Digital quantification of soft tissue volumetric changes after scaling and root planning.

BACKGROUND: Monitoring the outcome and evolution of periodontitis treatment requires analyzing changes in the periodontium. However, traditional methods for analyzing volumetric changes in periodontal soft tissues have limitations due to their invasiveness or inaccuracy. The aim of this study was to measure the volumetric changes in periodontal tissues following scaling and root planing treatment using digital methods, such as the superimposition of pre- and post-treatment STL files Material and Methods: The study started with an initial periodontal examination and intraoral scanning. Periodontal treatment was then performed, and at the one-month re-evaluation, the same records were repeated. Finally, the clinical data and STL files of pre- and post-treatment scans were compared. RESULTS: in terms of clinical data, there was a mean decrease in probing depth of 0.34 ± 0.54 mm and a significant decrease in bleeding rate. Digital measurements showed a mean loss in height of 0.196 ± 0.188 mm and width of 0.344 ± 0.338 mm. CONCLUSIONS: Quantifying periodontal tissue changes after scaling and root planing was possible by superimposing STL files. Post-treatment gingival tissue shrinkage occurred in both height and width, which was not visible with conventional recordings.

Behavioural, physiological and molecular responses of the Antarctic fairy shrimp Branchinecta gaini (Daday, 1910) to polystyrene nanoplastics.

Plastic pollution represents an emerging environmental issue in terrestrial Antarctica, especially in the Antarctic Peninsula and Maritime Antarctica, which have been recently recognized as hot spots for plastic litter. In these regions, freshwater (FW) environments such as lakes host isolated ecosystems and species that can be severely affected by increasing environmental and anthropogenic stressors, which include plastics that are still overlooked. In this study, we investigated for the first time the impact of nanoplastics on adults of the fairy shrimp Branchinecta gaini (Order Anostraca) populating Antarctic FW ecosystems, using surface charged polystyrene nanoparticles (PS NPs) as a proxy. Short-term acute toxicity (48 h) was investigated by exposing adults to carboxyl (-COOH, 60 nm) and amino-modified (-NH2, 50 nm) PS NPs at 1 and 5 µg mL-1. Biodisposition of PS NPs and lethal and sub-lethal effects (i.e., swimming, moulting, histology, gene expression) were assessed. Behaviour of PS NPs in Antarctic FW media was monitored through 48 h of exposure showing that both PS NPs kept their nanoscale size in the Antarctic FW media. Survival of fairy shrimp adults over short-term exposure was not affected, on the other hand an increase in moulting rate and alterations in the gut epithelium were observed upon exposure to both PS NPs. Significant alterations at the behavioural (ventilation rate) and molecular (up-regulation of Hsp70mit, Hsp83, Sod, P450) levels were related to PS NP surface charge and associated with PS-NH2 exposure only. Nanoplastics could represent a threat for Antarctic FW biodiversity and the Antarctic fairy shrimp could be a valuable model for assessing their impact on such remote and pristine aquatic ecosystems.

Long-term trends in particulate matter from wood burning in the United Kingdom: Dependence on weather and social factors.

Particulate matter from wood burning emissions (Cwood) was quantified at five locations in the United Kingdom (UK), comprising three rural and two urban sites between 2009 and 2021. The aethalometer method was used. Mean winter Cwood concentrations ranged from 0.26 µg m-3 (in rural Scotland) to 1.30 µg m-3 (London), which represented on average 4% (in rural environments) and 5% (urban) of PM10 concentrations; and 8% of PM2.5. Concentrations were greatest in the evenings in winter months, with larger evening concentrations in the weekends at the urban sites. Random-forest (RF) machine learning regression models were used to reconstruct Cwood concentrations using both meteorological and temporal explanatory variables at each site. The partial dependency plots indicated that temperature and wind speed were the meteorological variables explaining the greatest variability in Cwood, with larger concentrations during cold and calm conditions. Peaks of Cwood concentrations took place during and after events that are celebrated with bonfires. These were Guy Fawkes events in the urban areas and on New Year's Day at the rural sites; the later probably related to long-range transport. Time series were built using the RF. Having removed weather influences, long-term trends of Cwood were estimated using the Theil Sen method. Trends for 2015-2021 were downward at three of the locations (London, Glasgow and rural Scotland), with rates ranging from -5.5% year-1 to -2.5% year-1. The replacement of old fireplaces with lower emission wood stoves might explain the decrease in Cwood especially at the urban sites The two rural sites in England observed positive trends for the same period but this was not statistically significant.

