Publication date: Available online 3 March 2018
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Ingmar L. Defize, Bernadette Schurink, Teus J. Weijs, Tom A.P. Roeling, Jelle P. Ruurda, Richard van Hillegersberg, Ronald L.A.W. Bleys
BackgroundInjury and subsequent leakage of unrecognized thoracic duct tributaries during transthoracic esophagectomy may lead to chylothorax. Therefore, we hypothesized that thoracic duct anatomy at the diaphragm is more complex than currently recognized and aimed to provide a detailed description of the anatomy of the thoracic duct at the diaphragm.Basic proceduresThe thoracic duct and its tributaries were dissected in 7 (2 male and 5 female) embalmed human cadavers. The level of origin of the thoracic duct and the points where tributaries entered the thoracic duct were measured using landmarks easily identified during surgery: the aortic and esophageal hiatus and the arch of the azygos vein.Main findingsThe thoracic duct was formed in the thoracic cavity by the union of multiple abdominal tributaries in 6 cadavers. In 3 cadavers partially duplicated systems were present that communicated with interductal branches. The thoracic duct was formed by a median of 3 (IQR: 3–5) abdominal tributaries merging 8.3 centimeters (IQR: 7.3–9.3cm) above the aortic hiatus, 1.8 centimeters (IQR: −0.4–2.4cm) above the esophageal hiatus, and 12.3 centimeters (IQR: 14.0–−11.0cm) below the arch of the azygos vein.ConclusionThis study challenges the paradigm that abdominal lymphatics join in the abdomen to pass the diaphragm as a single thoracic duct. In this study, this occurred in 1/7 cadavers. Although small, the results of this series suggest that the formation of the thoracic duct above the diaphragm is more common than previously thought. This knowledge may be vital to prevent and treat post-operative chyle leakage.
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Σάββατο 3 Μαρτίου 2018
The anatomy of the thoracic duct at the level of the diaphragm: a cadaver study
Electrochemical testing of a novel alloy in natural and artificial body fluids
Publication date: Available online 3 March 2018
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Ioana Bunoiu, Mihaela Mindroiu, Claudiu Constantin Manole, Mihai Andrei, Adrian Nicoara, Ecaterina Vasilescu, Monica Popa, Andreea Cristiana Didilescu
There is a recent trend in tissue engineering and regenerative medicine to use nanotechnology and bionanomaterials to obtain materials that mimic the surface properties of a natural tissue. From this perspective, nanolevel tissue engineering can be viewed as a novel anatomy of the future. In this paper, a novel titanium-based alloy is studied following this strategy. The alloy nanostructuration is proposed as an improved alternative for restorative prosthodontics or an implantable biomaterial. Tests in i) standard solution of simulated body fluid (SBF) and ii) natural saliva were performed to investigate the alloy's electrochemical stability. The results show that nanochannel growth on the alloy surface confers a higher stability than that of the untreated one in both natural and simulated environments.
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Brachytherapy in Head and Neck Cancers: “Are We Doing It or Are We Done with It”
Abstract
We performed an e-Survey and reviewed the literature on the prevalence of use of brachytherapy in head and neck cancers in order to understand the patterns of care and probable application of this modality. A five-point questionnaire was prepared and sent to 300 oncologists through a web-based survey engine. This was done in preparation for my lecture on "Ongoing Research and Potential Research Avenues" in IBSCON held in Chennai in August 2016. SPSS software was used for the statistical analysis. Of a total of 300 emails that were sent out for the survey, 120 replies were received, which is 40%. Among the results of various questions, (i) 65% of the oncologists felt that there were > 300 ongoing studies in brachytherapy and out of them only 10–20 were on head and neck brachytherapy; (ii) 58% of the responders felt that external beam radiotherapy (EBRT) advances followed by lack of training and experience are the reasons for declining role of brachytherapy; (iii) among the responders, numbers of head and neck brachytherapy performed stand third after gynecological and breast brachytherapy. This survey shows that brachytherapy in head and neck cancers is an essential tool, but seldom practiced. If no path-breaking event happens, we may be dealing with it as a dying art.
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Aquatic Ecosystem Degradation of High Conservation Value Upland Swamps, Blue Mountains Australia
Abstract
Temperate highland peat swamps on sandstone (THPSS) are unique state and federally protected ecological communities. THPSS is a higher level classification which is comprised of multiple swamp communities which include Blue Mountains Swamps and Newnes Plateau Shrub Swamps. The Blue Mountains has a string of urban settlements surrounded by large expanses of undisturbed natural vegetation which have varied degrees of protection ranging from state forests to World Heritage national parks. This study investigated aquatic invertebrates from seven THPSS within the Greater Blue Mountains area. Four swamps drain catchments with varying degrees of urban development and associated impervious surfaces, and three swamps have non-urban, naturally vegetated catchments. Water chemistry of non-urban swamps was acidic (mean pH 4.70) and dilute (mean EC 26.7 uS/cm) and dominated by sodium and chloride ions with most other major ions at low concentrations often below detection limits (Belmer et al. 2015). In contrast, urban swamps had higher pH (mean 6.60) and salinity (mean 153.9 uS/cm) and were dominated by calcium and bicarbonate ions (Belmer et al. 2015). Aquatic macroinvertebrate abundance, family richness and % EPT taxa were all found to be lower within urban swamps when compared to non-urban swamps. These results support the hypothesis of Belmer et al. (2015) that urban runoff within THPSS catchments is affecting the condition of their aquatic ecosystems.
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Quantitative Proteomics Identify the Possible Tumor Suppressive Role of Protease-Activated Receptor-4 in Esophageal Squamous Cell Carcinoma Cells
Abstract
Exposure to carcinogens of tobacco smoke may result in methylation of protease-activated receptors-4 (PAR4) gene and further induces the loss of PAR4 expression, which is considered to be involved in carcinogenesis of esophageal squamous cell carcinoma (ESCC). Here we employed a TMT-based quantitative proteomic approach to identify PAR4-regulated changes of proteomic profiles in ESCC cells and to identify potentially therapeutic value. A total of 33 proteins were found significantly changed with 15 up-regulated and 18 down-regulated in PAR4-activating peptide (PAR4-AP) treated ESCC cells compared with controls. Bioinformatics analysis showed that key higher expressed proteins included those associated with apoptosis and tumor suppressor (e.g. CASP9), and lower expressed proteins included those associated with anti-apoptosis, autophagy and promoting cell proliferation (e.g. CHMP1B, PURA, PARG and HIST1H2AH). Western blot verified changes in five representative proteins including CASP9, CHMP1B, PURA, PARG and HIST1H2AH. Immunohistochemistry analysis showed that CHMP1B, PURA, PARG and HIST1H2AH expression in ESCC tissues were significantly higher than those in adjacent nontumorous tissues. Our findings will be helpful in further investigations into the functions and molecular mechanisms of PAR4 in ESCC.
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Adjuvant vinorelbine and cisplatin after complete resection of stage II and III non-small cell lung cancer: long-term follow-up of our study of Japanese patients
Abstract
Purpose
We reported previously a phase II study of adjuvant chemotherapy consisting of four cycles of vinorelbine (25 mg/m2) and cisplatin (40 mg/m2), given on days 1 and 8, every 4 weeks, to Japanese patients with completely resected stage II or III non-small cell lung cancer (NSCLC; UMIN 000005055). However, the follow-up was too short for us to evaluate a definitive 5-year overall survival rate and after-effects.
Methods
Between December 2006 and January 2011, 60 patients were enrolled in this study. We analyzed relapse-free and overall survival, long-lasting adverse effects, the influence of treatment on recurrent tumors, and the development of a second primary cancer, in relation with the regimen.
Results
After a median follow-up period of 95.8 months, the 5-year relapse-free and overall survival rates were 51.7 and 76.7%, respectively. Neuralgia developed in one patient and this was the only case of a long-lasting adverse effect. Recurrence developed in 31 patients, 29 of whom received intensive treatment. Although 16 s (or more) primary neoplasms developed among 13 patients, these were common carcinomas in Japan and did not include sarcoma or hematologic malignancies.
Conclusion
Adjuvant vinorelbine and cisplatin chemotherapy showed encouraging relapse-free and overall survival rates, and long-term safety in Japanese patients with resected NSCLC.
