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It has been postulated that the combination of intracavitary and interstitial brachytherapy (IC/IS) is effective and safe for large and irregularly shaped uterine cervical cancer patients. However, due to its invasiveness compared to conventional intracavitary brachytherapy (ICBT), it has to be said that the implementation speed of IC/IS is slow. Until now, there have been no guidelines for required equipment, human resources, and procedural guide focusing solely on IC/IS. The purpose of this guideline is to provide radiation oncologists and medical physicists who wish to start IC/IS with practical and comprehensive guidance for a safe IC/IS introduction and to help accelerate the spread of the utilization of IC/IS nationwide. This is the English translation of the Japanese IC/IS Guidelines, and it was created in an effort to share the Japanese approach to the management of locally advanced uterine cervical cancer worldwide.

This is an evidence-based guideline for prostate brachytherapy. Throughout levels of evidence quoted are those from the Oxford Centre for Evidence based Medicine (https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009). Prostate interstitial brachytherapy using either permanent or temporary implantation is an established and evolving treatment technique for non-metastatic prostate cancer. Permanent brachytherapy uses Low Dose Rate (LDR) sources, most commonly I-125, emitting photon radiation over months. Temporary brachytherapy involves first placing catheters within the prostate and, on confirmation of accurate positioning, temporarily introducing the radioactive source, generally High Dose Rate (HDR) radioactive sources of Ir-192 or less commonly Co-60. Pulsed dose rate (PDR) brachytherapy has also been used for prostate cancer [1] but few centres have adopted this approach. Previous GEC ESTRO recommendations have considered LDR and HDR separately [2-4] but as there is considerable overlap, this paper provides updated guidance for both treatment techniques. Prostate brachytherapy allows safe radiation dose escalation beyond that achieved using external beam radiotherapy alone as it has greater conformity around the prostate, sparing surrounding rectum, bladder, and penile bulb. In addition there are fewer issues with changes in prostate position during treatment delivery. Systematic review and randomised trials using both techniques as boost treatments demonstrate improved PSA control when compared to external beam radiotherapy alone [5-7].

Purpose: Aim of this study is to report the results of the radiotherapy quality assurance program of the PEACE V-STORM randomized phase II trial for pelvic nodal oligorecurrent prostate cancer (PCa). Material and methods: A benchmark case (BC) consisting of a postoperative case with 2 nodal recurrences was used for both stereotactic body radiotherapy (SBRT, 30 Gy/3 fx) and whole pelvic radiotherapy (WPRT, 45 Gy/25 fx + SIB boost to 65 Gy). Results: BC of 24 centers were analyzed. The overall grading for delineation variation of the 1st BC was rated as 'UV' (Unacceptable Variation) or 'AV' (Acceptable Variation) for 1 and 7 centers for SBRT (33%), and 3 and 8 centers for WPRT (46%), respectively. An inadequate upper limit of the WPRT CTV (n = 2), a missing delineation of the prostate bed (n = 1), and a missing nodal target volume (n = 1 for SBRT and WPRT) constituted the observed 'UV'. With the 2nd BC (n = 11), the overall delineation review showed 2 and 8 'AV' for SBRT and WPRT, respectively, with no 'UV'. For the plan review of the 2nd BC, all treatment plans were per protocol for WPRT. SBRT plans showed variability in dose normalization (Median D90% = 30.1 Gy, range 22.9-33.2 Gy and 30.6 Gy, range 26.8-34.2 Gy for nodes 1 and 2 respectively). Conclusions: Up to 46% of protocol deviations were observed in delineation of WPRT for nodal oligorecurrent PCa, while dosimetric results of SBRT showed the greatest disparities between centers. Repeated BC resulted in an improved adherence to the protocol, translating in an overall acceptable contouring and planning compliance rate among participating centers. Swiss Prostate Cancer Award grant from the Movember Foundation Belgian 'Kom Op Tegen Kanker' Scientific Association of Swiss Radiation Oncologists (SASRO) 6.901 JCR (2021) Q1, 56/245 Oncology 1.946 SJR (2021) Q1, 13/133 Hematology No data IDR 2021 UEM

Study design Expert Consensus Study. Objectives This expert panel was created to establish best practice guidelines to identify and treat patients with poor bone health prior to elective spinal reconstruction. Summary of background data Currently, no guidelines exist for the management of osteoporosis and osteopenia in patients undergoing spinal reconstructive surgery. Untreated osteoporosis in spine reconstruction surgery is associated with higher complications and worse outcomes. Methods A multidisciplinary panel with 20 experts was assembled including orthopedic and neurological surgeons, endocrinologists, and rheumatologists. Surveys and discussions regarding the current literature were held according to Delphi method until a final set of guidelines was created with over 70% consensus. Results Panelists agreed that bone health should be considered in every patient prior to elective spinal reconstruction. All patients above 65 and those under 65 with particular risk factors (chronic glucocorticoid use, high fracture risk or previous fracture, limited mobility, and eight other key factors) should have a formal bone health evaluation prior to undergoing surgery. DXA scans of the hip are preferable due to their wide availability. Opportunistic CT Hounsfield Units of the vertebrae can be useful in identifying poor bone health. In the absence of contraindications, anabolic agents are considered first line therapy due to their bone building properties as compared to antiresorptive medications. Medications should be administered preoperatively for at least 2 months and postoperatively for minimum 8 months. Conclusions Based on the consensus of a multidisciplinary panel of experts, we propose best practice guidelines for assessment and treatment of poor bone health prior to elective spinal reconstructive surgery. Patients above age 65 and those with particular risk factors under 65 should undergo formal bone health evaluation. We also established guidelines on perioperative optimization, utility of various diagnostic modalities, and the optimal medical management of bone health in this population.Level of Evidence: 5.