[Adequacy of the pharmacological prescription during the admission in a geriatric hospital. Clinical experiencie with STOPP/START criteria]. / Adecuación de la prescripción farmacológica durante el ingreso en un centro sociosanitario: experiencia clínica con los criterios STOPP/START.

BACKGROUND AND OBJECTIVES: The elderly patient is particularly vulnerable to potentially inappropriate prescription (PIP) due to physiological reasons, comorbidity, polypharmacy or the different pharmacokinetics/pharmacodynamics of drugs. The aim of this study was to determine the prevalence of PIP according to the STOPP-START criteria in patients over 65 years admitted into a geriatric hospital, as well as to appraise its acceptance by geriatricians. MATERIAL AND METHODS: Retrospective observational study. Patients older than 65 years consecutively admitted to medium/long-stay units were included. The study information was obtained by reviewing the clinical record of the patients. The PIP according to the STOPP-START criteria were assessed by the geriatrician, who decided whether or not to modify the medication and recorded the reasons. RESULTS: 247 patients were included, mean age was 82.6 years (SD 7.3), 72.1% of patients were female and a median of 7 drugs (25-75 percentile: 4-9). 78.9% (95%CI: 73.3-83.9) of patients had at least one PIP STOPP-START at admission, 44.9% (95%CI: 38.6-51.4) PIP-STOPP and 59.5% (95%CI: 53.1-65.7) PIP-START. At hospital discharge, the prevalence of PIP-STOPP-START was 46.2% (95%CI: 39.8-52.6), 19.0% (95%CI: 14.3-24.5) of PIP-STOPP and 34.4% (95%CI: 28.5-40.7) PIP-START. CONCLUSIONS: The comprehensive geriatric assessment and the use of the STOPP-START criteria can significantly reduce the prevalence of PIP among patients admitted to a geriatric hospital. Nevertheless, issues such as frailty, multimorbidity and functional goals would be taken into account in the appropriateness of the prescription.

Atmospheric microplastic deposition in an urban environment and an evaluation of transport.

Microplastics are a global environmental issue contaminating aquatic and terrestrial environments. They have been reported in atmospheric deposition, and indoor and outdoor air, raising concern for public health due to the potential for exposure. Moreover, the atmosphere presents a new vehicle for microplastics to enter the wider environment, yet our knowledge of the quantities, characteristics and pathways of airborne microplastics is sparse. Here we show microplastics in atmospheric deposition in a major population centre, central London. Microplastics were found in all samples, with deposition rates ranging from 575 to 1008 microplastics/m2/d. They were found in various shapes, of which fibrous microplastics accounted for the great majority (92%). Across all samples, 15 different petrochemical-based polymers were identified. Bivariate polar plots indicated dependency on wind, with different source areas for fibrous and non-fibrous airborne microplastics. This is the first evidence of airborne microplastics in London and confirms the need to include airborne pathways when consolidating microplastic impacts on the wider environment and human health.

Assessment of the capacity of a pyrophosphate-based mouth rinse to inhibit the formation of supragingival dental calculus. A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: This study aimed to analyze the efficacy of an anti-calculus mouth rinse and its possible adverse effects on the mucosa and teeth. MATERIAL AND METHODS: This randomized double-blind placebo-controlled clinical trial included 40 patients with treated and managed periodontal disease, all with a history of rapid calculus formation. Patients used a pyrophosphate-based test mouth rinse (B) or a placebo (A). A range of parameters were measured for: saliva (saliva flow, pH and chemical composition); calculus (Volpe-Manhold [V-M] index, weight, and volume); adverse effects on mucosa and teeth; and the patients' subjective perceptive of mouth rinse efficacy. RESULTS: the test mouth rinse B produced reductions in urea, uric acid, and phosphorous, calcium, saliva flow, and increases in pH. V-M index and calculus weight decreased after using the test mouth rinse. Calculus volume decreased with both mouth rinses. No changes to the mucosa or teeth were observed. Patients perceived that the test mouth rinse was more effective. CONCLUSIONS: The test/B and placebo mouth rinses both modified certain parameters in saliva composition, particularly reductions in urea, uric acid, and phosphorous. Calcium tended to increase after using the test-B mouth rinse. The results did not demonstrate the anticalculus efficacy of the pyrophosphate-based mouth rinse or positive effects on saliva flow or composition. This field requires further research, as no product has been developed that prevents calculus formation completely.

