OtoRhinoLaryngology News: 08/20/17

Κυριακή 20 Αυγούστου 2017

Optimizing tumor immune response through combination of radiation and immunotherapy

Abstract

Radiation therapy and immunotherapy are two highly evolving modalities for the treatment of solid tumors. Immunotherapeutic drugs can either stimulate the immune system via immunogenic pathways or target co-inhibitory checkpoints. An augmented tumor cell recognition by host immune cells can be achieved post-irradiation, as irradiated tissues can release chemical signals which are sensed by the immune system resulting in its activation. Different strategies combining both treatment modalities were tested in order to achieve a better therapeutic response and longer tumor control. Both regimens act synergistically to one another with complimentary mechanisms. In this review, we explore the scientific basis behind such a combination, starting initially with a brief historical overview behind utilizing radiation and immunotherapies for solid tumors, followed by the different types of these two modalities, and the biological concept behind their synergistic effect. We also shed light on the common side effects and toxicities associated with radiation and immunotherapy. Finally, we discuss previous clinical trials tackling this multimodality combination and highlight future ongoing research.

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At-home cancer screening: a solution for China and other developing countries with a large population and limited number of healthcare practitioners

Abstract

Five-year survival rate for patients with all cancers combined, in China, is only 30.9%, which is much lower than those in developed countries. The three main reasons for the low cancer curative rates in China include differences in the spectrum of cancer types, in early detection rates, and in the percentage of cancer patients receiving standardized treatment between China and developed countries. The most important mechanism for improving the curative rate is to improve early detection rates of major cancers in China using novel and affordable technologies that can be operated at home by the patients themselves. This attempt could be helpful in setting up a practical example for other developing countries with limited medical resources and a limited number of healthcare practitioners.

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Title: A novel stereotaxic system for implanting a curved lead to two intracranial targets with high accuracy

Publication date: Available online 20 August 2017
Source:Journal of Neuroscience Methods
Author(s): Chen-Yu Ding, Liang-Hong Yu, Yuan-Xiang Lin, Fan Chen, Wei-Xiong Wang, Zhang-Ya Lin, De-Zhi Kang
BackgroundThe multi-target deep brain stimulation (DBS) aimed at improving symptoms related to different nuclei is a promising research direction. However, to implant a single lead into multiple targets simultaneously is difficult with the current lead implantation method.New MethodWe proposed a novel stereotaxic system used for implanting a curved lead to any two targets of the brain, and used the theoretical "curved lead method". First, a customized novel stereotaxic system was fabricated, and a solid cranial model with six fixed internal targets was made; second, CT scan was performed to locate the fixed internal targets; third, five curved leads were implanted to five selected pairs of targets, each following the calculated parameters of "curved lead pathway" with the novel stereotaxic system, respectively. Finally, CT scans were performed again to determine the exact locations of the curved leads.ResultsThe five curved leads accurately passed through the five pairs of combined targets, respectively, and the average vector error of curved lead implantation was 0.70±0.24mm.Comparison with Existing Method(s): In most situations, performing a multiple-target DBS procedure with the current stereotaxic systems means increased number of implanted leads, increased incidence of operative complications, and increased medical costs. However, the novel stereotaxic system could guide a single lead to reach two selected targets of the brain with high accuracy.ConclusionsThe novel stereotaxic system enables curved lead implantation with high accuracy, and can be considered as a useful complement to the current stereotaxic system.

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Comparison of recommendations for screening mammography using CISNET models

BACKGROUND

Currently, there are several different recommendations for screening mammography from major national health care organizations, including: 1) annual screening at ages 40 to 84 years; 2) screening annually at ages 45 to 54 years, then biennially at ages 55 to 79 years; and 3) biennial screening at ages 50 to 74 years.

METHODS

Mean values of six Cancer Intervention and Surveillance Modeling Network (CISNET) models were used to compare these three screening mammography recommendations in terms of benefits and risks.

RESULTS

Mean mortality reduction was greatest with the recommendation of annual screening at ages 40 to 84 years (39.6%), compared with the hybrid recommendation of screening annually at ages 45 to 54 years, then biennially at ages 55 to 79 years (30.8%), and the recommendation of biennial screening at ages 50 to 74 years (23.2%). For a single-year cohort of US women aged 40 years, assuming 100% compliance, more breast cancers deaths would be averted over their lifetime with annual screening starting at age 40 (29,369) than with the hybrid recommendation (22,829) or biennial screening ages 50-74 (17,153 based on 2009 CISNET estimates, 15,599 based on 2016 CISNET estimates). To achieve the greatest mortality benefit, this single-year cohort of women would have the greatest total number of screening mammograms, benign recalls, and benign biopsies performed over the course of screening by following annual screening starting at age 40 years (90.2 million, 6.8 million, and 481,269, respectively) than by following the hybrid recommendation (49.0 million, 4.1 million, and 286,288, respectively) or biennial screening at ages 50 to 74 years (27.3 million, 2.3 million, and 162,885, respectively).

CONCLUSION

CISNET models demonstrate that the greatest mortality reduction is achieved with annual screening of women starting at age 40 years. Cancer 2017. © 2017 American Cancer Society.

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On assessing the effect of breast cancer screening schemes

Our goal should be to provide truthful, balanced information so that women can make informed choices about when to start screening for breast cancer. A woman who is making a decision about screening is more interested in her personal chances of benefit and risk of harm and is less interested in the benefits to the population.

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Association of sickle cell haemoglobinopathies with dental and jaw bone abnormalities

Abstract

Objective

To estimate the association between sickle cell anaemia or trait with dental and jaw bone abnormalities.

Subjects And Methods

Subjects (n=369) were allocated to three groups: sickle cell anaemia, trait and control. Dental shape, number, size and position and changes in pulp chamber, root and periapex were analysed by intra-oral periapical radiographs. Integrity of lamina dura, quality of cancellous bone and bone trabeculation were also evaluated. Prevalence ratios (PR) were calculated (α=0.05).

Results

Sickle cell anaemia had higher prevalence (PR:8.31) and number of teeth (PR:13.40) with external resorption; higher number of teeth with pulp calcification; partial and total loss of lamina dura and higher prevalence of changes in trabecular structure of maxilla (PR:6.45) and mandible (PR:5.34). Sickle cell trait showed higher prevalence (PR:1.26) and higher number of teeth (PR:1.98) with partial loss of lamina dura; higher number of teeth with hypercementosis, changes in shape, size, periapex, total loss of lamina dura and higher prevalence of changes in mandibular trabecular bone (PR:1.43).

Conclusion

Pulp calcification and external resorption of the root were the most frequent dental alterations in sickle cell anaemia group, while in trait was higher frequency of changes in shape, size, periapex and root. Jaw bone changes were most prevalent in both homozygous and heterozygous subjects.

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Genetic variants of microRNA processing genes and risk of non-syndromic orofacial clefts

Abstract

Objective

MicroRNAs (miRNAs) processing genes play important roles in the craniofacial development. The aim of the present study was to explore the associations between single nucleotide polymorphisms (SNPs) of miRNA processing genes with the risk of non-syndromic orofacial clefts (NSOC).

Methods

We genotyped 12 potentially functional SNPs from seven miRNA processing genes (GEMIN3, DROSHA, DGCR8, GEMIN4, PIWIL1, XPO5, and DICER) in a case-control study of 602 NSOC cases and 605 controls.

Results

Two SNPs were associated with the susceptibility of CL/P: rs10719 in DROSHA led to an increased risk of cleft lip with or without palate (CL/P) (GA/AA: P=0.024, OR=1.33, 95% CI=[1.04, 1.70]; GG+GA/AA: P=0.037, OR=1.29, 95% CI=[1.02, 1.63]), while rs493760 in DROSHA (CC/TT: P=0.049, OR=0.58, 95% CI=[0.34, 0.99]) could reduce the risk of CL/P. In addition, rs10719 (A)-rs493760 (C) haplotype contributed to a decreased risk of CL/P (OR=0.77, 95% CI=[0.63, 0.94]), whereas the rs10719 (G)-rs493760 (C) haplotype contributed to the increased risk of cleft palate only (CPO) (OR=2.70, 95% CI=[1.15, 6.35]). However, there was no difference observed in these SNPs after the Bonferroni correction.

Conclusion

Taken together, our results provided the potential evidence that rs10719 and rs493760 might contribute to the risk of CL/P, and suggested potential genetic basis and mechanisms of CL/P. The lack of association between these SNPs and CPO might be due to the limited sample size of CPO subgroup.

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Susceptibility of partially-desalivated rats to erosive tooth wear by calcium-supplemented beverages

Abstract

Objectives

To investigate the susceptibility of partially-desalivated rats to erosive tooth wear (ETW); the anti-erosive effect of a calcium-supplemented beverage; and the quantification of ETW by micro-computed tomography (micro-CT).