The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical guidance for cardiologists, neurologists, geriatricians, and general practitioners in the Asia-Pacific region. In these years, many important new data regarding stroke prevention in AF were reported. The practice guidelines subcommittee members comprehensively reviewed updated information on stroke prevention in AF, and summarized them in this 2021 focused update of the 2017 consensus guidelines of the APHRS on stroke prevention in AF. We highlighted and focused on several issues, including the importance of the AF Better Care pathway, the advantages of non-vitamin K antagonist oral anticoagulants (NOACs) for Asians, the considerations of use of NOACs for Asian AF patients with single one stroke risk factor beyond gender, the role of lifestyle factors on stroke risk, the use of oral anticoagulants during the “coronavirus disease 2019” pandemic, etc. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician's decision remains the most important factor in the management of AF.

BACKGROUND AND STUDY AIMS: Appendiceal neuroendocrine neo-plasms (aNENs) are a diverse group of malignant neoplasms of varying biological behavior for which information about manage-ment and outcome is sparse, with the majority of available studies being retrospective, including only a limited number of patients, and therefore not necessarily reflecting the reality in the community. In the present study clinical, epidemiological and pathological data of appendiceal neuroendocrine neoplasms in Belgium is provided and compared with current literature. METHODS: A population-based study was conducted by linking data of the Belgian Cancer Registry with medical procedures in the Belgian Health Insurance database for patients diagnosed with aNEN between 2010 and 2015. RESULTS: We found an aNEN incidence of 0.97/100.000 person years in Belgium. Neuroendocrine carcinoma of the appendix are rare. Most appendiceal neuroendocrine tumors (aNETs) are small G1 tumors. Positive lymph nodes are often found in tumors larger than 2cm, especially aNET G2. CONCLUSION: A rapid uptake of changing classifications was seen in the community. However, systematic reporting of risk factors for small aNEN can still be improved and should be stimulated. In 9% of cases, reclassifications had to be made, pointing out that in a retrospective analysis, original pathological reports should be checked for specific parameters, before reliable conclusions can be drawn. ispartof: ACTA GASTRO-ENTEROLOGICA BELGICA vol:84 issue:3 pages:458-466 ispartof: location:Belgium status: published

Background Improved knowledge of the molecular pathophysiology and immunopathogenesis of cholestatic liver diseases in recent years has led to an increased interest in developing novel therapies. Patients with cholestatic liver disease often require different approaches to assessment and management of suspected drug-induced liver injury (DILI) compared to those with healthy livers and those with parenchymal liver diseases. At present, there are no regulatory guidelines or society position papers, that systematically address best practices pertaining to detection of DILI in these patients. Aims To outline best practices for detection, assessment and management of suspected acute DILI during clinical trials in adults with the cholestatic liver diseases - Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC). Methods This is one of the several papers developed by the IQ DILI Initiative, which is comprised of members from 16 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. The contents are the result of an extensive literature review, as well as in-depth discussions among industry, regulatory and academic DILI experts, to achieve consensus recommendations on DILI-related issues occurring during clinical trials for cholestatic liver diseases. Results Recommended best practices are outlined pertaining to hepatic eligibility criteria, monitoring of liver tests, approach to a suspected DILI signal, and hepatic discontinuation rules. Conclusions This paper provides a framework for the approach to detection, assessment and management of suspected acute DILI occurring during clinical trials in adults with cholestatic liver disease.

Background and purpose For skull base tumors, target definition is the key to safe high-dose treatments because surrounding normal tissues are very sensitive to radiation. In the present work we established a joint ESTRO ACROP guideline for the target volume definition of skull base tumors. Material and methods A comprehensive literature search was conducted in PubMed using various combinations of the following medical subjects headings (MeSH) and free-text words: “radiation therapy” or “stereotactic radiosurgery” or “proton therapy” or “particle beam therapy” and “skull base neoplasms” “pituitary neoplasms”, “meningioma”, “craniopharyngioma”, “chordoma”, “chondrosarcoma”, “acoustic neuroma/vestibular schwannoma”, “organs at risk”, “gross tumor volume”, “clinical tumor volume”, “planning tumor volume”, “target volume”, “target delineation”, “dose constraints”. The ACROP committee identified sixteen European experts in close interaction with the ESTRO clinical committee who analyzed and discussed the body of evidence concerning target delineation. Results All experts agree that magnetic resonance (MR) images with high three-dimensional spatial accuracy and tissue-contrast definition, both T2-weighted and volumetric T1-weighted sequences, are required to improve target delineation. In detail, several key issues were identified and discussed: i) radiation techniques and immobilization, ii) imaging techniques and target delineation, and iii) technical aspects of radiation treatments including planning techniques and dose-fractionation schedules. Specific target delineation issues with regard to different skull base tumors, including pituitary adenomas, meningiomas, craniopharyngiomas, acoustic neuromas, chordomas and chondrosarcomas are presented. Conclusions This ESTRO ACROP guideline achieved detailed recommendations on target volume definition for skull base tumors, as well as comprehensive advice about imaging modalities and radiation techniques.

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of alpha-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided.

