fissures were studied with radiological computed tomography images. Aperture fissura pterygomaxillaris measurements were taken in an upper (Measure A), middle (Measure B) and lower craneo-caudal third (Measure C). Intra-subject differences were studied between the measurements taken of each patient's right and left fissures, and the inter-subject measures in which fissures were compared according to patients' age and gender. The obtained results showed no significant differences between each patient's right and left fissures in any three measurements taken. Intra-subject differences were not significant for gender or age. No statistically significant differences were found for the inter-subject measures between the measures of fissures according to patients' age. However, our data revealed that males' fissurae pterygomaxillares were significantly larger than those of females in all three measures. Having analysed fissures, a typological classification was made according to the morphological patterns found. A 2-mm limiting measure was considered, and Measures A, B and C of each fissure were classified depending on whether they had a value above or equal to 2 mm, or below 2 mm. With this classification criterion, four fissurae pterygomaxillares types were obtained. Type I and II fissure values (with a higher prevalence) were equal to or were greater than 2 mm in all three measures, or in two measures. Type III fissure values were only greater than or equal to 2 mm in Measure A, whereas all the Type IV fissure values were below 2 mm. Future studies are necessary to correlate the fissure types successfully proposed in the surgical ganglion pterygopalatinum approach.

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Comparative anatomy of neonates of the three major mammalian groups (monotremes, marsupials, placentals) and implications for the ancestral mammalian neonate morphotype

Abstract

The existing different modes of reproduction in monotremes, marsupials and placentals are the main source for our current understanding of the origin and evolution of the mammalian reproduction. The reproductive strategies and, in particular, the maturity states of the neonates differ remarkably between the three groups. Monotremes, for example, are the only extant mammals that lay eggs and incubate them for the last third of their embryonic development. In contrast, marsupials and placentals are viviparous and rely on intra-uterine development of the neonates via choriovitelline (mainly marsupials) and chorioallantoic (mainly placentals) placentae. The maturity of a newborn is closely linked to the parental care strategy once the neonate is born. The varying developmental degrees of neonates are the main focus of this study. Monotremes and marsupials produce highly altricial and nearly embryonic offspring. Placental mammals always give birth to more developed newborns with the widest range from altricial to precocial. The ability of a newborn to survive and grow in the environment it was born in depends highly on the degree of maturation of vital organs at the time of birth. Here, the anatomy of four neonates of the three major extant mammalian groups is compared. The basis for this study is histological and ultrastructural serial sections of a hatchling of Ornithorhynchus anatinus (Monotremata), and neonates of Monodelphis domestica (Marsupialia), Mesocricetus auratus (altricial Placentalia) and Macroscelides proboscideus (precocial Placentalia). Special attention was given to the developmental stages of the organs skin, lung, liver and kidney, which are considered crucial for the maintenance of vital functions. The state of the organs of newborn monotremes and marsupials are found to be able to support a minimum of vital functions outside the uterus. They are sufficient to survive, but without capacities for additional energetic challenges. The organs of the altricial placental neonate are further developed, able to support the maintenance of vital functions and short-term metabolic increase. The precocial placental newborn shows the most advanced state of organ development, to allow the maintenance of vital functions, stable thermoregulation and high energetic performance. The ancestral condition of a mammalian neonate is interpreted to be similar to the state of organ development found in the newborns of marsupials and monotremes. In comparison, the newborns of altricial and precocial placentals are derived from the ancestral state to a more mature developmental degree associated with advanced organ systems.

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Interplay of upper and lower motor neuron degeneration in amyotrophic lateral sclerosis

Publication date: November 2017
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Mamede de Carvalho, Artiom Poliakov, Cristiano Tavares, Michael Swash
ObjectiveWe studied motor unit recruitment to test a new method to identify motor unit firing rate (FR) variability.MethodsWe studied 68 ALS patients, with and without upper neuron signs (UMN) in lower limbs, 24 patients with primary lateral sclerosis (PLS), 13 patients with spinal cord lesion and 39 normal subjects. All recordings were made from tibialis anterior muscles of normal strength. Subjects performed a very slight contraction in order to activate 2 motor units in each recording. 5–7 motor unit pairs were recorded in each subject. Mean consecutive differences (MCD) were calculated for each pair of potentials. The mean MCD for each muscle was estimated as the mean from the total number of pairs recorded. Ap value<0.01 was accepted as significant.ResultsMCD of FR frequency was less in the subjects with spinal cord lesion and PLS. In addition, the FR frequency of the 1st motor unit in a pair of units was markedly reduced in PLS, and in subjects with spinal cord lesions.ConclusionThese results support a lower threshold and reduced FR fluctuation in spinal motor neurons of spastic patients.SignificanceThis method can be developed for detection of UMN lesions.



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Skeletal Metastasis—an Epidemiological Study

Abstract

Metastasis is the commonest bone tumors. The commonest primary metastasis to the bone are the breast, lung, prostate, kidney, and thyroid. The bone is the third common site of metastatic disease, only the lung and the liver have higher metastatic rate than skeleton. We have no epidemiological studies conducted to evaluate the various aspects of skeletal metastasis like age, sex distribution, presentation, common sites of primary and associated secondary metastases, and investigation from Indian subcontinent. Here we are presenting the first epidemiological study of skeletal metastasis from our region. We have conducted a prospective descriptive study in the Departments of Orthopedics and Radiotherapy, Government Medical College, Kozhikode, during the period of 2007 to 2009. One hundred eleven patients were included in the study above the age of 30 years. Clinical examination and investigation were done on these patients. Skeletal metastasis commonly occurs in the fifth decade of life with modest male preponderance. In most of the cases, the primary site of malignancy was undetected at the time of presentation. Pain was the commonest presented complaint of the patient. The spine is the commonest site affected and the lung was the common site of primary metastasis. Most of the cases were detected by radiogram and confirmation was obtained by minimally invasive technique like FNAC or CNB.

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