Methods

The study population consisted of thirty-eight rats, divided into partially-desalivated (n=19) and normal salivary flow (n=19). They were randomly allocated into 3 subgroups (n=6-7): A-diet soda, B-diet soda+calcium, C-water (control). Solutions were provided ad-libitum for 28 days, and the rats were euthanized afterwards. Each left hemi-mandible was scanned using micro-CT for enamel volume (3 molars) calculation. Visual analysis of photographs of the lingual surface of 1^st molars was performed independently by 3 blinded examiners. Data were statistically analysed (α=0.05).

Results

Micro-CT revealed no significant differences between partially-desalivated or normal groups. Rats consuming A had more enamel loss than those consuming B or C, which did not differ from each other. For visual analysis, desalivation did not affect ETW. Rats consuming C showed the lowest ETW, followed by B and then A, for both partially-desalivated and normal rats. Spearman correlation between the two ETW quantification methods was -0.65.

Conclusions

Partial desalivation did not increase ETW. Ca-containing beverage prevented ETW. Micro-CT quantified ETW, although it was not as sensitive as visual analysis.

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Meet Enchant

An overview of the Enchant hearing instrument family from Sonic.

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Could Eosinophilia predict clinical severity in nasal polyps?

Although nasal polyps are one of the most frequent diseases, their etiopathogenesis remains unclear.Since eosinophils are the main inflammatory cells in the substantial proportion of nasal polyp tissues, they ...

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Cutaneous lupus erythematosus. Quality of life and related factors in a cohort of 260 patients of A Coruña, Spain

Abstract

Dermatological disease has a significant impact on quality of life (QoL). However, information is scarce for cutaneous lupus erythematosus (CLE) in this regard. Thus, the manifestation of and co-morbidities associated with CLE were assessed in the current study to determine factors predictive of QoL impairment. A descriptive cross-sectional study was performed on predominantly Caucasian patients with CLE, recruited at our institution between April 2013 and August 2016 (α = 0.050; precision ± 6.5%).

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Comparison of pyoderma gangrenosum and hypertensive ischemic leg ulcer Martorell in a Swiss cohort

Abstract

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis presenting with painful and sterile skin ulcerations (1). Its aetiology remains largely unknown although an autoinflammatory background seems possible. Several comorbidities as well as triggering factors such as surgery, trauma or pharmacological therapies have been associated with the development of PG (2). Different topical and systemic treatments are recommended for PG, most commonly topical steroids or calcineurin inhibitors as well as systemic steroids, dapsone, infliximab and others, as well as by our group and others canakinumab and ustekinumab (3, 4).

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Genetics of Alzheimer’s Disease: the Importance of Polygenic and Epistatic Components

Abstract

Purpose of Review

We aimed to summarize the recent advances in genetic findings of Alzheimer's disease (AD), focusing on traditional single-marker and gene approaches and non-traditional ones, i.e., polygenic and epistatic components.

Recent Findings

Genetic studies have progressed over the last few decades from linkage to genome-wide association studies (GWAS), and most recently studies utilizing high-throughput sequencing. So far, GWASs have identified several common variants characterized by small effect sizes (besides APOE-ε4). Sequencing has facilitated the study of rare variants with larger effects. Nevertheless, missing heritability for AD remains extensive; a possible explanation might lie in the existence of polygenic and epistatic components.

Summary

We review findings achieved by single-marker approaches, but also polygenic and epistatic associations. The latter two are critical, yet-underexplored mechanisms. Genes involved in complex diseases are likely regulated by mechanisms and pathways involving many other genes, an aspect potentially missed by traditional approaches.

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Distinct processing of ambiguous speech in people with non-clinical auditory verbal hallucinations

Abstract

Auditory verbal hallucinations (hearing voices) are typically associated with psychosis, but a minority of the general population also experience them frequently and without distress. Such 'non-clinical' experiences offer a rare and unique opportunity to study hallucinations apart from confounding clinical factors, thus allowing for the identification of symptom-specific mechanisms. Recent theories propose that hallucinations result from an imbalance of prior expectation and sensory information, but whether such an imbalance also influences auditory-perceptual processes remains unknown. We examine for the first time the cortical processing of ambiguous speech in people without psychosis who regularly hear voices. Twelve non-clinical voice-hearers and 17 matched controls completed a functional magnetic resonance imaging scan while passively listening to degraded speech ('sine-wave' speech), that was either potentially intelligible or unintelligible. Voice-hearers reported recognizing the presence of speech in the stimuli before controls, and before being explicitly informed of its intelligibility. Across both groups, intelligible sine-wave speech engaged a typical left-lateralized speech processing network. Notably, however, voice-hearers showed stronger intelligibility responses than controls in the dorsal anterior cingulate cortex and in the superior frontal gyrus. This suggests an enhanced involvement of attention and sensorimotor processes, selectively when speech was potentially intelligible. Altogether, these behavioural and neural findings indicate that people with hallucinatory experiences show distinct responses to meaningful auditory stimuli. A greater weighting towards prior knowledge and expectation might cause non-veridical auditory sensations in these individuals, but it might also spontaneously facilitate perceptual processing where such knowledge is required. This has implications for the understanding of hallucinations in clinical and non-clinical populations, and is consistent with current 'predictive processing' theories of psychosis.

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Risk factors for epistaxis in patients followed in general practices in Germany.

Risk factors for epistaxis in patients followed in general practices in Germany.

Rhinology. 2017 Aug 19;:

Authors: Seidel DU, Jacob L, Kostev K, Sesterhenn AM

Abstract
BACKGROUND: The goal of the present study was to analyze the risk factors for epistaxis in patients followed in general practices in Germany. METHODS: The current study sample included patients aged 18 years or older who received a first epistaxis diagnosis between January 2012 and December 2016 (index date). Epistaxis patients and controls without epistaxis were matched (1:1) on the basis of age, gender, insurance status and physician. RESULTS: A total of 16,801 patients with epistaxis and 16,801 control subjects were included in this study. Of the subjects, 53.2% were men, and the mean age was 59.6 years (SD=21.2 years). Epistaxis was found to be positively associated with hypertension, obesity, chronic sinusitis, other disorders of the nose and nasal sinuses, anxiety disorder, and adjustment disorder (ORs ranging from 1.13 to 1.44). Epistaxis was also associated with the prescription of vitamin K antagonists, preparations from the heparin group, platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors, direct factor Xa inhibitors, other antithrombotic agents, selective serotonin reuptake inhibitors and nasal steroids (ORs ranging from 1.15 to 3.55). CONCLUSIONS: Overall, epistaxis risk is increased by multiple medical and psychiatric disorders. Several antithrombotic and nasal steroid therapies are also associated with this risk.</p&gt.

PMID: 28821888 [PubMed - as supplied by publisher]

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Factors Determining the Outcome in Trigeminal Neuralgia Treated With Percutaneous Balloon Compression

Publication date: November 2017
Source:World Neurosurgery, Volume 107
Author(s): Tugrul Cem Unal, Omer Faruk Unal, Orhan Barlas, Kemal Hepgul, Achmet Ali, Aydin Aydoseli, Yavuz Aras, Pulat Akin Sabanci, Altay Sencer, Nail Izgi
ObjectiveTo analyze 3T magnetic resonance imaging (MRI) findings and clinical features of patients with trigeminal neuralgia (TN) who underwent percutaneous balloon compression and to determine whether these findings had an impact on prognosis of TN.MethodsA retrospective review of patients with TN who underwent percutaneous balloon compression in the Neurosurgery Department at Istanbul Faculty of Medicine between January 1, 2007, and January 1, 2016, was undertaken. Of 105 patients who underwent percutaneous balloon compression, 27 patients who received surgical treatment for the first time for typical TN were included in the study. Follow-up data, clinical features, and 3T MRI findings were analyzed retrospectively. MRI findings and clinical features of patients with and without recurrence of TN were compared. The correlation between fractional anisotropy (FA) values and recurrence was investigated.ResultsDuring follow-up, 9 (33%) patients had recurrence. The patients with recurrence had longer duration of symptoms (P = 0.032), higher FA difference (P = 0.042), and higher FA difference rate (P = 0.023). A trend toward early recurrence was found in patients with higher FA difference rate, although this was not significant (P = 0.051, R = 0.319).ConclusionsSymptom duration was longer and microstructural changes were more apparent in patients with recurrence. In addition to age, comorbidities, and other clinical and radiographic features, symptom duration and FA values obtained with 3T MRI might be valuable information in surgical decision making.