Gastroenteropancreatic neuroendocrine neoplasms grade 3 (GEP-NENs G3) are rare tumors. These highly aggressive neoplasms are traditionally treated with platinum-based chemotherapy in combination with etoposide. Immune checkpoint proteins such as programmed cell death ligand (PD-L1) may have a role in different cancers allowing them escape the immune system and hence, progress. We aimed to investigate the immunohistochemical expression of PD-L1 in GEP-NEN G3 and evaluate its correlation to clinical parameters. In a cohort of 136 patients, 14 (10%) expressed PD-L1 immunoreactivity; four (3%) patients in the tumor cells and 10 (7%) had immunoreactive immune cells. PD-L1 expression did not correlate to clinical parameters, progression-free survival or overall survival. We conclude that PD-L1 expression is present only in a subset of GEP-NEN G3 patients. Further studies are needed to fully understand the role of PD-L1 in patients with GEP-NEN G3, including the future possibility for treatment with immune checkpoint inhibitors. publishedVersion

Until vaccination for the SARS‐CoV‐2 becomes a reality, it appears that the infection is here to stay. With many countries lifting lockdown restrictions, aesthetic clinics have started reopening with strict standard operating procedures in place. It is pertinent that the physician today understands the infection, disinfection measures, and personal protective equipment to reduce chances of viral transmission and provide safe clinical settings for oneself, the staff and the patients. An online meeting of eight experts in the field of aesthetic dermatology was convened, which particularly focussed on PPE in detail, risk categorization of aesthetic procedures, preprocedure recommendations, and generalized and specialized SOP's for aesthetic procedures. These recommendations were aimed to bridge the gap between published guidelines and clinical practice and are by no means fully conclusive, but signify learnings over the past few months in an active clinical aesthetic practice.

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB—Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

Background Strict infection control measures in response to the current COVID‐19 pandemic are expected to remain for an extended period. In aesthetic clinics, most procedures are provided on one to one basis by the physician or therapist. In such a scenario, guidelines detailing the infection control measures for aesthetic clinics are of particular importance. Methods An online meeting of an international group of experts in the field of aesthetic medicine, with experience in administration of an aesthetic clinic, was convened. The meeting aimed to provide a set of consensus guidelines to protect clinic staff and patients from SARS‐CoV‐2 infection. Results Consensus guidelines for ‘preferred practices' were provided for scheduling of patients, patient evaluation and triaging, and for safety precautions about the different procedures. Procedures were categorized into low‐risk, moderate risk, and high‐risk based on the likelihood of transmission of SARS‐CoV‐2 virus from the patient to the treating physician or therapist. Conclusions While not intended to be complete or exhaustive, these guidelines provide sound infection control measures for aesthetic practices. Since guidelines regarding safety measures and use of PPEs may vary from country to country, the local guidelines should also be followed to prevent COVID‐19 infection in aesthetic clinics. This article is protected by copyright. All rights reserved.

BackgroundTetrahydrobiopterin (BH4) deficiencies comprise a group of six rare neurometabolic disorders characterized by insufficient synthesis of the monoamine neurotransmitters dopamine and serotonin due to a disturbance of BH4biosynthesis or recycling. Hyperphenylalaninemia (HPA) is the first diagnostic hallmark for most BH4deficiencies, apart from autosomal dominant guanosine triphosphate cyclohydrolase I deficiency and sepiapterin reductase deficiency. Early supplementation of neurotransmitter precursors and where appropriate, treatment of HPA results in significant improvement of motor and cognitive function. Management approaches differ across the world and therefore these guidelines have been developed aiming to harmonize and optimize patient care. Representatives of the International Working Group on Neurotransmitter related Disorders (iNTD) developed the guidelines according to the SIGN (Scottish Intercollegiate Guidelines Network) methodology by evaluating all available evidence for the diagnosis and treatment of BH4deficiencies.ConclusionAlthough the total body of evidence in the literature was mainly rated as low or very low, these consensus guidelines will help to harmonize clinical practice and to standardize and improve care for BH4deficient patients.

It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron emission tomography (PET) data. To facilitate comparison of findings across studies, we first recommend publication standards for tracer characteristics, image acquisition, image preprocessing, and outcome estimation for PET neuroimaging data. The co-authors of this paper, representing more than 25 PET centers worldwide, voted to classify information as mandatory, recommended, or optional. Second, we describe a framework to facilitate data archiving and data sharing within and across centers. Because of the high cost of PET neuroimaging studies, sample sizes tend to be small and relatively few sites worldwide have the required multidisciplinary expertise to properly conduct and analyze PET studies. Data sharing will make it easier to combine datasets from different centers to achieve larger sample sizes and stronger statistical power to test hypotheses. The combining of datasets from different centers may be enhanced by adoption of a common set of best practices in data acquisition and analysis. ispartof: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM vol:40 issue:8 pages:1576-1585 ispartof: location:United States status: published

Background: the novel coronavirus (COVID-19) pandemic is expected to last for an extended time, making strict safety precautions for office procedures unavoidable. The lockdown is going to be lifted in many areas, and strict guidelines detailing the infection control measures for aesthetic clinics are going to be of particular importance. Methods: a virtual meeting was conducted with the members (n = 12) of the European Academy of Facial Plastic Surgery Focus Group to outline the safety protocol for the nonsurgical facial aesthetic procedures for aesthetic practices in order to protect the clinic staff and the patients from SARS-CoV-2 infection. The data analysis was undertaken by thematic and iterative approach. Results: consensus guidelines for nonsurgical facial aesthetic procedures based on current knowledge are provided for three levels: precautions before visiting the clinic, precautions during the clinic visit, and precautions after the clinic visit. Conclusions: sound infection control measures are mandatory for nonsurgical aesthetic practices all around the world. These may vary from country to country, but this logical approach can be customized according to the respective country laws and guidelines., NA

As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of "European Guidelines for the Management of RDS" by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, need for appropriate maternal transfer to a perinatal centre and timely use of antenatal steroids. Delivery room management has become more evidence-based, and protocols for lung protection including initiation of CPAP and titration of oxygen should be implemented immediately after birth. Surfactant replacement therapy is a crucial part of management of RDS, and newer protocols for its use recommend early administration and avoidance of mechanical ventilation. Methods of maintaining babies on non-invasive respiratory support have been further developed and may cause less distress and reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation using caffeine and, if necessary, postnatal steroids are also important considerations. Protocols for optimising general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome. (c) 2019 S. Karger AG, Basel