Optical and electrical properties of MoO2 and MoO3 thin films prepared from the chemically driven isothermal close space vapor transport technique.

Chemically-driven isothermal close space vapour transport was used to prepare pure MoO2 thin films which were eventually converted to MoO3 by annealing in air. According to temperature-dependent Raman measurements, the MoO2/MoO3 phase transformation was found to occur in the 225 °C-350 °C range while no other phases were detected during the transition. A clear change in composition as well as noticeable modifications of the band gap and the absorption coefficient confirmed the conversion from MoO2 to MoO3. An extensive characterization of these two pure phases was carried out. In particular, a procedure was developed to determine the dispersion relation of the refractive index of MoO2 from the shift of the interference fringes of the used SiO2/Si substrate. The obtained data of the refractive index was corrected taking into account the porosity of the samples calculated from elastic backscattering spectrometry. The Debye temperature and the residual resistivity were extracted from the electrical resistivity temperature dependence using the Bloch-Grüneisen equation. MoO3 converted samples presented a very high resistivity and a typical semiconducting behavior. They also showed intense and broad luminescence spectra composed by several contributions whose temperature behavior was examined. Furthermore, surface photovoltage spectra were taken and their relation with the photoluminescence is discussed.

Correction to: SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016).

Due to a technical issue, the family name of the author.

Long-term abiraterone withdrawal syndrome.

WHAT IS KNOWN AND OBJECTIVE: Abiraterone acetate (AA) is an androgen receptor axis inhibitor, indicated together with prednisone, for metastatic castration-resistant prostate cancer. Withdrawal syndrome for classical antiandrogen treatments is well known, but not so known for AA. Abiraterone withdrawal syndrome (AWS) could be related to simultaneous prednisone discontinuation or to an androgenic effect of AA metabolites. CASE DESCRIPTION: A case is described of a patient with long-term AWS without prednisone discontinuation. The clinical and prostate-specific antigen (PSA) response allowed an 8-month delay in docetaxel treatment. WHAT IS NEW AND CONCLUSION: Prednisone did not play a role in AWS in this case. The long-term response allowed a delay in future treatment.

Prospective Clinical Study of Zirconia Full-coverage Restorations on Teeth Prepared With Biologically Oriented Preparation Technique on Gingival Health: Results After Two-year Follow-up.

OBJECTIVES: To evaluate the clinical behavior of one-piece complete-coverage crowns and fixed partial dentures (FPDs) on teeth with vertical preparation without finish line biologically oriented preparation technique (BOPT). METHODS AND MATERIALS: This prospective study included 52 patients requiring treatment with restorations in the esthetic region: 74 crowns and 27 FPDs. The sample included a total of 149 teeth that were prepared vertically without finish line. The sample was divided into two groups: one-piece crowns and FPDs, all with zirconia cores, feldspathic ceramic veneer, and a 0.5-mm prosthetic finish line of zirconia. All procedures were carried out at the University of Valencia from 2013 to 2014. The following parameters were evaluated over a two-year follow-up: oral hygiene, periodontal state, gingival thickening, gingival margin stability, the presence of complications, and restoration survival rate. Patient satisfaction with treatment was assessed by means of a visual analogue scale (VAS). RESULTS: Two years after treatment, 80.5% of treated teeth remained free of gingival inflammation and bleeding. Mean gingival thickening was 0.41 ± 0.28 mm for one-piece crowns and 0.38 ± 0.36 mm for FPDs. Gingival margin stability was 100%, but 2% of the sample presented biological complications. The VAS patient satisfaction scores were eight out of a maximum score of 10. CONCLUSIONS: Two years after treatment, vertical preparation without finish line produces gingival thickening, margin stability, and optimal esthetics. Neither crowns nor FPDs presented any mechanical complications.

Effects of Benazepril on Survival of Dogs with Chronic Kidney Disease: A Multicenter, Randomized, Blinded, Placebo-Controlled Clinical Trial.

