How effective is laparoscopic redo-antireflux surgery?

BACKGROUND: The failure-rate after primary antireflux surgery ranges from 3 to 30%. Reasons for failures are multifactorial. The aim of this study is to gain insight into the complex reasons for, and management of, failure after antireflux surgery. METHODS: Patients were selected for redo-surgery after a diagnostic workup consisting of history and physical examination, upper gastrointestinal endoscopy, quality-of-life assessment, screening for somatoform disorders, esophageal manometry, 24-hour-pH-impedance monitoring, and selective radiographic studies such as Barium-sandwich for esophageal passage and delayed gastric emptying. Perioperative and follow-up data were compiled between 2004 and 2017. RESULTS: In total, 578 datasets were analyzed. The patient cohort undergoing a first redo-procedure (n = 401) consisted of 36 patients after in-house primary LF and 365 external referrals (mean age: 62.1 years [25-87]; mean BMI 26 [20-34]). The majority of patients underwent a repeated total or partial laparoscopic fundoplication. Major reasons for failure were migration and insufficient mobilization during the primary operation. With each increasing number of required redo-operations, the complexity of the redo-procedure itself increased, follow-up quality-of-life decreased (GIQLI: 106; 101; and 100), and complication rate increased (intraoperative: 6,4-10%; postoperative: 4,5-19%/first to third redo). After three redo-operations, resections were frequently necessary (morbidity: 42%). CONCLUSIONS: Providing a careful patient selection, primary redo-antireflux procedures have proven to be highly successful. It is often the final chance for a satisfying result may be achieved upon performing a second redo-procedure. A third revision may solve critical problems, such as severe pain and/or inadequate nutritional intake. When resection is required, quality of life cannot be entirely normalized.

Primary laparoscopic fundoplication in selected patients with gastroesophageal reflux disease.

BACKGROUND: Despite proton pump inhibitors being a powerful therapeutic tool, laparoscopic fundoplication (LF) has proven successful in the treatment of gastroesophageal reflux disease (GERD), through mechanical augmentation of a weak antireflux barrier and the advantages of minimally invasive access. A critical patient selection for LF, based on thorough preoperative assessment, is important for the management of GERD-patients. The purpose of this study is to provide an overview on the management of GERD-patients treated by primary LF in a specialized center and to illustrate the possible outcome after several years. METHODS: Patients were selected after going through diagnostic workup consisting of patient's history and physical examination, upper gastrointestinal endoscopy, assessment of gastrointestinal Quality of Life Index, screening for somatoform disorders, functional assessment by esophageal manometry, (impedance)-24-hour-pH-monitoring, and selective radiographic studies. The indication for LF was based on EAES-guidelines. Either a floppy and short Nissen fundoplication was performed or a posterior Toupet-hemifundoplication was chosen. A long-term follow-up assessment was attempted after surgery. RESULTS: In total, n = 1131 patients were evaluated (603 males; 528 females; mean age; 48.3 years; and mean body mass index: 27). The mean duration between onset of symptoms and surgery was 8 years. Nissen: n = 873, Toupet: n = 258; conversion rateerativ: 0.5%; morbidity 4%, mortality: 1 (1131). Mean follow-up (n = 898; 79%): 5.6 years; pre/post-op results: esophagitis: 66%/12.1%; Gastrointestinal Quality of Life Index: median: 92/119; daily proton pump inhibitors-intake after surgery: 8%; and operative revisions 4.3%. CONCLUSIONS: In conclusion, our data show that careful patient selection for laparoscopic fundoplication and well-established technical concepts of mechanical sphincter augmentation can provide satisfying results in the majority of patients with severe GERD.

Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD-VIVIAD.

BACKGROUND: Varoglutamstat (formerly PQ912) is a small molecule that inhibits the activity of the glutaminyl cyclase to reduce the level of pyroglutamate-A-beta (pGluAB42). Recent studies confirm that pGluAB42 is a particular amyloid form that is highly synaptotoxic and plays a significant role in the development of AD. METHODS: This paper describes the design and methodology behind the phase 2b VIVIAD-trial in AD. The aim of this study is to evaluate varoglutamstat in a state-of-the-art designed, placebo-controlled, double-blind, randomized clinical trial for safety and tolerability, efficacy on cognition, and effects on brain activity and AD biomarkers. In addition to its main purpose, the trial will explore potential associations between novel and established biomarkers and their individual and composite relation to disease characteristics. RESULTS: To be expected early 2023 CONCLUSION: This state of the art phase 2b study will yield important results for the field with respect to trial methodology and for the treatment of AD with a small molecule directed against pyroglutamate-A-beta. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04498650.

