N-type calcium channel blockers: Novel therapeutics for the treatment of pain

Highly selective Cav2.2 voltage-gated calcium channel (VGCC) inhibitors have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Cone snail venoms provided the first drug in class with FDA approval granted in 2005 to Prialt (ω-conotoxin MVIIA, Elan) for the treatment of neuropathic pain. Since this pioneering work, major efforts underway to develop alternative small molecule inhibitors of Cav2.2 calcium channel have met with varied success. This review focuses on the properties of the Cav2.2 calcium channel in different pain states, the action of ω-conotoxins GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved Cav2.2 calcium channel therapeutics, and finally the development of small molecules for the treatment of chronic pain.

Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice

Background Recent in vivo and in vitro studies in non-neuronal and neuronal tissues have shown that different pathways of macrophage activation result in cells with different properties. Interleukin (IL)-6 triggers the classically activated inflammatory macrophages (M1 phenotype), whereas the alternatively activated macrophages (M2 phenotype) are anti-inflammatory. The objective of this study was to clarify the effects of a temporal blockade of IL-6/IL-6 receptor (IL-6R) engagement, using an anti-mouse IL-6R monoclonal antibody (MR16-1), on macrophage activation and the inflammatory response in the acute phase after spinal cord injury (SCI) in mice. Methods MR16-1 antibodies versus isotype control antibodies or saline alone were administered immediately after thoracic SCI in mice. SC tissue repair was compared between the two groups by Luxol fast blue (LFB) staining for myelination and immunoreactivity for the neuronal markers growth-associated protein (GAP)-43 and neurofilament heavy 200 kDa (NF-H) and for locomotor function. The expression of T helper (Th)1 cytokines (interferon (IFN)-? and tumor necrosis factor-a) and Th2 cytokines (IL-4, IL-13) was determined by immunoblot analysis. The presence of M1 (inducible nitric oxide synthase (iNOS)-positive, CD16/32-positive) and M2 (arginase 1-positive, CD206-positive) macrophages was determined by immunohistology. Using flow cytometry, we also quantified IFN-? and IL-4 levels in neutrophils, microglia, and macrophages, and Mac-2 (macrophage antigen-2) and Mac-3 in M2 macrophages and microglia. Results LFB-positive spared myelin was increased in the MR16-1-treated group compared with the controls, and this increase correlated with enhanced positivity for GAP-43 or NF-H, and improved locomotor Basso Mouse Scale scores. Immunoblot analysis of the MR16-1-treated samples identified downregulation of Th1 and upregulation of Th2 cytokines. Whereas iNOS-positive, CD16/32-positive M1 macrophages were the predominant phenotype in the injured SC of non-treated control mice, MR16-1 treatment promoted arginase 1-positive, CD206-positive M2 macrophages, with preferential localization of these cells at the injury site. MR16-1 treatment suppressed the number of IFN-?-positive neutrophils, and increased the number of microglia present and their positivity for IL-4. Among the arginase 1-positive M2 macrophages, MR16-1 treatment increased positivity for Mac-2 and Mac-3, suggestive of increased phagocytic behavior. Conclusion The results suggest that temporal blockade of IL-6 signaling after SCI abrogates damaging inflammatory activity and promotes functional recovery by promoting the formation of alternatively activated M2 macrophages.

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia:the ECLIPSE trial

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena(®), Bayer) compared with usual medical treatment, with exploration of women's perspectives on treatment. DESIGN: A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. SETTING: Women who presented in primary care. PARTICIPANTS: A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. INTERVENTIONS: LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. OUTCOME MEASURES: The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. RESULTS: The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI -0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women's experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments. CONCLUSIONS: The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women's assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86566246. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information.