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Kinase Activity in Recurring Primary Skull Base Chordomas and Chondrosarcomas: Identification of Novel Pathways of Oncogenesis and Potential Drug Targets

Publication date: November 2017
Source:World Neurosurgery, Volume 107
Author(s): Philip D. Tatman, Joshua Osbun, Youssef Yakkioui, Sumanpret Kaur, Carolina Parada, Tina Busald, Donald Born, Owais Ahmad, Jing Zhang, Manuel Ferreira
BackgroundChordomas and chondrosarcomas can occur in the skull base. Currently, 45% of chordomas and 56% of chondrosarcomas recur within 5 years of surgery. The role of adjuvant therapy is highly debated. No pharmacotherapies have been approved by the U.S. Food and Drug Administration for chordomas or chondrosarcomas. High propensity for recurrence and lack of definitive adjuvant therapy necessitate additional basic science research to identify molecular anomalies associated with recurrent disease.MethodsWe pooled tumor lysates from patients based on clinical criteria into 4 groups: primary chordomas, primary chordomas that recurred, primary chondrosarcomas, and primary chondrosarcomas that recurred. We used a peptide labeling method, isobaric tags for relative and absolute quantitation, to uniquely identify each tumor group. Phosphorylated peptides were identified and quantified via mass spectroscopy to determine and predict active kinases.ResultsSix groups of phosphorylated peptides were associated with primary tumors that later recurred. Specific kinases associated with primary chordomas that recurred were FES and FER. Specific kinases associated with primary chondrosarcomas that recurred were FES, FER, SRC family kinases, PKC, ROCK, and mitogen-activated protein kinase signaling (JNK, ERK1, p38).ConclusionsThese data provide clinicians with a means to screen skull base chordomas and chondrosarcomas to help identify tumors with a propensity to recur. Many of these kinases can be efficaciously inhibited by Food and Drug Administration–approved drugs that have not yet been used in clinical trials for treatment of skull base chordomas or chondrosarcomas. Validation of kinases identified in this study may advance treatment options for patients with these tumors.

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Multicenter Retrospective Cohort Study of “Talk and Die” After Traumatic Brain Injury

Publication date: November 2017
Source:World Neurosurgery, Volume 107
Author(s): Keita Shibahashi, Kazuhiro Sugiyama, Yoshihiro Okura, Hidenori Hoda, Yuichi Hamabe
BackgroundPatients who "talk and die" after traumatic brain injury (TBI) are potentially salvageable. The reported incidences and risk factors for the "talk and die" phenomenon are conflicting and do not take into account recent improvements in trauma care. The aim of this study was to determine the incidences of "talk and die" after TBI in a modern trauma care system, as well as associated risk factors.MethodsWe identified patients who experienced TBI (abbreviated injury scale 3–5) between 2004 and 2015 who talked on admission (i.e., their verbal component on the Glasgow Coma Scale was ≥3 on admission) using a nationwide trauma registry (the Japan Trauma Data Bank). The end point was in-hospital mortality. We compared patients who talked and died with those who talked and survived.ResultsDuring the study period, 236,698 patients were registered in the database. Of the 24,833 patients who were eligible for analysis, 956 (4.0%) patients subsequently died in the hospital. The in-hospital mortality rate significantly decreased over the past 12 years. Older age; male sex; a higher injury severity score; a lower Glasgow Coma Scale score; comorbidities (congestive heart failure, chronic kidney disease, liver cirrhosis, and hematologic disorders); hypotension on arrival; subdural hemorrhage; contusion; and vault fracture were independently associated with higher in-hospital mortality.ConclusionEven in modern trauma care systems, some patients still talk and die after TBI. We identified certain risk factors in patients with TBI that elicit the requirement for close observation, even if these patients talk after TBI.

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Correlación entre medidas de evaluación perceptual GRB y cociente de contacto

Publication date: Available online 19 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Rodrigo Maximiliano Jerez
ObjetivoEl objetivo del presente trabajo es correlacionar los parámetros perceptuales de grade, roughness y breathiness de la escala GRBAS con el cociente de contacto (CQ) obtenido por medio de electroglotografía.Material y métodoSe analizaron 70 muestras de voces normales y patológicas por medio de análisis auditivo-perceptual y electroglotografía. El análisis perceptual fue llevado a cabo por dos jueces expertos en función de los parámetros grade, roughness y breathiness. Los valores de CQ fueron obtenidos por medio del sistema VoceVista Versión 3.3.7.ResultadosLos resultados demuestran correlación fuerte entre CQ y soplo (r = -0,869), mientras que, entre grado de disfonía y CQ (r = -0,567), y aspereza y CQ (r = 0,643) la correlación es media.ConclusionesEs posible establecer relaciones entre el comportamiento vibratorio de los pliegues vocales y el fenómeno resultante que percibimos auditivamente. El parámetro más relevante al respecto fue breathiness. La correlación entre grade, roughness y CQ fue más débil.ObjectiveThe aim of the present workis to correlate the perceptual parameters grade, roughness and breathiness of the GRB scale with the contact quotient (CQ) obtained by electroglotography.Material and method70 samples of normal and pathological voices were analyzed by means of auditory-perceptual analysis and electroglotography. The perceptual analysis was carried out by two expert judges depending on the parameters grade, roughness and breathiness. The CQ values were obtained through the VoceVista System Version 3.3.7.ResultsThe results show a strong correlation between CQ and breathiness (r = -0.869), whereas between grade of dysphonia and CQ (r = -0.567), and roughness and CQ (r = 0.643) the correlation is average.ConclusionsIt is possible to establish relationships between the vibrational behavior of the vocal folds and the resulting phenomenon that we perceive auditively. The most relevant parameter in this respect was breathiness. The correlation between grade, roughness and CQ was weaker.

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Perinatal complications in patients with unisutural craniosynostosis: An international multicentre retrospective cohort study

Publication date: Available online 19 August 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Martijn J. Cornelissen, Madiha Söfteland, Inge Apon, Lars Ladfors, Irene MJ. Mathijssen, Titia E. Cohen-Overbeek, Gouke J. Bonsel, Lars Kölby
PurposeCraniosynostosis may lead to hampered fetal head moulding and birth complications. To study the interaction between single suture craniosynostosis and delivery complications, an international, multicentre, retrospective cohort study was performed.Materials and MethodsAll infants born between 2006 and 2012 in the Netherlands and Sweden with sagittal or metopic suture synostosis were included. All births were included as a reference population. The primary outcome measure was rate of medically assisted labour. The secondary outcomes included method of conception, term of birth and fetal position.ResultsWe included 152 trigonocephaly patients, 272 scaphocephaly patients and 1.954.141 controls. A higher rate of assisted reproductive technology (ART) was found in patients with trigonocephaly (13%) and scaphocephaly (7%) compared to controls (3%, p<0.001). Scaphocephaly resulted in more postterm births (8% vs 4%, p<0.001). Trigonocephaly patients showed more preterm births (11% vs 6%, p<0.001), breech position was more frequent (10% vs 4%, p=0.003) and labour was more often induced. Rate of assisted delivery, including cesarean section, was significantly higher in both patient groups.ConclusionsScaphocephaly leads to more postterm births and an increased rate of cesarean sections. Trigonocephaly is related to ART, and in addition higher rates of breech position and cesarean section are found. Prenatal detection of single suture craniosynostosis could improve perinatal care.

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Trends in antibiotic prescribing by dental practitioners in Germany

Publication date: Available online 19 August 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Frank Halling, Andreas Neff, Paul Heymann, Thomas Ziebart
PurposeTo analyze the structure of antibiotic prescriptions by dentists in Germany during a time-period of four years in relation to medical antibiotic prescriptions.Materials and methodsWe collected nationwide data from all statutory health insurances on dental prescriptions of systemic antibiotics from 2012 to 2015. The annual reports of the "Research Institute for Local Health Care Systems" (WIdO, Berlin) provided the basis for this longitudinal data base analysis. The types of antibiotics, the number of prescriptions and the prescribed 'defined daily doses' (DDD) were analyzed. The results were compared to antibiotic prescriptions of German physicians.ResultsAn average of 8.8% per year of all antibiotic prescriptions are issued by dentists. The mostly prescribed antibiotic is amoxicillin. The share of amoxicillin on all dental prescriptions increased from 35.6% in 2012 to 45.8% in 2015 (p<0.01). About three-quarters of all dentally prescribed DDD can be attributed to amoxicillin and clindamycin. On the part of the physicians the proportion of clindamycin is 18fold lower than in the dental field.ConclusionsDental and medical antibiotic prescriptions in Germany show statistically significant differences regarding the shares of the prescribed antibiotics. In an international comparison the high proportion of Clindamycin in Germany is noticeable.