Severity of GERD and disease progression.

BACKGROUND: Many factors may play a role in the severity and progression of gastroesophageal reflux disease (GERD) since pathophysiology is multifactorial. Data regarding the progression of GERD are controversial: some reports of increased esophageal acid exposure (EAE) and mucosal damage were considered as evidence for a stable disease course, while others interprete these findings as disease progression. The aim of this study is to analyze a large patient-population with persisting symptoms indicative of GERD under protonpumpinhibitor-therapy and identify components characterizing disease severity and progression. METHODS: Patients with symptoms indicative of GERD were included in the study in a tertiary referral center (Frankfurt, Germany). All selected patients were under long-term protonpumpinhibitor-therapy with persistant symptoms. All patients underwent investigations to collect data on their physical status, EAE, severity of esophagitis, anatomical changes, and esophageal functional defects as well as their relation to the duration of the disease. Incidence over time was plotted as survival curves and tested with Log-rank tests for the four main disease markers. Multivariate modeling with COX-regression model was used to estimate the general impact of the four main disease markers on the time course of the disease. In order to elucidate possible causal relationships over time, a path analysis (structural equation model) was calculated. RESULTS: From the database with 1480 data sets, 972 patients were evaluated (542 males, 430 females). The mean age was 50.5 years (range18-89). The mean body mass index was 27.2(19-48). The mean time between the onset of symptoms and the diagnostic investigations was 8.2 years (1-50). A longer disease history for GERD was significantly associated with a higher risk for LES-incompetence. The mean duration from symptom onset to the time of clinical investigation was 9 years for patients with LES-incompetence (n = 563), compared to a mean of 6 years for those with mechanically intact LES (n = 95). A longer period from symptom onset to diagnostics was significantly associated with higher acid exposure. The pathway analysis was significant for the following model: 'history' (P < 0.001➔LES-incompetence & Hiatal Hernia➔(p < 0,001)➔pH-score (P < 0.001).Conclusion: LES-incompetence, the functional deterioration of the LES, and the anatomical alteration at the esophagogastric junction (Hiatal Hernia) as well as an increased EAE were associated with a long history of suffering from GERD. Path modeling suggests a causal sequence overtime of the main disease-parameters, tentatively allowing for a prediction of the course of the disease.

United States' experience in nuchal translucency measurement: variation according to provider characteristics in over five million ultrasound examinations.

OBJECTIVE: The Nuchal Translucency Quality Review (NTQR) program has provided standardized education, credentialing and epidemiological monitoring of nuchal translucency (NT) measurements since 2005. Our aim was to review the effect on NT measurement of provider characteristics since the program's inception. METHODS: We evaluated the distribution of NT measurements performed between January 2005 and December 2019, for each of the three primary performance indicators of NT measurement (NT median multiples of the median (MoM), SD of log10 NT MoM and slope of NT with respect to crown-rump length (CRL)) for all providers within the NTQR program with more than 30 paired NT/CRL results. Provider characteristics explored as potential sources of variability included: number of NT ultrasound examinations performed annually (annual scan volume of the provider), duration of participation in the NTQR program, initial credentialing by an alternative pathway, provider type (physician vs sonographer) and number of NT-credentialed providers within the practice (size of practice). Each of these provider characteristics was evaluated for its effect on NT median MoM and geometric mean of the NT median MoM weighted for the number of ultrasound scans, and multiple regression was performed across all variables to control for potential confounders. RESULTS: Of 5 216 663 NT measurements from 9340 providers at 3319 sites, the majority (75%) of providers had an NT median MoM within the acceptable range of 0.9-1.1 and 85.5% had NT median MoM not statistically significantly outside this range. Provider characteristics associated with measurement within the expected range of performance included higher volume of NT scans performed annually, practice at a site with larger numbers of other NT-credentialed providers, longer duration of participation in the NTQR program and alternative initial credentialing pathway. CONCLUSIONS: Annual scan volume, duration of participation in the NTQR program, alternative initial credentialing pathway and number of other NT-credentialed providers within the practice are all associated with outcome metrics indicating quality of performance. It is critical that providers participate in ongoing quality assessment of NT measurement to maintain consistency and precision. Ongoing assessment programs with continuous feedback and education are necessary to maintain quality care. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

HoloSelecta dataset: 10'035 GTIN-labelled product instances in vending machines for object detection of packaged products in retail environments.