Predictors of client retention in alternative -to -prison substance abuse programs

Increased treatment retention among substance abusing individuals has been associated with reduced drug use, fewer arrests, and decreased unemployment, as well as a reduction in health risk behaviors. This longitudinal study examined the predictors of client retention for alternative to prison substance abuse treatment programs through assessing the roles of motivational factors and the client-worker relationship. The sample was comprised of 141 male felony offenders who were legally mandated to community based long-term residential drug treatment programs. ^ The primary measures used in the study were the consecutive days a participant remained in treatment, Stages of Change Readiness Model and Treatment Eagerness Scale (SOCRATES), the Working Alliance Inventory (WAI), and The Readiness Ruler. Hierarchical multiple regression analysis was conducted for four hypotheses (a) participants who are more motivated to change at the time of entry will remain in treatment longer, (b) participants who have a strong therapeutic alliance will remain in treatment a greater number of consecutive days than participants who have weaker therapeutic alliance, (c) motivation to change, as measured at treatment entry, will be positively related to therapeutic alliance, (d) during the course of treatment variation in motivation to change will be predicted by the therapeutic alliance. ^ Results support the following conclusions: Among clients in alternative-to prison programs the number of days in treatment is positively related to their motivation to change. The therapeutic alliance is not a predictor of the number of days in treatment. Motivation to change, particularly recognition of a drug problem, is positively related to the therapeutic alliance. Changes in motivation to change in response to treatment are positively related to the therapeutic alliance among clients in an alternative to prison substance abuse treatment programs. These results carry forward prior research and have implications for social work practice, research, and social welfare policy. ^

Predictors of client retention in alternative to prison substance abuse programs

Increased treatment retention among substance abusing individuals has been associated with reduced drug use, fewer arrests, and decreased unemployment, as well as a reduction in health risk behaviors. This longitudinal study examined the predictors of client retention for alternative to prison substance abuse treatment programs through assessing the roles of motivational factors and the client-worker relationship. The sample was comprised of 141 male felony offenders who were legally mandated to community based long-term residential drug treatment programs. The primary measures used in the study were the consecutive days a participant remained in treatment, Stages of Change Readiness Model and Treatment Eagerness Scale (SOCRATES), the Working Alliance Inventory (WAI), and The Readiness Ruler. Hierarchical multiple regression analysis was conducted for four hypotheses (a) participants who are more motivated to change at the time of entry will remain in treatment longer, (b) participants who have a strong therapeutic alliance will remain in treatment a greater number of consecutive days than participants who have weaker therapeutic alliance, (c) motivation to change, as measured at treatment entry, will be positively related to therapeutic alliance, (d) during the course of treatment variation in motivation to change will be predicted by the therapeutic alliance. Results support the following conclusions: Among clients in alternative-to prison programs the number of days in treatment is positively related to their motivation to change. The therapeutic alliance is not a predictor of the number of days in treatment. Motivation to change, particularly recognition of a drug problem, is positively related to the therapeutic alliance. Changes in motivation to change in response to treatment are positively related to the therapeutic alliance among clients in an alternative to prison substance abuse treatment programs. These results carry forward prior research and have implications for social work practice, research, and social welfare policy.

Radiotherapy Treatment Assessment using DCE-MRI

Abstract

The goal of modern radiotherapy is to precisely deliver a prescribed radiation dose to delineated target volumes that contain a significant amount of tumor cells while sparing the surrounding healthy tissues/organs. Precise delineation of treatment and avoidance volumes is the key for the precision radiation therapy. In recent years, considerable clinical and research efforts have been devoted to integrate MRI into radiotherapy workflow motivated by the superior soft tissue contrast and functional imaging possibility. Dynamic contrast-enhanced MRI (DCE-MRI) is a noninvasive technique that measures properties of tissue microvasculature. Its sensitivity to radiation-induced vascular pharmacokinetic (PK) changes has been preliminary demonstrated. In spite of its great potential, two major challenges have limited DCE-MRI’s clinical application in radiotherapy assessment: the technical limitations of accurate DCE-MRI imaging implementation and the need of novel DCE-MRI data analysis methods for richer functional heterogeneity information.

This study aims at improving current DCE-MRI techniques and developing new DCE-MRI analysis methods for particular radiotherapy assessment. Thus, the study is naturally divided into two parts. The first part focuses on DCE-MRI temporal resolution as one of the key DCE-MRI technical factors, and some improvements regarding DCE-MRI temporal resolution are proposed; the second part explores the potential value of image heterogeneity analysis and multiple PK model combination for therapeutic response assessment, and several novel DCE-MRI data analysis methods are developed.

I. Improvement of DCE-MRI temporal resolution. First, the feasibility of improving DCE-MRI temporal resolution via image undersampling was studied. Specifically, a novel MR image iterative reconstruction algorithm was studied for DCE-MRI reconstruction. This algorithm was built on the recently developed compress sensing (CS) theory. By utilizing a limited k-space acquisition with shorter imaging time, images can be reconstructed in an iterative fashion under the regularization of a newly proposed total generalized variation (TGV) penalty term. In the retrospective study of brain radiosurgery patient DCE-MRI scans under IRB-approval, the clinically obtained image data was selected as reference data, and the simulated accelerated k-space acquisition was generated via undersampling the reference image full k-space with designed sampling grids. Two undersampling strategies were proposed: 1) a radial multi-ray grid with a special angular distribution was adopted to sample each slice of the full k-space; 2) a Cartesian random sampling grid series with spatiotemporal constraints from adjacent frames was adopted to sample the dynamic k-space series at a slice location. Two sets of PK parameters’ maps were generated from the undersampled data and from the fully-sampled data, respectively. Multiple quantitative measurements and statistical studies were performed to evaluate the accuracy of PK maps generated from the undersampled data in reference to the PK maps generated from the fully-sampled data. Results showed that at a simulated acceleration factor of four, PK maps could be faithfully calculated from the DCE images that were reconstructed using undersampled data, and no statistically significant differences were found between the regional PK mean values from undersampled and fully-sampled data sets. DCE-MRI acceleration using the investigated image reconstruction method has been suggested as feasible and promising.

Second, for high temporal resolution DCE-MRI, a new PK model fitting method was developed to solve PK parameters for better calculation accuracy and efficiency. This method is based on a derivative-based deformation of the commonly used Tofts PK model, which is presented as an integrative expression. This method also includes an advanced Kolmogorov-Zurbenko (KZ) filter to remove the potential noise effect in data and solve the PK parameter as a linear problem in matrix format. In the computer simulation study, PK parameters representing typical intracranial values were selected as references to simulated DCE-MRI data for different temporal resolution and different data noise level. Results showed that at both high temporal resolutions (<1s) and clinically feasible temporal resolution (~5s), this new method was able to calculate PK parameters more accurate than the current calculation methods at clinically relevant noise levels; at high temporal resolutions, the calculation efficiency of this new method was superior to current methods in an order of 102. In a retrospective of clinical brain DCE-MRI scans, the PK maps derived from the proposed method were comparable with the results from current methods. Based on these results, it can be concluded that this new method can be used for accurate and efficient PK model fitting for high temporal resolution DCE-MRI.

II. Development of DCE-MRI analysis methods for therapeutic response assessment. This part aims at methodology developments in two approaches. The first one is to develop model-free analysis method for DCE-MRI functional heterogeneity evaluation. This approach is inspired by the rationale that radiotherapy-induced functional change could be heterogeneous across the treatment area. The first effort was spent on a translational investigation of classic fractal dimension theory for DCE-MRI therapeutic response assessment. In a small-animal anti-angiogenesis drug therapy experiment, the randomly assigned treatment/control groups received multiple fraction treatments with one pre-treatment and multiple post-treatment high spatiotemporal DCE-MRI scans. In the post-treatment scan two weeks after the start, the investigated Rényi dimensions of the classic PK rate constant map demonstrated significant differences between the treatment and the control groups; when Rényi dimensions were adopted for treatment/control group classification, the achieved accuracy was higher than the accuracy from using conventional PK parameter statistics. Following this pilot work, two novel texture analysis methods were proposed. First, a new technique called Gray Level Local Power Matrix (GLLPM) was developed. It intends to solve the lack of temporal information and poor calculation efficiency of the commonly used Gray Level Co-Occurrence Matrix (GLCOM) techniques. In the same small animal experiment, the dynamic curves of Haralick texture features derived from the GLLPM had an overall better performance than the corresponding curves derived from current GLCOM techniques in treatment/control separation and classification. The second developed method is dynamic Fractal Signature Dissimilarity (FSD) analysis. Inspired by the classic fractal dimension theory, this method measures the dynamics of tumor heterogeneity during the contrast agent uptake in a quantitative fashion on DCE images. In the small animal experiment mentioned before, the selected parameters from dynamic FSD analysis showed significant differences between treatment/control groups as early as after 1 treatment fraction; in contrast, metrics from conventional PK analysis showed significant differences only after 3 treatment fractions. When using dynamic FSD parameters, the treatment/control group classification after 1st treatment fraction was improved than using conventional PK statistics. These results suggest the promising application of this novel method for capturing early therapeutic response.