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Effects of low-level laser therapy and platelet concentrate on bone repair: Histological, histomorphometric, immunohistochemical, and radiographic study

Publication date: Available online 19 August 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Thiago Hoffman Jonasson, Rafael Zancan, Lucas de Azevedo Oliveira, Ana Claudia Fonseca, Marcela Claudino da Silva, Allan Fernando Giovanini, João Cesar Zielak, Melissa Rodrigues de Araujo
PurposeLow-level laser therapy (LLLT) can increase bone metabolism, cell proliferation, and maturation, and reduce inflammation, while platelet concentrate (PC) assists bone healing process by releasing proteins and growth factors. Here, we evaluated the efficacy of combined LLLT and PC therapy in the healing of critical-size bone defects.Materials and MethodsCalvarial critical-size defects 5 mm in diameter were made in 48 Wistar rats. Bones were removed, milled, and used as autogenous bone grafts. Animals were randomized into four groups: LP (LLLT+PC), PC, L (LLLT), and C (control, autogenous graft only). Animals were sacrificed at day 30 and 60 post-surgery. Specimens were submitted to radiographic (digital and conventional), histological, histomorphometric, and immunohistochemical analyses.ResultsDigital radiography was shown to be a better image analysis method compared with conventional radiography. Histological analysis demonstrated a significant difference in bone formation between animals in group L (p=0.049) at day 60 than in other groups. Higher rates of inflammatory infiltrates and fibrosis were observed in the LP and PC groups at days 30 and 60, whereas the groups not receiving PC showed a higher rate of bone maturity. The inflammatory processes were reduced in the animals in the L group, together with new bone formation and maturation. Groups L and C had higher scores of positive osteocalcin immunostaining in bone and extracellular matrix.ConclusionsLLLT reduces inflammation and contributes to increased bone formation. PC treatment was shown to maintain connective tissue and to induce fibrosis during bone repair. Combined LLLT and PC treatment did not improve bone repair.

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Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts

Publication date: Available online 19 August 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Maria José H. Nagata, Michel R. Messora, Cristina Antoniali, Stephen E. Fucini, Natália de Campos, Natália M. Pola, Carolina S. Santinoni, Flávia A.C. Furlaneto, Edilson Ervolino

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Determining the fate of cranial sutures after surgical correction of non-syndromic craniosynostosis

Publication date: Available online 19 August 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): So Young Kim, Hyung-Jin Shi, So Young Lim
Purpose"Secondary craniosynostosis" (SCS) refers to a loss of sutures after corrective vault reconstruction. There are no prior studies that comprehensively review SCS in various types of non-syndromic craniosynostosis. We assessed idiopathic and iatrogenic SCS using 3-dimensional computed tomography (3D CT). We also performed a systematic review to estimate the overall incidence of SCS in each craniosynostosis type, and to characterize its clinical features.Materials and MethodsWe retrospectively reviewed the CT images of patients who underwent surgical correction of craniosynostosis for all types of craniosynostosis between August 1999 and December 2015. A literature search of the Medline and Ovid databases was conducted in October 2016 using the search term "secondary craniosynostosis."ResultsIn our series, iatrogenic SCS was observed in all patients who had manipulated normal patent sutures to variable extents. Three (17.6%) cases of idiopathic SCS developed on sagittal sutures, and were confirmed with a 12-month follow-up CT. In a pooled analysis of 10 articles, overall SCS developed in 123 of 1205 patients (10.2%). Iatrogenic SCS cases made up 87 of 1205 cases (7.2%), whereas 38 (3.1%) were idiopathic. Idiopathic SCS most commonly developed at the bi-coronal suture (n = 32, 84.2%), followed by the sagittal suture (n = 4, 10.5%) and uni-coronal suture (n = 1, 2.6%).ConclusionThis is the first review not only to describe SCS in all types of non-syndromic craniosynostosis, but also to classify SCS into iatrogenic and idiopathic types based on the underlying pathogenesis.

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Perinatal complications in patients with unisutural craniosynostosis: An international multicentre retrospective cohort study

Trends in antibiotic prescribing by dental practitioners in Germany

Effects of low-level laser therapy and platelet concentrate on bone repair: Histological, histomorphometric, immunohistochemical, and radiographic study

Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts

Determining the fate of cranial sutures after surgical correction of non-syndromic craniosynostosis

Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11)

Abstract

Background

We evaluated circulating levels of immunosuppressive regulatory T cells (T_regs) and other lymphocyte subsets in patients with newly diagnosed medulloblastoma (MBL) undergoing surgery compared to a control cohort of patients undergo craniectomy for correction of Chiari malformation (CM) and further determined the impact of standard irradiation and chemotherapy on this cell population.

Methods

Eligibility criteria for this biologic study included age 4–21 years, patients with CM undergoing craniectomy (as non-malignant surgical controls) and receiving dexamethasone for prevention of post-operative nausea, and those with newly diagnosed posterior fossa tumors (PFT) undergoing surgical resection and receiving dexamethasone as an anti-edema measure. Patients with confirmed MBL were also followed for longitudinal blood collection and analysis during radiotherapy and chemotherapy.

Results

A total of 54 subjects were enrolled on the study [22-CM, 18-MBL, and 14-PFT]. Absolute number and percentage T_regs (defined as CD4⁺CD25⁺FoxP3⁺CD127^low/−) at baseline were decreased in MBL and PFT compared to CM [p = 0.0016 and 0.001, respectively). Patients with MBL and PFT had significantly reduced overall CD4⁺ T cell count (p = 0.0014 and 0.0054, respectively) compared to those with CM. Radiation and chemotherapy treatment in patients with MBL reduced overall lymphocyte counts; however, within the CD4⁺ T cell compartment, T_regs increased during treatment but gradually declined post therapy.

Conclusions

Our results demonstrate that patients with MBL and PFT exhibit overall reduced CD4⁺ T cell counts at diagnosis but not an elevated proportion of T_regs. Standard treatment exacerbates lymphopenia in those with MBL while enriching for immunosuppressive T_regs over time.

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Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11)

Abstract

Background

Methods

Results

Conclusions

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Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11)

Abstract

Background

Methods

Results

Conclusions

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Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11)

Abstract

Background

Methods

Results

Conclusions

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Awakening immunity against cancer: a 2017 primer for clinicians

Ovarian cancer recurrence and early detection: may HE4 play a key role in this open challenge? A systematic review of literature

Abstract

Despite the improvement in overall survival for ovarian cancer (OC) patients, a fraction of patients with advanced-stage disease fails to respond to primary therapy and relapses in 70% of cases. For this reason, new predictive and monitoring tools are needed to identify OC recurrence and new biomarkers were studied, among which human epididymis 4 (HE4), primarily expressed in the reproductive and respiratory tracts, is one of the most promising, reporting a good sensitivity and specificity in detecting OC, overcoming the traditional role of carbohydrate antigen 125 (CA-125). In this review, we aim to discuss the latest evidence reported in the literature about the use of HE4 to monitor ovarian cancer treatment and to detect OC recurrence. We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library) from January 1952 to June 2017. The search identified seven papers in line with eligibility criteria for this systematic review; all of them demonstrated a good performance of HE4 in OC recurrence. The challenge to anticipate the diagnosis of OC recurrence and to translate this early diagnosis of relapse in a survival and quality of life improvement is still open, and as reported in this review, HE4 may play a key role in this scenario. More studies are needed to validate and reinforce the role of HE4 in ovarian cancer recurrence and in its early detection.

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Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine

Abstract

Purpose

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. While the alkylating agent temozolomide (TMZ) has prolonged overall survival, resistance evolution represents an important clinical problem. Therefore, we studied the effectiveness of radiotherapy and CCNU in an in vitro model of acquired TMZ resistance.

Methods

We studied the MGMT-methylated GBM cell line U251 and its in vitro derived TMZ-resistant subline, U251/TMZ-R. Cytotoxicity of TMZ, CCNU, and radiation was tested. Both cell lines were analyzed for MGMT promotor status and expression of mismatch repair genes (MMR). The influence of MMR inhibition by cadmium chloride (CdCl₂) on the effects of both drugs was evaluated.

Results

During the resistance evolution process in vitro, U251/TMZ-R developed MMR deficiency, but MGMT status did not change. U251/TMZ-R cells were more resistant to TMZ than parental U251 cells (cell viability: 92.0% in U251/TMZ-R/69.2% in U251; p = 0.032) yet more sensitive to CCNU (56.4%/80.8%; p = 0.023). The effectiveness of radiotherapy was not reduced in the TMZ-resistant cell line. Combination of CCNU and TMZ showed promising results for both cell lines and overcame resistance. CdCl₂-induced MMR deficiency increased cytotoxicity of CCNU.