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Readiness of US General Surgery Residents for Independent Practice: Erratum
Questions Regarding Statistical Inferences, Quality of Life, and Conclusions From the COBRA Study
Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS)
Objective: The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study. Summary of Background Data: Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option. Methods: We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year. Results: At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months. Conclusions: Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2seh64w
Prevent the Bleed: How Surgeons Can Lead the National Conversation About Firearm Safety Forward
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2scVxkP
Dissecting Surgeon Behavior: Leveraging the Theoretical Domains Framework to Facilitate Evidence-based Surgical Practice
No abstract availablefrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2sbBLX5
A British Perspective on the American College of Surgeons Conversation About Firearm Safety
Randomized Controlled Trial of Liberal Versus Restricted Fluid Management in Patients Undergoing Pancreatectomy: Erratum
Hospital Standards to Promote Optimal Surgical Care of the Older Adult: A Report From the Coalition for Quality in Geriatric Surgery
Objective: The aim of this study was to establish high-quality, valid standards to improve surgical care of the older adult. Background: The aging population increases demand for high-quality surgical care. Building upon prior guidelines, quality indicators, and pilot projects, the Coalition for Quality in Geriatric Surgery (CQGS) includes 58 diverse stakeholder organizations committed to improving geriatric surgery. Methods: Using a modified RAND-UCLA Appropriateness Methodology, 44 of 58 CQGS Stakeholders twice rated validity (primary outcome) and feasibility for 308 standards, ranging from goals and decision-making, pre-operative assessment and optimization, perioperative and postoperative care, to transitions of care beyond the acute care hospital. Results: Three hundred six of 308 (99%) standards were rated as valid to improve quality of geriatric surgery. There were 4 sections. Section 1 included 157 (57%) standards and focused on goals and decision-making, preoperative optimization, and transitions into and out of the hospital. Section 2 included 84 (27.3%) standards focused on in-hospital care, across the immediate preoperative, intraoperative, and postoperative phases. Section 3 included 59 (19.1%) standards about program management, including personnel and committee structure, credentialing, and education. Section 4 included 8 (2.6%) standards establishing overarching concepts for data collection and patient follow-up. Two hundred ninety of 308 standards (94.2%) were rated as feasible; 18 (5.8%) were rated as uncertain in feasibility. Conclusions: CQGS Stakeholders rated the vast majority of standards of care as highly valid (99%) and feasible (94%) for improving the quality of surgical care provided to older adults. Future work will focus on a pilot phase to better understand and address challenges to implementation of the standards.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nKE1za
Using Confidential Clinical Data Registries for Public Reporting and Pay for Performance
Laparoscopic Versus Open Liver Resection for Colorectal Liver Metastases—Which Is a More Suitable Standard Practice?
Pushing the Envelope in Perihiler Cholangiocellularcarcinoma Surgery: TIPE-ALPPS
Social Media as a Platform for Surgical Learning: Use and Engagement Patterns Among Robotic Surgeons
In response to technological advances and growing dispersion of surgical practice around the globe, social media platforms have emerged in recent years as channels for surgeons to share experiences, ask questions, and learn from one another. To better understand surgeons' engagement with these platforms, we analyzed data from a closed-membership Facebook group for robotic surgeons. Our analysis revealed that surgeons posted more frequently on midweek days, and further that text posts received significantly more comments, and significantly fewer "likes," than posts containing links, photos, or videos. We discuss the implications of these use and engagement patterns for the viability of social media platforms as tools for surgeons to learn vicariously from their peers' experiences and expertise.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CYpy88
Design Principles for Building a Leadership Development Program in a Department of Surgery
No abstract availablefrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FQ7BMe
Magnetic Surgery: Results From First Prospective Clinical Trial in 50 Patients
Objective: To evaluate a new magnetic surgical system during reduced-port laparoscopic cholecystectomy in a prospective, multicenter clinical trial. Background: Laparoscopic instrumentation coupled by magnetic fields may enhance surgeon performance by allowing for shaft-less retraction and mobilization. The movements can be performed under direct visualization, generating different angles of traction and reducing the number of trocars to perform the procedure. This may reduce well-known associated complications of trocars, including incisional pain, scarring, infection, bowel, and vascular injuries, among others. Methods: A prospective, multicenter, single-arm, open-label study was performed to assess the safety and performance of a magnetic surgical system (Levita Magnetics' Surgical System). The investigational device was used during a 3-port laparoscopic technique. The primary endpoints evaluated were safety and feasibility of the device to adequately mobilize the gallbladder to achieve effective exposure of the targeted surgical site. Patients were followed for 30 days postprocedure. Results: Between January 2014 and March 2015, 50 patients presenting with benign gallbladder disease were recruited. Forty-five women and 5 men with an average age of 39 years (18–59), average body mass index of 27 kg/m2 (20.4–34.1) and an average abdominal wall thickness of 2.6 cm (1.8–4.6). The procedures were successfully performed in all 50 patients. No device-related serious adverse events were reported. Surgeons rated as "excellent" (90%) or "sufficient" (10%) the exposure of the surgical site. Conclusions: This clinical trial shows that this new magnetic surgical system is safe and effective in reduced-port laparoscopic cholecystectomy.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FbSD22
Minimally Invasive Thoracic Surgery 3.0: Lessons Learned From the History of Lung Cancer Surgery
Volume Increases and Shared Decision-making in Joint Replacement Bundles
Prevalence of Musculoskeletal Disorders Among Surgeons Performing Minimally Invasive Surgery: A Systematic Review
Objective: The aim of this study was to review musculoskeletal disorder (MSD) prevalence among surgeons performing minimally invasive surgery. Background: Advancements in laparoscopic surgery have primarily focused on enhancing patient benefits. However, compared with open surgery, laparoscopic surgery imposes greater ergonomic constraints on surgeons. Recent reports indicate a 73% to 88% prevalence of physical complaints among laparoscopic surgeons, which is greater than in the general working population, supporting the need to address the surgeons' physical health. Methods: To summarize the prevalence of MSDs among surgeons performing laparoscopic surgery, we performed a systematic review of studies addressing physical ergonomics as a determinant, and reporting MSD prevalence. On April 15 2016, we searched Pubmed, EMBASE, the Cochrane Library, Web of Science, CINAHL, and PsychINFO. Meta-analyses were performed using the Hartung-Knapp-Sidik-Jonkman method. Results: We identified 35 articles, including 7112 respondents. The weighted average prevalence of complaints was 74% [95% confidence interval (95% CI) 65–83]. We found high inconsistency across study results (I2 = 98.3%) and the overall response rate was low. If all nonresponders were without complaints, the prevalence would be 22% (95% CI 16–30). Conclusions: From the available literature, we found a 74% prevalence of physical complaints among laparoscopic surgeons. However, the low response rates and the high inconsistency across studies leave some uncertainty, suggesting an actual prevalence of between 22% and 74%. Fatigue and MSDs impact psychomotor performance; therefore, these results warrant further investigation. Continuous changes are enacted to increase patient safety and surgical care quality, and should also include efforts to improve surgeons' well-being.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FPajBp
In the Next Issue
The Global Incidence of Appendicitis: A Systematic Review of Population-based Studies
Objective: We compared the incidence of appendicitis or appendectomy across the world and evaluated temporal trends. Summary Background Data: Population-based studies reported the incidence of appendicitis. Methods: We searched MEDLINE and EMBASE databases for population-based studies reporting the incidence of appendicitis or appendectomy. Time trends were explored using Poisson regression and reported as annual percent change (APC) with 95% confidence intervals (CI). APC were stratified by time periods and pooled using random effects models. Incidence since 2000 was pooled for regions in the Western world. Results: The search retrieved 10,247 citations with 120 studies reporting on the incidence of appendicitis or appendectomy. During the 21st century the pooled incidence of appendicitis or appendectomy (in per 100,000 person-years) was 100 (95% CI: 91, 110) in Northern America, and the estimated number of cases in 2015 was 378,614. The pooled incidence ranged from 105 in Eastern Europe to 151 in Western Europe. In Western countries, the incidence of appendectomy steadily decreased since 1990 (APC after 1989=−1.54; 95% CI: −2.22, −0.86), whereas the incidence of appendicitis stabilized (APC=−0.36; 95% CI: −0.97, 0.26) for both perforated (APC=0.95; 95% CI: −0.25, 2.17) and nonperforated appendicitis (APC=0.44; 95% CI: −0.84, 1.73). In the 21st century, the incidence of appendicitis or appendectomy is high in newly industrialized countries in Asia (South Korea pooled: 206), the Middle East (Turkey pooled: 160), and Southern America (Chile: 202). Conclusions: Appendicitis is a global disease. The incidence of appendicitis is stable in most Western countries. Data from newly industrialized countries is sparse, but suggests that appendicitis is rising rapidly.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I0YLff
The Risk of Adverse Pregnancy Outcomes Following Nonobstetric Surgery During Pregnancy: Estimates From a Retrospective Cohort Study of 6.5 Million Pregnancies
Objective: The aim of this study was to estimate the risk of adverse birth outcomes for women who underwent nonobstetric surgery during pregnancy compared with those who did not. Background: Previous research suggests that nonobstetric surgery occurs during 1% to 2% of pregnancies. However, there is limited evidence quantifying risks to the mother or pregnancy of such surgery. Methods: We examined maternity admissions using hospital administrative data collected between April 1, 2002, and March 31, 2012, and identified pregnancies wherein nonobstetric surgery occurred. We used logistic regression models to determine the adjusted relative risk, attributable risk, and number needed to harm of nonobstetric surgical procedures for adverse birth outcomes. Results: We identified 6,486,280 pregnancies. In 47,628 of these pregnancies, nonobstetric surgery had occurred. We found that nonobstetric surgery during pregnancy was associated with a higher risk of adverse birth outcomes, although the attributable risk was generally low. We estimated that every 287 surgical operations were associated with 1 additional stillbirth, every 31 operations associated with 1 additional preterm delivery, every 39 operations associated with 1 additional low birth weight baby, every 25 operations associated with 1 additional caesarean section, and every 50 operations associated with 1 additional long inpatient stay. Conclusions: Although we have no means of disentangling the effect of the surgery from the effect of the underlying condition, we found that the risk associated with nonobstetric surgery was relatively low, confirming that surgical procedures during pregnancy are generally safe. We believe that our findings improve upon previous research, and are useful reference points for any discussion of risk with prospective patients.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oO9NvE
Phosphorus Loss Mitigation in Leachate and Surface Runoff from Clay Loam Soil Using Four Lime-Based Materials
Abstract
The increased eutrophication phenomenon in Quebec lakes calls for an urgent phosphorus-reducing strategy to meet the Quebec water quality standard of 0.03 mg L−1 for phosphorus (P). The objective of this research was to evaluate the application of four lime-based products in reducing P losses through subsurface leachate and surface runoff and to determine their optimum application. Two sets of experiments were conducted: laboratory leaching study and runoff study with a rainfall simulator, using a clay loam soil collected from the Pike river watershed. The former followed a flow method with a full factorial design in three replicates. Soil columns were amended with different application dosages of lime ranging from 0 to 2% by soil weight. The results showed that all four lime-based products could be promising amendments in reducing P losses in the leachate. According to statistical analysis of ANOVA, high calcium hydrated lime and lime kiln dust #2 were found to be the most effective with an optimum application dosage of 1% while reducing total dissolved phosphorus concentrations in leachate from 0.057 to 0.009 and 0.023 mg L−1, respectively. For the runoff study, a rainfall simulator with a maximum rainfall intensity of 2 cm h−1 was built. High calcium hydrated lime and lime kiln dust #2 were able to reduce total dissolved phosphorus to 0.034 and 0.037 mg L−1, respectively. However, particulate phosphorus was significantly increased at the studied application rate. The results from this study can offer a promising measure in reducing total dissolved phosphorus in groundwater while providing a solution to the existing environment issue of eutrophication.