The second approach of developing novel DCE-MRI methods is to combine PK information from multiple PK models. Currently, the classic Tofts model or its alternative version has been widely adopted for DCE-MRI analysis as a gold-standard approach for therapeutic response assessment. Previously, a shutter-speed (SS) model was proposed to incorporate transcytolemmal water exchange effect into contrast agent concentration quantification. In spite of richer biological assumption, its application in therapeutic response assessment is limited. It might be intriguing to combine the information from the SS model and from the classic Tofts model to explore potential new biological information for treatment assessment. The feasibility of this idea was investigated in the same small animal experiment. The SS model was compared against the Tofts model for therapeutic response assessment using PK parameter regional mean value comparison. Based on the modeled transcytolemmal water exchange rate, a biological subvolume was proposed and was automatically identified using histogram analysis. Within the biological subvolume, the PK rate constant derived from the SS model were proved to be superior to the one from Tofts model in treatment/control separation and classification. Furthermore, novel biomarkers were designed to integrate PK rate constants from these two models. When being evaluated in the biological subvolume, this biomarker was able to reflect significant treatment/control difference in both post-treatment evaluation. These results confirm the potential value of SS model as well as its combination with Tofts model for therapeutic response assessment.

In summary, this study addressed two problems of DCE-MRI application in radiotherapy assessment. In the first part, a method of accelerating DCE-MRI acquisition for better temporal resolution was investigated, and a novel PK model fitting algorithm was proposed for high temporal resolution DCE-MRI. In the second part, two model-free texture analysis methods and a multiple-model analysis method were developed for DCE-MRI therapeutic response assessment. The presented works could benefit the future DCE-MRI routine clinical application in radiotherapy assessment.

Chitosan scaffold as an alternative adsorbent for the removal of hazardous food dyes from aqueous solutions

Hypothesis: The dye adsorption with chitosan is considered an eco-friendly alternative technology in relation to the existing water treatment technologies. However, the application of chitosan for dyes removal is limited, due to its low surface area and porosity. Then we prepared a chitosan scaffold with a megaporous structure as an alternative adsorbent to remove food dyes from solutions. Experiments: The chitosan scaffold was characterized by infrared spectroscopy, scanning electron microscopy and structural characteristics. The potential of chitosan scaffold to remove five food dyes from solutions was investigated by equilibrium isotherms and thermodynamic study. The scaffold–dyes interactions were elucidated, and desorption studies were carried out. Findings: The chitosan scaffold presented pore sizes from 50 to 200 lm, porosity of 92.2 ± 1.2% and specific surface area of 1135 ± 2 m2 g 1. The two-step Langmuir model was suitable to represent the equilibrium data. The adsorption was spontaneous, favorable, exothermic and enthalpy-controlled process. Electrostatic interactions occurred between chitosan scaffold and dyes. Desorption was possible with NaOH solution (0.10 mol L 1). The chitosan megaporous scaffold showed good structural characteristics and high adsorption capacities (788–3316 mg g 1).

Investigation into various fungicides and alternative solutions for controlling postharvest diseases in papaya fruit

In Australia, Sportak® (a.i., prochloraz) has been registered since the early 1980's for the postharvest control of both anthracnose and stem-end rots in papaya fruit, despite the persistence of fruit breakdown due to disease during transit and at market destinations. Consequently, the Australian papaya industry has been concerned over the efficacy of prochloraz and whether substitute or alternative solutions were available for better disease control, particularly during times of peak disease pressure. This study therefore investigated the effects of various postharvest treatments for disease control in papaya. Fruit were harvested at colour break from coastal farms in Far North Queensland and treated with commercial rates of various fungicides, including prochloraz, imazalil, thiabendazole and fludioxonil. Additional solutions known to inhibit disease were examined, including chitosan and carnauba wax both with and without ammonium carbonate (AC). Following treatment, fruit were ripened and assessed for quality over their shelf life. Fludioxonil when applied as a hot dip was found to be a more efficacious treatment for control of disease in papaya than prochloraz. The other fungicides were moderately effective, as both thiabendazol and prochloraz exhibited an intermediate response and imazalil was the least effective. Disease severity was lowest in fruit treated with AC followed by chitosan, whilst chitosan delayed degreening. Overall, the study found that hot fludioxonil provided an effective replacement of the currently registered chemical prochloraz, and that alternate solutions such chitosan and AC may also be beneficial, particularly for low chemical input farming systems.

Endoscopic incision for the treatment of refractory esophageal anastomotic strictures: outcomes of 13 cases with a minimum follow-up of 12 months

Background and aim: Endoscopic incision is an alternative method for refractory esophageal strictures; however, little is known about its long-term efficacy. The aim of the study is to assess the long-term outcomes of endoscopic incision for treating refractory esophageal anastomotic strictures. Methods: Between September 2011 and September 2014, 13 patients with refractory esophageal anastomotic strictures were treated with endoscopic incision. Their clinical data were retrospectively collected to evaluate the efficacy and safety of the technique. Results: All the 13 patients underwent the procedure successfully with median operation duration of 15 minutes. A total of 27 sessions were necessary to maintain lumen patency until September 2015, and 7 patients needed retreatment. The symptoms relieved in all the cases, and the median dysphagia score decreased from 4 to 1 during a median follow-up of 24 months. The median diameter of stricture was enlarged from 4 mm to 12 mm. As a short-term effect, dysphagia symptoms improved in 100% (13/13), 84.6% (11/13) and 76.9% (10/13) of the patients one, three and six months after a single treatment. As long-term effect, the dysphagia improved in 61.5% (8/13), 63.6% (7/11) and 60% (6/10) of the patients 12, 18 and 24 months after a single treatment. Conclusions: The efficacy of endoscopic incision is favorable in the short term. However, retreatment is needed to maintain the long-term lumen patency for parts of the patients.

From the field to the table: ionizing radiation as a feasible postharvest treatment for fresh and dried plant foods

Food irradiation is a treatment that involves subjecting in-bulk or packaged food to a controlled dose of ionizing radiation, with a clearly defined goal. It has been used for disinfestation and sanitization of food commodities and to retard postharvest ripening and senescence processes, being a sustainable alternative to chemical agents 1 . Doses up to 10 kGy are approved by several international authorities for not offering negative effects to food from a nutrition and toxicology point of view 2 . However, the adoption of this technology for food applications has been a slow process due to some misunderstandings by the consumer who often chooses non-irradiated foods. In this study, the effects of the ionizing radiation treatment on physical, chemical and bioactive properties of dried herbs and its suitability for preserving quality attributes of fresh vegetables during cold storage were evaluated. The studied herbs, perennial spotted rockrose (Tuberaria lignosa (Sweet) Samp.) and common mallow (Malva neglecta Wallr.) were freeze-dried and then irradiated up to 10 kGy in a Cobalt-60 chamber. The selected vegetables, watercress (Nasturtium officinale R. Br.) and buckler sorrel (Rumex induratus Boiss. Reut.) were rinsed in tap water, packaged in polyethylene bags, submitted to irradiation doses up to 6 kGy and then were stored at 4 C for a period of up to 12 days. Physical, chemical and bioactive parameters of irradiated and non-irradiated samples were evaluated using different methodologies the colour was measured with a colorimeter, individual chemical compounds were analyzed by chromatographic techniques, antioxidant properties were evaluated using in vitro assays based on different reaction mechanisms, and other quality analyses were performed following official methods of analysis. The irradiation treatment did not significantly affect the colour of the perennial spotted rockrose samples, or its phenolic composition and antioxidant activity 3 . Medium doses preserved the colour of common mallow and a low dose did not induce any adverse effect in the organic acids profile. The green colour of the irradiated vegetables was maintained during cold storage but the treatment had pros and cons in other quality attributes. The 2 kGy dose preserved free sugars and favoured polyunsaturated fatty acids (PUFA) while the 5 kGy dose favoured tocopherols and preserved the antioxidant properties in watercress samples. The 6 kGy dose was a suitable option for preserving PUFA and the ω-6 ω-3 fatty acids ratio in buckler sorrel samples. This comprehensive experimental work allowed selecting appropriate processing doses for the studied plant foods in order to preserve its quality attributes and edibility.

COMBUSTION and PYROLYSIS of A SLUDGE FROM WASTEWATER TREATMENT PLANT

The possibility of thermal treatment plants of municipal wastewater is an alternative solution for the final disposition of the sludge produced on small cities as Barueri, a small town of São Paulo State, Brazil. Combustion and pyrolysis of that municipal waste, occurring respectively in air and nitrogen, have been studied by thermogravimetry (TG) and differential thermal analysis (DTA). The main steps of each case were analyzed and Kissinger plots were used to estimate respective activation energies. DTG peaks are more indicated to represent the condition of maximum reaction rates than DTA peaks.

Flexible endoscopic treatment of Zenker's diverticulum: thirteen years' experience in Spain

Introduction: Flexible endoscopic treatment is one of the alternative approaches for the management of Zenker's diverticum. The present paper shows our short-term and long-term results with flexible endoscopic cricopharyngeal myotomy/septotomy. Patients and methods: A retrospective analysis of our experience in patients with Zenker's diverticulum treated using a flexible endoscope, assisted by a flexible diverticuloscope, between 2002 and 2015. Myotomy/septotomy was performed with a needle-knife papillotome under deep sedation or general anesthesia. Results: Among the 64 patients treated, two died within 10 days of surgery from causes not directly related to the procedure, and one presented with pharyngo-esophageal perforation, which recovered with conservative management at 47 days after admission. Four additional patients were lost to short-term follow-up. Among the 57 remaining patients, 52 had complete relief of dysphagia after 6 weeks. Eleven of these had recurrent symptoms on the mid and the long term. Eight were retreated with the same flexible endoscopic technique, one with a hybrid endoscopic approach, one with classical open surgery and one refused retreatment. After a mean follow-up of 2 years and a half, 33 of 37 patients reported absent or minimal dysphagia, controllable with punctual dietary restrictions. Conclusions: Flexible endoscopic treatment for Zenker's diverticulum is effective and safe. It represents an option on an equal footing to rigid endoscopy and classical open surgery and may also be used when the latter two are technically impracticable or contraindicated.

Endoscopy as a diagnostic and therapeutic alternative technique of taeniasis

Despite a low incidence in developed countries, gastrointestinal taeniasis should be suspected in patients with abdominal pain, diarrhea, anemia, and/or malabsorption of unknown origin, even more so if they come from endemic regions or areas with poor hygienic and alimentary habits. Diagnosis is traditionally reached by identifying the parasite in stools, but more recently both serological and immunological approaches are also available. Based on a patient diagnosed by gastroscopy, a literature review was undertaken of patients diagnosed by endoscopy. We discuss endoscopy as diagnostic modality, and the effectiveness and safety that endoscopic treatment may provide in view of the potential risk for neurocysticercosis.

The medico-legal importance of establishing human identity by palatal rugoscopy: evaluation of the immutability and individuality of palatal rugae under the influence of ante mortem orthodontic treatment

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