Purpose: To identify a surrogate marker for late xerostomia 12 months after radiation therapy(Xer12m), according to information obtained shortly after treatment.Methods and Materials: Differences in parotid gland (PG) were quantified in image biomarkers (ΔIBMs) before and 6 weeks after radiation therapy in 107 patients. By performing stepwise forward selection, ΔIBMs that were associated with Xer12m were selected. Subsequently other variables, such as PG dose and acute xerostomia scores, were added to improve the prediction performance. All models were internally validated.Results: Prediction of Xer12m based on PG surface reduction (ΔPG-surface) was good (area under the receiver operating characteristic curve, 0.82). Parotid gland dose was related to ΔPG-surface (PR2 = 0.27). The addition of acute xerostomia scores to the ΔPG-surface improved the prediction of Xer12m significantly, and vice versa. The final model including ΔPG-surface and acute xerostomia had outstanding performance in predicting Xer12m early after radiation therapy (area under the receiver operating characteristic curve, 0.90).Conclusions: Parotid gland surface reduction was associated with late xerostomia. The early posttreatment model with ΔPG-surface and acute xerostomia scores can be considered as a surrogate marker for late xerostomia.

The expeditious diagnosis and treatment of high-grade cervical precancers are fundamental to cervical cancer prevention. However, during the COVID-19 pandemic healthcare systems have at times restricted in-person visits to those deemed urgent. Professional societies provided some guidance to clinicians regarding ways in which traditional cervical cancer screening might be modified, but many gaps remained. To address these gaps, leaders of screening programs at an academic medical center and an urban safety net hospital in California formed a rapid-action committee to provide guidance to its practitioners. Patients were divided into 6 categories corresponding to various stages in the screening process and ranked by risk of underlying high-grade cervical precancer and cancer. Tiers corresponding to the intensity of the local pandemic were constructed, and clinical delays were lengthened for the lowest-risk patients as tiers escalated. The final product was a management grid designed to escalate and de-escalate with changes in the local epidemiology of the COVID-19 pandemic. While this effort resulted in substantial delays in clinical screening services as mandated by the healthcare systems, the population effects of delaying on both cervical cancer outcomes as well as the beneficial effects related to decreasing transmission of severe acute respiratory coronavirus 2 have yet to be elucidated.

Objective: This article outlines the consensus guidelines for symptomatic treatment for children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Syndrome Associated with Streptococcal Infection (PANDAS). Methods: Extant literature on behavioral, psychotherapeutic, and psychopharmacologic treatments for PANS and PANDAS was reviewed. Members of the PANS Research Consortium pooled their clinical experiences to find agreement on treatment of PANS and PANDAS symptoms. Results: Current guidelines result from consensus among the Consortium members. Conclusion: While underlying infectious and inflammatory processes in PANS and PANDAS patients are treated, psychiatric and behavioral symptoms need simultaneous treatment to decrease suffering and improve adherence to therapeutic intervention. Psychological, behavioral, and psychopharmacologic interventions tailored to each child's presentation can provide symptom improvement and improve functioning during both the acute and chronic stages of illness. In general, typical evidence-based interventions are appropriate for the varied symptoms of PANS and PANDAS. Individual differences in expected response to psychotropic medication may require marked reduction of initial treatment dose. Antimicrobials and immunomodulatory therapies may be indicated, as discussed in Parts 2 and 3 of this guideline series.

Objective. Chronic pain conditions profoundly affect the daily living of a significant number of people and are a major economic and social burden, particularly in developing countries. The Change Pain Latin America (CPLA) advisory panel aimed to identify the most appropriate guidelines for the treatment of neuropathic pain (NP) and chronic low back pain (CLBP) for use across Latin America. Methods. Published systematic reviews or practice guidelines were identified by a systematic search of PubMed, the Guidelines Clearinghouse, and Google. Articles were screened by an independent reviewer, and potential candidate guidelines were selected for more in-depth review. A shortlist of suitable guidelines was selected and critically evaluated by the CPLA advisory panel. Results. Searches identified 674 and 604 guideline articles for NP and CLBP, respectively. Of these, 14 guidelines were shortlisted for consensus consideration, with the following final selections made: • 'Recommendations for the pharmacological management of neuropathic pain from the Neuropathic Pain Special Interest Group in 2015-pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis.' • 'Diagnosis and treatment of low back pain: A joint clinical practice guideline from the American College of Physicians and the American Pain Society' (2007). Conclusions. The selected guidelines were endorsed by all members of the CPLA advisory board as the best fit for use across Latin America. In addition, regional considerations were discussed and recorded. We have included this expert local insight and advice to enhance the implementation of each guideline across all Latin American countries. © 2017 American Academy of Pain Medicine.

METHODS: After primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff's (K) alpha

Background and purpose: Current models for the prediction of late patient-rated moderate-to-severe xerostomia (XER12m) and sticky saliva (STIC12m) after radiotherapy are based on dose-volume parameters and baseline xerostomia (XERbase) or sticky saliva (STICbase) scores. The purpose is to improve prediction of XER12m, and STIC12m with patient-specific characteristics, based on CT image biomarkers (IBMs).Methods: Planning CT-scans and patient-rated outcome measures were prospectively collected for 249 head and neck cancer patients treated with definitive radiotherapy with or without systemic treatment. The potential IBMs represent geometric. CT intensity and textural characteristics of the parotid and sub mandibular glands. Lasso regularisation was used to create multivariable logistic regression models, which were internally validated by bootstrapping.Results: The prediction of XER12m could be improved significantly by adding the IBM "Short Run Emphasis" (SRE), which quantifies heterogeneity of parotid tissue, to a model with mean contra-lateral parotid gland dose and XERbase. For STIC12m, the IBM maximum CT intensity of the submandibular gland was selected in addition to STICbase and mean dose to submandibular glands.Conclusion: Prediction of XER12m and STIC12m was improved by including IBMs representing heterogeneity and density of the salivary glands, respectively. These IBMs could guide additional research to the patient-specific response of healthy tissue to radiation dose. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

OBJECTIVE. The purpose of this article is to discuss the evolution of MRI in prostate cancer from the early 1980s to the current day, providing analysis of the key studies on this topic. CONCLUSION. The rapid diffusion of MRI technology has meant that residual variability remains between centers regarding the quality of acquisition and the quality and standardization of reporting.

Background Although in recent years there has been a strong increase in published research on theories (e.g. realist evaluation, normalization process theory) driving and guiding process evaluations of complex interventions, there is limited guidance to help rehabilitation researchers design and carry out process evaluations. This can lead to the risk of process evaluations being unsystematic. This paper reports on the development of new consensus guidelines that address the specific challenges of conducting process evaluations alongside clinical trials of rehabilitation interventions. Methods A formal consensus process was carried out based on a modified nominal group technique, which comprised two phases. Phase I was informed by the findings of a systematic review, and included a nominal group meeting with an expert panel of participants to rate and discuss the proposed statements. Phase II was an in depth semi-structured telephone interviews with expert panel participants in order to further discuss the structure and contents of the revised guidelines. Frequency of rating responses to each statement was calculated and thematic analysis was carried out on all qualitative data. Results The guidelines for carrying out process evaluations within complex intervention rehabilitation research were produced by combining findings from Phase I and Phase II. The consensus guidelines include recommendations that are grouped in seven sections. These sections are theoretical work, design and methods, context, recruitment and retention, intervention staff, delivery of the intervention and results. These sections represent different aspects or stages of the evaluation process. Conclusion The consensus guidelines here presented can play a role at assisting rehabilitation researchers at the time of designing and conducting process evaluations alongside trials of complex interventions. The guidelines break new ground in terms of concepts and theory and works towards a consensus in regards to how rehabilitation researchers should go about carrying out process evaluations and how this evaluation should be linked into the proposed trials. These guidelines may be used, adapted and tested by rehabilitation researchers depending on the research stage or study design (e.g. feasibility trial, pilot trial, etc.). Electronic supplementary material The online version of this article (10.1186/s12874-018-0647-y) contains supplementary material, which is available to authorized users.

Highlights • Consensus Guidelines have been developed for the management of OED through a pandemic outbreak. • Risk stratification is suggested so that high-risk cases are prioritised for face-to-face review. • Remote consultations may be a useful method for ensuring continuity of review for lower risk cases., Objectives Oral Epithelial Dysplasia (OED) is associated with an increased risk of oral cancer development. The SARS-CoV-2 pandemic is necessitating the suspension or dramatic reduction of face-to-face non-urgent elective services, including OED clinics. Little is known regarding the potential impact of elective services suspension upon the risk of OED progression, and whether alternative strategies (e.g. remote consultations) may be introduced to ensure OED surveillance. The aim of this paper is to provide expert-opinion consensus recommendations for the management of OED during the current and future pandemic outbreaks. Materials and methods A working group of nine UK-based senior clinicians and academics in Oral and Maxillofacial Surgery and Oral Medicine was created and twelve consensus statements were developed using a modified-Delphi process. Greater than 80% agreement was considered a consensus. Results Consensus was achieved for all twelve statements (89–100% agreement). The group agreed that, during the temporary suspension of elective services associated with COVID-19 pandemic outbreaks, patients with OED can be risk stratified to determine the length of accepted delay in face-to-face consultation. Remote consultations with patient-provided clinical photographs may be a useful way of maintaining a level of surveillance in this group of patients. Conclusions Using an expert working group methodology, we have developed consensus recommendations for the monitoring of individuals with OED during pandemic outbreaks associated with temporary suspension of elective services. This has identified areas of future research and highlighted the need for a stronger evidence base to inform the set-up and delivery of surveillance regimens for patients with OED.

Objectives:The aim of this study was to systematically review the rates of nonadherence to oral maintenance treatment in adolescents with inflammatory bowel disease (IBD), and to describe perceived barriers to adherence and psychosocial factors involved.Methods:The article considered studies published in MEDLINE, Embase, and PsycINFO up to March 2015. Studies that had collected data on adherence to thiopurines or aminosalicylates in a cohort of adolescents with IBD. Case reports and case series were excluded.Results:A total of 25 studies were included. Lack of uniformity of outcome measures made pooling of data impossible. Rates of medication nonadherence ranged from 2% to 93%. The most frequently reported barriers were just forgot, wasn't home, and interferes with activity. Family dysfunction, peer victimization, poor health-related quality of life, poor child-coping strategies, anxiety, and depressive symptoms were associated with medication nonadherence.Conclusions:Nonadherence to oral maintenance therapy in adolescents with IBD is a significant health care problem and can lead to unnecessary escalation in therapy. Difficulties in family and social interactions, and psychosocial dysfunction can jeopardize IBD treatment outcome and should receive attention early in the course of the disease.

Performing well-designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, 4 organizations (the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition; European Crohn's and Colitis Organization; the Canadian Children IBD Network; and the Global Pediatric IBD Network) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94 of 100 (94%) voting committees' members that placebo should only be used if there is genuine equipoise between the active treatment and placebo; for example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an add-on to an effective therapy or to evaluate exit-strategies of maintenance therapy after long-term deep remission. It has been, however, agreed that no child enrolled in a trial should receive a known inferior treatment both within and outside the trial. This also includes withholding therapy in children who show clinical response after a short induction therapy. Given the similarity between pediatric and adult IBD regarding pathophysiology and response to treatments, drugs generally cannot be considered being in genuine equipoise with placebo if it has proven efficacy in adults. Continued collaboration of all stakeholders is needed to facilitate drug development and evaluation in pediatric IBD.

Context: Pulmonary carcinoids (PCs) belong to neuroendocrine tumors that often overexpress somatostatin receptors (SSTRs). This overexpression provides a molecular basis for tumor imaging and treatment with somatostatin analogs. Objective: To evaluate SSTR1 to SSTR5 distribution in a large set of PC tumors and to investigate whether the expression is associated with clinicopathological and outcome data. Design, Setting, and Patients: This retrospective study was conducted at Helsinki University Hospital and University of Helsinki. It included 178 PC tumors coupled with patients' clinical data retrieved through Finnish biobanks. After histological reclassification, tissue specimens were processed into next-generation tissue microarray format and stained immunohistochemically with monoclonal SSTR1 to SSTR5 antibodies. Main Outcome Measure: SSTR1 to SSTR5 expression in PC tumors. Results: Expression of SSTR1 to SSTR5 was detected in 52%, 75%, 56%, 16%, and 32% of the tumors, respectively. Membrane-bound staining was observed for all receptors. SSTR2 negativity and SSTR4 positivity was associated with lymph node involvement at the time of surgery (P = 0.014 and P = 0.017, respectively) and with distant metastasis (P = 0.027 and P = 0.015, respectively). SSTR3 and SSTR4 expression was associated with increased risk of shorter survival [P = 0.046, hazard ratio (HR) 4.703, 95% CI 1.027 to 21.533; and P = 0.013, HR 6.64, 95% CI 1.48 to 29.64, respectively], whereas expression of SSTR1 and SSTR2 was associated with improved outcome (P = 0.021, HR 0.167, 95% CI 0.037 to 0.765; and P = 0.022, HR 0.08, 95% CI 0.01 to 0.70, respectively). Conclusion: SSTR1 to SSTR5 expression is observed in PCs. As SSTR expression is associated with the tumor's metastatic potential and patient outcome, these receptors may offer the possibility for individualized prognosis estimation.

Background and Aims: Conventional follow-up of teenagers with inflammatory bowel diseases [IBD] is done during scheduled outpatient visits regardless of how well the patient feels. We designed a telemonitoring strategy for early recognition of flares and compared its efficacy with conventional follow-up. Methods: We used a multicentre randomized trial in patients aged 10-19 years with IBD in clinical remission at baseline. Participants assigned to telemonitoring received automated alerts to complete a symptom score and send a stool sample for measurement of calprotectin. This resulted in an individual prediction for flare with associated treatment advice and test interval. In conventional follow-up the health check interval was left to the physician's discretion. The primary endpoint was cumulative incidence of disease flares. Secondary endpoints were percentage of participants with a positive change in quality-of-life and cost-effectiveness of the intervention. Results: We included 170 participants [84 telemonitoring; 86 conventional follow-up]. At 52 weeks the mean number of face-to-face visits was significantly lower in the telemonitoring group compared to conventional follow-up [3.6 vs 4.3, p < 0.001]. The incidence of flares [33 vs 34%, p = 0.93] and the proportion of participants reporting positive change in quality-of-life [54 vs 44%, p = 0.27] were similar. Mean annual cost-saving was €89 and increased to €360 in those compliant to the protocol. Conclusions: Telemonitoring is as safe as conventional follow-up, and reduces outpatient visits and societal costs. The positive impact on quality-of-life was similar in the two groups. This strategy is attractive for teenagers and families, and health professionals may be interested in using it to keep teenagers who are well out of hospital and ease pressure on overstretched outpatient services. Trial registration: NTR3759 [Netherlands Trial Registry].

Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period.Methods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States).Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo) adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score >= 3]; 61.1% Ki67 expression low (Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in> 90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.

High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter-and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (= 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS and OS were analyzed with Kaplan-Meier (log-rank), cox proportional hazard ratios and confidence intervals. No statistical differences were observed in PFS or OS when comparing patients receiving long infusion (median PFS 3.8 months, median OS 14.5 months), short infusion (PFS 5.6 months, OS 11.0 months) or oral etoposide (PFS 5.4 months, OS 11.3 months). We observed equal efficacy for the three administration routes suggesting oral etoposide may be safe and efficient in treating high-grade GEP-NEN, G3 patients scheduled for cisplatin/carboplatin + etoposide therapy.

Over the last few decades, significant improvements have been made in the radiotherapy (RT) treatment of head and neck malignancies. The progressive introduction of intensity-modulated RT and the use of multimodality imaging for target volume and organs at risk delineation, together with the use of altered fractionation regimens and concomitant administration of chemotherapy or targeted agents, have accompanied efficacy improvements in RT. Altogether, such improvements have translated into improvement in locoregional control and overall survival probability, with a decrease in the long-term adverse effects of RT and an improvement in quality of life. Further progress in the treatment of head and neck malignancies may come from a better integration of molecular imaging to identify tumor subvolumes that may require additional radiation doses (ie, dose painting) and from treatment adaptation tracing changes in patient anatomy during treatment. Proton therapy generates even more exquisite dose distribution in some patients, thus potentially further improving patient outcomes. However, the clinical benefit of these approaches, although promising, for patients with head and neck cancer need to be demonstrated in prospective randomized studies. In this context, our article will review some of these advances, with special emphasis on target volume and organ-at-risk delineation, use of molecular imaging for tumor delineation, dose painting for dose escalation, dose adaptation throughout treatment, and potential benefit of proton therapy. (C) 2015 by American Society of Clinical Oncology

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC–inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. Conclusion: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC–inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518–527).