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Review of “Who Makes It to the End? A Novel Predictive Model for Identifying Surgical Residents at Risk for Attrition” by Yeo HL, Abelson JS, Mao J, Lewis F, Michelassi F, Bell R, Sedrakyan A, Sosa JA in Ann Surg 266: 499–507, 2017
Factors Influencing Perception of Facial Attractiveness: Gender and Dental Education
Purpose: This study was conducted to investigate the gender- and dental education-specific differences in perception of facial attractiveness for varying ratio of lower face contour. Methods: Two hundred eleven students (110 male respondents and 110 female respondents; aged between 20–38 years old) were requested to rate facial figures with alterations to the bigonial width and the vertical length of the lower face. We produced a standard figure which is based on the "golden ratio" and 4 additional series of figures with either horizontal or vertical alterations to the contour of lower face. The preference for each figure was evaluated using a Visual Analog Scale. The Kruskal Wallis test was used for differences in the preferences for each figure and the Mann–Whitney U test was used to evaluate gender-specific differences and differences by dental education. Results: In general, the highest preference score was indicated for the standard figure, whereas facial figure with large bigonial width and chin length had the lowest score. Male respondents showed significantly higher preference score for facial contour that had a 0.1 proportional increase in the facial height-bigonial width ratio over that of the standard figure. For horizontal alterations to the facial profiles, there were no significant differences in the preferences by the level of dental education. For vertically altered images, the average Visual Analog Scale was significantly lower among the dentally-educated for facial image that had a proportional 0.22 and 0.42 increase in the ratio between the vertical length of the chin and the lip. Conclusion: Generally, the standard image based on the golden ratio was the most. Slender face was appealed more to males than to females, and facial image with an increased lower facial height were perceived to be much less attractive to the dentally-educated respondents, which suggests that the dental education might have some influence in sensitivity to vertical changes in lower face.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fk6giH
Re-Engineering the Cleft Craft Surgery: Function is an Essential Element of the Repair
No abstract availablefrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tdEpMi
Mucosal Dehiscence After Alveolar Bone Graft in Cleft
Cleft lip and palate patient represent a challenging experience for the surgeon. This kind of patients had to be followed by a multidisciplinary team from the beginning to the end to avoid the deformation sequelae. During the several surgical procedures, the bone graft represents a possible procedure that, through the new procedure, could be avoided. Unfortunately, patient treated following the previous procedure must be submitted to alveolar bone graft to coordinate the arch, to restore the maxillary integrity, to allow the correct dentition.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FmqgRV
Critical Appraisal in Plastic Surgery: Nullius in Verba
No abstract availablefrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fm17qA
Cell Polarity and PAR Complex Likely to Be Involved in Dexamethasone-Induced Cleft Palate
Accumulating studies demonstrated that PAR complex contributed to the establishment and maintenance of cell polarity which was fundamental to many aspects of cell and developmental biology. The purpose of this study was to investigate whether dexamethasone (DEX) could downregulate the PAR complex and disrupt cell polarity in palatal epithelium during palatal fusion in mice. The C57BL/6J mice were selected for the experiment. Pregnant mice in control group and DEX-treated group were injected intraperitoneally with 0.9% sodium chloride 0.1 mL, which contained DEX 6 mg/kg respectively, every day from E10 to E12. The palatal epithelia morphology was observed with hematoxylin and eosin and scanning electron microscopy. Immunofluorescence staining, western blot, and real-time polymerase chain reaction were performed to detect the expression of PAR3/PAR6/aPKC. After being treated with DEX, the palatal shelves showed delayed development and became shorter and smaller. During the process of palatogenesis, PAR3 and PAR6 expressed in the palatal epithelium, and aPKC expressed in both the epithelium and the mesenchyme. Dexamethasone could downregulate the expression levels of PAR3/PAR6/aPKC in both protein and gene level. In conclusions, DEX affected the PAR complex of mouse embryonic palate, and could perturb the PAR complex and the cell polarity of medial edge epithelium cells, and caused the failure of palatal fusion.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fmq9FZ
Repair of the Nasal Floor by the Cleft Margin Flap in Bilateral Complete Cleft Lip
Bilateral complete cleft lip deformity has been the most challenging to plastic surgeons, and lots of methods of repair have been described in the literature. The basic principles are to achieve continuity of the orbicularis oris muscle, a balanced Cupid's bow with nasal ala, and a complete reconstruction of the nasal floor. The last one is, however, easily neglected. A well-reconstructed nasal floor serves as a good support of the nasal cartilage, which minimizes secondary deformity. In addition, a nasal floor with sufficient soft tissue and minimal contracture makes bone grafting easier in the future. The cleft margin flap was first introduced by Tajima in 1983 and used for the nasal floor repair in the unilateral complete cleft lip. The authors have used this technique in bilateral complete cleft lip repair, and from our practice, tension-free repairs of the nasal floors could easily be achieved by the cleft margin flaps. The results were satisfying and no significant scar contracture or deformity of the nasal floor was observed during follow-up. The authors conclude that the cleft margin flaps are viable and alternative choices for the repair of the nasal floors in bilateral complete cleft lip without major complications.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tivedQ
Surgical Management of Migraine Headache
Migraine surgery has been recently reported as an alternative to medical management to provide long-term relief in migraine sufferers. A prospective study was designed wherein patients diagnosed with migraine were screened for surgery by injecting botulinum toxin type A at the primary trigger site. Surgery consisted of corrugator supercilii muscle resection to decompress supra-trochlear and supra-orbital nerves with avulsion of zygomaticotemporal branch of trigeminal nerve. Using pre and postsurgery questionnaires, information regarding the degree of reduction of migraines with regard to severity and frequency; and surgical site problems was acquired. Thirty patients volunteered for migraine surgery. Mean migraine headaches reduced from 15.2 ± 6.3 episodes per month to 1.9 ± 2.4 episodes per month (P from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tecnQT
Alignment Strategy for Constricted Maxillary Dental Arch in Patients With Unilateral Cleft Lip and Palate Using Fixed Orthodontic Appliance
The purpose of this study was to compare the alignment pattern of the constricted maxillary dental arch by fixed orthodontic treatment (FOT) in the well-aligned and constricted arches of unilateral cleft lip and palate (UCLP) patients. 19 UCLP patients were divided into Group 1 (well-aligned arch, n = 9) and Group 2 (constricted arch, n = 10). After the cephalometric and maxillary dental arch variables before (T1) and after FOT (T2) were measured, statistical analysis was performed. There were no significant differences in the surgical timing of cheiloplasty, palatoplasty, and secondary alveolar bone grafting and in the surgical method of cheiloplasty between the 2 groups. However, Group 2 had a higher percentage of palatoplasty method, which could leave the denuded bone for secondary healing than Group 1 (P from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fmq5WL
Nontraumatic Intradiploic Epidermoid Cyst and Older Age: Association or Causality?
Background: Intradiploic epidermoid cysts (IEC) are rare, benign lesions derived from ectodermal remnants during neural tube closure. Their origin is still debated or unknown. Objective: Analyzing of the patients with intradiploic epidermoid cysts operated in the authors' department. Methods: The patients with IEC who were operated in the authors' department between January 2014 and December 2015 were investigated from data file. Results: Six patients with IEC were found, reviewed the literature, and noted that these cysts usually occur in adults. There are only 3 young cases that occurred after head injury. Conclusion: It was shown that the nontraumatic IEC are more frequent in older ages. In youngs, it can generally be embryologic or rarely of mechanical origin following trauma. Cranial trauma may be important for developing of IEC. Trauma may lead to inclusion of epidermal cells into the diploe of the skull and may be a reason of intradiploic epidermoid cyst in older age. The effect of older age, and gender difference on occurrence should be investigated.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2telSQa
Nasopharyngoscopic Analyses through Anterior Maxillary Distraction Osteogenesis for Adolescent Patients With Cleft Palate
Anterior maxillary distraction osteogenesis (AMDO) is a novel technique for correcting hypoplastic maxilla by sagittal expansion of the maxilla. Recent reports suggest that AMDO does not have an effect on fragile velopharyngeal function in patients with cleft palate. Furthermore, no studies have evaluated the impact of AMDO on velopharyngeal function. We adopted AMDO to correct severe hypoplastic maxilla in adolescent patients with cleft palate and evaluated its impact on velopharyngeal space and function in 8 patients aged 12 to 21 years who underwent AMDO from 2006 to 2014. All the patients had received treatment for cleft palate; however, they still exhibited marginal velopharyngeal insufficiency. The mean activation of the distractor was 10.9 ± 0.9 mm. We determined changes in velopharyngeal closure ratio and closure pattern via nasopharyngoscopy. Additionally, skeletal changes were evaluated using lateral cephalograms. The mean horizontal advancement in the cephalogram obtained 1 year after the distraction was +6.4 mm. Nasopharyngoscopic examination revealed that no deterioration of velopharyngeal gap had occurred after AMDO in all 8 patients. The velopharyngeal closure pattern changed from coronal to circular in 1 patient. Our results indicate that AMDO achieved correction of hypoplastic maxilla without deterioration in velopharyngeal gap and function. Therefore, AMDO is an effective and optimal approach for correcting hypoplastic maxilla especially in patients with fragile velopharyngeal function, such as those with cleft palate.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fmq1X1
Surgical Treatment of Synovial Chondromatosis in the Inferior Compartment of the Temporomandibular Joint With Articular Disc Involvement
The authors report an unusual case of painful synovial chondromatosis originated in the inferior compartment of the temporomandibular joint (TMJ) with articular disc involvement in a 56-year-old woman with complaint of severe pain in the right preauricular region. Magnetic resonance images showed advanced destruction of the right articular disc anteriorly displaced, condylar erosion, and distinct nodules within an extremely expanded inferior joint compartment with large amount of fluid, as well as a large TMJ effusion. A scintigraphy showed elevated bone uptake in the right TMJ, demonstrating intense bone remodeling activity in the region. After a right internal maxillary artery embolization, the patient underwent open surgery. The intraoperative procedures, including articular disc removal, condylar remodeling, and replacement of the articular disc, are described in detail. Synovial chondromatosis of the TMJ is a rare disease, especially when it affects the inferior compartment and the articular disc. Initial diagnosis is challenging and imaging techniques (magnetic resonance imaging and scintigraphy) play an important role in identifying signs, making accurate diagnosis, and offering additional information not available with conventional imaging, such as TMJ inflammation or remodeling. In these patients, open surgery may be considered a definitive treatment, since the postoperative recurrence rate is very low.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tfvom0
Complications From Surgically Assisted Rapid Maxillary Expansion With HAAS and HYRAX Expanders
The current study aimed at comparing the number and type of undesired outcomes during and after the maxillary expansion performed with HYRAX and HAAS expanders. A total of 90 patients (41 males and 49 females, 45.6% and 54.4%, respectively) aged 18 to 59 (mean age of 26.1; standard deviation [SD] = 7.4) underwent subtotal Le Fort I osteotomy and pterygomaxillary disjunction following surgically assisted rapid maxillary expansion (SARME) carried out using HAAS (n = 29; 48.3% male and 51.7% female; mean age = 27: SD = 7.7) and HYRAX (n = 61; 44.3% male and 55.7% female; mean age = 26; SD = 7.2) expanders. Post-SARME dento-gingival, radiographic, and clinical undesired outcomes were evaluated. A total of 16 (17.8%) patients experienced at least 1 undesired outcome—7 (7.8%) and 9 (10.0%) in HAAS and HYRAX group, respectively. The most common undesired outcomes were radiographic asymmetric expansion—2 (2.2%) and 3 (3.3%) in HAAS and HYRAX group, respectively—followed by pain during out-of-clinic expansion 4 (4.4%) in HAAS group only—dental darkening 5 (5.5%) in HYRAX group, only, requiring root canal treatment, and local infection—2 (2.2%), 1 in each HAAS and HYRAX groups. Excepting for complications arising from the acrylic stop plate in HAAS expander, the number and severity of complications observed in the current study did not differ due to the use of HAAS and HYRAX appliances to perform maxillary expansion. Hygiene issues do not rule out the use of HAAS. The wider maxillary expansion performed, the more frequent are the cases of asymmetric expansion.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fmqx7p
Age-Related Volumetric Changes in Mandibular Condyles
A precise knowledge of the condylar changes with advancing age may improve understanding of pathophysiological alterations of the mandibular condyles. However, the majority of studies focusses on morphological changes, although volumetric analysis based upon cone beam computerized tomography may provide important additional data to characterize mandibular condyles. Therefore, we aimed to provide and compare volumetric data of mandibular condyles of a young and old patient group. This is a retrospective chart review of 195 patients with cone beam computerized tomography between 2007 and 2016. Student t test, analysis of variance, and Pearson correlation test were performed to analyze associations between categorical and continuous variables. P valuesfrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tepMbN
Evaluating Resident Perspectives on International Humanitarian Missions
Background: Opportunities for international missions are highly sought after by medical students, residents, and attending plastic surgeons. The educational benefits and ethical considerations of trainees participating in these ventures have been extensively debated. At the time of this writing, many surgical training programs lack the necessary infrastructure or funds to support missions of this sort. Despite the increasing interest, the perceived benefit of international work has not yet been well studied. The authors seek to evaluate residents' perspectives on the personal and educational benefits of international mission work. Methods: A 24-item online questionnaire was designed to measure residents' perspectives on humanitarian missions. Residents' perceptions on how participation in these missions may have influenced their career path were also evaluated. This questionnaire was disseminated to the plastic surgery residents in Accreditation Council for Graduate Medical Education (ACGME) accredited programs in the United States during the 2015 to 2016 academic year. Results: Of the 123 responses collected, 49 (40%) indicated that they had participated in international mission work prior to beginning residency, while 74 (60%) had not. Fifty-seven percent (n = 25) of those who had participated agreed that this experience impacted their choice to pursue plastic surgery as a specialty. Twenty-nine (24%) participated in 1 or more missions during residency. The most common type of mission work focused on cleft lip/palate repairs (n = 24) followed by nonsurgical medical relief (n = 18) and general plastics/combined (n = 6). Most respondents reported trips lasting 6 to 8 days (n = 29, 48%), though several reported trips lasting 9 to 10 days (n = 6, 10%) and 11 days or more (n = 16, 27%). When asked about the volume of procedures performed, 32 (65%) reported participating in more than 15 procedures, with 15 (31%) residents reporting participation in 26 procedures or more. When asked to evaluate the educational benefits in light of the 6 core competencies from the ACGME, there was an overwhelmingly positive response. Conclusions: Residents perceive international mission experiences to be valuable for professional development as well as an effective tool for surgical education, particularly in the setting of competency-based education goals and these ventures should be supported by training programs. An appropriately planned mission experience can impact the professional and educational development of the trainee.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FhpeXv
Ecthyma Gangrenosum in the Eyelid
No abstract availablefrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tiZepS
Comparison of Postoperative Outcomes Between Monitored Anesthesia Care and General Anesthesia in Closed Reduction of Nasal Fracture
Fracture of nasal bone is among the most common facial bone fractures. Reduction of nasal bone fracture is able to be performed under local or general anesthesia. The aim of this study is to compare monitored anesthetic care (MAC) and general anesthesia (GA) based on intraoperative vital signs, and the adverse effects after closed reduction of nasal bone fractures. The authors performed a retrospective study of 45 patients who underwent a closed reduction of nasal bone fracture between January 1, 2016 and December 31, 2016. Patients are divided into an MAC group (n = 17) or GA group (n = 28). A sore throat, postoperative pain scores, nausea, vomiting, hospital stay, operation time, and the result of surgery are compared between the groups. All the patients have interviewed their satisfaction of aesthetic and functional outcome. The operation time and hospital stay were lower in the MAC group. There is no difference in a sore throat, postoperative pain score, and the result of surgery significantly. In the MAC and GA groups, there was no statistically significant difference in the postoperative cosmetic and functional satisfaction scores. Closed reduction of nasal bone fracture using MAC is as safe and efficient as GA. However, MAC anesthesia may not be feasible if airway discomfort due to bleeding is expected, or fracture is severe and multiple manipulations are required. Therefore, MAC is considered to be a good alternative when patients undergoing short-term or small operations do not prefer general anesthesia.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fl7k5T
Maxillary Osteomyelitis Caused by Kocuria Species in a Patient Who Is on Long-Term Uncontrolled Use of Methylprednisolone
Uncontrolled use of medicines bring with it serious health problems. Long-term and uncontrolled use of steroids, without the supervision of a healthcare professional, may cause unexpected infections due to immunosuppression. The authors present a patient with maxillary osteomyelitis caused by Kocuria species in a 41-year-old male who has been receiving methylprednisolone without control for 1.5 years.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tiZ7dW
The Impact of Type-D Personality on Oral Health-Related Quality of Life in Cleft Lip and Palate Adolescents
The purpose of this study was to investigate the oral health-related quality of life and type-D personality in cleft lip/palate (CLP) patients and the relationship between type-D personality and oral health-related quality of life (OHRQoL) in CLP patients. Fifty patients with CLP within age range from 8 to 15 years were chosen and asked to complete both Child Oral Health Impact Profile (COHI) and Type-D scale (DS14) questionnaire. Moreover, the participants of a control group matched with CLP patients were asked to complete the DS14 questionnaire. A significant difference between boys and girls on the subscale "emotional well-being" of COHIP (P = 0.001) and a positive significant correlation between "oral symptoms" and age (P = 0.029) were found among CLP patients. The prevalence of type-D personality was equal between clefts and nonclefts groups. However, there was a significant relationship between type-D personality and OHRQoL in CLP patients regarding mean scores of overall COHIP and its subscales (Pfrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FigX5E
Mandibular Reconstruction by Osteogenic Distraction Due to Two Different Injuries
Varied factors, whether intrinsic or extrinsic, may lead to a decrease in the bone volume of the jaws. Trauma and pathology can be listed as examples of such factors. The aim of this study is to present the osteogenic distraction technique as alternative to augmentation of low mandibular bone volume caused by different etiologies. The first case reports a mandibular marginal resection of ameloblastoma and the second one reports a male patient presenting mandibular fracture sequelae. Both cases were treated according to the osteogenic distraction technique. Several factors have influence on the decision of treatment management of these conditions. Although autogenous bonegraft is considered criterion standard for alveolar reconstruction, its high rates of resorption and the morbidity associated to donor sites lead surgeons to seek for other surgical alternatives such as osteogenic distraction. Therefore, it also aims to expose the advantages and benefits of this technique as well as the satisfactory results achieved.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tiYYqU
Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations
Asthma is one of the most common chronic diseases, with an estimated 300 million people affected worldwide. Acute exacerbations of asthma are frightening for patients, cause considerable illness and death, and account for a large proportion of the overall costs related to asthma. Although plans for…
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Escalating Inhaled Glucocorticoids to Prevent Asthma Exacerbations
Inhaled glucocorticoids are pivotal to achieve asthma control and disease stability in both children and adults; despite their use, with or without other treatments, many patients with asthma have ongoing episodic disease exacerbations. Often, these are linked to provocative factors such as viral…
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Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations
Asthma exacerbations are common events, particularly in school-age children. Exacerbations are costly and are associated with considerable complications. In addition, asthma exacerbations may lead to progressive loss of lung function and greater asthma severity over time. Although conventional…
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Innate immunity gene expression by epithelial cells of upper respiratory tract in children with adenoid hypertrophy
A major role of the innate immunity in the defence of mucosal tissue is well established. However, a balance between the main components of the immunity such as toll-like receptors (TLRs) and defensins in the pathology of upper respiratory tract in children has not been addressed yet. Our aim was to investigate the gene expression of some TLRs as well as alpha and beta-defensins in children suffered from adenoid hyperthrophy in comparison with healthy children.
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Treatment of pediatric esthesioneuroblastoma with smell preservation
Olfactory neuroblastoma is a rare malignant tumor of neuroectodermal origin and represents the most common cancer of the nasal cavity in pediatric age. The gold standard of treatment consists of en bloc resection, numerous studies have shown as the endoscopic approaches permit good control of the disease improving the quality of life after the treatment. Herein we describe the case of a 13-year-old patient referred to our outpatient clinic with a polypoid multi-lobed lesion occupying the left nasal cavity and imaging that confirmed a left-sided nasal mass without cribriform plate involvement (Kadish B).
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Environmental factors associated with allergic rhinitis symptoms in Japanese university students: A cross-sectional study
Numerous studies have reported that various environmental factors during early life are key determinants for developing allergic disease. Herein, we aimed to investigate the impact of environmental factors on allergic rhinitis.
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Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab
Abstract
Background
The objective of this study was to evaluate the efficacy and safety of concurrent immune checkpoint inhibitor therapy and radiotherapy (immunoradiotherapy) in patients with metastatic melanoma after progression on nivolumab.
Patients and methods
A retrospective review was performed on 16 consecutive patients with metastatic melanoma treated with concurrent immunoradiotherapy after progression on nivolumab. Best responses to immunoradiotherapy were assessed either inside or outside of the radiation fields. The target lesions ratio (the sum of the diameters of the target lesions inside the irradiated fields/all target lesions) was also assessed.
Results
Among the patients, seven received ipilimumab and radiotherapy (Ipi-RT), six received nivolumab and radiotherapy (Nivo-RT), and three sequentially received Ipi-RT and Nivo-RT. The overall response rate (all patients regardless of inside or outside radiation fields) was 30%. The response rate inside the radiation fields was 68.8% for all patients combined. The response rates of Ipi-RT and Nivo-RT inside the radiation fields were 37.5 and 100% (P = 0.03), respectively. Grade 3 adverse events were observed in three patients treated with Ipi-RT. The target lesions ratio was a predictive marker of disease control rate among patients treated with Nivo-RT.
Conclusions
This study showed that concurrent immunoradiotherapy is an option for patients with metastatic melanoma after progression on nivolumab.
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Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer
Abstract
Purpose
For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen.
Methods
Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined. Patients were classified according to the designated dose levels of chemoradiotherapy using the GnP regimen. After additional 6 cycles of the GnP regimen were administered, surgery was considered if the patients had stable disease and tumor marker levels had normalized.
Results
DLT (grade 4 thrombocytopenia) was observed only in 1 of 12 patients, and the RD was set at level 3. Grade 3–4 leukopenia was observed in 9 (75.0%) patients, and neutropenia in 7 (58.3%). The response rate was 41.7%, and the disease control rate was 100%. Conversion surgery was performed in 6 (50%) patients, and curative resection (R0) was performed in all 6 patients (100%). Stratification according to the Evans classification system demonstrated one patient with grade 1b, one with grade 2, two with grade 3, and two with grade 4 disease.
Conclusion
The RD for weekly administration was 800 mg/m2 for gemcitabine and 100 mg/m2 for nab-paclitaxel with a 50.4 Gy radiation. The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery, and should be evaluated further in a phase II trial.
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Addition of bevacizumab to gemcitabine for platinum-resistant recurrent ovarian cancer: a retrospective analysis
Abstract
Purpose
To compare a cohort of patients with platinum-resistant recurrent ovarian cancer (PROC) treated with bevacizumab and gemcitabine (Bev–Gem) to that of patients treated only with gemcitabine (Gem).
Methods
Between 2011 and 2017, we identified the Bev–Gem and Gem PROC groups. The regimen included 1000 mg/m2 of Gem on days 1, 8, and 15, and 15 mg/m2 of Bev on day 1, every 4 weeks. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of the administration of Bev–Gem or Gem until disease progression or death.
Results
The Bev–Gem and Gem groups included 18 and 29 patients, respectively. More patients had advanced stage disease in the Bev–Gem group (p = 0.048); no other characteristics differed between the groups. The response rates [ratio of complete remission (CR) to partial remission (PR)] of Bev–Gem and Gem were 38.9 and 3.4%, respectively (p < 0.01). The clinical benefit rates [combined percentages of CR, PR, and stable disease] of the Bev–Gem and Gem groups were 88.9 and 41.4%, respectively (p = 0.04). PFS and OS of the Bev–Gem group were superior (p < 0.01, p = 0.03, respectively). Bev–Gem was the better prognostic factor of both PFS [hazard ratio (HR) 0.17, p < 0.01] and OS (HR 0.31, p = 0.01). The frequency of hematologic and non-hematologic adverse effects was similar in each group.
Conclusion
Bev–Gem regimens improved PFS and OS for PROC. Furthermore, the adverse effects of Bev–Gem were tolerable. Thus, Bev–Gem could be a candidate treatment strategy for PROC.
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S-1 (Teysuno) and gemcitabine in Caucasian patients with unresectable pancreatic adenocarcinoma
Abstract
Purpose
Gemcitabine has been standard of care in advanced pancreatic adenocarcinomas (PC) for almost two decades. Randomized, primarily Japanese, studies have shown promising efficacy when combined with S-1 (GemS-1); however, no data are published in Caucasian patients. We report the first study with a combination of GemS-1 in an unselected cohort of Caucasian PC patients.
Methods
In this observational cohort study, we analyzed efficacy and toxicity prospectively.
Results
From July 2012 to July 2014, 64 patients received at least one cycle of GemS-1. 16 patients started therapy with gemcitabine and capecitabine (GemCap) but switched to GemS-1 after median 3 cycles of GemCap due to toxicity (hand-foot syndrome). 48 patients received GemS-1 as initial therapy. For the complete cohort, median age was 68 years (range 44–80); 22 patients (34%) had locally advanced PC; 42 patients (66%) had metastatic disease. Five patients had received prior adjuvant therapy with gemcitabine and 9 pts had received prior first-line therapy. The most common adverse event was fatigue (86%), however, only grade 3 in 3%. Five patients (8%) developed febrile neutropenia. Median PFS was 8.1 (95% CI 6.9–9.0) months and median OS was 11.7 (95% CI 10.7–13.1) months in the whole GemS-1 population. In the 48 patients starting with GemS-1, median PFS was 7.7 (95% CI 6.7–8.9) months and median OS was 11.5 (95% CI 9.7–12.3) months.
Conclusions
The combination of gemcitabine and S-1 is safe and associated with promising efficacy in a Caucasian population; however, this needs to be confirmed in prospective clinical trials.