To assess the potential of current neural network architectures to reliably identify packaged products within a retail environment, we created an open-source dataset of 295 shelf images of vending machines with 10'035 labelled instances of 109 products. The dataset contains photos of vending machines by the provider Selecta, the largest European operator of vending machines. The vending machines are a mix of machines in public and private office spaces. The vending machines contain food as well as beverage products. The product instances in the vending machine images are labelled with bounding boxes, where a bounding box encapsulates the entire product with as little overlap as possible. The labels corresponding to the bounding box consist of a structured, human-readable labels including brand, product name and size as well as the GTIN of the product. The GTIN is the global standard to identify products in the retail environment and therefore increases the value as a dataset for the retail industry. Contrary to typical object detection datasets that choose labels at a higher level such as a can or bottle for a much wider variety of objects, this dataset chooses a far more detailed label that depends less on the shape but rather on the exact design of the product. The dataset falls into the category of object detection datasets with a large number of objects, which next to the GTIN label, represents a main differentiator of the dataset to other object detection datasets.

German Respiratory Society guidelines for diagnosis and treatment of adults suffering from acute, subacute and chronic cough.

The present 2019 S2k consensus guideline of the German Respiratory Society was written for pneumologists - in contrast to the more general predecessor's S3 guidelines from 2004 to 2010 -, since 2014 the German College of General Practitioners and Family Physicians (DEGAM) published their own cough guidelines. The guidelines contain 48 recommendations agreed upon the consensus and 16 statements, which are explained in the background text in the following nine chapters: epidemiology, physiology, classification, acute, subacute or chronic cough, diagnostics and therapy; an extra chapter was dedicated to chronic idiopathic/refractory cough. Further emphasis of the guidelines is the physiology of cough in anticipation of the introduction of new drugs, as well as detailed treatment for cough triggered by affectations of the upper respiratory tract or gastroesophageal reflux. The guideline should provide the pneumologist with the latest knowledge for neighboring disciplines required for diagnosis and therapy of cough. The clinical chapters also contain a short summary, practical recommendations and a bibliography of their own. Three new simplified algorithms for acute, subacute and chronic cough, round off the diagnostics chapter.

Efeito de frações inspiradas de oxigênio e modalidades ventilatórias diferentes sobre a idade de cães / [Effects of oxygeninspired fractions and different ventilatory modalities on the age of dogs]

Objetivou-se avaliar diferentes modalidades ventilatórias em cães de diferentes idades submetidos à fração inspirada de oxigênio (FiO2) de 40% e 100%. Foram utilizados 36 cães de três grupos etários (GJ: 0-5; GA: 5-10 e GG: 10-15 anos), sem padronização de peso, sexo, raça e procedimento cirúrgico. Foram pré-medicados com acepromazina e morfina (0,02 e 0,5mg/kg), induzidos à anestesia geral com propofol dose-efeito, manutenção do plano anestésico com isoflurano em 1,3 V% e fornecimento de oxigênio conforme a FiO2 estabelecida para o grupo. Os animais foram submetidos a quatro diferentes modalidades ventilatórias: ventilação espontânea (VE), ventilação ciclada a volume (VCV), ventilação ciclada a pressão (VCP) e ventilação ciclada a pressão com PEEP (VCPP), e permaneceram 30 minutos em cada modalidade. Os parâmetros cardiovasculares mantiveram-se estáveis para todas as FiO2, modalidades ventilatórias e idades. Com relação aos parâmetros ventilatórios, na FiO2 100%, foram observados PaCO2 de 45mmHge e 29% de shunt, enquanto a FiO2 40% apresentou PaCO2 de 43 mmHg e 13% de shunt. Em relação às diferentes idades, os animais adultos e geriátricos apresentaram maiores valores de shunt (26% e 22%) e PaCO2 (44mm/Hg e 46mm/Hg). Conclui-se que a fração inspirada de 40% e a modalidade ventilatória ciclada a volume mostraram-se mais eficientes.(AU)

The objective was to evaluate different ventilatory modalities in dogs of different ages submitted to the inspired fraction of oxygen (FiO2) of 40% and 100%. Thirty-six dogs from three age groups (GJ 0-5, GA 5-10 and GG 10-15 years) were used, without standardization of weight, gender, race and surgical procedure. They were premedicated with acepromazine and morphine (0.02 and 0.5mg/kg), induced to general anesthesia with propofol dose/effect, maintenance of the anesthetic plane with isoflurane in 1.3V% and oxygen supply according to FiO2 established for the group. The animals were submitted to 4 different ventilation modalities, spontaneous ventilation (VS), volume-cycled ventilation (VCV), pressure-cycled ventilation (VCP) and pressure-cycled ventilation with PEEP (VCPP) and remained 30 minutes in each modality. The cardiovascular parameters remained stable for all FiO2, ventilatory modalities and ages. Regarding ventilatory parameters, in FiO2 and PaCO2 of 45mmHg and 29% of shunt, in FiO2 100%, PaCO2 of 43mmHg and 13% of shunt were observed. Regarding the different ages, adult and geriatric animals presented higher values of Shunt (26 and 22%) and PaCO2 (44 and 46mmHg). It was concluded that the inspired fraction of 40% and the volume-cycled ventilatory modality were more efficient.(AU)

Use of benchmarking to monitor and analyze effects of herd size and herd milk yield on cattle health and welfare in Austrian dairy farms.

The modernization and intensification of the dairy industry has led to larger herd sizes and higher milk production, both globally and in Austria. Benchmarking allows the monitoring of animal health and welfare as well as the identification of potential for improvement by comparing certain parameters with other farms with similar management environments. Using data from the Austrian routine recording system of various traits of milk production, fertility, and health, farmers and their veterinarians (with the consent of the farmer) can compare farm parameters with detailed data available from their district or state and ensure more efficient herd management. The aim of the present study was to provide an overview of dairy milk production in Austria based on the annual herd health reports and to examine the effects of herd size and milk production on fertility and health parameters. Annual herd health reports from all farms participating in the health monitoring system were considered, and analyses were conducted across breeds. A large variation between farms was observed. The results showed that, based on parameters of milk yield and herd size for the range of farms within this study, it cannot be concluded that these circumstances automatically lead to poor animal health. Farms with very small herd sizes differed significantly from those with larger herd sizes. Overall herd size effects were however small in Austria. Higher milk production based on a single farm does not necessarily cause more health and fertility problems; however, we detected a tendency for an increased risk of fertility, udder, and metabolic diagnoses. An active health management program might result in higher incidence rates for fertility or udder diagnoses, as a veterinary treatment might be economically superior if, for example, the calving interval can be shortened or the somatic cell count can be reduced. The results of the present study showed that it is advisable to use different benchmarks in combination for monitoring health, as well as for deciding on strategies to improve overall herd health management. Animal health reports on Austrian dairy cows are continuously being developed and new parameters integrated.

Identification of a tumor-specific allo-HLA-restricted γδTCR.

γδT cells are key players in cancer immune surveillance because of their ability to recognize malignant transformed cells, which makes them promising therapeutic tools in the treatment of cancer. However, the biological mechanisms of how γδT-cell receptors (TCRs) interact with their ligands are poorly understood. Within this context, we describe the novel allo-HLA-restricted and CD8α-dependent Vγ5Vδ1TCR. In contrast to the previous assumption of the general allo-HLA reactivity of a minor fraction of γδTCRs, we show that classic anti-HLA-directed, γδTCR-mediated reactivity can selectively act on hematological and solid tumor cells, while not harming healthy tissues in vitro and in vivo. We identified the molecular interface with proximity to the peptide-binding groove of HLA-A*24:02 as the essential determinant for recognition and describe the critical role of CD8 as a coreceptor. We conclude that alloreactive γδT-cell repertoires provide therapeutic opportunities, either within the context of haplotransplantation or as individual γδTCRs for genetic engineering of tumor-reactive T cells.

Soft X-ray microscopy for probing of topical tacrolimus delivery via micelles.

The penetration of topically applied tacrolimus formulated in micelles into murine skin is reported, measured by X-ray microscopy. Tacrolimus and micelles are probed for the first time by this high spatial resolution technique by element-selective excitation in the C 1s- and O 1s-regimes. This method allows selective detection of the distribution and penetration depth of drugs and carrier molecules into biologic tissues. It is observed that small, but distinct quantities of the drug and micelles, acting as a drug carrier, penetrate the stratum corneum. A comparison is made with the paraffin-based commercial tacrolimus ointment Protopic®, where local drug concentrations show to be low. A slight increase in local drug concentration in the stratum corneum is observed, if tacrolimus is formulated in micelles, as compared to Protopic®. This underscores the importance of the drug formulations for effective drug delivery. Time-resolved penetration shows presence of drug in the stratum corneum 100 min after formulation application, with penetration to deeper skin layers at 1000 min. High resolution micrographs give indications for a penetration pathway along the lipid membranes between corneocytes, but also suggest that the compound may penetrate corneocytes.

[Guidelines of the German Respiratory Society for Diagnosis and Treatment of Adults Suffering from Acute, Subacute and Chronic Cough]. / Leitlinie der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin zur Diagnostik und Therapie von erwachsenen Patienten mit Husten.

The present 2019 S2k consensus guideline of the German Respiratory Society was written - in contrast to the predecessor more general S3 guidelines from 2004 and 2010 - for pneumologists, since 2014 the German College of General Practitioners and Family Physicians (DEGAM) published his own cough guidelines.The guideline contains 48 recommendations agreed by consensus and 16 statements, which are explained in the background text in the following nine chapters: epidemiology, physiology, classification, acute, subacute or chronic cough, diagnostics and therapy; an extra chapter was dedicated to chronic idiopathic cough. Further emphasis of the guideline is the physiology of cough in anticipation of the introduction of new drugs, as well as detailed treatises on cough triggered by affections in the upper respiratory tract or by gastroesophageal reflux. The guideline should provide the pneumologist with the latest knowledge from neighboring disciplines required for diagnosis and therapy of cough. The clinical chapters also contain a short summary, practical recommendations and a bibliography of their own. Three new, simplified algorithms for acute, subacute and chronic cough round off the Diagnostics chapter.

The German trial on Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE): a multicenter, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. METHODS: The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0-2 vs. 3-6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. RESULTS: The trial was stopped prematurely for slow recruitment after 41 patients had been randomized, 21 of them treated with dexamethasone and 20 with placebo. No difference was observed in the primary endpoint. In the full analysis set (n = 19 in each group), 12 patients in each treatment arm achieved a mRS of 0-2. Similarly, we did not observe significant differences in the secondary endpoints (GOS, mRS, quality of life, neuropsychological testing). CONCLUSION: GACHE being prematurely terminated demonstrated challenges encountered performing randomized, placebo-controlled trials in rare life threatening neurological diseases. Based upon our trial results the use of adjuvant steroids in addition to antiviral treatment remains experimental and is at the decision of the individual treating physician. Unfortunately, the small number of study participants does not allow firm conclusions. TRIAL REGISTRATION: EudraCT-Nr. 2005-003201-81.

The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Foregut symptoms, somatoform tendencies, and the selection of patients for antireflux surgery.

A large variety of foregut symptoms can occur in patients with gastroesophageal reflux disease (GERD), which can overlap with other disorders such as somatoform disorders and dyspepsia. Due to unclear diagnostic situations, these patients are often not adequately treated. The aim of this study was the evaluation of patients with foregut symptoms, referred for possible antireflux surgery, regarding their relationship with GERD and somatization tendencies based on control data from an unselected population. Symptom evaluation and somatization screening were initiated both in volunteers and in patients with foregut symptoms and GERD. Unselected volunteers from a village population were also evaluated by symptom analysis and for somatisation tendency. In addition, patients with foregut symptoms were diagnosed for GERD, and symptom analysis and psychodiagnostic evaluation were performed. There is no major significant difference in the symptom-spectrum in patients with foregut symptoms, whether they have a proven pathologic acid exposure from GERD or not. The probability for the risk of somatization was 5.6% in the unselected population of nonpatient volunteers (n = 267). In patients with foregut symptoms (n = 750), the probability for the presence of somatoform tendencies was approximately 20%, independent whether these patients had a documented GERD or a normal esophageal acid exposure, implicating further diagnostic work-up for the selection of patients for antireflux surgery. There is a remarkable symptom load and variety in patients with GERD, in patients with foregut symptoms, and in an unselected population of volunteers. There is no difference in the risk for somatization between patients with foregut symptoms and those with documented GERD. Therapeutic decision making especially prior to antireflux surgery requires an awareness of mental and emotional challenges.

Correlação entre as escalas analógica visual, de Glasgow, Colorado e Melbourne na avaliação de dor pós-operatória em cadelas submetidas à mastectomia total unilateral / Correlation between visual analog scales, Glasgow, Colorado and Melbourne in the evaluation of postoperative pain in dogs undergoing total unilateral mastectomy

Objetivou-se correlacionar a necessidade de resgate analgésico pós-operatório por meio das escalas analógica visual (EVA), de Glasgow, Colorado e Melbourne, por meio de um avaliador experiente (AE) e outro não experiente (ANE), em cadelas submetidas à mastectomia unilateral total. Foram utilizadas 24 cadelas, hígidas, internadas 24 horas antes do procedimento cirúrgico, para avaliação do seu comportamento, com o auxílio das escalas descritas acima no momento basal (M0). Foram pré-medicadas com acepromazina e morfina (0,02 e 0,5mg/kg) e induzidas à anestesia geral com propofol (4mg/kg), mantidas em plano anestésico com CAM de isoflurano 1%. A manutenção analgésica transoperatória foi realizada com cetamina e fentanil (10µg/kg/min e 10µg/kg/h). As demais avaliações ocorreram em uma, duas, quatro, seis, oito, 12 e 24 horas de pós-operatório, sendo os resgates realizados com morfina (0,5mg/kg), pela via intramuscular, quando fosse observada uma pontuação maior ou igual a 50, seis, dois e nove pontos, respectivamente, para as escalas descritas, quando observada pelo AE e quando ao menos duas das escalas demonstrassem esses valores. Houve aumento dos escores de dor do M1 ao M12 para o AE e para o ANE para a EVA. Na análise de Colorado, maiores pontuações de dor ocorreram em relação ao M0 entre o M2 e o M8 para o AE e do M1 ao M12 para o ANE. Na análise de Glasgow, maiores escores foram detectados entre o M1 e o M12 para o AE e do M1 ao M24 para o ANE. E para a de Melbourne, maiores valores foram observados do M1 e do M24 para o AE e o ANE. A melhor correlação entre as escalas foi de 0,775 entre Glasgow e Colorado e entre os avaliadores de 0,925 para a Glasgow. Conclui-se que a escala de Glasgow apresentou-se mais sensível para detectar resgates analgésicos em cadelas submetidas à mastectomia total unilateral, que a inexperiência do avaliador não compromete a qualidade das avaliações de dor e sugere-se reduzir a pontuação da EVA e Melbourne para aumentar a sua capacidade em detectar resgates analgésicos pós-operatórios.(AU)

The objective was to relate the need for analgesic postoperative recovery through Visual Analogue Scale (VAS), Glasgow, Colorado and Melbourne, by an experienced assessor (AE) and other non-experienced ones (ANE), in bitches undergoing total unilateral mastectomy. Otherwise healthy bitches, a total of 24, were admitted 24 hours before the surgical procedure for assessment of behavior with the help of the above scales to determine the baseline (M0) moment. They were pre-medicated with morphine and acepromazine (0,02 and 0,5 mg/kg) and general anesthesia was induced with propofol (4 mg/kg) and maintained with isoflurane at 1% MAC. The analgesic during surgery was maintained with ketamine and fentanyl (10 µg/kg/min and 10 µg/kg/h). The other evaluations were performed at 1, 2, 4, 6, 8, 12 and 24 hours postoperatively, and redemptions made with intramuscular morphine (0,5 mg/kg) when a greater than or equal score of 50, 6, 2 and 9 points was observed respectively for the described ranges, as observed by the AE and when at least two scales demonstrated these values. There was an increase of M1 to M12 pain scores for AE and the ANE for VAS. In Colorado analyses, the highest painful scores occurred in relation to M0 between M2 and M8 to the AE and M1 to M12 for ANE. In Glasgow analyses, higher scores were detected between M1 to M12 for AE and M1 to M24 for ANE. And for the Melbourne highest values were observed in M1 and M24 for AE and ANE. The best correlation between the scales was 0,775 between Glasgow and Colorado and of the evaluators of 0,925 to Glasgow. The Glasgow scale was shown to be more sensitive to detect painkiller redemptions in dogs undergoing total unilateral mastectomy, the inexperience of the appraiser does not compromise the quality of painful reviews, and it is suggested to reduce the score VAS and Melbourne to increase it is ability to detect rescue postoperative analgesics.(AU)