Conclusion

Our results confirm MMR deficiency as a crucial process for resistance evolution to TMZ. MMR-deficient TMZ-resistant GBM cells were particularly sensitive to CCNU and to combined CCNU/TMZ. Effectiveness of radiotherapy was preserved in TMZ-resistant cells. Consequently, CCNU might be preferentially considered as a treatment option for recurrent MGMT-methylated GBM and may even be suitable for prevention of resistance evolution in primary treatment.

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Assessment of an air pollution monitoring network to generate urban air pollution maps using Shannon information index, fuzzy overlay, and Dempster-Shafer theory, A case study: Tehran, Iran

Publication date: October 2017
Source:Atmospheric Environment, Volume 167
Author(s): Parham Pahlavani, Hossein Sheikhian, Behnaz Bigdeli
Air pollution assessment is an imperative part of megacities planning and control. Hence, a new comprehensive approach for air pollution monitoring and assessment was introduced in this research. It comprises of three main sections: optimizing the existing air pollutant monitoring network, locating new stations to complete the coverage of the existing network, and finally, generating an air pollution map. In the first section, Shannon information index was used to find less informative stations to be candidate for removal. Then, a methodology was proposed to determine the areas which are not sufficiently covered by the current network. These areas are candidates for establishing new monitoring stations. The current air pollution monitoring network of Tehran was used as a case study, where the air pollution issue has been worsened due to the huge population, considerable commuters' absorption and topographic barriers. In this regard, O3, NO, NO2, NOx, CO, PM10, and PM2.5 were considered as the main pollutants of Tehran. Optimization step concluded that all the 16 active monitoring stations should be preserved. Analysis showed that about 35% of the Tehran's area is not properly covered by monitoring stations and about 30% of the area needs additional stations. The winter period in Tehran always faces the most severe air pollution in the year. Hence, to produce the air pollution map of Tehran, three-month of winter measurements of the mentioned pollutants, repeated for five years in the same period, were selected and extended to the entire area using the kriging method. Experts specified the contribution of each pollutant in overall air pollution. Experts' rankings aggregated by a fuzzy-overlay process. Resulted maps characterized the study area with crucial air pollution situation. According to the maps, more than 45% of the city area faced high pollution in the study period, while only less than 10% of the area showed low pollution. This situation confirms the need for effective plans to mitigate the severity of the problem. In addition, an effort made to investigate the rationality of the acquired air pollution map respect to the urban, cultural, and environmental characteristics of Tehran, which also confirmed the results.

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Conidiobolomycosis: An Unusual Fungal Disease—Our Experience

Abstract

Conidiobolomycosis is a rare mycotic disease caused by Conidiobolus coronatus. Very few cases have been reported in English literature. Often it is clinically misdiagnosed as soft tissue tumour. A prospective case study was done from 2006 to 2015 in a tertiary care hospital of West Bengal, India. The objectives of our study were to describe the epidemiological and clinical features and treatment of Conidiobolomycosis to prevent disfigurement. Patients clinically suspected to be suffering from Conidiobolomycosis were subjected to biopsy followed by histopathological and mycological examinations. Then they were treated with oral saturated solution of potassium iodide along with other drugs. Total six cases were histopathologically proved to be suffering from Conidiobolomycosis. Fungus was isolated and identified in one case. Complete resolution was seen in five patients. Conidiobolomycosis should be brought into mind as differential diagnosis of subcutaneous swelling in the rhinofacial region.

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Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine

Abstract

Purpose

Methods

Results

Conclusion

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Downregulation of SMARCB1 /INI1 expression in pediatric chordomas correlates with upregulation of miR-671-5p and miR-193a-5p expressions

Abstract

Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs). Although mutation/loss of 22q has strongly established the loss of SMARCB1/INI1 in cancers, the cause in CCs remains elusive. Recent studies suggest role of miRNAs in regulation of SMARCB1/INI1 expressions. We examined 5 reported/target predicted miRNAs to SMARCB1/INI1 in SMARCB1/INI1 immunonegative and immunopositive cases, and found upregulation of miR-671-5p and miR-193a-5p in SMARCB1/INI1-immunonegative cases. Notably, these two miRNAs were significantly predicted to target TGF-β signaling, suggestive of dysregulation of developmental and osteoblast regulation pathway in CCs. Overall, we suggest miR-671-5p- and miR-193a-5p-mediated epigenetic mode of SMARCB1/INI1 loss and downregulated TGF-β pathway in CCs.

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Effects of cavity reconstruction on morbidity and quality of life after canal wall down tympanoplasty

Publication date: Available online 19 August 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Sinan Uluyol, Omer Ugur, Ilker Burak Arslan, Ozlem Yagiz, Murat Gumussoy, Ibrahim Cukurova
IntroductionCanal wall down (CWD) tympanomastoidectomy is commonly used to treat advanced chronic otitis media or cholesteatoma. The advantages of CWD mastoidectomy are excellent exposure for disease eradication and postoperative control of residual disease; its disadvantages include the accumulation of debris requiring life-long otological maintenance and cleaning, continuous ear drainage, fungal cavity infections, and the occurrence of dizziness and vertigo by changing temperature or pressure.ObjectiveTo evaluate whether cavity-induced problems can be eliminated and patient comfort can be increased with mastoid cavity reconstruction.MethodsIn total, 11 patients who underwent mastoid cavity reconstruction between March 2013 and June 2013 comprised the study group, and 11 patients who had dry, epithelialized CWD cavities were recruited as the control group. The study examined three parameters: epithelial migration, air caloric testing, and the Glasgow Benefit Inventory (GBI). Epithelial migration, air caloric testing, and the GBI were studied in the study and control groups.ResultsThe epithelial migration rate was significantly faster in study group (1.63±0.5mm/week) than control group (0.94±0.37mm/week) (p=0.003, p<0.05). The mean slow component velocity of nystagmus of the study group (13.33±5.36°/s) was significantly lower when compared to control group (32.11±9.12°/s) (p=0.018). The overall GBI score was −7.21, and the general subscale, physical and social health scores were −9.71, −21.09, and +20.35, respectively in the control group. These were +33.93, +35.59, +33.31, and +29.61, respectively in the study group. All but the social health score improved significantly (0.007, 0.008, 0.018, and 0.181, respectively).ConclusionsCavity reconstruction improves epithelial migration, normalizes caloric responses and increases the quality of life. Thus, cavity rehabilitation eliminates open-cavity-induced problems by restoring the functional anatomy of the ear.

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Conidiobolomycosis: An Unusual Fungal Disease—Our Experience

Abstract

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Interlaboratory variability of Ki67 staining in breast cancer

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): Cornelia M. Focke, Horst Bürger, Paul J. van Diest, Kai Finsterbusch, Doreen Gläser, Eberhard Korsching, Thomas Decker
BackgroundPostanalytic issues of Ki67 assessment in breast cancers like counting method standardisation and interrater bias have been subject of various studies, but little is known about analytic variability of Ki67 staining between pathology labs. Our aim was to study interlaboratory variability of Ki67 staining in breast cancer using tissue microarrays (TMAs) and central assessment to minimise preanalytic and postanalytic influences.MethodsThirty European pathology labs stained serial slides of a TMA set of breast cancer tissues with Ki67 according to their routine in-house protocol. The Ki67-labelling index (Ki67-LI) of 70 matched samples was centrally assessed by one observer who counted all cancer cells per sample. We then tested for differences between the labs in Ki67-LI medians by analysing variance on ranks and in proportions of tumours classified as luminal A after dichotomising oestrogen receptor–positive cancers into cancers showing low (<14%, luminal A) and high (≥14%, luminal B HER2 negative) Ki67-LI using Cochran's Q.ResultsSubstantial differences between the 30 labs were indicated for median Ki67-LI (0.65%–33.0%, p < 0.0001) and proportion of cancers classified as luminal A (17%–57%, p < 0.0001). The differences remained significant when labs using the same antibody (MIB-1, SP6, or 30-9) were analysed separately or labs without prior participation in external quality assurance programs were excluded (p < 0.0001, respectively).ConclusionSubstantial variability in Ki67 staining of breast cancer tissue was found between 30 routine pathology labs. Clinical use of the Ki67-LI for therapeutic decisions should be considered only fully aware of lab-specific reference values.