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Phase 1 summary of plasma concentration–QTc analysis for idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors and AML
Abstract
Purpose
Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic oral p53 activator. The aim of this analysis is to examine the potential of idasanutlin to prolong the corrected QT (QTc) interval by evaluating the relationship between plasma idasanutlin concentration and QTc interval.
Method
Intensive plasma concentration QTc interval data were collected at the same timepoints, from three idasanutlin (RO5503781) phase 1 studies in patients with solid tumors and AML. QTc data in absolute values and changes from baseline (Δ) were analyzed for a potential association with plasma idasanutlin concentrations with a linear mixed effect model. Categorical analysis was also performed.
Results
A total of 282 patients were exposed to idasanutlin and had at least one observation of QTc and idasanutlin plasma concentration. There was no apparent increase of QTcF or ΔQTcF in a wide idasanutlin plasma concentration range, even at concentrations exceeding the exposure matching the dose adopted in the ongoing phase 3 study (300-mg BID). Categorical analysis did not detect a potential signal of QT prolongation.
Conclusion
The concentration–QTc analysis indicates that idasanutlin does not prolong the QT interval within the targeted concentration range currently in consideration for clinical development.
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Role of TPMT and ITPA variants in mercaptopurine disposition
Abstract
Purpose
To explore the levels of thioguanine incorporated into DNA (DNA-TG), and erythrocyte levels of 6-thioguanine nucleotides (Ery-TGN) and methylated metabolites (Ery-MeMP) during 6-mercaptopurine (6MP)/Methotrexate (MTX) therapy of childhood acute lymphoblastic leukemia (ALL) and the relation to inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT) gene variants.
Methods
Blood samples were drawn during 6MP/MTX maintenance therapy from 132 children treated for ALL at Rigshospitalet, Copenhagen. The samples were analysed for thiopurine metabolites and compared to TPMT (rs1800460 and rs1142345) and ITPA (rs1127354) genotypes.
Results
Median DNA-TG (mDNA-TG) levels were higher in TPMT and ITPA low-activity patients as compared to wildtype patients (TPMTLA 549 vs. 364 fmol/µg DNA, p = 0.007, ITPALA 465 vs. 387 fmol/µg DNA, p = 0.04). mDNA-TG levels were positively correlated to median Ery-TGN (mEry-TGN)(rs = 0.37, p = 0.001), but plateaued at higher mEry-TGN levels. DNA-TG indices (mDNA-TG/mEry-TGN) were 42% higher in TPMTWT patients as compared to TPMTLA patients but no difference in DNA-TG indices was observed between ITPAWT and ITPALA patients (median 1.7 vs. 1.6 fmol/µg DNA/ nmol/mmol Hb, p = 0.81). DNA-TG indices increased with median Ery-MeMP (mEry-MeMP) levels (rs = 0.25, p = 0.001).
Conclusions
TPMT and ITPA genotypes significantly influence the metabolism of 6MP. DNA-TG may prove to be a more relevant pharmacokinetic parameter for monitoring 6MP treatment intensity than cytosolic metabolites. Prospective trials are needed to evaluate the usefulness of DNA-TGN for individual dose adjustments in childhood ALL maintenance therapy.
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Long-term results of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer
Abstract
Purpose
The purpose of this phase I/II study was to evaluate the feasibility and efficacy of S-1 plus cisplatin at the recommended schedule with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC).
Methods
Eligible patients with LA-NSCLC were treated with cisplatin intravenously at a dose of 60 mg/m2 on day 8 plus oral S-1 at a dosage of 40 mg/m2 twice per day for two different treatment schedules for up to 4 cycles. Patients also concurrently received 60 Gy of thoracic radiation in 30 fractions. The primary endpoint of the phase II study was the proportion of patients who survived for more than 2 years.
Results
Between August 2005 and October 2010, a total of 45 patients were enrolled in this phase I/II study; their long-term survival was then followed for a median period of 5.8 years. Nineteen of the 39 patients in the phase II study survived for more than 2 years and met the primary endpoint of the study. The median overall survival period was 24.9 months [95% confidence interval (CI) 17.4–74.5 months], and the 2- and 5-year overall survival rates were 51.0 and 43.0%, respectively. The response rate was 85%, and the median progression-free survival period was 13.8 months (95% CI 9.5–27.1 months). Hematological toxicity was mild. Grade 3 febrile neutropenia and pneumonitis was observed in 5 and 5%, respectively.
Conclusion
Our study indicated that S-1 plus cisplatin with concurrent thoracic radiotherapy yielded encouraging survival outcomes and an acceptable safety profile for LA-NSCLC.
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A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer
Abstract
Purpose
Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of approximately 16 months. Novel methods to improve outcomes are needed. Nab-paclitaxel (Abraxane) has shown efficacy in pancreatic cancer and is FDA-approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced pancreatic carcinoma.
Methods
We performed a phase 1 study using a 3 + 3 dose escalation strategy to determine the safety and tolerability of dose-escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with two cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy.
Results
Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n = 3) or 125 mg/m2 (n = 6). There were no observed grade 3 gastrointestinal toxicities. One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%) and neutropenia (11%). No grade 4 toxicities were observed. Following chemoradiotherapy, four patients (borderline resectable, n = 2 and unresectable, n = 2) underwent surgical resection, all with negative margins and with significant treatment effect with limited tumor viability.
Conclusions
The combination of fractionated radiation and weekly full dose nab-paclitaxel was safe and well-tolerated.
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2-Deoxy- d -glucose enhances TRAIL-induced apoptosis in human gastric cancer cells through downregulating JNK-mediated cytoprotective autophagy
Abstract
Purpose
TNF-related apoptosis-inducing ligand (TRAIL) resistance significantly limits its use in clinical practice. It has been reported that 2-deoxy-d-glucose (2-DG) can enhance TRAIL's cytotoxicity. Our studies were designed to investigate the mechanisms of 2-DG reversing TRAIL resistance therapy in gastric cancer cells.
Methods
Gastric cancer cells (MGC803, SGC7901) were treated with 2-DG and TRAIL. Cell viability was determined by CCK-8 assay and detection of apoptosis by flow cytometry. Autophagic and apoptosis protein expression and c-Jun NH2-terminal kinase (JNK) phosphorylation were determined by Western blotting. Autophagy response and JNK activities were inhibited by specific inhibitor, 3MA or SP600125, respectively. LDH release assay was used to detect cytotoxicity.
Results
We confirmed that TRAIL triggered an autophagic response in TRAIL-resistant gastric cancer cells, MGC803 and SGC7901, and depended on JNK activation. Blocking autophagy or JNK activation with specific inhibitor, 3MA or SP600125, potentiated cell death and caspase-3 activation. Furthermore, we confirmed that 2-DG inhibited the viability of gastric cancer cells, phosphorylation of JNK induced by TRAIL and increased gastric cancer cells to TRAIL-induced apoptosis.
Conclusions
Taken together, we show that 2-DG can sensitize TRAIL-induced apoptosis, at least in part, through suppressing JNK-mediated cytoprotective autophagic signaling in MGC803 and SGC7901cells. These results may have significant implications for the development of new strategies to reverse TRAIL resistance in gastric tumor.
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Effects of posaconazole (a strong CYP3A4 inhibitor), two new tablet formulations, and food on the pharmacokinetics of idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors
Abstract
Purpose
Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic oral p53 activator. To optimize its dosing conditions, a number of clinical pharmacology characteristics were examined in this multi-center trial in patients with advanced solid tumors.
Method
This was an open-label, single-dose, crossover clinical pharmacology study investigating the effects of strong CYP3A4 inhibition with posaconazole (Part 1), two new oral formulations (Part 2), as well as high-energy/high-fat and low-energy/low-fat meals (Part 3) on the relative bioavailability of idasanutlin. After completing Part 1, 2, or 3, patients could have participated in an optional treatment with idasanutlin. Clinical endpoints were pharmacokinetics (PK), pharmacodynamics (PD) of MIC-1 elevation (Part 1 only), and safety/tolerability.
Results
The administration of posaconazole 400 mg BID × 7 days with idasanutlin 800 mg resulted in a slight decrease (7%) in Cmax and a modest increase (31%) in AUC for idasanutlin, a marked reduction in Cmax (~ 60%) and AUC0 (~ 50%) for M4 metabolite, and a minimal increase (~ 24%) in serum MIC-1 levels. Cmax and AUC were both 45% higher for the SDP formulation. While the low-fat meal caused a less than 20% increase in all PK exposure parameters with the 90% CI values just outside the upper end of the equivalence criteria (80–125%), the high-fat meal reached bioequivalence with dosing under fasting.
Conclusion
In patients with solid tumors, multiple doses of posaconazole, a strong CYP3A4 inhibitor, minimally affected idasanutlin PK and PD without clinical significance. The SDP formulation improved rBA/exposures by ~ 50% without major food effect.
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A note on improved statistical approaches to account for pseudoprogression
Abstract
Responses to immuno-oncology agents are often subject to misinterpretation as apparent tumor growth due to immune infiltration leads to the appearance of progressive disease and can result in the discontinuation of effective therapeutic agents. Better statistical strategies to determine experimental outcomes are needed to distinguish between true and pseudoprogression. We applied time-to-event statistical analyses methods that account for study design features and capture the longitudinal and panoramic aspects of pseudoprogression to test superiority of a combination of RRx-001, a novel tumor-associated macrophage polarizing agent in Phase 2, and an anti-PD-L1 antibody in a myeloma preclinical model, comparing to traditional, mean-based mixed effects modeling approaches that did not show statistical significance. Nonparametric p values for the difference of cumulative incidence rates of time to ≥ 50% tumor growth reduction and its associated restricted mean survival times are computed and found to be statistically significant. Kaplan–Meier description of time-to-volume reduction (≥ 50%) coupled with Cox's proportional hazards model follows the data longitudinally and therefore permits an analysis of immune infiltration resolution, making it an improved method for analysis of preclinical experiments with immuno-oncology agents.
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Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma
Abstract
Purpose
The purpose of this study was to assess the efficacy and safety of cetuximab plus platinum-based chemotherapy for patients specifically diagnosed with recurrent or metastatic oral squamous cell carcinoma (OSCC).
Methods
We conducted a multicenter retrospective observational study of patients who underwent first-line cetuximab plus platinum-based chemotherapy between December 2012 and June 2015. 65 patients received weekly cetuximab (week 1, 400 mg/m2; subsequent weeks, 250 mg/m2) plus a maximum of six 3-weekly cycles of cisplatin (80 or 100 mg/m2, day 1) or carboplatin (at an area under the curve of 5 mg/mL/min as a 1-h intravenous infusion on day 1) and 5-fluorouracil (800 or 1000 mg/m2/day, days 1–4). Patients with stable disease who received cetuximab plus platinum-based chemotherapy continued to receive cetuximab until disease progression or unacceptable toxicities, whichever occurred first.
Results
The median follow-up was 10.5 (range 1.2–34.2) months. The best overall response and the disease control rates were 46.2 and 67.7%, respectively. The median overall survival and progression-free survival rates were 12.1 and 7.8 months, respectively. The most common grades 3–4 adverse events were skin rash (9.2%) followed by leukopenia (6.2%). None of the adverse events were fatal.
Conclusion
The results of our multicenter retrospective study, which was the largest of its kind to date, suggest that first-line cetuximab plus platinum-based chemotherapy is suitable and well-tolerated for the systemic therapy of recurrent or metastatic OSCC.
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A novel way to manage trastuzumab cardiotoxicity
Abstract
Purpose
Trastuzumab is the most widely prescribed anti-HER2 humanized monoclonal antibody. Cardiac toxicity is the only limiting toxicity of trastuzumab and it is of particular concern in patients with complete response, since the drug needs to be stopped, with a risk of disease relapse. To date, no pharmacological data on trastuzumab cardiotoxicity in patients have been made available. Here, we provide proof of concept, demonstrating that it was possible to prevent trastuzumab-induced cardiotoxicity by modifying the drug administration schedule.
Methods
In this paper, we report the case of a patient with metastatic breast cancer responding to trastuzumab, who developed severe cardiac toxicity twice using a 3-weekly regimen. Considering preclinical pharmacological data on trastuzumab cardiotoxicity, we hypothesized that a weekly schedule of trastuzumab with lower peaks of serum concentration could be safe while remaining efficient. With the patient's consent, we started a weekly combination of carboplatin (AUC2) and trastuzumab (2 mg/kg) with close monitoring of trastuzumab concentrations.
Results
We successfully controlled the disease for an additional 6 months with relevant trough concentrations of trastuzumab of around 50 mg/L. Another important aspect is that, with this weekly schedule, we observed no cardiac toxicity, and the left ventricular ejection fraction remained stabilized, at over 50%.
Conclusions
Trastuzumab is the most widely prescribed anti-HER2 monoclonal antibody for the treatment of HER2 metastatic breast cancer, and it is the only drug that has been approved for the treatment of localized HER2 breast cancer, 1-year treatment being required after surgery. In case of cardiac toxicity, particularly in women over 60 years of age, a weekly regimen with lower peaks of concentration could be an alternative to the standard 3-weekly regimen.
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A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies
Abstract
Purpose
The artemisinin class of anti-malarial drugs has shown significant anti-cancer activity in pre-clinical models. Proposed anti-cancer mechanisms include DNA damage, inhibition of angiogenesis, TRAIL-mediated apoptosis, and inhibition of signaling pathways. We performed a phase I study to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of intravenous artesunate (IV AS).
Methods
Patients were enrolled in an accelerated titration dose escalation study with planned dose levels of 8, 12, 18, 25, 34 and 45 mg/kg given on days 1 and 8 of a 21-day cycle. Toxicities were assessed using the NCI CTCAE (ver. 4.0), and response was assessed using RECIST criteria (version 1.1). Pharmacokinetic (PK) studies were performed during cycle 1.
Results
A total of 19 pts were enrolled, 18 of whom were evaluable for toxicity and 15 were evaluable for efficacy. DLTs were seen at dosages of 12 (1 of 6 patients), 18 (1 of 6) and 25 mg/kg (2 of 2), and were neutropenic fever (Gr 4), hypersensitivity reaction (Gr 3), liver function test abnormalities (Gr 3/4) along with neutropenic fever, and nausea/vomiting (Gr 3) despite supportive care. The MTD was determined to be 18 mg/kg. No responses were observed, while four patients had stable disease, including three with prolonged stable disease for 8, 10, and 11 cycles, for a disease control rate of 27%. PK parameters of AS and its active metabolite, dihydroartemisinin (DHA), correlated with dose.
Conclusion
The MTD of intravenous artesunate is 18 mg/kg on this schedule. Treatment was well tolerated. Modest clinical activity was seen in this pre-treated population.
ClinicalTrials.gov Identifier
NCT02353026.
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Grinspan’s Syndrome: A Rare Case with Malignant Transformation
Aim. Oral lichen planus (OLP) is one of the common chronic inflammatory, noninfectious, and precancerous oral mucosal diseases that affect the stratified squamous epithelium in adults. Grinspan et al. reported an association of OLP with diabetes mellitus and vascular hypertension and called that Grinspan's syndrome in 1966. We aim to present a case of Grinspan's syndrome with malignant transformation. Case Presentation. A 60-year-old man who presented with a ten-year history of OLP diagnosed clinically and histologically was referred to our otolaryngology department with a painless swallowing in the left buccal mucosa for 3 months. Clinical examination revealed several plaques, striated white lesions in the buccal mucosa bilaterally, and an exophytic tumor in the left buccal mucosa. Histopathological examination showed lichen planus bilaterally and oral squamous cell carcinoma in the left buccal mucosa. The tumor had been developed on the preexisting areas of lichen planus which had been histologically proven before. The tumor was removed completely, and the tissue defect on the buccal mucosa was repaired with a split-thickness skin graft. Conclusion. Patients with OLP should be followed up periodically in a long term at close intervals for early diagnosis of malignant transformation.
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Low Frequency repetitive Transcranial Magnetic Stimulation: Potential role in treatment of patients with hemispheric cerebellar strokes
Source:Brain Stimulation
Author(s): Isabelle Buard, Jean M. Berliner, Benzi M. Kluger
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Has the question “Number of pulses or number of sessions for rTMS in major depression” been answered adequately?
Source:Brain Stimulation
Author(s): Christos Theleritis, Constantin R. Soldatos
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Detection of GSK-3β activation index in pediatric chronic tonsillitis is an indicator for chronic recurrent inflammation
Chronic tonsillitis (TC) is among the most common bacterial diseases in pediatric otolaryngology. We aimed to evaluate the expression of glycogen synthase kinase 3β (GSK-3β) in a cohort of children with chronic tonsillitis (TC), and the correlation between GSK-3β activity index and inflammatory profiles of TC.
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Dynamic imaging with sialography combined with sialendoscopy to manage a foreign body in Stensen's duct
We describe sialography as a dynamic imaging modality useful in establishing the diagnosis and planning for treatment of a parotid gland ductal foreign body.
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Transoral robotic excision of laryngeal papillomas with Flex® Robotic System — A novel surgical approach
Recurrent respiratory papillomatosis results in hoarseness, stridor and airway obstruction. Management is surgical, with most surgeons using microdebrider or laser. Transoral robotic surgery (TORS) has been successfully utilised for the excision of oropharyngeal malignancies and paediatric airway surgery. This is the first case report of TORS being used for the excision of laryngeal papillomas.
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Does blindness affect ocular vestibular evoked myogenic potentials?
The aim of the present study was to investigate the influence of blindness on ocular vestibular evoked myogenic potentials (oVEMP) responses.
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Individualized colorectal cancer screening based on the clinical risk factors: beyond family history of colorectal cancer
Individuals without a family history of colorectal cancer (CRC) are screened uniformly despite interpersonal risk. To assess individual risk, we examined the age-specific prevalence of advanced colorectal neoplasia (ACRN) according to clinical risk factors and fecal immunochemical test (FIT) results.
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Visceral obesity as a risk factor for colorectal adenoma occurrence in surveillance colonoscopy
The aim of this study was to examine the prospective association between visceral obesity and the incidence and recurrence of colorectal adenoma.
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Feasibility and safety of micro-forceps biopsy in the diagnosis of pancreatic cysts
The tissue acquisition and diagnostic yield of cyst fluid cytology is low-to-moderate and rarely provides a specific diagnosis. The aim of this study was to compare the tissue acquisition and diagnostic tissue yield of micro-forceps biopsy (MFB) with cyst fluid cytology.
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The effects of botulinum toxin injections on plantar flexor spasticity in different phases after stroke. A secondary analysis from a double-blind, randomized trial
There are no guidelines on the ideal time to inject botulinum toxin (BT-A) for lower leg spasticity in stroke patients. An early injection may produce unwanted weakness, interfering with gait recovery.
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Support device for percutaneous endoscopic gastrostomy tube
During the treatment for head and neck cancer patients often require a percutaneous endoscopic gastrostomy (PEG) to maintain adequate nutritional intake.1 Complications associated with a PEG include leakage,2 widening of the stoma, and dislodgement of the tube.3 These complications may in turn result in the need for placement of a new tube.
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Placement of an arch bar for intermaxillary fixation using two wires for each dental arch
If a single long wire is used for each dental arch it may loosen as the wire stretches,1 and several wires take more time to fix to the arch bars.2 We describe a alternative method of placement using a wire 20–25cm long for each side of each dental arch. This prevents loosening of the arch bar and reduces the time taken to do it.
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Meta-Analysis of Renal Function Following Suprarenal or Infrarenal Endovascular Aneurysm Repair
Publication date: Available online 3 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Philip W. Stather, James Ferguson, Ayoola Awopetu, Jonathan R. Boyle
Objective/BackgroundThe effect of suprarenal (SR) as opposed to infrarenal (IR) fixation on renal outcomes post-endovascular aneurysm repair (EVAR) remains controversial. This meta-analysis aims to update current understanding of this issue.MethodsA prior meta-analysis was updated through a Preferred Reporting Items for Systematic reviews and Meta-Analyses search for additional studies published in the last 3 years reporting on renal dysfunction or related outcomes post-EVAR. Random effects meta-analysis was undertaken using SPSS.ResultsA total of 25 non-randomised studies comparing SR with IR fixation were included, totalling 54,832 patients. In total, 16,634 underwent SR and 38,198 IR. Baseline characteristics, including age, baseline estimated glomerular filtration rate, diabetes, cardiac disease, and smoking, were similar between the groups. There was a small but significant difference in outcomes for renal dysfunction at the study end point (SR 5.98% vs. IR 4.83%; odds ratio [OR] 1.29, 95% confidence interval [CI] 1.28–1.40 [p < .001]); however, at 30 days and 12 months there was no significant difference, and this did not hold up to sensitivity analysis. Incidence of renal infarcts (SR 6.6% vs. IR 2.3%; OR 2.78, 95% CI 1.46–5.29 [p = .002]), renal stenosis (SR 2.4% vs. IR 0.8%; OR 2.89, 95% CI 1.00–8.38 [p = .05]), and renal artery occlusion (SR 2.4% vs. IR 1.2%; OR 2.21, 95% CI 1.15–4.25 [p = 0.02]) favoured IR fixation; however, there was no difference in haemodialysis rates.ConclusionThis meta-analysis has identified small but significantly worse renal outcomes in patients having SR fixation devices compared with IR; however, there was no difference in dialysis rates and a small effect on renal dysfunction, which did not stand up to rigorous sensitivity analysis. This should be taken into consideration during graft selection, and further studies must assess renal outcomes in the longer term, and in those with pre-existing renal dysfunction.
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Prevalence of Abdominal Aortic Aneurysms in the General Population and in Subgroups at High Cardiovascular Risk in Italy. Results of the RoCAV Population Based Study
Publication date: Available online 3 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Francesco Gianfagna, Giovanni Veronesi, Matteo Tozzi, Antonino Tarallo, Rossana Borchini, Marco M. Ferrario, Lorenza Bertù, Andrea Montonati, Patrizio Castelli
ObjectivesPrevalence data on abdominal aortic aneurysm (AAA) in women, subjects younger than 65 years and in subgroups carrying specific risk factors are scarce. AAA prevalence was evaluated in an Italian population including women and younger subjects, stratifying for the presence of cardiovascular disease (CVD) risk factors and CVD risk score.Materials and methodsA population based cross-sectional study was conducted between 2013 and 2016. Men aged 50–75 and women aged 60–75 years, resident in the city of Varese (northern Italy), were randomly selected from the civil registry. A vascular surgeon performed an abdominal aortic ultrasound scan at four sites using the leading edge to leading edge method. CVD risk score was computed using the ESC-SCORE algorithm. The age and gender specific prevalence was estimated, stratifying by the presence of CVD and cardiovascular risk factors.ResultsAmong the 3755 subjects with a valid ultrasound measurement, 63 subjects with an AAA were identified (5 referred for surgical intervention), among whom 34 were not previously known (30 men 1.3%, 95% CI 0.9–1.8; 4 women 0.3%, 95% CI 0.1–0.8). Considering age classes in men only, the highest prevalence of screen detected AAA was found in subjects aged 65–70 (1.2%; 95% CI 0.4–2.5) and 70–75 (2.5%; 95% CI 1.4–4.0) years. Among 65–75 year old men, the highest AAA prevalence was found in subjects with a previous myocardial infarction (MI 4.9%, 95% CI 2.0–9.9) and in ever-smokers reporting more than 15 pack years of smoking (4.1%, 95% CI 2.5–6.3). Among the younger subjects, those having an ESC-SCORE higher than 5% or a previous CVD (MI or stroke) showed a prevalence of 1.4% (95% CI 0.3–4.2; prevalence including subaneurysms 6.7%, 95% CI 3.7–11.0%).ConclusionsIn the study population, both a general screening program in 65–75 year old men and an approach targeted to subgroups at higher risk merit evaluation in a cost-effectiveness study. In 50–64 year old men, strategies for population selection should consider CVD risk stratification tools.
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Local mechanisms regulating selective cargo entry and long-range trafficking in axons
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Laura F Gumy, Casper C Hoogenraad
The polarized long-distance transport of neuronal cargoes depends on the presence of functional and structural axonal subcompartments. Given the heterogeneity of neuronal cargoes, selective sorting and entry occurs in the proximal axon where multiple subcellular specializations such as the axon initial segment, the pre-axonal exclusion zone, the MAP2 pre-axonal filtering zone and the Tau diffusion barrier provide different levels of regulation. Cargoes allowed to pass through the proximal axon spread into the more distal parts. Recent findings show that diverse cargo distributions along the axon depend on the compartmentalized organization of the cytoskeleton and the local regulation of multiple motor proteins by microtubule associated proteins. In this review, we focus on the local mechanisms that control cargo motility and discuss how they play a role in the overall circulation of axonal cargoes.
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The biological and behavioral computations that influence dopamine responses
Source:Current Opinion in Neurobiology, Volume 49
Author(s): WR Stauffer
Phasic dopamine responses demonstrate remarkable simplicity; they code for the differences between received and predicted reward values. Yet this simplicity belies the subtle complexity of the psychological, computational, and contextual factors that influence this signal. Advances in behavioral paradigms and models, in monkeys and rodents, have demonstrated that phasic dopamine responses reflect numerous behavioral computations and factors including choice, subjective value, confidence, and context. The application of optogenetics has provided evidence that dopamine reward prediction error responses cause value learning. Furthermore, studies using advanced circuit tracing techniques have begun to uncover the biological network implementation of the reward learning algorithm. The purpose of this review is to summarize the recent advances in dopamine neurophysiology and synthesize an updated account of the behavioral function of dopamine signals.
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Prefabricated fibula free flap with dental implants for mandibular reconstruction
Publication date: Available online 2 March 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): D. Pauchet, J.-L. Pigot, F. Chabolle, C.-A. Bach
Free fibula transplant is routinely used for mandibular reconstruction in head and neck cancer. Dental rehabilitation, the objective of mandibular reconstruction, requires the use of dental implants as supports for fixed or removable dentures. Positioning of fibular bone grafts and implants determines implant osseointegration and the possibilities of dental rehabilitation.Prefabrication of a fibula free flap with dental implants prior to harvesting as a free flap can promote implant osseointegration. The position of the implants must then be precisely planned.Virtual surgery and computer-assisted design and prefabrication techniques are used to plan the reconstruction and then reproduce this planning by means of tailored fibula and mandible cutting guides, thereby ensuring correct positioning of fibular bone fragments and implants.The prefabricated fibula free flap technique requires two surgical procedures (prefabrication and flap transfer) and precise preoperative planning.Prefabricated fibula free flap with dental implants, by improving the quality of osseointegration of the implants before flap transfer, extends the possibilities of prosthetic rehabilitation in complex secondary mandibular reconstructions.
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Germline control of somatic Kras mutations in mouse lung tumors
Abstract
Somatic KRAS mutations are common in human lung adenocarcinomas and are associated with worse prognosis. In mice, Kras is frequently mutated in both spontaneous and experimentally induced lung tumors, although the pattern of mutation varies among strains, suggesting that such mutations are not random events. We tested if the occurrence of Kras mutations is under genetic control in two mouse intercrosses. Codon 61 mutations were prevalent, but the patterns of nucleotide changes differed between the intercrosses. Whole genome analysis with SNPs in (A/J x C57BL/6)F4 mice revealed a significant linkage between a locus on chromosome 19 and two particular codon 61 variants (CTA and CGA). In (AIRmax x AIRmin)F2 mice, there was a significant linkage between SNPs located on distal chromosome 6 (around 135 Mbp) and the frequency of codon 61 mutation. These results reveal the presence of two loci, on chromosomes 6 and 19, that modulate Kras mutation frequency in different mouse intercrosses. These findings indicate that somatic mutation frequency and type are not simple random events, but are under genetic control. This article is protected by copyright. All rights reserved
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