Fluorescence and Cerenkov luminescence imaging. Applications in small animal research.

This review addresses small animal optical imaging (OI) applications in diverse fields of basic research. In the past, OI has proven to be cost- and time-effective, allows real-time imaging as well as high-throughput analysis and does not imply the usage of ionizing radiation (with the exception of Cerenkov imaging applications). Therefore, this technique is widely spread - not only geographically, but also among very different fields of basic research - and is represented by a large body of publications. Originally used in oncology research, OI is nowadays emerging in further areas like inflammation and infectious disease as well as neurology. Besides fluorescent probe-based contrast, the feasibility of Cerenkov luminescence imaging (CLI) has been recently shown in small animals and thus represents a new route for future applications. Thus, this review will focus on examples for OI applications in inflammation, infectious disease, cell tracking as well as neurology, and provides an overview over CLI.

CXCR1 Regulates Pulmonary Anti-Pseudomonas Host Defense.

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-P. aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway P. aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against P. aeruginosa. Mechanistically, CXCR1 regulates anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases.

Jackhammer esophagus: high-resolution manometry and therapeutic approach using peroral endoscopic myotomy (POEM).

We present the first report on peroral endoscopic myotomy (POEM) in the treatment of jackhammer esophagus. A 34-year-old female patient was newly diagnosed with a jackhammer esophagus. After failure of medical treatment, the patient underwent POEM procedure for myotomy of the spastic segment. Postoperatively, a mild emphysema and pneumothorax occurred that required drainage and antibiotic therapy until full recovery. Discharge was possible after 5 days. Six months later, she presented with recurrent but mild pain due to a remnant spastic segment proximal to the myotomy. Endoscopic balloon dilation was performed twice within 6 weeks with full symptomatic relief of pain and mild symptoms of dysphagia.

The potential and perspective of peroral endoscopic esophageal myotomy for achalasia.

The therapeutic spectrum of this disorder consists of medical therapy, endoscopic balloon dilatation, endoscopic Botox injection, open or laparoscopic cardia myotomy, and most recently transesophageal endoscopic myotomy (POEM peroral endoscopic myotomy). The most important requirement is a well-experienced team in interventional flexible endoscopy. The endoscopist as well as the assisting staff should have experience in advanced therapeutic endoscopic techniques and hemostasis to handle all necessary endoscopic instruments such as injection needles, needle knife, triangle knife, coagulation graspers, and endoscopic clip handling and closures. In addition, advanced surgical and especially laparoscopic skills and experience as well as surgical knowledge about esophageal disease must be available in case of conversion and/or consultation. Prior to this procedure, the patient undergoes a detailed diagnostic work-up to confirm the diagnosis of achalasia. The procedures are performed in general anesthesia. The patient is brought in a supine position, and the abdomen is free for inspection and palpation during the procedure. The myotomy can be performed in different locations around the esophageal circumference. In Europe, several centers with large experience in esophageal disease, laparoscopy, and especially advanced interventional endoscopy have started to introduce this POEM-technique in their clinical practice. Initial success and low complication rates are quite promising and show a great future perspective for this technique. In the USA, POEM is a procedure with a substantial increase in numbers performed in the past years with a low complication rate. The largest series are performed in Asia with a great clinical success. The perspective of POEM may be the lesser access trauma. Its potential can be also realized in Redo cases, where experienced centers have initial experience with POEM after POEM and POEM after LHMD.