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Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): Sebastian May-Wilson, Amit Sud, Philip J. Law, Kimmo Palin, Sari Tuupanen, Alexandra Gylfe, Ulrika A. Hänninen, Tatiana Cajuso, Tomas Tanskanen, Johanna Kondelin, Eevi Kaasinen, Antti-Pekka Sarin, Johan G. Eriksson, Harri Rissanen, Paul Knekt, Eero Pukkala, Pekka Jousilahti, Veikko Salomaa, Samuli Ripatti, Aarno Palotie, Laura Renkonen-Sinisalo, Anna Lepistö, Jan Böhm, Jukka-Pekka Mecklin, Nada A. Al-Tassan, Claire Palles, Susan M. Farrington, Maria N. Timofeeva, Brian F. Meyer, Salma M. Wakil, Harry Campbell, Christopher G. Smith, Shelley Idziaszczyk, Timothy S. Maughan, David Fisher, Rachel Kerr, David Kerr, Michael N. Passarelli, Jane C. Figueiredo, Daniel D. Buchanan, Aung K. Win, John L. Hopper, Mark A. Jenkins, Noralane M. Lindor, Polly A. Newcomb, Steven Gallinger, David Conti, Fred Schumacher, Graham Casey, Lauri A. Aaltonen, Jeremy P. Cheadle, Ian P. Tomlinson, Malcolm G. Dunlop, Richard S. Houlston
BackgroundWhile dietary fat has been established as a risk factor for colorectal cancer (CRC), associations between fatty acids (FAs) and CRC have been inconsistent. Using Mendelian randomisation (MR), we sought to evaluate associations between polyunsaturated (PUFA), monounsaturated (MUFA) and saturated FAs (SFAs) and CRC risk.MethodsWe analysed genotype data on 9254 CRC cases and 18,386 controls of European ancestry. Externally weighted polygenic risk scores were generated and used to evaluate associations with CRC per one standard deviation increase in genetically defined plasma FA levels.ResultsRisk reduction was observed for oleic and palmitoleic MUFAs (OROA = 0.77, 95% CI: 0.65–0.92, P = 3.9 × 10⁻³; ORPOA = 0.36, 95% CI: 0.15–0.84, P = 0.018). PUFAs linoleic and arachidonic acid had negative and positive associations with CRC respectively (ORLA = 0.95, 95% CI: 0.93–0.98, P = 3.7 × 10⁻⁴; ORAA = 1.05, 95% CI: 1.02–1.07, P = 1.7 × 10⁻⁴). The SFA stearic acid was associated with increased CRC risk (ORSA = 1.17, 95% CI: 1.01–1.35, P = 0.041).ConclusionResults from our analysis are broadly consistent with a pro-inflammatory FA profile having a detrimental effect in terms of CRC risk.

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Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil–cisplatin regimen in oesophageal cancer

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): C. Bascoul-Mollevi, S. Gourgou, M.-P. Galais, J.-L. Raoul, O. Bouché, J.-Y. Douillard, A. Adenis, P.-L. Etienne, B. Juzyna, L. Bedenne, T. Conroy
BackgroundA recent prospective randomised trial did not reveal significant differences in median progression-free survival between two chemoradiotherapy (CRT) regimens for inoperable non-metastatic oesophageal cancer patients. This secondary analysis aimed to describe the impact of CRT on health-related quality of life (HRQOL), physical functioning, dysphagia, fatigue and pain and to evaluate whether baseline HRQOL domains can predict overall survival.Patients and methodsA total of 267 patients were randomly assigned to receive with 50 Gy of radiotherapy in 25 fractions six cycles of FOLFOX or four cycles of fluorouracil and cisplatin on day 1. HRQOL was prospectively assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 with the oesophageal cancer module (QLQ-OES18).ResultsBoth groups showed high baseline compliance. Subsequently, compliance reduced to 41% at the 6-month follow-up. Baseline HRQOL scores showed no statistical differences between treatment arms. During treatment, both groups exhibited lower physical and social functioning and increased fatigue and dyspnoea, although dysphagia moderately improved in the fluorouracil–cisplatin arm only (p = 0.047).During follow-up, HRQOL scores revealed no significant differences between chemotherapy regimens. Linear mixed model exhibited a treatment-by-time interaction effect for dysphagia (p = 0.017) with a greater decrease in dysphagia in the fluorouracil–cisplatin group. Time until definitive deterioration analysis showed no significant differences in global HRQOL, functional or main symptom domains. However, time until definitive deterioration was significantly longer for the fluorouracil and cisplatin arm compared with FOLFOX for appetite loss (p = 0.002), QLQ-OES-18 pain (p = 0.008), trouble swallowing saliva (p = 0.011) and trouble talking (p = 0.020).ConclusionAnalyses of HRQOL scores revealed no statistically significant differences between patients with inoperable non-metastatic oesophageal cancer treated by FOLFOX versus those treated with a fluorouracil–cisplatin regimen as part of definitive CRT.

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A geographic information system-based method for estimating cancer rates in non-census defined geographical areas

Abstract

Purpose

To address locally relevant cancer-related health issues, health departments frequently need data beyond that contained in standard census area-based statistics. We describe a geographic information system-based method for calculating age-standardized cancer incidence rates in non-census defined geographical areas using publically available data.

Methods

Aggregated records of cancer cases diagnosed from 2009 through 2013 in each of Chicago's 77 census-defined community areas were obtained from the Illinois State Cancer Registry. Areal interpolation through dasymetric mapping of census blocks was used to redistribute populations and case counts from community areas to Chicago's 50 politically defined aldermanic wards, and ward-level age-standardized 5-year cumulative incidence rates were calculated.

Results

Potential errors in redistributing populations between geographies were limited to <1.5% of the total population, and agreement between our ward population estimates and those from a frequently cited reference set of estimates was high (Pearson correlation r = 0.99, mean difference = −4 persons). A map overlay of safety-net primary care clinic locations and ward-level incidence rates for advanced-staged cancers revealed potential pathways for prevention.

Conclusions

Areal interpolation through dasymetric mapping can estimate cancer rates in non-census defined geographies. This can address gaps in local cancer-related health data, inform health resource advocacy, and guide community-centered cancer prevention and control.

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Can complementary medicine increase adherence to chemotherapy dosing protocol? A controlled study in an integrative oncology setting

Abstract

Context and objectives

The impact of complementary and integrative medicine (CIM) on adherence to chemotherapy regimens is unclear. We explored the effect of patient-tailored CIM treatments on the relative dose intensity (RDI) of chemotherapy among patients with breast and gynecological cancer.

Methods

Chemotherapy-treated patients with breast or gynecological cancer were referred by their oncology healthcare professional to a CIM treatment program. Adherence to integrative care (AIC) was defined as ≥4 CIM treatments, with ≤30 days between each treatment. Relative dose intensity (RDI) of chemotherapy was compared between CIM-treated patients and controls, and among adherence sub-groups.

Results

RDI was calculated for 106-treated patients (62 AIC) and 75 controls. Baseline-to-6-week RDI values were similar in both study arms, with a lower % RDI <1.0 among controls at 12 weeks (47 vs. 57.5%; P = 0.036). Adherence sub-groups had similar RDI values, though at 6 weeks, the AIC group had lower % RDI <1.0 (33.9 vs. 54.5%, P = 0.046). Total administered medication dose/planned dose was higher in the AIC group at 6 weeks for paclitaxel (82%/50%, P = 0.025) and carboplatin (87%/67%, P = 0.028), with no difference in cytoxan/adriamycin dosages.

Conclusion

A patient-tailored CIM program for patients with breast or gynecological cancer may be associated with a lower percentage of reduced RDI at 6 weeks, this in a sub-group of patients with higher adherence to CIM, and for specific chemotherapy agents, though this benefit did not persist after 12 weeks. Further research is needed to better understand the impact of CIM in cancer care.

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Simulation for Assessment of Milestones in Emergency Medicine Residents

Abstract

Introduction

All residency programs in the United States are required to report their residents' progress on the Milestones to the Accreditation Council for Graduate Medical Education (ACGME) biannually. Since the development and institution of this competency-based assessment framework, residency programs have been attempting to ascertain the best ways to assess resident performance on these metrics. Simulation was recommended by the ACGME as one method of assessment for many of the milestone subcompetencies. We developed 3 simulation scenarios with scenario specific Milestone based assessment tools. We aimed to gather validity evidence for this tool.

Methods

We conducted a prospective observational study to investigate the validity evidence for 3 mannequin-based simulation scenarios for assessing individual residents on Emergency Medicine (EM) milestones. The subcompetencies (i.e. PC1, PC2, PC3) included were identified via a modified Delphi technique using a group of experienced EM simulationists. The scenario specific checklist items were designed based on the individual milestone items within each EM subcompetency chosen for assessment and reviewed by experienced EM simulationists. Two independent live raters who were EM faculty at the respective study sites scored each scenario following brief rater training. The interrater reliability (IRR) of the assessment tool was determined by measuring intraclass correlation coefficient (ICC) for the sum of the checklist (CL) items as well as the global rating scales (GRS) for each scenario. Comparing GRS and CL scores between various PGY levels was performed with ANOVA.

Results

Eight subcompetencies were chosen to assess with 3 simulation cases, using 118 subjects. Evidence of test content, internal structure, response process and relations with other variables were found. The ICCs for the sum of the CL items and the GRSs were > 0.8 for all cases, with one exception (clinical management GRS 0.74 in sepsis case). The Sum of Checklist items and GRSs (p<0.05) discriminated between post graduate (PGY) levels on all cases. However, when the specific CL items were mapped back to milestones in various proficiency levels, the milestones in the higher proficiency levels (level 3 & 4) did not often discriminate between various PGY levels. Level 3 milestone items discriminated between PGY levels on 5 out of 12 occasions they were assessed, and Level 4 items discriminated only 2 out of 12 times they were assessed.

Conclusion

Three simulation cases with scenario specific assessment tools allowed evaluation of EM residents on proficiency levels 1-4 within 8 of the EM Milestone subcompetencies. Evidence of test content, internal structure, response process and relations with other variables were found. Good to excellent IRR and the ability to discriminate between various PGY levels was found for both the sum of CL items and GRSs. However, there was a lack of a positive relationship between advancing PGY level and the completion of higher level milestone items (levels 3 and 4).

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Prospective Validation of a Clinical Score for Males Presenting with an Acute Scrotum

Abstract

Objective

To validate the Testicular Workup for Ischemia and Suspected Torsion (TWIST) score among pediatric emergency medicine providers for the evaluation of pediatric males presenting with testicular pain and swelling (acute scrotum).

Methods

We conducted a prospective cohort study of males 3 months to 18 years old presenting with an acute scrotum. History and physical examination findings, including components of the TWIST score (hard testicle, absent cremasteric reflex, nausea/vomiting, and high riding testicle) as well as diagnostic results (ultrasound, urine, sexually transmitted infection (STI) testing) were recorded. Testicular torsion was confirmed by surgical exploration. Frequencies of patient characteristics, TWIST components, and tests were calculated. We performed the kappa statistic for inter-rater reliability and calculated the test characteristics and receiver operator curves for the TWIST score (range 0-7).

Results

During the study period 258 males were enrolled in the study; 19 (7.4%) had testicular torsion. The mean age was 9.8 years (± 0.3 years). The high-risk TWIST score of 7 had 100% specificity (95% confidence interval (CI) 98%, 100%) with 100% positive predictive value (95% CI 40%, 100%) for testicular torsion. The area under the curve was 0.82. The kappa statistic for the overall TWIST score was fair at 0.39.

Conclusions

In this prospective validation of the TWIST score among pediatric emergency providers, the high-risk score demonstrated strong test characteristics for testicular torsion. The TWIST score could be used as part of a standardized approach for evaluation of the pediatric acute scrotum to provide more efficient and effective care.

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Expansion of blood IgG4+ Bcells, Th2 and Tregulatory cells in IgG4-related disease

Publication date: Available online 19 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Jorn J. Heeringa, A. Faiz Karim, Jan A.M. van Laar, Robert M. Verdijk, Dion Paridaens, P. Martin van Hagen, Menno C. van Zelm
BackgroundIgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition affecting various organs and has a diverse clinical presentation. Fibrosis and accumulation of IgG4+ plasma cells in tissue are hallmarks of the disease and IgG4-RD is associated with elevated IgG4 serum levels. However, disease pathogenesis is still unclear and these cellular and molecular parameters are neither sensitive nor specific for diagnosis of IgG4-RD.ObjectiveWe here sought to develop a flowcytometric gating strategy to reliably identify blood IgG4+ B-cells to study their cellular and molecular characteristics and investigate their contribution in disease pathogenesis.MethodsSixteen patients with histologically confirmed IgG4-RD, 11 patients with sarcoidosis and 30 healthy individuals were included for 11-color flowcytometric analysis of peripheral blood for IgG4-expressing B cells and T-helper (Th) subsets. In addition, detailed analysis of activation markers and chemokine receptors was performed on IgG4-expressing B cells and IgG4 transcripts were analyzed for somatic hypermutations.ResultsCellular and molecular analyses revealed increased numbers of blood IgG4+ memory B-cells in patients with IgG4-RD. These cells showed reduced expression of CD27 and CXCR5 and increased signs of antibody maturation. Furthermore, IgG4-RD patients, but not patients with sarcoidosis, had increased numbers of circulating plasma blasts and CD21^low B-cells, as well as Th2 and regulatory T-cells, indicating of a common disease pathogenesis in IgG4-RD.ConclusionThese results provide new insights into the dysregulated IgG4 response in patients with IgG4-RD. A specific "peripheral lymphocyte signature" observed in patients with IgG4-RD, could support diagnosis and treatment monitoring.

Teaser

We here provide new insights into IgG4+ B-cells, and how their detection contributes to diagnosis and monitoring of treatment success in patients with IgG4-related disease.

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Corrigendum to “The Relationship between Population T4/TSH Set Point Data and T4/TSH Physiology”

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Hypermetabolic Thyroid Incidentaloma on Positron Emission Tomography: Review of Laboratory, Radiologic, and Pathologic Characteristics

Introduction. Incidental hypermetabolic thyroid lesions on Positron Emission Tomography have significant clinical value and may harbor malignancy. In this study we evaluated laboratory, radiologic, and pathologic characteristics of incidental hypermetabolic thyroid lesions. Materials and Methods. We evaluated 18 patients prospectively with various malignancies and hypermetabolic thyroid incidentaloma. The thyroid function tests, ultrasound assessment, and guided FNA biopsy were performed on all cases. Results. We included 9 male and 9 female patients with mean age of 51 years. Most common malignancy was colon cancer. Metabolic activity quantification using maximum standard uptake value demonstrated range between 1.4 and 65.4 with mean value of 9.4. We found highest metabolic activity in patients with lung adenocarcinoma, B-cell lymphoma, and colon adenocarcinoma. On ultrasound exam most thyroid lesions were of solid, hypoechoic, noncalcified nature with either normal or peripheral increased vascularity. FNA biopsy report was benign in 15 cases and malignant or highly suggestive for malignancy in 3 other cases. Two of the three malignant cases demonstrated metabolic activity higher than average SUV max. Conclusion. Most thyroid hypermetabolic incidentalomas are benign lesions, while higher values of SUV max are in favor of malignancy. This mandates further evaluation of incidentally found thyroid hypermetabolic lesions on routine PET/CT scans.

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Awakening immunity against cancer: a 2017 primer for clinicians

Abstract

Cancer immunotherapy has finally joined the pillars of cancer treatment—surgery, radiation, chemotherapy, hormonal therapy, and targeted therapy—in improving cancer patient lives. In the last 5 years, the development of immune checkpoint inhibitor and T cell therapy, particularly chimeric antigen receptor (CAR) T-cell therapy, has been remarkable for the speed, scale, and number of drug approvals. Still, these treatments may also bring unusual adverse effects and clinical outcomes including unprecedented long-term survival. Interrogating the tumor microenvironment and identifying better biomarkers hold the key to improving cancer immunotherapies. CAR T-cell therapy has dramatic effect on leukemias and lymphomas with significant cure rates, but has yet to show comparable effect on solid tumors. Cutting-edge technology will improve both processing and clinical effect of such therapies. Asia has the largest, most rapidly aging population and the largest number of cancer patients in the world. Research and development and clinical trial conduct of cancer immunotherapy in Asia remain nascent, but should be a crucial priority.

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The effect of thyroid autoantibody positivity on the functions of internal ear.

The effect of thyroid autoantibody positivity on the functions of internal ear.

Eur Arch Otorhinolaryngol. 2017 Aug 18;:

Authors: Gunes A, Karakus MF, Telli TA, Gunes NA, Mutlu M

Abstract
The objective of the study is to investigate if any significant difference exists in hearing thresholds and tympanometric examination results among patients whose thyroid antibody positivity was detected approximately 1 year or at least 5 years ago. Study population aged less than 40 years consisted of 17 patients who had thyroid antibody positivities for an average of 1 year (first group), 15 patients who were followed up for at least 5 years for thyroid antibody positivity (second group), and 18 volunteers (third group). Tympanometric examination results, stapes reflex, SRT, SD, and pure tone values were examined. When the second group and the third group were compared, significant results were obtained at hearing frequencies between 500 and 4000 Hz. When the first group and the third group were compared, only at 1000 Hz threshold significant results were obtained. During evaluation of hearing frequencies between 250 and 8000 Hz, significant results were not observed between the second group and the first group. When the first and the second groups were compared with the control group, significant results were obtained as for tympanometric examination findings and significant results were not observed between the second group and the first group. A significant difference was not detected as for the results of stapes reflex. Since thyroid antibody positivity affects the functions of internal ear, these patients should be more closely monitored. Since these effects become deeper in line with increased exposure to autoantibody positivity, variations in auditory responses should be more attentively monitored.

PMID: 28821945 [PubMed - as supplied by publisher]

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Whole-exome sequencing to identify the cause of congenital sensorineural hearing loss in carriers of a heterozygous GJB2 mutation.

Whole-exome sequencing to identify the cause of congenital sensorineural hearing loss in carriers of a heterozygous GJB2 mutation.

Eur Arch Otorhinolaryngol. 2017 Aug 18;:

Authors: Parzefall T, Frohne A, Koenighofer M, Kirchnawy A, Streubel B, Schoefer C, Frei K, Lucas T

Abstract
Bi-allelic variations in the gap junction protein beta-2 (GJB2) gene cause up to 50% of cases of newborn hearing loss. Heterozygous pathogenic GJB2 variations are also fivefold overrepresented in idiopathic patient groups compared to the normal-hearing population. Whether hearing loss in this group is due to unidentified additional variations within GJB2 or variations in other deafness genes is unknown in most cases. Whole-exome sequencing offers an effective approach in the search for causative variations in patients with Mendelian diseases. In this prospective genetic cohort study, we initially investigated a family of Turkish origin suffering from congenital autosomal recessive hearing loss. An index patient and his normal-hearing father, both bearing a single heterozygous pathogenic c.262G>T (p.Ala88Ser) GJB2 transversion as well as the normal-hearing mother were investigated by means of whole-exome sequencing. Subsequently the genetic screening was extended to a hearing-impaired cohort of 24 families of Turkish origin. A homozygous missense c.5492G>T transversion (p.Gly1831Val) in the Myosin 15a gene, previously linked to deafness, was identified as causative in the index family. This very rare variant is not listed in any population in the Genome Aggregation Database. Subsequent screening of index patients from additional families of Turkish origin with recessive hearing loss identified the c.5492G>T variation in an additional family. Whole-exome sequencing may effectively identify the causes of idiopathic hearing loss in patients bearing heterozygous GJB2 variations.

PMID: 28821934 [PubMed - as supplied by publisher]

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Profiling Cancer Risk in Oral Potentially Malignant Disorders – a Patient Cohort Study

Abstract

Background

Oral potentially malignant disorders harbour variable and unpredictable risk for squamous carcinoma development. Whilst current management strategies utilise histopathological diagnoses, dysplasia grading and targeted intervention for 'high risk' lesions, clinicians are unable to predict malignant potential.

Methods

Detailed, retrospective clinico-pathological analysis of potentially malignant lesions undergoing malignant transformation, from a 590 patient cohort treated by interventional laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was documented at study census date (31 December 2014).

Results

99 patients (16.8%) developed cancer: 71 (12%) seen 'unexpectedly' upon excision and 28 (4.8%) progressing to malignancy at a median of 87.3 months post-surgery. 30 'unexpected' excisions were micro-invasive (42.3%) arising primarily in severely dysplastic precursors (75%) at ventro-lateral tongue and floor of mouth sites (54.5%); 1 patient (1.4%) had a cancer-related death, whilst 58 (81.7%) were disease free. 19 of 28 'progressive' cancers (67.9%) arose at new sites, with erythroleukoplakia a significant predictor of malignancy (p=0.0019). 9 (32.1%) developed at the same precursor site, with 6 (77.7%) on the ventro-lateral tongue and floor of mouth. 3 (10.7%) were micro-invasive, 9 patients (32.1%) died from metastatic disease and 12 (42.9%) were disease free (p<0.001).

Conclusion

Squamous carcinoma may arise at the site of a precursor lesion as transformation or new-site development via field cancerisation. Whilst interventional surgery facilitates early diagnosis and treatment of occult disease, thus reducing risk from same-site transformation, new-site cancer is a significant long-term risk for potentially malignant disorder patients.

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Artepillin C as a targeting survivin molecule in oral squamous cell carcinoma cells in vitro: a preliminary study

Abstract

Background

Survivin, a member of the inhibitor of apoptosis family, is overexpressed in most human tumors, but undetectable in normal adult tissues. It is a promising target molecule in cancer treatment, since interference in its function promotes apoptosis. Artepillin C, a major, biologically active ingredient of Brazilian propolis, possesses anticancer activity against several cancer cells with different tissue origins. However, little is known about its bioactivity on oral squamous cell carcinoma cells or its effect on survivin expression. The aim of this study was to investigate the cytotoxic and anti-survivin activities of artepillin C in oral squamous cell carcinoma cells.

Methods

HSC-3 human oral squamous cell carcinoma cells were treated with varying doses of artepillin C for up to 72 hours. Cell viability was measured by WST-1, and the cytotoxic effects of artepillin C on HSC-3 cells were quantified with flow cytometry. The survivin levels were determined by ELISA.

Results

Artepillin C exhibited dose- and time-dependent cytotoxic effects on HSC-3 cells. Flow cytometric analysis showed that 22% of untreated HSC-3 cells underwent spontaneous cell death, whereas 77.32% of the cells were killed in response to the highest dose of artepillin C at 72 hours. Survivin expression was reduced in treated cells.

Conclusions

HSC-3 cells are vulnerable to artepillin C in a dose- and time-dependent manner. HSC-3 cell death induced by artepillin C, at least in part, was a result of a decrease in survivin levels.

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Infant Acceptance of Primary Tastes and Fat Emulsion: Developmental Changes and Links with Maternal and Infant Characteristics.

Infant Acceptance of Primary Tastes and Fat Emulsion: Developmental Changes and Links with Maternal and Infant Characteristics.

Chem Senses. 2017 Sep 01;42(7):593-603

Authors: Schwartz C, Chabanet C, Szleper E, Feyen V, Issanchou S, Nicklaus S

Abstract
Previous studies on taste acceptance have been conducted taste-by-taste and with a cross-sectional design. The aim of this study was to longitudinally evaluate the acceptance of sweet, salty, bitter, sour and umami solutions, and a fat emulsion comparatively in a birth cohort from 3 to 20 months old. The acceptance of each taste relative to water was defined using proportional variables that are based on ingestion (IR) or liking evaluated by the experimenter (LR). These data were analyzed with mixed models that accounted for age and subject effects (minimum 152 observations/age/taste; maximum 216). For saltiness, acceptance increased sharply between 3 and 12 months old. The trajectories of acceptance were parallel for sweetness, sourness, and the umami tastes between 3 and 20 months old, with sweetness being preferred. Between 12 and 20 months old, the acceptance of all tastes, except bitterness, decreased, and at 20 months old, only sweetness was not rejected. The acceptance of bitterness remained stable. For the fat emulsion, acceptance evolved from indifference to rejection. The acceptance of saltiness and umami tastes were lower in girls than boys at 20 months old. The acceptance of the fat emulsion was higher in infants who were born heavier and taller. At 20 months old, the fat emulsion acceptance was higher in infants who were born from mothers with a higher prepregnancy body mass index. Finally, the taste differential reactivity (the standard deviation of the IRs) significantly increased from 3 to 20 months old.

PMID: 28821180 [PubMed - in process]

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Pungency Evaluation of Hydroxyl-Sanshool Compounds After Dissolution in Taste Carriers Per Time-Related Characteristics.

Pungency Evaluation of Hydroxyl-Sanshool Compounds After Dissolution in Taste Carriers Per Time-Related Characteristics.

Chem Senses. 2017 Sep 01;42(7):575-584

Authors: Zhang L, Shi B, Wang H, Zhao L, Chen Z

Abstract
This study was conducted to investigate the sensory characteristics and temporal migration of hydroxyl-sanshool compounds at slight and moderate concentrations after dissolution in ethanol-water, saccharose, NaCl, and MSG via 2-AFC, time intensity (TI) and temporal dominance of sensations (TDS) methods. The pungency detection threshold (DT) was suppressed in saccharose while NaCl and MSG solutions showed no effect on pungency DT. The area under the curve (AUC) of pungency increased in NaCl and MSG solutions and decreased significantly in saccharose solution. Imax (maximal intensity) also increased in NaCl and MSG at low concentrations of hydroxyl-sanshool compounds. The temporally dominant sensations and migration of said sensations across the oral cavity differed among different carriers. Low levels of pungency compounds were characterized by tingling first in the tongue tip and ending in the lips, while moderate levels of the compound produced tingling, astringency, vibrating, and numbing from the tongue tip to the bilateral sides of the tongue, lips, palate, cheek mucosa, and surface of the tongue over time. There were significant differences in the maximum rate, peak time, and duration of any dominant sensation, as well as in the duration of sensation in the lips, tongue tip, and bilateral sides of the tongue. This study provides a dynamic profile of consuming pungent food, which provides a reference not only for the design of new food products with desirable pungency, but also as a scientific basis for the application of pungent compounds within the food and catering industry.

PMID: 28821179 [PubMed - in process]

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Αρχειοθήκη ιστολογίου

Κυριακή 20 Αυγούστου 2017

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