BACKGROUND: Chronic kidney disease (CKD) is an important cause of morbidity and mortality in dogs. OBJECTIVE: To evaluate the efficacy in prolonging survival and safety of benazepril administration to dogs with CKD. ANIMALS: Forty-nine client-owned dogs with CKD. METHODS: Dogs were randomized to benazepril (0.25 to <0.5 mg/kg) or placebo once daily for up to 2 years in a prospective, multicenter, blinded clinical trial. The primary endpoint variable was the renal survival time, defined as the time from inclusion in the study to the treatment failure endpoint of death or euthanasia or need for administration of parenteral fluids related to renal failure. RESULTS: No benefit of benazepril versus placebo was detected for renal survival time in all dogs; median (95% confidence interval (CI)) survival times were 305 (53-575) days in the benazepril group and 287 (152-not available) in the placebo group (P = .53). Renal survival times were not significantly longer with benazepril compared to placebo for subgroups: hazard ratios (95% CI) were 0.50 (0.21-1.22) with P = .12 for initial urine protein-to-creatinine ratio (UPC) >0.5, and 0.38 (0.12-1.19) with P = .080 for initial UPC >0.5 plus plasma creatinine ≤440 µmol/L. Proteinuria, assessed from the UPC, was significantly (P = .0032) lower after treatment with benazepril compared to placebo. There were no significant differences between groups for clinical signs or frequencies of adverse events. CONCLUSIONS AND CLINICAL RELEVANCE: Benazepril significantly reduced proteinuria in dogs with CKD. Insufficient numbers of dogs were recruited to allow conclusions on survival time.

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

BACKGROUND: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION: Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER: NCT02288936 (PREMIERE trial).

Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport.

Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89±0.81µgcm-2h-1 whereas the highest iontophoretic transport was 46.4±3.6µgcm-2h-1. These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations.

SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016).

The goal of this article is to provide recommendations for the diagnosis and treatment of muscle-invasive and metastatic bladder cancer. The diagnosis of muscle-invasive bladder cancer is made by pathologic evaluation after transurethral resection. Recently, a molecular classification has been proposed. Staging of muscle-invasive bladder cancer must be done by computed tomography scans of the chest, abdomen and pelvis and classified on the basis of UICC system. Radical cystectomy and lymph node dissection are the treatment of choice. In muscle-invasive bladder cancer, neoadjuvant chemotherapy should be recommended in patients with good performance status and no renal function impairment. Although there is insufficient evidence for use of adjuvant chemotherapy, its use must be considered when neoadjuvant therapy had not been administered in high-risk patients. Multimodality bladder-preserving treatment in localized disease is an alternative in selected and compliant patients for whom cystectomy is not considered for clinical or personal reasons. In metastatic disease, the first-line treatment for patients must be based on cisplatin-containing combination. Vinflunine is the only drug approved for use in second line in Europe. Recently, immunotherapy treatment has demonstrated activity in this setting.

SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016)

The goal of this article is to provide recommendations for the diagnosis and treatment of muscle-invasive and metastatic bladder cancer. The diagnosis of muscle-invasive bladder cancer is made by pathologic evaluation after transurethral resection. Recently, a molecular classification has been proposed. Staging of muscle-invasive bladder cancer must be done by computed tomography scans of the chest, abdomen and pelvis and classified on the basis of UICC system. Radical cystectomy and lymph node dissection are the treatment of choice. In muscle-invasive bladder cancer, neoadjuvant chemotherapy should be recommended in patients with good performance status and no renal function impairment. Although there is insufficient evidence for use of adjuvant chemotherapy, its use must be considered when neoadjuvant therapy had not been administered in high-risk patients. Multimodality bladder-preserving treatment in localized disease is an alternative in selected and compliant patients for whom cystectomy is not considered for clinical or personal reasons. In metastatic disease, the first-line treatment for patients must be based on cisplatin-containing combination. Vinflunine is the only drug approved for use in second line in Europe. Recently, immunotherapy treatment has demonstrated activity in this setting (AU)

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Preoperative low-dose weekly cisplatin and continuous infusion fluorouracil plus hyperfractionated radiotherapy in stage II-III esophageal carcinoma