BACKGROUND: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreactive p53 protein in GEP-NEC.MATERIALS AND METHODS: Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS).RESULTS: All tumor tissues were immunoreactive for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS in patients with colorectal tumors (HR = 2.1, p = 0.03) in a univariate analysis as well as to poorer PFS (HR = 2.6, p = 0.03) and OS (HR = 3.4, p = 0.02) in patients with colorectal tumors with distant metastases, a correlation which remained significant in the multivariate analyses.CONCLUSION: In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.

The management of patients with pancreatic cancer has advanced over the last few years. We convey a multidisciplinary group of experts in an attempt to stablish practical guidelines for the diagnoses, staging and management of these patients. This paper summarizes the main conclusions of the working group. Patients with suspected pancreatic ductal adenocarcinoma should be rapidly evaluated and referred to high-volume centers. Multidisciplinary supervision is critical for proper diagnoses, staging and to frame a treatment plan. Surgical resection together with chemotherapy offers the highest chance for cure in early stage disease. Patients with advanced disease should be classified in treatment groups to guide systemic treatment. New chemotherapeutic regimens have resulted in improved survival. Symptomatic management is critical in this disease. Enrollment in a clinical trial is, in general, recommended., The support for medical writing was supported by Fundacion ECO.

Acute disseminated encephalomyelitis (ADEM) is an immunologically mediated inflammatory disease of the central nervous system that typically occurs after a viral infection or recent vaccination, and is most commonly seen in the pediatric population. In 2007 the International Pediatric Multiple Sclerosis Study Group proposed a consensus definition for ADEM for application in research and clinical settings. This article gives an overview of ADEM in children, focusing on differences that have emerged since the consensus definition was established. Although the focus is on neuroimaging in these patients, a synopsis of the clinical features, immunopathogenesis, treatment, and prognosis of ADEM is provided.

BACKGROUND: This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery is uncertain.METHODS: Data from patients with a diagnosis of hgPNEC determined between 1998 and 2012 were retrospectively registered at 10 Nordic university hospitals. Kaplan-Meier curves were used to compare the overall survival of different treatment groups, and Cox-regression analysis was used to evaluate factors potentially influencing survival.RESULTS: The study registered 119 patients. The median survival period from the time of metastasis was 23 months for patients undergoing initial resection of localized nonmetastatic disease and chemotherapy at the time of recurrence (n = 14), 29 months for patients undergoing resection of the primary tumor and resection/radiofrequency ablation of synchronous metastatic liver disease (n = 12), and 13 months for patients with synchronous metastatic disease given systemic chemotherapy alone (n = 78). The 3-year survival rate after surgery of the primary tumor and metastatic disease was 69 %. Resection of the primary tumor was an independent factor for improved survival after occurrence of metastatic disease.CONCLUSIONS: Patients with resected localized nonmetastatic hgPNEC and later metastatic disease seemed to benefit from initial resection of the primary tumor. Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment.

There is a constant demand for the quantification of drug metabolites within post-mortem toxicology. Especially electrospray ionization-mass spectrometry techniques necessitate that calibration is carried out using primary reference standards due to the non-uniform ionization efficiency between parent drugs and their metabolites. As reference standards for metabolites are not readily available and their costs are high, alternative methods for immediate quantification are required. In this study, ultra-high performance liquid chromatography coupled with photodiode array detection and corona charged aerosol detection was utilized for the concurrent quantification of 23 drug metabolites using the corresponding parent drug for calibration. Based on this secondary calibration, the quantitative results for the N-demethylated metabolites by each detector were similar to those obtained by the ordinary calibration using reference standards. For O-demethylated metabolites, the differences in detector response caused somewhat larger biases using the secondary calibration. Using the validated secondary calibration, the blood sample data gathered from 633 post-mortem cases was retrospectively reprocessed to discover the combined metabolite-parent concentrations and metabolite to parent ratios for six toxicologically relevant drugs. These results, representing all causes of death, were compared to published data from therapeutic drug monitoring and post-mortem toxicology. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Treatment of adolescents with growth hormone deficiency (GHD) during the transition period is a controversial issue. This paper is a contribution from the Italian community of paediatric and adult endocrinologists surveyed in a Delphi panel. The Delphi method is a structured communication technique, originally developed as a systematic, interactive forecasting method that relies on a panel of experts. The experts answer questionnaires in two or more rounds. There was substantial agreement on the definition of the problems associated with the diagnosis and treatment of adolescents with GHD in the transition period, as well as on the identification of the controversial issues which need further studies. There is general consensus on the need of re-testing all isolated idiopathic GHD after at least 30-day withdrawn from treatment, while in patients with multiple pituitary deficiency and low IGF-I levels there is generally no need to re-test. In patients with permanent or confirmed GHD, a starting low rhGH dose (0.01-0.03 mg per day) to be adjusted according to IGF-I concentrations is also widely accepted. For those continuing treatment, the optimal therapeutic schedule to obtain full somatic maturation, normalization of body composition and bone density, cardiovascular function and Quality of Life, need to be evaluated.

Background: The microbiological procedures for cystic fibrosis (CF) samples of 17 participating Spanish centers were examined to verify their compliance with current international and national guidelines and to implement the best standards of care for microbiology practices. A 47-item questionnaire covering different CF microbiology aspects was sent to participant laboratories. Telephone interviews were performed when necessary. Data about samples processing for bacteria, mycobacteria and fungi were collected. Results: Gene sequencing (71%), MALDI-TOF (59%) or both (94%) were available for most laboratories. Susceptibility testing was performed by automated microdilution systems (94%) and manual diffusion methods (59%). However, a low use of selective media for Staphylococcus aureus (59%) and Burkholderia cepacia complex (71%), and of epidemiological typing methods (41%) was reported. Conclusions: Most Spanish laboratories are in agreement with consensus guidelines for the processing of CF respiratory samples, but need to improve in the use of specific selective media and typing methods for epidemiologic studies., JdDC is supported by a Rio Hortega contract (ref. CM14/00059) founded by Ministerio de Economia y Competitividad. Instituto de Salud Carlos III of Spain. The authors declare that this work was supported by Instituto de Salud Carlos III of Spain (research grants PI12/00103, PI13/00205 and PI12/00734) and cofinanced by the European Development Regional Fund (A Way to Achieve Europe program; Spanish Network for Research in Infectious Diseases grant REIPI RD12/0015). There are no competing financial or non-financial interests in the manuscript.

Background Recurrence rates following radiotherapy for prostate cancer in the post-operative adjuvant or salvage setting remain substantial. Previous work from our institution demonstrated that published prostate bed CTV guidelines frequently do not cover the pre-operative MRI defined prostate. Inadequate target delineation may contribute to the high recurrence rates, but increasing target volumes may increase dose to organs at risk. Methods We propose guidelines for delineating post-prostatectomy target volumes based upon an individual’s co-registered pre-operative MRI. MRI-based CTVs and PTVs were compared to those created using the RTOG guidelines in 30 patients. Contours were analysed in terms of absolute volume, intersection volume (Jaccard Index) and the ability to meet the RADICALS and QUANTEC rectal and bladder constraints (tomotherapy IMRT plans with PTV coverage of V98% ≥98%). Results CTV MRI was a mean of 18.6% larger than CTV RTOG: CTV MRI mean 138 cc (range 72.3 - 222.2 cc), CTV RTOG mean 116.3 cc (range 62.1 - 176.6 cc), (p

The South African Heart Association (SA Heart) together with two of its special-interest groups, the South African Society of Cardiovascular Intervention (SASCI) and the Society of Cardiothoracic Surgeons in South Africa (SCTSSA), represent the scientific, educational and professional interests of South African cardiac specialists, with a combined membership of over 200 members. These two interest groups exclusively represent practicing cardiologists and cardiothoracic surgeons in South Africa. SASCI and SCTSSA are dedicated to maintaining the highest standards of specialist practice and the highest quality of patient care. As a result, SASCI and SCTSSA seek to serve as a knowledge resource for patients and funders in matters related to new technology used in the cardiac interventional and surgical disciplines.

Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines form performing HSCT in MS. This conference was organized in order to : (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution.

Objectives The management of the abdominal compartment syndrome (ACS) and the open abdomen (OA) are important to improve survival after major vascular surgery, in particular ruptured abdominal aortic aneurysm (RAAA). The aim is to summarize contemporary knowledge in this field. Methods The consensus definitions of the World Society of the Abdominal Compartment Syndrome (WSACS) that were published in 2006 and the clinical practice guidelines published in 2007 were updated in 2013. Structured clinical questions were formulated (modified Delphi method), and the evidence base to answer those questions was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. Results Most of the previous definitions were kept untouched, or were slightly modified. Four new definitions were added, including a definition of OA and of lateralization of the abdominal wall, an important clinical problem to approach during prolonged OA treatment. A classification system of the OA was added. Seven recommendations were formulated, in summary: Trans-bladder intra-abdominal pressure (IAP) should be monitored in patients at risk. Protocolized monitoring and management are recommended, and decompression laparotomy if ACS. When OA, protocolized efforts to obtain an early abdominal fascial closure, and strategies utilizing negative pressure wound therapy should be used, versus not. In most cases the evidence was graded as weak or very weak. In six of the structured clinical questions, no recommendation could be made. Conclusion This review summarizes changes in definitions and management guidelines of relevance to vascular surgery, and data on the incidence of ACS after open and endovascular aortic surgery.

Despite the high prevalence of enuresis, the professional training of doctors in the evaluation and management of this condition is often minimal and/or inconsistent. Therefore, patient care is neither optimal nor efficient, which can have a profound impact on affected children and their families. Once comprehensive history taking and evaluation has eliminated daytime symptoms or comorbidities, monosymptomatic enuresis can be managed efficaciously in the majority of patients. Non-monosymptomatic enuresis is often a more complex condition; these patients may benefit from referral to specialty care centers. We outline two alternative strategies to determine the most appropriate course of care. The first is a basic assessment covering only the essential components of diagnostic investigation which can be carried out in one office visit. The second strategy includes several additional evaluations including completion of a voiding diary, which requires extra time during the initial consultation and two office visits before treatment or specialty referral is provided. This should yield greater success than first-line treatment. Conclusion: This guideline, endorsed by major international pediatric urology and nephrology societies, aims to equip a general pediatric practice in both primary and secondary care with simple yet comprehensive guidelines and practical tools (i.e., checklists, diary templates, and quick-reference flowcharts) for complete evaluation and successful treatment of enuresis.

Purpose Positron emission tomography (PET) using 6-[18F]fluoro-L-dihydroxyphenylalanine (18F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. 18F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total 18F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Methods Seventy-seven consecutive carcinoid patients who underwent an 18F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on 18F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. Results All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. 18F-dopa PET detected 979 lesions. SUVmax on 18F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Conclusion Tumour load per patient measured with 18F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity.

The serum immunoglobulin-free light chain (FLC) assay measures levels of free kappa and lambda immunoglobulin light chains. There are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity, and negates the need for 24-h urine studies for diagnoses other than light chain amyloidosis (AL). Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL, oligosecretory myeloma and nearly two-thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial FLC measurements outperform PEL and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using FLC assay in place of 24-h urine PEL for monitoring or for serial measurements in PCD with measurable disease by serum or urine PEL. This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD.