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Τρίτη 10 Οκτωβρίου 2017
Endobronchial Ultrasound-guided Transbronchial Needle Injection of Liposomal Amphotericin B for the Treatment of Symptomatic Aspergilloma
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The Effect of Dextromethorphan Premedication on Cough and Patient Tolerance During Flexible Bronchoscopy: A Randomized, Double-blind, Placebo-controlled Trial
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To do or not to do? Plasma exchange and timing of steroid administration in PML
ABSTRACT
Objective: To retrospectively analyze the effect of plasma exchange (PLEX, yes=PLEX+, no=PLEX-) and steroids administration timing (prophylactically –proST- or therapeutically –therST-) on the longitudinal clinical course of patients with natalizumab related progressive multifocal leukoencephalopathy (PML) and full blown immune reconstitution inflammatory syndrome (PML-IRIS).
Methods: Clinical and radiological data of 42 Italian patients with PML were analyzed. Patient's data are available until 12 months after PML diagnosis. PLEX and steroids treatment as time-dependent covariates were entered in: i) a Cox model to investigate their impact on full blown PML-IRIS latency; ii) an ANOVA to investigate their impact on IRIS duration; iii) a linear mixed model to assess their impact on the longitudinal clinical course (measured by means of EDSS).
Results: Treatment with PLEX was not associated to PML-IRIS latency (HR=1.05, p=0.92), but once IRIS emerged, its duration was significantly longer in patients who underwent PLEX (101 vs 54 days in PLEX+ and PLEX- patients, p=0.028). Receiving proST vs therST was not associated to IRIS latency (HR=0.67, p=0.39) or duration (p=0.95). Patients who underwent proST had a significant higher EDSS increase during PML (0.09 EDSS points per month, p=0.04) as compared to those who had therST.
Interpretation: this study highlights that: i) caution on the use of PLEX should be considered as the current data do not support a beneficial effect of PLEX; ii) caution on the early use of steroids is suggested since their prophylactic use to prevent full blown PML-IRIS seems to negatively impact on the longitudinal disability course. This article is protected by copyright. All rights reserved.
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The preadolescent acne microbiome: A prospective, randomized, pilot study investigating characterization and effects of acne therapy
Abstract
Background/Objectives
Acne, a common pediatric disease, tends to be more comedonal in preadolescents, whereas older individuals are more likely to have inflammatory lesions in addition to comedones. Thus the microbiome of preadolescents may be different. In this pilot study we aimed to characterize the preadolescent acne microbiome, compare the microbiome in preadolescents with and without acne, and investigate changes in the microbiome after topical treatment with benzoyl peroxide or a retinoid in a small cohort of preadolescents.
Methods
Participants were 7-10 years of age with (intervention group) or without (control group) acne and were recruited during routine outpatient dermatology visits. Baseline questionnaires, physical examination, and pore strip application were performed for all participants. Intervention group participants were randomized to receive topical therapy with benzoyl peroxide 5% gel or cream or tretinoin 0.025% cream. Participants with acne were followed up 8-10 weeks later and pore strip application was repeated.
Results
Preadolescents with acne were colonized with a greater diversity of cutaneous bacteria than controls and the most commonly identified bacterium was Streptococcus. The number of bacterial species and phylogenetic diversity decreased after treatment with benzoyl peroxide and tretinoin.
Conclusion
The predominant bacteria in microbiome studies of adult acne is Propionibacterium, whereas in this pediatric population we saw a lot of Streptococcus bacteria. After treatment, the microbiomes of intervention group participants more closely resembled those of control group participants.
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Pediatric keloids: A 6-year retrospective review
Abstract
Background/Objectives
Keloids are reportedly rare at the extremes of life. We sought to describe the epidemiology of pediatric keloids seen at the plastic surgery outpatient department of the University College Hospital, Ibadan.
Methods
We retrospectively reviewed all children younger than 19 years who presented with nonburn keloids between 2008 and 2014. Data were obtained on age; duration, size, and location of the keloid; family history; mode of treatment; and outcome. Outcome variables were recurrence and wound complications. Data were analyzed using the Pearson chi-square test for discreet variables and the independent-sample t test for continuous variables. P < .05 was taken as statistically significant.
Results
Within the review period, 304 patients presented with keloids, of whom 40 (13.1%) were younger than 19 years. There was a female preponderance (n = 23, 57.5%). The mean age at onset of the keloid was 9.3 years (range 3 months-18 years). Thirty (75%) patients had keloids in the head and neck region. Keloids were sporadic in 31 (77.5%) patients. Nineteen (47.5%) patients had multimodal treatment for keloid. The recurrence rate was 20%. Recurrence was significantly associated with the size of the lesion (P = .003).
Conclusion
Keloids during childhood are not rare. More attention should be paid to the management of keloids in this age group.
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Agminated segmental plaque-type blue nevus associated with hypertrichosis and soft tissue hypertrophy: Report of a case and review of the literature
Abstract
Blue nevi are common skin neoplasms that typically present as asymptomatic solitary papules, although they may rarely occur in an agminated configuration. We describe a case of agminated blue nevus in a segmental facial distribution associated with soft tissue hypertrophy and hypertrichosis in a 16-year-old boy and present a review of the literature. Although they are generally considered to be benign, concurrent soft tissue changes occurring within an agminated blue nevus should be investigated thoroughly to exclude alternate diagnoses.
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Perineal groove in female infants: A case series and literature review
Abstract
Background
Perineal groove is a rare congenital malformation that is unknown to many clinicians and is often misdiagnosed. Although it may be self-resolving during childhood, this nonepithelized mucous membrane can pose the risk of local irritation and infection, particularly urinary tract infection.
Methods
A retrospective study of female infants diagnosed with a perineal groove was performed, demographic characteristics and clinical features were analyzed, and a photographic review was conducted.
Results
Five patients with perineal groove were observed in our clinic in 2015-16. The mean age was 14 months. None had symptoms, and no treatment was required. During follow-up of 1 year, all remained asymptomatic.
Conclusions
Our retrospective review suggests that perineal groove may be an underdiagnosed condition. Most cases resolve spontaneously, but confusion in diagnosis may lead to misdiagnosis or misinterpretation of sexual abuse and unnecessary treatments.
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Oral and maxillofacial manifestations of chronic kidney disease - mineral and bone disorder: a multicentric retrospective study
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Flávia Sirotheau Corrêa Pontes, Márcio Ajudarte Lopes, Lucas Lacerda de Souza, Diogo dos Santos da Mata Rezende, Alan Roger Santos-Silva, Jacks Jorge Junior, Wagner Gomes da Silva, Fábio Ramôa Pires, André Caroli Rocha, Wladimir Gushiken de Campos, Milena Coelho Fernandes Caldato, Regina Matsunaga Martin, Felipe Paiva Fonseca, Hélder Antônio Rebelo Pontes
ObjectiveTo describe the oral and maxillofacial manifestations of patients diagnosed with chronic kidney disease - mineral and bone disorders (CKD-MBD).Material and methodsOver a 13-year period, clinicopathological data of patients diagnosed with CKD-MBD who demonstrated oral and maxillofacial alterations were retrieved from the files of four Brazilian institutions. Data included clinical, radiographic, microscopic and biochemical findings, treatment employed and follow-up status.ResultsTwenty-one cases were identified, 13 cases as brown tumor of hyperparathyroidism (BTH) and 8 as osteitis fibrosa/renal osteodystrophy (OF/RO) (4 of them clinically consistent with Sagliker syndrome). The mean age was 32.7 years and the mandible was the most affected site (42.8%). OF/RO showed an ill defined "ground glass" radiographic appearance, and BTH well-defined radiolucent images. Biochemically, the following mean values were obtained: parathyroid hormone 1,511.07pg/ml, Calcium 9.25mg/dl, Phosphorus 5.19mg/dl, Alkaline phosphatase 941.55U/L, Urea 125.42mg/dL and Creatinine 7.14mg/dL. Treatment comprised vitamin D and calcium intake, parathyroidectomy, hemodialysis, renal transplantation and local surgery. During follow-up, 5 BTH patients were free of lesions, whereas 2 affected by OF/RO/Sagliker syndrome died.ConclusionsOral and maxillofacial manifestations of BTH and OF/RO are uncommon, but they can be associated with an important life threatening scenario.
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Erratum to: Delayed post-operative tension pneumocephalus and pneumorrhachis
Unfortunately, two author names were missed out in author group of the original publication.
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A guide for effective anatomical vascularization studies: useful ex vivo methods for both CT and MRI imaging before dissection
Abstract
The objective of this study was to develop a simple and useful injection protocol for imaging cadaveric vascularization and dissection. Mixtures of contrast agent and cast product should provide adequate contrast for two types of ex vivo imaging (MRI and CT) and should harden to allow gross dissection of the injected structures. We tested the most popular contrast agents and cast products, and selected the optimal mixture composition based on their availability and ease of use. All mixtures were first tested in vitro to adjust dilution parameters of each contrast agent and to fine-tune MR imaging acquisition sequences. Mixtures were then injected in 24 pig livers and one human pancreas for MR and computed tomography (CT) imaging before anatomical dissection. Colorized latex, gadobutrol and barite mixture met the above objective. Mixtures composed of copper sulfate (CuSO4) gadoxetic acid (for MRI) and iodine (for CT) gave an inhomogeneous signal or extravasation of the contrast agent. Agar did not harden sufficiently for gross dissection but appears useful for CT and magnetic resonance imaging (MRI) studies without dissection. Silicone was very hard to inject but achieved the goals of the study. Resin is particularly difficult to use but could replace latex as an alternative for corrosion instead of dissection. This injection protocol allows CT and MRI images to be obtained of cadaveric vascularization and anatomical casts in the same anatomic specimen. Post-imaging processing software allow easy 3D reconstruction of complex anatomical structures using this technique. Applications are numerous, e.g. surgical training, teaching methods, postmortem anatomic studies, pathologic studies, and forensic diagnoses.
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The biorhythm of human skeletal growth
Abstract
Evidence of a periodic biorhythm is retained in tooth enamel in the form of Retzius lines. The periodicity of Retzius lines (RP) correlates with body mass and the scheduling of life history events when compared between some mammalian species. The correlation has led to the development of the inter-specific Havers–Halberg oscillation (HHO) hypothesis, which holds great potential for studying aspects of a fossil species biology from teeth. Yet, our understanding of if, or how, the HHO relates to human skeletal growth is limited. The goal here is to explore associations between the biorhythm and two hard tissues that form at different times during human ontogeny, within the context of the HHO. First, we investigate the relationship of RP to permanent molar enamel thickness and the underlying daily rate that ameloblasts secrete enamel during childhood. Following this, we develop preliminary research conducted on small samples of adult human bone by testing associations between RP, adult femoral length (as a proxy for attained adult stature) and cortical osteocyte lacunae density (as a proxy for the rate of osteocyte proliferation). Results reveal RP is positively correlated with enamel thickness, negatively correlated with femoral length, but weakly associated with the rate of enamel secretion and osteocyte proliferation. These new data imply that a slower biorhythm predicts thicker enamel for children but shorter stature for adults. Our results develop the intra-specific HHO hypothesis suggesting that there is a common underlying systemic biorhythm that has a role in the final products of human enamel and bone growth.
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Basophils are recruited and localized at the site of tick bites in humans
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Reconsidering the H&E stain as the gold standard in assessing the depth of burn wounds
While histological examination is considered by most as the gold standard for burn depth assessment, it has no practical use in the clinical setting. It has, however, been used in the research setting, as a mean for evaluating emerging techniques of depth measurement. Due to the limitations of the H&E stain, other stains have also been explored, such as lactate dehydrogenase (LDH), as presented in this issue, in "Improving the Histologic Characterization of Burn Depth." As the determination of burn depth is not a typical subject in dermatopathology, a summary of selected techniques and the possible role for the LDH stain in future research, is described herein.
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Effects of surgical lesions on choline acetyltransferase activity in the cat cochlea
Source:Hearing Research
Author(s): Mark Frilling, Gregory J. Wiet, Donald A. Godfrey, Judy A. Parli, Jon D. Dunn, C. David Ross
Although it is well established that the choline acetyltransferase (ChAT, the enzyme for acetylcholine synthesis) in the mammalian cochlea is associated with its olivocochlear innervation, the distribution of this innervation in the cochlea varies somewhat among mammalian species. The quantitative distribution of ChAT activity in the cochlea has been reported for guinea pigs and rats. The present study reports the distribution of ChAT activity within the organ of Corti among the three turns of the cat cochlea and the effects of removing olivocochlear innervation either by a lateral cut aimed to totally transect the left olivocochlear bundle or a more medial cut additionally damaging the superior olivary complex on the same side. Similarly to results for guinea pig and rat, the distribution of ChAT activity in the cat outer hair cell region showed a decrease from base to apex, but, unlike in the guinea pig and rat, the cat inner hair cell region did not. As in the rat, little ChAT activity was measured in the outer supporting cell region. As previously reported for whole cat cochlea and for rat cochlear regions, transection of the olivocochlear bundle resulted in almost total loss of ChAT activity in the hair cell regions of the cat cochlea. Lesions of the superior olivary complex resulted in loss of ChAT activity in the inner hair cell region of all cochlear turns only on the lesion side but bilateral losses in the outer hair cell region of all turns. The results are consistent with previous evidence that virtually all cholinergic synapses in the mammalian cochlea are associated with its olivocochlear innervation, that the olivocochlear innervation to the inner hair cell region is predominantly ipsilateral, and that the olivocochlear innervation to the outer hair cells is bilateral.
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Association between weight gain during adjuvant chemotherapy for early-stage breast cancer and survival outcomes
Abstract
Obese and overweight women have an increased risk of breast cancer and worse outcomes at the time of diagnosis. Women tend to gain weight after breast cancer diagnosis and during chemotherapy for early-stage disease, which may in turn increase risk for worse outcomes. We examined if weight gained during adjuvant chemotherapy was associated with worse survival outcomes. We queried our database for data on patients who received adjuvant third-generation chemotherapy for early-stage breast cancer. Univariate and multivariate analyses by Cox regression were performed for survival outcomes across three categories according to BMI variation from start to end of chemotherapy: >0.5 kg/m2 loss or gain and stable BMI (±0.5 kg/m2). We included 1998 patients in this study. Women over 50 years old and postmenopausal were more likely to lose weight during adjuvant chemotherapy, whereas women under 30 years old gained more weight (P < 0.001). At 1 year postchemotherapy, patients tended to return to their original weight (ρ = −0.3, P < 0.001). On multivariate analysis, BMI increase of >0.5 kg/m2 compared to maintaining BMI was marginally associated with increased locoregional recurrence risk (HR: 2.53; 95% CI, 1.18–5.45; P = 0.017), adjusting for grade, stage, and radiation delivery. Weight variation during adjuvant chemotherapy for early-stage breast cancer may occur as both weight gain and weight loss in a balanced manner. Furthermore, this variation seems to be transient in nature and does not appear to significantly influence recurrence rates and overall survival.
Weight variation during adjuvant chemotherapy for early stage breast cancer may occur as both weight gain and weight loss in a balanced manner. Furthermore, this variation seems to be transient in nature and does not appear to significantly influence recurrence rates and overall survival.
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Targeting MTA1/HIF-1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression
Abstract
The metastasis-associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression-related epigenetic regulator, which is overexpressed in hormone-refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate-specific Pten-null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo. We generated and utilized a luciferase reporter in a prostate-specific Pten-null mouse model (Pb-Cre+; Ptenf/f; Rosa26Luc/+) to evaluate the anticancer efficacy of Pter/SAHA combinatorial approach. Our data showed that Pter sensitized tumor cells to SAHA treatment resulting in inhibiting tumor growth and additional decline of tumor progression. These effects were dependent on the reduction of MTA1-associated proangiogenic factors HIF-1α, VEGF, and IL-1β leading to decreased angiogenesis. In addition, treatment of PCa cell lines in vitro with combined Pter and low dose SAHA resulted in more potent inhibition of MTA1/HIF-1α than by high dose SAHA alone. Our study provides preclinical evidence that Pter/SAHA combination treatment inhibits MTA1/HIF-1α tumor-promoting signaling in PCa. The beneficial outcome of combinatorial strategy using a natural agent and an approved drug for higher efficacy and less toxicity supports further development of MTA1-targeted therapies in PCa.
Utilization of dietary bioactive molecules as chemo-sensitizers is an emerging approach in developing combination strategies that can potentially provide more efficacy and less toxicity for anticancer treatments. Our study offers preclinical proof for combinatorial strategy using natural product, pterostilbene, with histone deacetylase inhibitor, SAHA, as a MTA1-targeted interventional therapy to abrogate prostate cancer. Changes in MTA1-associated proangiogenic factors in serum may be used as molecular response biomarkers for such therapy.
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Missing ozone-induced potential aerosol formation in a suburban deciduous forest
Publication date: Available online 10 October 2017
Source:Atmospheric Environment
Author(s): T. Nakayama, Y. Kuruma, Y. Matsumi, Y. Morino, K. Sato, H. Tsurumaru, S. Ramasamy, Y. Sakamoto, S. Kato, Y. Miyazaki, T. Mochizuki, K. Kawamura, Y. Sadanaga, Y. Nakashima, K. Matsuda, Y. Kajii
As a new approach to investigating formation processes of secondary organic aerosol (SOA) in the atmosphere, ozone-induced potential aerosol formation was measured in summer at a suburban forest site surrounded by deciduous trees, near Tokyo, Japan. After passage through a reactor containing high concentrations of ozone, increases in total particle volume (average of 1.4 × 109 nm3/cm3, which corresponds to 17% that of pre-existing particles) were observed, especially during daytime. The observed aerosol formations were compared with the results of box model simulations using simultaneously measured concentrations of gaseous and particulate species. According to the model, the relative contributions of isoprene, monoterpene, and aromatic hydrocarbon oxidation to SOA formation in the reactor were 24, 21, and 55%, respectively. However, the model could explain, on average, only ∼40% of the observed particle formation, and large discrepancies between the observations and model were found, especially around noon and in the afternoon when the concentrations of isoprene and oxygenated volatile organic compounds were high. The results suggest a significant contribution of missing (unaccounted-for) SOA formation processes from identified and/or unidentified volatile organic compounds, especially those emitted during daytime. Further efforts should be made to explore and parameterize this missing SOA formation to assist in the improvement of atmospheric chemistry and climate models.
Graphical abstract
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Comment on: The over-Wise mammoplasty: a modified Wise pattern for large superficial breast tumors
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Lesions Responsible for Delayed Oral Transit Time in Post-stroke Dysphagia
Abstract
Introduction
Some stroke patients show oral phase dysphagia, characterized by a markedly prolonged oral transit time that hinders oral feeding. The aim of this study was to clarify the clinical characteristics and lesions responsible for delayed swallowing.
Methods
We reviewed 90 patients with stroke. The oral processing time plus the postfaucial aggregation time required to swallow semisolid food was assessed. The patients were divided into two groups according to oral transit time, and we analyzed the differences in characteristics such as demographic factors, lesion factors, and cognitive function. Logistic regression analyses were performed to examine the predictors of delayed oral transit time. Lesion location and volume were measured on brain magnetic resonance images. We generated statistic maps of lesions related to delayed oral phase in swallowing using voxel-based lesion symptom mapping (VLSM).
Results
The group of patients who showed delayed oral transit time had significantly low cognitive function. Also, in a regression model, delayed oral phase was predicted with low K-MMSE (Korean version of the Mini Mental Status Exam). Using VLSM, we found the lesion location to be associated with delayed oral phase after adjusting for K-MMSE score. Although these results did not reach statistical significance, they showed the lesion pattern with predominant distribution in the left frontal lobe.
Conclusion
Delayed oral phase in post-stroke patients was not negligible clinically. Patients' cognitive impairments affect the oral transit time. When adjusting it, we found a trend that the lesion responsible for delayed oral phase was located in the left frontal lobe, though the association did not reach significance. The delay might be related to praxis function.
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A Significant Association of Malnutrition with Dysphagia in Acute Patients
Abstract
Dysphagia and malnutrition seem to be associated, but little research in detail has been reported. We aimed to clarify the association between dysphagia and malnutrition by adopting accurate diagnosis and mathematical evaluation of dysphagia using videofluorography and nutritional assessment calculated by a well-established nutritional risk index. We conducted a retrospective analysis of 165 enrolled patients who were admitted to our hospital for acute diseases and underwent videofluorography on suspicion of dysphagia in the year 2016. We diagnosed high-risk dysphagia in patients with 8-point penetration–aspiration scale (PAS) score over 4. We used the geriatric nutritional risk index (GNRI) as a nutritional assessment tool. A GNRI score less than 91.2 corresponds to malnutrition. The median age of 165 enrolled patients was 76.0, and the number of female patients was 53. The mean GNRI was 81.2, and 134 patients (81.2%) had malnutrition. The number of the patients with a diagnosis of high-risk dysphagia was 54 (32.7%). The GNRI of patients with high-risk dysphagia was significantly less than that of patients without (mean value 77.7 ± 10.5 vs. 83.0 ± 10.5, P = 0.003). GNRI < 91.2 was independently and significantly associated with high-risk dysphagia (OR 3.094; CI 1.057–9.058; P = 0.039). Based on the current study, the authors propose evaluating nutritional status to predict dysphagia risk of patients in the acute phase.
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Down-regulation of miR-26a-5p in hepatocellular carcinoma: a qRT-PCR and bioinformatics study
Publication date: Available online 10 October 2017
Source:Pathology - Research and Practice
Author(s): Liang Liang, Jiang-hui Zeng, Jie-yu Wang, Rong-quan He, Jie Ma, Gang Chen, Xiao-yong Cai, Xiao-hua Hu
BackgroundTo practically verify the clinical value of miR-26a-5p and thoroughly explore its target genes as well as its potential functions in hepatocellular carcinoma (HCC).MethodsHCC and adjacent non-cancerous hepatic tissues of 95 HCC patients were collected for analysis using reverse transcription quantitative real-time PCR (qRT-PCR). For the bioinformatics analysis, we identified potential target genes for miR-26a-5p from differentially expressed genes (DEGs) in Gene Expression Omnibus (GEO) data sets and miRWalk predicted database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) analyses were applied to analyze the prospective mechanisms of the predicted target genes.ResultsMiR-26a-5p showed a significantly lower expression level in HCC tissues (1.56±1.07) than adjacent benign liver tissues (2.28±1.06, P <0.001). The area under the curve (AUC) of the receiver operating characteristic (ROC) was 0.665 (95% CI: 0.588-0.743, P <0.001). Significant correlations between miR-26a-5p expression and clinicopathological features such as gender (r=0.275, P <0.01), clinical TNM stage (r=−0.306, P <0.01), and metastasis (r=−0.321, P <0.01) were observed. To examine potential target genes, we obtained 175 genes for further function analysis, by attaining the intersection of 2062 up-regulated DEGs and 1390 online-predicted target genes. The GO and KEGG pathway annotation indicated focal adhesion, regulation of actin cytoskeleton and the PI3K-Akt signaling pathway as significant prospective mechanisms. The PPI network indicated that NRAS was the most essential hub gene in the whole network.ConclusionDown-regulated miR-26a-5p was closely correlated with the status of metastasis and the progression of HCC. MiR-26a-5p might play protective roles by targeting diverse genes and pathways.
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Aberrant promoter methylation of the PAQR3 gene is associated with prostate cancer
Publication date: Available online 10 October 2017
Source:Pathology - Research and Practice
Author(s): Kowit Lounglaithong, Andrey Bychkov, Pichet Sampatanukul
Methylation markers are promising tools for diagnosis, prognosis and targeted treatment of cancer. In prostate carcinoma, aberrant promoter hypermethylation occurs earlier in the disease course and more consistently than recurrent somatic mutations. PAQR3, a tumor suppressor gene, was recently found to be downregulated in prostate cancer cell lines. We hypothesized that promoter methylation could be responsible for PAQR3 silencing in prostate cancer tissues. We aimed to investigate PAQR3 promoter methylation in prostate cancer by comparing it to benign prostatic hyperplasia (BPH). A total of 154 human prostate tissue samples, including 92 cases with prostate cancer and 62 cases with BPH, were examined by methylation-specific PCR. Clinicopathological correlation between PAQR3 promoter methylation and prognostically relevant variables was studied by statistical analysis. Promoter methylation of PAQR3 was significantly more frequent in prostate carcinoma compared to BPH (73.9% vs. 25.8%, p <0.01). The high prevalence of PAQR3 methylation in cancer foci was also confirmed with microdissection technique in 12 samples of prostate adenocarcinoma. PAQR3 hypermethylation was associated with perineural invasion (p=0.03), an adverse clinicopathological feature of prostate cancer. We concluded that PAQR3 can be a promising methylation marker candidate for the detection and monitoring of prostate cancer.
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Over expression of HIF1α is associated with inactivation of both LimD1 and VHL in renal cell carcinoma: clinical importance
Publication date: Available online 10 October 2017
Source:Pathology - Research and Practice
Author(s): Subhayan Sur, Arun Kumar Maurya, Anup Roy, Tyson V. Sharp, Dilip Kumar Pal, Chinmay Kumar Panda
It is evident that the association of LimD1 and VHL could regulate stabilization of HIF1α protein. In this study, the expression of LimD1, VHL and HIF1α was analyzed in primary renal cell carcinoma (RCC) samples to understand their association with development of the disease. For this purpose, immunohistochemical expression analysis of LimD1, VHL and HIF1α was performed along with proliferation marker PCNA in 32 primary RCC samples in different subtypes at different clinical stages of Indian patients (year: 2014–2016). Significant decrease (P<0.05) in LimD1 and VHL expression was observed in different subtypes of RCC and in early invasive lesions. High nuclear expression of HIF1α was seen in different subtypes as well as in early invasive lesions. The LimD1 and VHL expression strongly correlated with each other, while inversely correlated with HIF1α. On the other hand, increased expression of PCNA was seen in different sub types and in early invasive lesions. The PCNA expression was negatively correlated with LimD1 and VHL expression and positively correlated with HIF1α. Thus, our data indicates that the reduced expression of LimD1 and VHL might have synergistic effect on induction of HIF1α resulting increased cellular proliferation and progression of the disease.
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Juvenile elastoma without germline mutations in LEMD3 gene: A case of Buschke-Ollendorff syndrome?
Abstract
We report the case of a 6-year-old Caucasian girl with clinical and histopathologic features of Buschke-Ollendorff syndrome. Histologic examination of skin lesions showed thick, curly, elastic fibers in the derma. Bone lesions compatible with Buschke-Ollendorff syndrome were found in the girl's mother. Mutations in LEMD3 are pathogenic for Buschke-Ollendorff syndrome. Analysis of all exons and exon-intron junctions of LEMD3 did not reveal any germline mutations.
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The effect of incidental dural lesions on outcome after decompression surgery for lumbar spinal stenosis: results of a multi-center study with 800 patients
Abstract
Purpose
Incidental durotomy is one of the most common complications in lumbar spine surgery. There are conflicting reports whether a dural lesion is associated with an inferior outcome after lumbar decompression. This study analyzed the effect of incidental durotomy in this specific group of patients (Dura+) and compared the results with the remaining cohort without dural laceration (Dura−).
Methods
This prospective multi-center study included 800 patients with lumbar spinal stenosis who underwent exclusive decompression surgery. All procedures were performed as part of a multi-center investigation at three highly specialized spine clinics. Outcome measures (ODI, EQ5D, VASback pain and VASleg pain) were obtained preoperatively as well as 3 and 12 months after surgery. The effect of an incidental durotomy on the clinical outcomes was analyzed statistically between the two cohorts.
Results
An intraoperative dura lesion was recorded in 6.5 % (n = 52/800) of all cases. Both cohorts (Dura+ and Dura−) did not reveal any differences regarding patient demographics, risk factors, or co-morbidities at baseline. The length of the hospital stay was significantly longer for the Dura+ cohort (8.0 vs. 6.4 days; p < 0.01). After 12 months, the Dura− cohort demonstrated a significantly greater improvement in VASback pain in comparison to the Dura+ cohort (Δ21.4 vs. Δ7.2 points; p < 0.05). The differences for the remaining outcome measures were not statistically significant (p > 0.05).
Conclusions
The results of this study reveal that an incidental durotomy was associated with a significant increase in the patient's length of stay, and risk for re-intervention for the treatment of persisting CSF leakage. In contrast to previous reports which have investigated the effects of incidental durotomies on the clinical outcome after lumbar decompression surgery, our data further suggest a possible inferior outcome in terms of low back pain improvement in the Dura+ cohort, which became clinically apparent at the 12-month follow-up period. Future studies should investigate whether a more pronounced decompression required for adequate exposure and repair of a dural laceration may, ultimately, result in increased segmental instability and in clinically undesirable low back pain.
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Adaptive self-organization in the embryo: its importance to adult anatomy and to tissue engineering
Abstract
The anatomy of healthy humans shows much minor variation, and twin-studies reveal at least some of this variation cannot be explained genetically. A plausible explanation is that fine-scale anatomy is not specified directly in a genetic programme, but emerges from self-organizing behaviours of cells that, for example, place a new capillary where it happens to be needed to prevent local hypoxia. Self-organizing behaviour can be identified by manipulating growing tissues (e.g. putting them under a spatial constraint) and observing an adaptive change that conserves the character of the normal tissue while altering its precise anatomy. Self-organization can be practically useful in tissue engineering but it is limited; generally, it is good for producing realistic small-scale anatomy but large-scale features will be missing. This is because self-organizing organoids miss critical symmetry-breaking influences present in the embryo: simulating these artificially, for example, with local signal sources, makes anatomy realistic even at large scales. A growing understanding of the mechanisms of self-organization is now allowing synthetic biologists to take their first tentative steps towards constructing artificial multicellular systems that spontaneously organize themselves into patterns, which may soon be extended into three-dimensional shapes.
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CPS49-induced neurotoxicity does not cause limb patterning anomalies in developing chicken embryos
Abstract
Thalidomide notoriously caused severe birth defects, particularly to the limbs, in those exposed in utero following maternal use of the drug to treat morning sickness. How the drug caused these birth defects remains unclear. Many theories have been proposed including actions on the forming blood vessels. However, thalidomide survivors also have altered nerve patterns and the drug is known for its neurotoxic actions in adults following prolonged use. We have previously shown that CPS49, an anti-angiogenic analog of thalidomide, causes a range of limb malformations in a time-sensitive manner in chicken embryos. Here we investigated whether CPS49 also is neurotoxic and whether effects on nerve development impact upon limb development. We found that CPS49 is neurotoxic, just like thalidomide, and can cause some neuronal loss late developing chicken limbs, but only when the limb is already innervated. However, CPS49 exposure does not cause defects in limb size when added to late developing chicken limbs. In contrast, in early limb buds which are not innervated, CPS49 exposure affects limb area significantly. To investigate in more detail the role of neurotoxicity and its impact on chicken limb development we inhibited nerve innervation at a range of developmental timepoints through using β-bungarotoxin. We found that neuronal inhibition or ablation before, during or after limb outgrowth and innervation does not result in obvious limb cartilage patterning or number changes. We conclude that while CPS49 is neurotoxic, given the late innervation of the developing limb, and that neuronal inhibition/ablation throughout limb development does not cause similar limb patterning anomalies to those seen in thalidomide survivors, nerve defects are not the primary underlying cause of the severe limb patterning defects induced by CPS49/thalidomide.
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The bony horncore of the common eland (Taurotragus oryx): composition and mechanical properties of a spiral fighting structure
Abstract
Horns are permanent structures projecting from the head of bovids, consisting of a bony horncore covered with a layer of skin and then a sheath of keratinous material showing variability of growth intensity based on nutrition. From the point of view of the horn's mechanical properties, the keratin sheath has been widely studied, but only a few studies have considered the complete structure of the horn and fewer studies have focused on the bony horncore and its characteristics. The latter showed the important role of the bony core, when cranial appendages are subject to mechanical stress (as happens during fighting). The mechanical properties of bone material, along with its mineral profile, are also important, because they can show effects of different factors, such as nutrition and mineral deficiencies in diet. For this reason, eight horncores of captive common eland male were sampled at four positions along the vertical axis of the horn. The main aim was to study variation in mechanical properties and the mineral content along the vertical axis of the horncores. We further analysed whether the spiral bony ridge present on eland horncores differs in any of the studied properties from adjacent parts of the horncore. In other antelopes, spiral ridges on the horns have been proposed to increase grip during wrestling between males. Cross-sections of the horncores were performed at four positions along the longitudinal axis and, for each position, two bone bars were extracted to be tested in impact and bending. Moreover, in the first sampling position (the closest position to the base) two bars were extracted from the spiralled bony area. The resulting fragments were used to measure ash content, bone density and mineral content. Results showed that horn bone decreased along the vertical axis, in ash (−36%), density (−32%), and in impact work 'U' (marginally significant but large effect: −48%). The concentration of several minerals decreased significantly (Mg, Cr, Mn and Tl by −33%, −25%, −31%, −43%, respectively) between the basal and the uppermost sampling site. The bone tissue of the horncore spiral compared with non-spiral bone of the same position showed a lower ash content (53% vs. 57%), Mg and Mn; in addition to showing approximately half values in work to peak force 'W', bending strength 'BS' and 'U', but not in Young's modulus of elasticity 'E'. In conclusion, similarly to the results in a totally different fighting bony structure, the antlers, the horncore of eland shows advantageous parameters in bone tissue of the base in respect to the tip, with higher values for mechanical properties, density and mineral profile. Moreover, the spiral bone tissue showed lower material mechanical properties. Probably the spiral tissue of the horn may have a role in deflecting potential cross-sectional fractures during wrestling. In addition, it may serve to improve the grip during wrestling, and we propose that it may also prevent risk of rotation of sheath with respect to internal bone not only in this, but also in other straight bovid horns.
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Anatomy and development of the extrahepatic biliary system in mouse and rat: a perspective on the evolutionary loss of the gallbladder
Abstract
The gallbladder is the hepatobiliary organ for storing and secreting bile fluid, and is a synapomorphy of extant vertebrates. However, this organ has been frequently lost in several lineages of birds and mammals, including rodents. Although it is known as the traditional problem, the differences in development between animals with and without gallbladders are not well understood. To address this research gap, we compared the anatomy and development of the hepatobiliary systems in mice (gallbladder is present) and rats (gallbladder is absent). Anatomically, almost all parts of the hepatobiliary system of rats are topographically the same as those of mice, but rats have lost the gallbladder and cystic duct completely. During morphogenesis, the gallbladder–cystic duct domain (Gb–Cd domain) and its primordium, the biliary bud, do not develop in the rat. In the early stages, SOX17, a master regulator of gallbladder formation, is positive in the murine biliary bud epithelium, as seen in other vertebrates with a gallbladder, but there is no SOX17-positive domain in the rat hepatobiliary primordia. These findings suggest that the evolutionary loss of the Gb–Cd domain should be translated simply as the absence of a biliary bud at an early stage, which may correlate with alterations in regulatory genes, such as Sox17, in the rat. A SOX17-positive biliary bud is clearly definable as a developmental module that may be involved in the frequent loss of gallbladder in mammals.
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Erythrokeratoderma - a manifestation associated with multiple types of ichthyoses with different gene defects
Erythrokeratoderma (OMIM #133200) refers to a group of closely related disorders of cornification manifesting with hyperkeratotic, often transient and migratory, erythematous figurate plaques with sharply demarcated borders that typically develop in early childhood with or without palmoplantar involvement.1 Erythrokeratodermas have been historically classified into the two main categories: (a) erythrokeratodermia variabilis et progressiva (EKVP, also known as erythrokeratoderma figurata variabilis and Mendes da Costa disease), and (b) progressive symmetric erythrokeratoderma (PSEK, also known as Gottron syndrome).
This article is protected by copyright. All rights reserved.
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The optimal regimen of brentuximab vedotin for CD30+ cutaneous lymphoma: Are we there yet?
Brentuximab vedotin (BV) is an anti-CD30 antibody–drug conjugate that is approved for refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma. In the ALCANZA trial, the proportion of CD30+ cutaneous T-cell lymphoma (CTCL) patients achieving an objective response lasting at least 4 months was 56.3% with BV versus 12.5% with conventional therapy (oral methotrexate or bexarotene), and progression-free survival, complete response rate and improvement in symptom burden were significantly improved.1 As in previous studies, 1.8 mg/kg dose was administered every 3 weeks in this study.1,2 We routinely use this regimen that has been well studied in clinical trials, starting with 1.8 mg/kg and decrease to 1.2 mg/kg if needed. The safety profile for BV is similar to conventional therapies and although peripheral neuropathy occurs in 67%, it usually resolves or improves after cessation or completion of treatment.1
This article is protected by copyright. All rights reserved.
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Second-line therapy in patients with metastatic castration-resistant prostate cancer with progression after or under docetaxel: A systematic review of nine randomized controlled trials
Publication date: Available online 10 October 2017
Source:Seminars in Oncology
Author(s): M.H.F. Poorthuis, R.W.M. Vernooij, R.J.A. van Moorselaar, Th.M. de Reijke
Treatment decision in patients with metastatic castration-resistant prostate cancer with progression after or under docetaxel are challenging. We systematically searched the published literature on all treatment options and assessed the risk of bias and quality of evidence. We found the best available evidence for effective prolongation of overall survival and progression-free survival for abiraterone acetate plus prednisone versus placebo plus prednisone and enzalutamide versus placebo. Other treatment modalities could be beneficial for individual patients by taking the selection criteria of the randomized clinical trials, the risk of bias, the subgroup analyses, and the quality of life and adverse events into consideration. Further research is needed to determine the sequence, timing and combination of different treatments.
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Metabolic Symbiosis in Cancer and Its Therapeutic Implication
Publication date: Available online 10 October 2017
Source:Seminars in Oncology
Author(s): Mark R. Lipstein, Ipsita Pal, Susan E. Bates, Changchun Deng
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Mitochondrial and glycolytic metabolic compartmentalization in Diffuse Large B Cell Lymphoma
Publication date: Available online 10 October 2017
Source:Seminars in Oncology
Author(s): Mahasweta Gooptu, Diana Whitaker-Menezes, John Sprandio, Marina Domingo-Vidal, Zhao Lin, Guldeep Uppal, Jerald Gong, Roberto Fratamico, Benjamin Leiby, Alina Dulau-Florea, Jaime Caro, Ubaldo Martinez-Outschoorn
Metabolic heterogeneity between neoplastic cells and surrounding stroma has been described in several epithelial malignancies; however, the metabolic phenotypes of neoplastic lymphocytes and neighboring stroma in diffuse large B-cell lymphoma (DLBCL) is unknown. We investigated the metabolic phenotypes of human DLBCL tumors by using immunohistochemical markers of glycolytic and mitochondrial oxidative phosphorylation (OXPHOS) metabolism. The lactate importer MCT4 is a marker of glycolysis, whereas the lactate importer MCT1 and TOMM20 are markers of OXPHOS metabolism. Staining patterns were assessed in 33 DLBCL samples as well as 18 control samples (non-neoplastic lymph nodes). TOMM20 and MCT1 were highly expressed in neoplastic lymphocytes, indicating an OXPHOS phenotype, whereas non-neoplastic lymphocytes in the control samples did not express these markers. Stromal cells in DLBCL samples strongly expressed MCT4, displaying a glycolytic phenotype, a feature not seen in stromal elements of non-neoplastic lymphatic tissue. Furthermore, the differential expression of lactate exporters (MCT4) on tumor associated stroma and lactate importers (MCT1) on neoplastic lymphocytes support the hypothesis that neoplastic cells are metabolically linked to the stroma likely via mutually beneficial reprogramming. MCT4 is a marker of tumor-associated stroma in neoplastic tissue. Our findings suggest that disruption of neoplastic-stromal cell metabolic heterogeneity including MCT1 and MCT4 blockade should b studied to determine if it could represent a novel treatment target in DLBCL.
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How are Multifactorial Beliefs about the Role of Genetics and Behavior in Cancer Causation associated with Cancer Risk Cognitions and Emotions in the U.S. Population?
Abstract
Objective
People who believe that cancer has both genetic and behavioral risk factors have more accurate mental models of cancer causation and may be more likely to engage in cancer screening behaviors than people who do not hold such multifactorial causal beliefs. This research explored possible health cognitions and emotions that might produce such differences.
Methods
Using nationally representative cross-sectional data from the U.S. Health Information National Trends Survey (N=2,719), we examined whether endorsing a multifactorial model of cancer causation was associated with perceptions of risk and other cancer-related cognitions and affect. Data were analyzed using linear regression with jackknife variance estimation and procedures to account for the complex survey design and weightings.
Results
Bivariate and multivariable analyses indicated that people who endorsed multifactorial beliefs about cancer had higher absolute risk perceptions, lower pessimism about cancer prevention, and higher worry about harm from environmental toxins that could be ingested or that emanate from consumer products (ps<0.05). Bivariate analyses indicated that multifactorial beliefs were also associated with higher feelings of risk, but multivariable analyses suggested that this effect was accounted for by the negative affect associated with reporting a family history of cancer. Multifactorial beliefs were not associated with believing that everything causes cancer or that there are too many cancer recommendations to follow (ps>0.05).
Conclusion
Holding multifactorial causal beliefs about cancer are associated with a constellation of risk perceptions, health cognitions, and affect that may motivate cancer prevention and detection behavior.
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Linguistic and Perceptual Mapping in Spatial Representations: An Attentional Account
Abstract
Building on evidence for embodied representations, we investigated whether Spanish spatial terms map onto the NEAR/FAR perceptual division of space. Using a long horizontal display, we measured congruency effects during the processing of spatial terms presented in NEAR or FAR space. Across three experiments, we manipulated the task demands in order to investigate the role of endogenous attention in linguistic and perceptual space mapping. We predicted congruency effects only when spatial properties were relevant for the task (reaching estimation task, Experiment 1) but not when attention was allocated to other features (lexical decision, Experiment 2; and color, Experiment 3). Results showed faster responses for words presented in Near-space in all experiments. Consistent with our hypothesis, congruency effects were observed only when a reaching estimate was requested. Our results add important evidence for the role of top-down processing in congruency effects from embodied representations of spatial terms.
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Spontaneous Emergence of Legibility in Writing Systems: The Case of Orientation Anisotropy
Abstract
Cultural forms are constrained by cognitive biases, and writing is thought to have evolved to fit basic visual preferences, but little is known about the history and mechanisms of that evolution. Cognitive constraints have been documented for the topology of script features, but not for their orientation. Orientation anisotropy in human vision, as revealed by the oblique effect, suggests that cardinal (vertical and horizontal) orientations, being easier to process, should be overrepresented in letters. As this study of 116 scripts shows, the orientation of strokes inside written characters massively favors cardinal directions, and it is organized in such a way as to make letter recognition easier: Cardinal and oblique strokes tend not to mix, and mirror symmetry is anisotropic, favoring vertical over horizontal symmetry. Phylogenetic analyses and recently invented scripts show that cultural evolution over the last three millennia cannot be the sole cause of these effects.
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Disentangling Effects of Input Frequency and Morphophonological Complexity on Children's Acquisition of Verb Inflection: An Elicited Production Study of Japanese
Abstract
This study aims to disentangle the often-confounded effects of input frequency and morphophonological complexity in the acquisition of inflection, by focusing on simple and complex verb forms in Japanese. Study 1 tested 28 children aged 3;3–4;3 on stative (complex) and simple past forms, and Study 2 tested 30 children aged 3;5–5;3 on completive (complex) and simple past forms, with both studies using a production priming paradigm. Mixed effects models for children's responses were built to test the prediction that children's verb use is explained by the relative bias in input frequency between the two inflectional forms. Although Study 1 did not show a significant effect of input bias (apparently due to problems with item selection), Study 2, which corrected for this problem, yielded the predicted relationship. These findings suggest that input frequency effects, at the level of different inflectional forms of the same verb stem, hold even after controlling for morphophonological complexity.
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Effects of Early Cues on the Processing of Chinese Relative Clauses: Evidence for Experience-Based Theories
Abstract
We used Chinese prenominal relative clauses (RCs) to test the predictions of two competing accounts of sentence comprehension difficulty: the experience-based account of Levy () and the Dependency Locality Theory (DLT; Gibson, ). Given that in Chinese RCs, a classifier and/or a passive marker BEI can be added to the sentence-initial position, we manipulated the presence/absence of classifiers and the presence/absence of BEI, such that BEI sentences were passivized subject-extracted RCs, and no-BEI sentences were standard object-extracted RCs. We conducted two self-paced reading experiments, using the same critical stimuli but somewhat different filler items. Reading time patterns from both experiments showed facilitative effects of BEI within and beyond RC regions, and delayed facilitative effects of classifiers, suggesting that cues that occur before a clear signal of an upcoming RC can help Chinese comprehenders to anticipate RC structures. The data patterns are not predicted by the DLT, but they are consistent with the predictions of experience-based theories.
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On neuromechanical approaches for the study of biological and robotic grasp and manipulation
Biological and robotic grasp and manipulation are undeniably similar at the level of mechanical task performance. However, their underlying fundamental biological vs. engineering mechanisms are, by definition,...
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Langer's axillary arch: a frequent but rarely discussed anatomical variant in the radiologic literature
Abstract
The axillopectoral muscle is a rarely discussed variant of muscular anatomy of the axilla, with various clinical implications. We report a case of a 7-year-old girl with multiple genetic and developmental abnormalities who presented with asymmetrical right axillary bulging of unknown etiology. MRI demonstrated a small accessory axillary muscle, known as Langer's axillary arch and/or the axillopectoral muscle. Other than soft-tissue asymmetry, the patient experienced no additional related symptoms. However, this is an important variant to be aware of, as it can easily be discovered on imaging and may be a causative agent for various upper extremity symptoms that may resolve with appropriate recognition and surgical intervention.
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Corrigendum to “Avoidable cancer cases in the Nordic countries – The impact of overweight and obesity” [Eur J Cancer 79 (2017) 106–118]
Source:European Journal of Cancer
Author(s): Therese M.-L. Andersson, Elisabete Weiderpass, Gerda Engholm, Anne-Sofie Q. Lund, Elinborg Olafsdottir, Eero Pukkala, Magnus Stenbeck, Hans Storm
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Identifying eustachian tube dysfunction prior to hyperbaric oxygen therapy: Who is at risk for intolerance?
Determine whether specific risk factors, symptoms and clinical examination findings are associated with hyperbaric oxygen therapy (HBOT) intolerance and subsequent tympanotomy tube placement.
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Peripheral nerve involvement in multiple sclerosis Demonstration by magnetic resonance neurography
Abstract
Objective:To detect and quantify peripheral nerve lesions in multiple sclerosis (MS) by magnetic resonance neurography (MRN).
Methods: 36 patients diagnosed with MS based on the 2010 McDonald criteria (34 with the relapsing-remitting form, 2 with clinically isolated syndrome) with and without disease modifying treatment were compared to 35 healthy age/sex-matched volunteers. All patients underwent detailed neurological and electrophysiological examinations. 3T MRN with large anatomical coverage of both legs and the lumbosacral plexus was performed by using 2D fat-saturated, T2-weighted and dual echo turbo-spin-echo sequences as well as a 3D T2-weighted, fat-saturated SPACE sequence. Besides qualitative visual nerve assessment, a T2w-signal quantification was performed by calculation of proton-spin-density and T2-relaxation time. Nerve diameter was measured as a morphometric criterion.
Results:T2w-hyperintense nerve lesions were detectable in all MS patients with a mean lesion number at thigh level of 151.5±5.7 vs. 19.1±2.4 in controls (p<0.0001). Nerve proton-spin-density was higher in MS (tibial/peroneal: 371.8±7.7/368.9±8.2) vs. controls (tibial/peroneal: 266.0±11.0/276.8±9.7;p<0.0001). In contrast, T2-relaxation time was significantly higher in controls (tibial/peroneal:82.0±2.1/78.3±1.7) vs. MS (tibial/peroneal:64.3±1.0/61.2±0.9; p<0.0001). Proximal tibial and peroneal nerve caliber was higher in MS (tibial:52.4±2.1mm2; peroneal:25.4±1.3mm2) vs. controls (tibial:45.2±1.4mm2; p<0.0015; peroneal:21.3±0.7mm2; p=0.0049).
Interpretation:Peripheral nerve lesions could be visualized and quantified in MS in vivo by high resolution MRN. Lesions are defined by an increase of proton-spin-density and a decrease of T2-relaxation time, indicating changes in the microstructural organization of the extracellular matrix in peripheral nerve tissue in MS. By showing involvement of the peripheral nervous system in MS, this proof-of-concept study may offer new insights into the pathophysiology and treatment of MS. This article is protected by copyright. All rights reserved.
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Single tooth torque correction in the lower frontal area by a completely customized lingual appliance
Aim of this study was to analyze the efficacy and precision of the completely customized lingual appliance (CCLA) regarding the single tooth torque correction. The study also examined external apical root reso...
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The effect of internal roughness and bonding on the fracture resistance and structural reliability of lithium disilicate ceramic
Source:Dental Materials
Author(s): Paul de Kok, Gabriel K.R. Pereira, Sara Fraga, Niek de Jager, Andressa B. Venturini, Cornelis J. Kleverlaan
ObjectiveTo evaluate the effect of internal roughness and bonding on the load to failure and structural reliability (Weibull analysis) of a lithium disilicate-based glass ceramic under different testing scenarios.MethodsIPS e.max CAD blocks (Ivoclar Vivadent AG) were shaped into cylinders (N=100), crystalized according to the manufacturer's instructions, and randomly assigned into two surface conditions: (1) polished surface (600-grit SiC polish papers), and (2) a roughened surface (air-abrasion with 50μm Al2O3). Two assemblies were investigated: a ceramic disc isolated (to isolate the effect of roughness); and a simplified tri-layer setup simulating the restoration of a posterior tooth (ceramic+cement+epoxy resin) to evaluated the influence of bonding isolated and the associated effect of both factors. Four different scenarios were tested: (1) isolated disc under static load (n=10); (2) disc bonded to an epoxy resin substrate and tested under a static load (n=10); (3) disc bonded and tested under fatigue (n=20); and (4) simulated-bonding tested statically (n=10). The data of load to failure were submitted to One-way ANOVA and Weibull analysis.ResultsAt a non-bonded scenario (isolated disc and simulated-bonding) a polished internal surface presented a higher characteristic strength. However, when bonding was present this difference became inexistent. No difference was found in terms of structural reliability (Weibull moduli) among the groups. FEA analysis shows that with bonding the tensile stress is better distributed, while in a non-bonded scenario higher tensile stresses occur at the bonding interface.SignificanceA rough internal surface impacted deleteriously the mechanical properties of lithium disilicate ceramic when it was not properly bonded to the substrate. However, bonding to the substrate appeared to play a more significant role in the fracture resistance than internal roughness.
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Critical features and challenges associated with imaging in patients undergoing cancer immunotherapy
Source:Critical Reviews in Oncology/Hematology
Author(s): Cinzia Solinas, Michele Porcu, Zuzana Hlavata, Pushpamali De Silva, Marco Puzzoni, Karen Willard-Gallo, Mario Scartozzi, Luca Saba
Manipulating an individual's immune system through immune checkpoint blockade is revolutionizing the paradigms of cancer treatment. Peculiar patterns and kinetics of response have been observed with these new drugs, rendering the assessment of tumor burden particularly challenging in cancer immunotherapy. The mechanisms of action for immune checkpoint blockade, based upon engagement of the adaptive immune system, can generate unusual response patterns, including pseudoprogression, hyperprogression, atypical and delayed responses. In patients treated with immune checkpoint blockade and radiotherapy, a reduction in tumor burden at metastatic sites distant from the irradiation field (abscopal effect) have been observed, with synergistic systemic immune effects provoked by this combination. New toxicities have also been observed, due to excessive immune activity in several organs, including lung, colon, liver and endocrine glands. Efforts to standardize assessment of cancer immunotherapy responses include novel consensus guidelines derived by modifying World Health Organization (WHO) and Response Evaluation Criteria In Solid Tumors (RECIST) criteria. The aim of this review is to evaluate imaging techniques currently used routinely in the clinic and those being used as investigational tools in immunotherapy clinical trials.
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Postoperative rehabilitation following thumb base surgery: a systematic review of the literature
Publication date: Available online 10 October 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Robbert M. Wouters, Jonathan Tsehaie, Steven E.R. Hovius, Burcu Dilek, Ruud W. Selles
ObjectiveTo provide an overview of rehabilitation for patients who underwent CMC-1 arthroplasty, with emphasis on early active mobilization.Data Sources/Study SelectionPubMed/MEDLINE, Embase, CINAHL and Cochrane were searched for articles written in English that described postoperative regime (including immobilization period/method and/or description of exercises/physical therapy, follow-up ≥six weeks) on CMC-1 arthroplasty.Data ExtractionThe PRISMA statement was used as guidance in this review and methodological quality was assessed using the Effective Public Health Practice Project quality assessment tool. Randomized studies were additionally scored using the Physiotherapy Evidence Database scale.Data SynthesisTwenty-seven studies were included, concerning 1015 participants in whom 1118 surgical procedures were performed. A summary on the components of postoperative rehabilitation used in the included studies on CMC-1 OA is presented for different surgical interventions. We found that early active recovery (including short immobilization, early initiation of ROM and strength exercises) provides positive outcomes on pain, limitations in ADL and grip & pinch strength, but comparative studies are lacking. Furthermore, three postoperative exercises/therapy phases were identified in the literature: the 'acute phase', the 'unloaded phase' and the 'functional phase', but again comparative studies are lacking.ConclusionsEarly active recovery is used more often in the literature and does not lead to worse outcomes or more complications. This systematic review provides guidance for clinicians in the content of postoperative rehabilitation on CMC-1 arthroplasty. The review also clearly identifies the almost complete lack of high quality, comparative studies on postoperative rehabilitation after CMC-1 arthroplasty.
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Medical Safety Huddles in Rehabilitation – A Novel Patient Safety Strategy
Publication date: Available online 10 October 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Meiqi Guo, Gaetan Tardif, Mark Bayley
ObjectiveTo describe the implementation process, outcomes, and lessons learned in the implementation of medical safety huddles, a novel patient safety monitoring strategy that promotes physician engagement with patient safety.DesignSingle-centre observational study.SettingThe Brain and Spinal Cord Injury Rehabilitation Program (BSCIRP) at an urban, academic adult rehabilitation hospital.Participants18 physicians associated with the program.InterventionsWeekly physicians' safety huddles were implemented to review, anticipate, and address patient safety issues.Main Outcome MeasuresThe main outcome measures were the number and nature of identified and anticipated patient safety incidents, actions taken and physician attendance during huddles. The number of adverse events in the program before and after huddle implementation were secondary measures.ResultsOver a 7-month period, average physician attendance at medical huddles was 76.0%. 1.0±0.8 patient safety incidents and 3.2±2.1 anticipated patient safety issues were identified in each weekly huddle. The majority of patient safety incidents identified were clinical administrative and clinical process-related, which differed from information gathered from the organization's pre-existing patient safety monitoring strategies. A total of 79 actions, or 3.3±1.8 actions/huddle were taken in response to improve patient safety for the program. Adverse events decreased from 31.2/month (95% confidence interval[CI] 27.0-35.3) to 22.9/month (CI 19.3-26.5) after implementation.Conclusion(s)Medical safety huddles are a novel strategy to engage physicians in patient safety and organizational quality improvement. They have the potential to enhance organizational anticipation of safety risks by supplementing existing methods. Other rehabilitation settings may wish to consider implementing and evaluating similar huddles into their existing patient safety and quality improvement frameworks.
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The trajectory of positive psychological change in a head and neck cancer population
A stressful event may be sufficient to challenge a strongly held set of assumptions about the world and the self. In some people this may lead to post-traumatic stress disorder (PTSD) and in others to positive psychological change (PPC), whereby a person's reactions to the challenge are beneficial. Little research has investigated PPC in people who have had head and neck cancer (HNC). The aim of this study was to identify demographic, clinical, and psychological factors associated with PPC over time.
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Hypoxic volume evaluated by 18F-fluoromisonidazole positron emission tomography (FMISO-PET) may be a prognostic factor in patients with oral squamous cell carcinoma: preliminary analyses
Tumour hypoxia can be detected by 18F-fluoromisonidazole positron emission tomography (FMISO-PET). Few studies have assessed the relationships of new PET parameters, including hypoxic volume (HV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG), with 5-year survival of patients treated surgically for oral squamous cell carcinoma (OSCC). This study evaluated the relationships between these PET parameters and 5-year survival in OSCC patients. Twenty-three patients (age 42–84 years; 15 male, eight female) with OSCC underwent FMISO- and 18F-fluoro-2-deoxyglucose (FDG)-PET computed tomography before surgery.
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The occurrence and characteristics of endoscopically unexpected malignant degeneration in large rectal adenomas
Large non-pedunculated rectal polyps are most commonly resected by endoscopic mucosal resection (EMR) or transanal endoscopic microsurgery (TEM). Despite preprocedural diagnostics, unexpected rectal cancer is incidentally encountered within the resected specimen. This study aimed to compare the diagnostic assessment and procedural characteristics of lesions with and without unexpected submucosal invasion.
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An unusual cause of bowel obstruction diagnosed by EUS
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Sleep problems in children with autism spectrum disorder and intellectual disability without autism spectrum disorder
The objective of this study was to evaluate the sleep problems and their correlations in children with autism spectrum disorder (ASD), intellectual disability without ASD (ID), and typically developing children (TDC).
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Correction: Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses [CORRECTIONS]
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New Methods To Analyze B Cell Immune Responses to Thymus-Dependent Antigen Sheep Red Blood Cells [NOVEL IMMUNOLOGICAL METHODS]
B cells contribute critically to an effective immune response by producing Ag-specific Abs. During the immune response to so-called "thymus-dependent Ags," activated B cells seek T cell help and form germinal centers. In contrast, thymus-independent Ags generally do not induce germinal center formation. In the germinal center, B cells undergo somatic hypermutation, affinity-based clonal expansion, and differentiation to produce plasma cells and memory B cells. Valuable insight into these processes has been gained by using model hapten–carrier complexes or SRBCs. SRBCs induce robust germinal center formation in mice. Therefore, this Ag is commonly used to study germinal center responses. In contrast to haptenated Ags, thus far it has been difficult to measure the titer of Ag-specific Abs or the expansion of Ag-specific B cells after immunization with SRBCs. We have developed new, simple methods to access these parameters, thus providing new tools to study germinal center and Ab responses.
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HVEM Imprints Memory Potential on Effector CD8 T Cells Required for Protective Mucosal Immunity [MUCOSAL IMMUNOLOGY]
Mucosal immunity to reinfection with a highly virulent virus requires the accumulation and persistence of memory CD8 T cells at the site of primary infection. These cells may derive from memory precursor effector cells (MPECs), which are distinct from short-lived effector cells that provide acute protection but are often destined to die. Using respiratory virus infection, we show that herpes virus entry mediator (HVEM; TNFRSF14), a member of the TNF receptor superfamily, provides key signals for MPEC persistence. HVEM-deficient CD8 T cells expanded normally but were skewed away from MPECs with resultant poor development of circulating and lung-resident memory cells. HVEM was selectively expressed on MPECs whereas MPECs deficient in HVEM failed to survive in adoptive transfer recipients. As a consequence, HVEM-deficient recipients failed to afford protection against respiratory reinfection with influenza virus. HVEM therefore represents a critical signal for MPECs and development of protective mucosal CD8 T cell memory.
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Anti-Inflammatory Role of Langerhans Cells and Apoptotic Keratinocytes in Ultraviolet-B-Induced Cutaneous Inflammation [INNATE IMMUNITY AND INFLAMMATION]
UV radiation, particularly UVB, is the major risk factor for the induction of skin cancer, and it induces skin inflammation and immunosuppression. Although reports documented that Langerhans cells (LCs) play various roles in photobiology, little is known about whether they contribute to UVB-induced cutaneous inflammation. Recently, the anti-inflammatory effect of apoptotic cells was noted. This study focuses on the roles of LCs and apoptotic cells in UVB-induced cutaneous inflammation. We show that LCs are essential for resolution of UVB-induced cutaneous inflammation. Administration of quinolyl-valyl-O-methylaspartyl-[2,6-difluophenoxy]-methyl ketone, a broad-spectrum caspase inhibitor with potent antiapoptotic properties, inhibited the formation of UVB-induced apoptotic cells and aggravated UVB-induced cutaneous inflammation in wild-type mice. In contrast, exacerbation of UVB-induced cutaneous inflammation following quinolyl-valyl-O-methylaspartyl-[2,6-difluophenoxy]-methyl ketone administration was not observed in LC-depleted mice. These results suggest that the interaction between LCs and apoptotic cells is critical for resolution of UVB-induced cutaneous inflammation. Interestingly, UVB-induced apoptotic keratinocytes were increased in LC-depleted mice. In addition, we revealed that UVB-induced apoptotic keratinocytes were phagocytosed by LCs ex vivo and that prolongation of UVB-induced cutaneous inflammation following treatment with Cytochalasin D, an inhibitor of phagocytosis, was partially attenuated in LC-depleted mice. Collectively, our findings demonstrate that the interaction between LCs and apoptotic cells, possibly via LC-mediated phagocytosis of apoptotic keratinocytes, has an essential anti-inflammatory role in the resolution of UVB-induced cutaneous inflammation.
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Activated Protein C Attenuates Severe Inflammation by Targeting VLA-3high Neutrophil Subpopulation in Mice [INNATE IMMUNITY AND INFLAMMATION]
The host injury involved in multiorgan system failure during severe inflammation is mediated, in part, by massive infiltration and sequestration of hyperactive neutrophils in the visceral organ. A recombinant form of human activated protein C (rhAPC) has shown cytoprotective and anti-inflammatory functions in some clinical and animal studies, but the direct mechanism is not fully understood. Recently, we reported that, during endotoxemia and severe polymicrobial peritonitis, integrin VLA-3 (CD49c/CD29) is specifically upregulated on hyperinflammatory neutrophils and that targeting the VLA-3high neutrophil subpopulation improved survival in mice. In this article, we report that rhAPC binds to human neutrophils via integrin VLA-3 (CD49c/CD29) with a higher affinity compared with other Arg-Gly-Asp binding integrins. Similarly, there is preferential binding of activated protein C (PC) to Gr1highCD11bhighVLA-3high cells isolated from the bone marrow of septic mice. Furthermore, specific binding of rhAPC to human neutrophils via VLA-3 was inhibited by an antagonistic peptide (LXY2). In addition, genetically modified mutant activated PC, with a high affinity for VLA-3, shows significantly improved binding to neutrophils compared with wild-type activated PC and significantly reduced neutrophil infiltration into the lungs of septic mice. These data indicate that variants of activated PC have a stronger affinity for integrin VLA-3, which reveals novel therapeutic possibilities.
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IL-17A Produced by Innate Lymphoid Cells Is Essential for Intestinal Ischemia-Reperfusion Injury [INNATE IMMUNITY AND INFLAMMATION]
Ischemia-reperfusion (IR) injury to the small intestine following clamping of the superior mesenteric artery results in an intense local inflammatory response that is characterized by villous damage and neutrophil infiltration. IL-17A, a cytokine produced by a variety of cells in response to inflammatory cytokines released following tissue injury, has been implicated in IR injury. Using Il17a–/–, Il23r–/–, and Rorc–/– mice and administration of anti–IL-17A and anti–IL-23 neutralizing Abs to wild-type mice, we demonstrate that intestinal IR injury depends on IL-17A and that IL-17A is downstream of the binding of autoantibody to ischemia-conditioned tissues and subsequent complement activation. Using bone marrow chimeras, we demonstrate that the IL-17A required for intestinal IR injury is derived from hematopoietic cells. Finally, by transferring autoantibody-rich sera into Rag2c–/– and Rag2–/– mice, we demonstrate that innate lymphoid cells are the main producers of IL-17A in intestinal IR injury. We propose that local production of IL-17A by innate lymphoid cells is crucial for the development of intestinal IR injury and may provide a therapeutic target for clinical exploitation.
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Cyclodextrin Reduces Cholesterol Crystal-Induced Inflammation by Modulating Complement Activation [INNATE IMMUNITY AND INFLAMMATION]
Cholesterol crystals (CC) are abundant in atherosclerotic plaques and promote inflammatory responses via the complement system and inflammasome activation. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (BCD) is a compound that solubilizes lipophilic substances. Recently we have shown that BCD has an anti-inflammatory effect on CC via suppression of the inflammasome and liver X receptor activation. The putative effects of BCD on CC-induced complement activation remain unknown. In this study, we found that BCD bound to CC and reduced deposition of Igs, pattern recognition molecules, and complement factors on CC in human plasma. Furthermore, BCD decreased complement activation as measured by terminal complement complex and lowered the expression of complement receptors on monocytes in whole blood in response to CC exposure. In line with this, BCD also reduced reactive oxygen species formation caused by CC in whole blood. Furthermore, BCD attenuated the CC-induced proinflammatory cytokine responses (e.g., IL-1α, MIP-1α, TNF, IL-6, and IL-8) as well as regulated a range of CC-induced genes in human PBMC. BCD also regulated complement-related genes in human carotid plaques treated ex vivo. Formation of terminal complement complex on other complement-activating structures such as monosodium urate crystals and zymosan was not affected by BCD. These data demonstrate that BCD inhibits CC-induced inflammatory responses, which may be explained by BCD-mediated attenuation of complement activation. Thus, these findings support the potential for using BCD in treatment of atherosclerosis.
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Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation [INNATE IMMUNITY AND INFLAMMATION]
Chorioamnionitis, premature rupture of fetal membranes (FMs), and subsequent preterm birth are associated with local infection and inflammation, particularly IL-1β production. Although bacterial infections are commonly identified, other microorganisms may play a role in the pathogenesis. Because viral pandemics, such as influenza, Ebola, and Zika, are becoming more common, and pregnant women are at increased risk for associated complications, this study evaluated the impact that viral infection had on human FM innate immune responses. This study shows that a herpes viral infection of FMs sensitizes the tissue to low levels of bacterial LPS, giving rise to an exaggerated IL-1β response. Using an ex vivo human FM explant system and an in vivo mouse model of pregnancy, we report that the mechanism by which this aggravated inflammation arises is through the inhibition of the TAM receptor, MERTK, and activation of the inflammasome. The TAM receptor ligand, growth arrest specific 6, re-establishes the normal FM response to LPS by restoring and augmenting TAM receptor and ligand expression, as well as by preventing the exacerbated IL-1β processing and secretion. These findings indicate a novel mechanism by which viruses alter normal FM immune responses to bacteria, potentially giving rise to adverse pregnancy outcomes.
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A Chlamydia-Specific TCR-Transgenic Mouse Demonstrates Th1 Polyfunctionality with Enhanced Effector Function [INFECTIOUS DISEASE AND HOST RESPONSE]
Chlamydia is responsible for millions of new infections annually, and current efforts focus on understanding cellular immunity for targeted vaccine development. The Chlamydia-specific CD4 T cell response is characterized by the production of IFN-, and polyfunctional Th1 responses are associated with enhanced protection. A major limitation in studying these responses is the paucity of tools available for detection, quantification, and characterization of polyfunctional Ag-specific T cells. We addressed this problem by developing a TCR-transgenic (Tg) mouse with CD4 T cells that respond to a common Ag in Chlamydia muridarum and Chlamydia trachomatis. Using an adoptive-transfer approach, we show that naive Tg CD4 T cells become activated, proliferate, migrate to the infected tissue, and acquire a polyfunctional Th1 phenotype in infected mice. Polyfunctional Tg Th1 effectors demonstrated enhanced IFN- production compared with polyclonal cells, protected immune-deficient mice against lethality, mediated bacterial clearance, and orchestrated an anamnestic response. Adoptive transfer of Chlamydia-specific CD4 TCR-Tg T cells with polyfunctional capacity offers a powerful approach for analysis of protective effector and memory responses against chlamydial infection and demonstrates that an effective monoclonal CD4 T cell response may successfully guide subunit vaccination strategies.
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An Anti-Inflammatory Role for NLRP10 in Murine Cutaneous Leishmaniasis [INFECTIOUS DISEASE AND HOST RESPONSE]
The role of the nucleotide-binding domain and leucine-rich repeat containing receptor NLRP10 in disease is incompletely understood. Using three mouse strains lacking the gene encoding NLRP10, only one of which had a coincidental mutation in DOCK8, we documented a role for NLRP10 as a suppressor of the cutaneous inflammatory response to Leishmania major infection. There was no evidence that the enhanced local inflammation was due to enhanced inflammasome activity. NLRP10/DOCK8-deficient mice harbored lower parasite burdens at the cutaneous site of inoculation compared with wild-type controls, whereas NLRP10-deficient mice and controls had similar parasite loads, suggesting that DOCK8 promotes local growth of parasites in the skin, whereas NLRP10 does not. NLRP10-deficient mice developed vigorous adaptive immune responses, indicating that there was not a global defect in the development of Ag-specific cytokine production. Bone marrow chimeras showed that the anti-inflammatory role of NLRP10 was mediated by NLRP10 expressed in resident cells in the skin rather than by bone marrow–derived cells. These data suggest a novel role for NLRP10 in the resolution of local inflammatory responses during L. major infection.
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NKG2D Signaling between Human NK Cells Enhances TACE-Mediated TNF-{alpha} Release [INNATE IMMUNITY AND INFLAMMATION]
NK group 2 member D (NKG2D) is a strong NK cell–activating receptor, with engagement by ligands triggering granule release and cytokine production. The function of NKG2D signaling in NK cells has largely been studied in the context of engagement of the receptor by ligands expressed on the surface of target cells. We report that upon activation with IL-12, IL-15, and IL-18 human NK cells express NKG2D ligands of the UL16 binding protein family on the cell surface. NKG2D-ligand interaction between cytokine-stimulated NK cells increases the activity of the metalloprotease TNF-α–converting enzyme. This enhanced TNF-α–converting enzyme activity significantly increases the release of TNF-α and UL16 binding protein from the surface of the NK cells. These results demonstrate that NKG2D signaling is critical for maximal TNF-α release by NK cells. Further, they demonstrate a role for NKG2D-ligand interaction via homotypic NK cell contact in NK cell effector function.
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IL-4/IL-13 Signaling Inhibits the Potential of Early Thymic Progenitors To Commit to the T Cell Lineage [IMMUNE SYSTEM DEVELOPMENT]
Early thymic progenitors (ETPs) are endowed with diverse potencies and can give rise to myeloid and lymphoid lineage progenitors. How the thymic environment guides ETP commitment and maturation toward a specific lineage remains obscure. We have previously shown that ETPs expressing the heteroreceptor (HR) comprising IL-4Rα and IL-13Rα1 give rise to myeloid cells but not T cells. In this article, we show that signaling through the HR inhibits ETP maturation to the T cell lineage but enacts commitment toward the myeloid cells. Indeed, HR+ ETPs, but not HR– ETPs, exhibit activated STAT6 transcription factor, which parallels with downregulation of Notch1, a critical factor for T cell development. Meanwhile, the myeloid-specific transcription factor C/EBPα, usually under the control of Notch1, is upregulated. Furthermore, in vivo inhibition of STAT6 phosphorylation restores Notch1 expression in HR+ ETPs, which regain T lineage potential. In addition, upon stimulation with IL-4 or IL-13, HR– ETPs expressing virally transduced HR also exhibit STAT6 phosphorylation and downregulation of Notch1, leading to inhibition of lymphoid, but not myeloid, lineage potential. These observations indicate that environmental cytokines play a role in conditioning ETP lineage choice, which would impact T cell development.
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Trapezius flaps for reconstruction of head and neck defects following oncological resection-a systematic review
Publication date: Available online 10 October 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Conor M. Sugrue, Grainne Rooney, Ryan M. Sugrue
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Knowledge and care seeking practices for ear infections among parents of under five children in Kigali, Rwanda: a cross-sectional study
Infections affecting the middle ear are a common childhood occurrence. Some cases may present with ear discharge through a tympanic membrane perforation which may heal spontaneously. However, up to 5% or more ...
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Institutional Experience with Ostomies Created During Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion
Abstract
Background
Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) is a complex procedure that often requires ostomy creation to protect high-risk anastomoses. This study aimed to evaluate the authors' institutional experience with CRS-HIPEC-associated ostomies, determine predictors of ostomy creation and reversal, and assess their impact on survival.
Methods
The study analyzed clinicopathologic, perioperative, and oncologic data from a prospective database of 1435 CRS-HIPEC procedures for peritoneal metastases. The Kaplan–Meier method was used to estimate survival. Multivariate analyses identified associations with ostomy creation/reversal and survival.
Results
Ostomies were created in 34% of the patients, most commonly loop ileostomies (82%). Loop ileostomies were reversed in the majority of patients (83%), whereas non-loop ileostomies were infrequently reversed (< 10% reversal rate). In a multivariate logistic regression model, intermediate or high tumor grade, colectomy/proctectomy, longer operative time, and lower Charlson comorbidity index were associated with loop ileostomy creation, whereas incomplete macroscopic resection, colorectal histology, and major postoperative complications were associated with non-reversal of loop ileostomy. In a multivariate Cox proportional hazards model, intermediate or high tumor grade and non-reversal of loop ileostomy were associated with worse overall survival.
Conclusions
Loop ileostomies were almost always reversed, whereas non-loop ileostomies were almost always permanent. Hospital readmissions for loop ileostomy-related complications were common. Therefore, formal outpatient protocols for prevention and management should be implemented. Non-reversal of loop ileostomy was associated with very poor survival.
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Glycan diversity in the vomeronasal organ of the Korean roe deer, Capreolus pygargus: A lectin histochemical study
Source:Acta Histochemica
Author(s): Taekyun Shin, Jeongtae Kim, Yuna Choi, Meejung Ahn
Glycans in the epithelium play an important role in cell-to-cell communication and adhesion. No detailed evaluation of glycoconjugates in the vomeronasal organs (VNO) of the roe deer has been published previously. The aim of this study was to characterize glycan epitopes in the vomeronasal sensory epithelium (VSE) and non-sensory epithelium (VNSE) using lectin histochemistry. Glycan epitopes identified by lectin histochemistry were grouped as follows: N‐acetylglucosamine (s-WGA, WGA, BSL-II, DSL, LEL, STL), mannose (Con A, LCA, PSA), galactose (RCA120, BSL-I, Jacalin, PNA, ECL), N-acetylgalactosamine (VVA, DBA, SBA, and SJA), fucose (UEA-I) and complex type N-glycan (PHA-E and PHA-L) groups. The free border of the VSE was positive for all 21 lectins, and 18 of the lectins (excluding DBA, SJA, and PHA-L) showed weak and/or moderate staining in the receptor cells. The supporting cells were weakly positive for 19 lectins (excluding PNA and SJA). Moreover, 17 lectins (excluding BSL-II, Jacalin, PNA, and SJA) were expressed in the basal cells. In the VNSE of roe deer, the free border showed staining for all 21 lectins examined. The ciliated cells were positive for 16 lectins (excluding BSL-II, DSL, PNA, VVA, and SJA). Furthermore, 15 lectins (excluding DSL, LEL, ECL, UEA-I, PHA-E, and PHA-L) were expressed in goblet cells. Twenty lectins (excluding SJA) were expressed in the acini of the vomeronasal glands. Collectively, both VSE and VNSE were rich in N-acetylglucosamine, mannose, galactose, N‐acetylgalactosamine, fucose, and complex-type N-glycans, although the different cell types of the VSE and VNSE expressed different glycoconjugates of varying intensities, suggesting that these carbohydrate residues may be involved in odor perception as well as cell-to-cell communication in the VNO.
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Nomenclature in Ventral Hernia Repair
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The Depth from the Skin to the Celiac Artery Measured Using Computed Tomography is a Simple Predictive Index for Longer Operation Time During Laparoscopic Distal Gastrectomy
Abstract
Background
Body mass index (BMI) is commonly used to classify obesity. However, BMI does not always reflect the degree of visceral fat. This study aimed to clarify the usefulness of measuring the depth from the skin to the celiac artery using computed tomography, as a simple predictive index for longer operation time during laparoscopic distal gastrectomy (LDG).
Methods
From September 2012 to March 2016, 66 patients who underwent LDG with D1+ lymph node dissection were included. The depth from the skin to the bifurcation of the celiac artery was defined as 'skin-to-celiac artery distance (SCD).' The patients were divided into two groups based on the median operation time. [Time scenarios from omentum incision to specimen extirpation and infrapyloric and suprapancreatic lymph node dissections (I-LND, S-LND) were assessed.] The factors eliciting a longer operation time than the median operation time were investigated.
Results
From omentum incision to specimen extirpation, BMI, thickness of subcutaneous fat (TSF), and SCD (P = 0.002, P = 0.039, P < 0.001) were the factors associated with longer operation time. Furthermore, BMI, TSF, and SCD in I-LND (P = 0.008, P = 0.022, P < 0.001) and BMI and SCD in S-LND (P < 0.001, P < 0.001) were associated with longer operation time. The multivariate analysis showed that a long SCD was the only significant independent factor to predict an operation time longer than the median operation time (P = 0.001). The best cutoff level of SCD calculated using the receiver operating characteristic curve was 88 mm.
Conclusions
This study demonstrated that SCD is a simple predictive index for longer operation time during LDG.
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Fixed Dosing of Monoclonal Antibodies in Oncology
AbstractMost monoclonal antibodies in oncology are administered in body–size‐based dosing schedules. This is believed to correct for variability in both drug distribution and elimination between patients. However, monoclonal antibodies typically distribute to the blood plasma and extracellular fluids only, which increase less than proportionally with the increase in body weight. Elimination takes place via proteolytic catabolism, a nonspecific immunoglobulin G elimination pathway, and intracellular degradation after binding to the target. The latter is the primary route of elimination and is related to target expression levels rather than body size. Taken together, the minor effects of body size on distribution and elimination of monoclonal antibodies and their usually wide therapeutic window do not support body–size‐based dosing. We evaluated effects of body weight on volume of distribution and clearance of monoclonal antibodies in oncology and show that a fixed dose for most of these drugs is justified based on pharmacokinetics. A survey of the savings after fixed dosing of monoclonal antibodies at our hospital showed that fixed dosing can reduce costs of health care, especially when pooling of preparations is not possible (which is often the case in smaller hospitals). In conclusion, based on pharmacokinetic parameters of monoclonal antibodies, there is a rationale for fixed dosing of these drugs in oncology. Therefore, we believe that fixed dosing is justified and can improve efficiency of the compounding. Moreover, drug spillage can be reduced and medication errors may become less likely.Implications for Practice.The currently available knowledge of elimination of monoclonal antibodies combined with the publicly available data from clinical trials and extensive population pharmacokinetic (PopPK) modeling justifies fixed dosing. Interpatient variation in exposure is comparable after body weight and fixed dosing and most monoclonal antibodies show relatively flat dose‐response relationships. For monoclonal antibodies, this results in wide therapeutic windows and no reduced clinical efficacy after fixed dosing. Therefore, we believe that fixed dosing at a well‐selected dose can increase medication safety and help in reduction of costs of health care without the loss of efficacy or safety margins.
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A Phase II Study with Lead‐In Safety Cohort of 5‐Fluorouracil, Oxaliplatin, and Lapatinib in Combination with Radiation Therapy as Neoadjuvant Treatment for Patients with Localized HER2‐Positive Esophagogastric Adenocarcinomas
AbstractLessons Learned.Neoadjuvant 5‐fluorouracil, oxaliplatin, and lapatinib in combination with radiation therapy is safe for neoadjuvant treatment for patients with localized human epidermal growth receptor 2‐positive esophagogastric adenocarcinoma.Evaluation of this drug combination in a larger patient pool would allow for more accurate analysis of its efficacy. Background.The optimal design of neoadjuvant chemoradiation for the treatment of localized esophagogastric cancers is the subject of much debate. In this nonrandomized trial, we evaluated neoadjuvant 5‐fluorouracil (5‐FU), oxaliplatin, and lapatinib in combination with radiation therapy as neoadjuvant treatment for patients with localized human epidermal growth receptor 2 (HER2)‐positive esophagogastric adenocarcinomas.Methods.Patients received neoadjuvant 5‐FU (225 mg/m2 continuous intravenous infusion, days 1–42), oxaliplatin (85 mg/m2 intravenously [IV], days 1, 15, and 29), and lapatinib (six patients, 1,000 mg p.o., days 1–42; six patients, 750 mg p.o., days 1–42) plus radiation (1.8 Gy/day Monday through Friday for 50.4 Gy total). Following restaging, eligible patients underwent definitive resection, and pathologic response to neoadjuvant therapy was assessed. Planned enrollment was 42 patients. The primary endpoint was the pathologic complete response (pCR) rate.Results.Twelve patients (median age 64 years; 67% male) received a median of 5.6 weeks of treatment (range: 1.1–8.4). The pCR rate was 8%; four of the 12 patients underwent tumor resection and one patient had a pCR, with pathologic partial response in the remaining three. The most common lapatinib‐related adverse events included (all grades) nausea (67%) and diarrhea (58%), although these were all grade 1 or 2. Enrollment was halted due to low accrual.Conclusion.The treatment regimen was determined to be safe. The study was terminated early due to low accrual.
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