BACKGROUND: The optimal regimen of preoperative chemoradiotherapy for resectable esophageal cancer has not been established. We evaluated accelerated hyperfractionated radiotherapy (RT) concurrent to low-dose weekly cisplatin and continuous infusion fluorouracil (LDCI-FU) followed by esophagectomy in patients with locally advanced squamous cell carcinoma (SCC) of the esophagus. METHODS: Patients with clinical stage II or III SCC of the esophagus received cisplatin 30 mg/m2/week (days 1, 8, 15), LDCI-FU 300 mg/m2/day (days 1-21), and concomitant RT to a dose of 45 Gy (150 cGy/fraction, 2 fractions/day) on tumor and affected lymph nodes, followed by radical esophagectomy. RESULTS: From 1997 to 2012, 64 patients were treated with this regimen. Twenty-four patients (37 %) had grade 3 esophagitis, 18 (28 %) of whom required hospitalization. The risk of hospitalization was reduced by placement of a jejunostomy tube before starting induction chemoradiotherapy. Six patients (9 %) had grade 3-4 neutropenia. Fifty-three patients (83 %) underwent esophageal resection and complete resection was achieved in 45 (70 %). The overall median survival was 28 months (95 % CI: 20.4-35.6) and 5-year survival was 38 %. In the 18 patients attaining a pathological complete response, median survival was 132 months and 5-year survival was 72 %. Positron emission tomography standardized uptake values (PET SUVmax) post-chemoradiotherapy were associated with pathological response (p = 0.03) and survival (p = 0.04). CONCLUSIONS: Intensive preoperative hyperfractionated RT concomitant to low-dose cisplatin and LDCI-FU is effective in patients with locally advanced SCC of the esophagus, with good pathological response and survival and manageable toxicities. Post-chemoradiotherapy PET SUV max shows promise as a potential prognostic factor

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Adverse urinary effects of allopurinol in dogs with leishmaniasis.

OBJECTIVE: The objective of this study was to describe the adverse effects of allopurinol on the urinary system during treatment of canine leishmaniasis. METHODS: Retrospective case series of 42 dogs that developed xanthinuria while receiving allopurinol treatment for leishmaniasis. RESULTS: Of 320 dogs diagnosed with leishmaniasis, 42 (13%) developed adverse urinary effects. Thirteen (of 42) dogs (31%) developed xanthinuria, renal mineralisation and urolithiasis; 11 (26·2%) showed xanthinuria with renal mineralisation; 9 (21·4%) had xanthinuria with urolithiasis and 9 (21·4%) developed xanthinuria alone. Urinary clinical signs developed in 19 dogs (45·2%). CLINICAL SIGNIFICANCE: This study demonstrates that urolithiasis and renal mineralisation can occur in dogs receiving allopurinol therapy. Dogs receiving therapy should be monitored for the development of urinary adverse effects from the beginning of treatment.

Preoperative low-dose weekly cisplatin and continuous infusion fluorouracil plus hyperfractionated radiotherapy in stage II-III esophageal carcinoma.

BACKGROUND: The optimal regimen of preoperative chemoradiotherapy for resectable esophageal cancer has not been established. We evaluated accelerated hyperfractionated radiotherapy (RT) concurrent to low-dose weekly cisplatin and continuous infusion fluorouracil (LDCI-FU) followed by esophagectomy in patients with locally advanced squamous cell carcinoma (SCC) of the esophagus. METHODS: Patients with clinical stage II or III SCC of the esophagus received cisplatin 30 mg/m2/week (days 1, 8, 15), LDCI-FU 300 mg/m2/day (days 1-21), and concomitant RT to a dose of 45 Gy (150 cGy/fraction, 2 fractions/day) on tumor and affected lymph nodes, followed by radical esophagectomy. RESULTS: From 1997 to 2012, 64 patients were treated with this regimen. Twenty-four patients (37 %) had grade 3 esophagitis, 18 (28 %) of whom required hospitalization. The risk of hospitalization was reduced by placement of a jejunostomy tube before starting induction chemoradiotherapy. Six patients (9 %) had grade 3-4 neutropenia. Fifty-three patients (83 %) underwent esophageal resection and complete resection was achieved in 45 (70 %). The overall median survival was 28 months (95 % CI: 20.4-35.6) and 5-year survival was 38 %. In the 18 patients attaining a pathological complete response, median survival was 132 months and 5-year survival was 72 %. Positron emission tomography standardized uptake values (PET SUVmax) post-chemoradiotherapy were associated with pathological response (p = 0.03) and survival (p = 0.04). CONCLUSIONS: Intensive preoperative hyperfractionated RT concomitant to low-dose cisplatin and LDCI-FU is effective in patients with locally advanced SCC of the esophagus, with good pathological response and survival and manageable toxicities. Post-chemoradiotherapy PET SUVmax shows promise as a potential prognostic factor.

Development of antimigraine transdermal delivery systems of pizotifen malate.

The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate.