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To evaluate ease of use, user preference, and effort required to use nasal glucagon (NG) versus injectable glucagon needing reconstitution (IG) in simulations of severe hypoglycemia (SH)-a challenge for caregivers of a person with diabetes (PWD) in real-life.In this randomized, crossover study, high-fidelity manikins placed in mock representative high-stress environments were used to simulate an SH rescue. Thirty-two trained (by PWDs) and 33 untrained participants attempted NG and IG administrations and then completed questionnaires regarding ease of use, preference, and workload for each device.More trained users agreed that NG was easy to use (87.1% vs 54.8%) and prepare (80.6% vs 51.6%) and had confidence to use NG correctly (93.5% vs 54.8%) than those who agreed the same for IG (P.05). Untrained users reported similar differences, favoring NG in all parameters. In direct device comparison across all simulations, 80.6% of trained users and 93.5% of untrained users preferred NG over IG-a preference largely sustained regardless of the success or failure of administration. Among PWDs, 90.3% considered NG device as safer than IG during an SH event. In the assessment of workload required to administer glucagon, the weighted mean National Aeronautics and Space Administration Task Load Index scores were 37.8 for NG and 48.4 for IG (P = .0020).Participants in this study considered NG easier, more preferred, required less effort for administration, and more intuitive to use than reconstitutable IG, irrespective of whether there was prior training. NG improves the potential for successful administration of glucagon, better preparedness, and increased adoption of glucagon for SH rescue.

Introduction Information on experience/management of severe hypoglycaemic events (SHEs) among people with insulin-treated diabetes (PWD) and caregivers (CGs) providing care to PWD was sought. Materials and methods An online cross-sectional survey was conducted in eight countries. Inclusion criteria: PWD (aged ≥ 18 years; self-reported type 1 [T1D] or insulin-treated type 2 [T2D] diabetes; experienced ≥1 SHE [hypoglycaemia requiring external assistance] in past 3 years); CGs (layperson aged ≥18 years; caring for PWD meeting all criteria above except age [≥4 years]). This descriptive analysis provides data from Spain. SHE-associated data relate to the most recent SHE. Results Across all groups (T1D PWD, n = 106; T2D PWD, n = 88, T1D CG, n = 87; T2D CG, n = 96), 76–89% reported that the SHE occurred at home; most common cause was eating less than planned (38–53%). Most usual action during the SHE was to intake carbohydrates (67–84%); glucagon use was low (9–36%). Discussion of the SHE with their healthcare provider (HCP) was reported by 70–75% of PWD. During the SHE, 35–69% of PWD/CGs reported feeling scared, unprepared and/or helpless. Conclusions Most SHEs occurred outside the healthcare setting; treatment therefore depends greatly on CGs. SHEs have a negative emotional impact on PWD/CGs, underscoring the need for HCPs to discuss SHEs with PWD/CGs, and to provide tools and strategies to prevent and effectively manage SHEs.

Background:To validate the Belgian Plan Risk Manifestations (PRIMA) model, actual patient presentation rates (PPRs) from Belgium’s largest football stadium were compared with predictions provided by existing models and the Belgian PRIMA model.Methods:Actual patient presentations gathered from 41 football games (2010-2019) played at the King Baudouin Stadium (Brussels, Belgium) were compared with predictions by existing models and the PRIMA model. All attendees who sought medical help from in-event health services (IEHS) in the stadium or called 1-1-2 within the closed perimeter around the stadium were included. Data were analyzed by ANOVA, Pearson correlation tests, and Wilcoxon singed-rank test.Results:A total of 1,630,549 people attended the matches, with 626 people needing first aid. Both the PRIMA and the Hartman model over-estimated the number of patient encounters for each occasion. The Arbon model under-estimated patient encounters for 9.75% (95% CI, 0.49-19.01) of the events. When comparing deviations in predictions between the PRIMA model to the other models, there was a significant difference in the mean deviation (Arbon: Z = −5.566, P Conclusion:When comparing the predicted patient encounters, only the Arbon model under-predicted patient presentations, but the Hartman and the PRIMA models consistently over-predicted. Because of continuous over-prediction, the PRIMA model showed significant differences in mean deviation of predicted PPR. The results of this study suggest that the PRIMA model can be used during planning for domestic and international football matches played at the King Baudouin Stadium, but more data and further research are needed.

Objective:To compare actual patient presentation rates from Belgium’s largest public open-air cultural festival with predictions provided by existing models and the Belgian Plan Risk Manifestations model.Methods:Retrospectively, actual patient presentation rates gathered from the Ghent Festivities (Belgium) during 2013–2019 were compared to predicted patient presentation rates by the Arbon, Hartman, and PRIMA models.Results:During 7 editions, 8673000 people visited the Ghent Festivities; 9146 sought medical assistance resulting in a mean patient presentation rate (PPR) of 1.05. The PRIMA model overestimated the number of patient encounters for each occasion. The other models had a high rate of underprediction. When comparing deviations in predictions between the PRIMA model to the other models, there is a significant difference in the mean deviation (Arbon: T = 0.000, P < 0.0001, r = −0.8701; Hartman: T = 0.000, P < 0.0001, r = −0.869).Conclusion:Despite the differences between the predictions of all 3 models, our results suggest that the PRIMA model is a valid tool to predict patient presentations to IEHS during public cultural MG. However, to substantiate the PRIMA model even further, more research is needed to further validate the model for a broad range of MG.

Assess long-term outcomes of prostatic artery embolization (PAE) for patients with benign prostatic hyperplasia (BPH).Single centre retrospective study from 2009-2019 including 1072 patients who received PAE and had available follow-up. Patients were evaluated yearly at 1-10 years post PAE using the International Prostate Symptom Score (IPSS) and quality of life (QoL), prostate volume (PV), prostate-specific antigen (PSA), peak urinary flow rate (Qmax) and postvoid residual (PVR) volume. The need for prostatic medication, re-intervention rates, repeat PAE and prostatectomy rates were assessed with Kaplan-Meier survival analysis and compared between different embolic agents using Cox regression analysis.Mean follow-up time was 4.39 ± 2.37 years. At last follow-up visit, mean IPSS and QoL improvements were - 10.14 ± 8.34 (p .0001) and - 1.87 ± 1.48 (p .0001) points, mean PV reduction was - 6.82 ± 41.11 cmPAE induces durable long-term LUTS relief, with re-intervention rates of 20% in the first 5 years and 30%-60% 5 years post-PAE.

The objective of the CRASH (Conversations and Reactions Around Severe Hypoglycemia) survey was to further our understanding of the characteristics, experience, behavior and conversations with healthcare professionals (HCPs) of people with diabetes (PWD) receiving insulin, and of caregivers (CGs) caring for such people, concerning hypoglycemia requiring external assistance (severe hypoglycemic events [SHEs]).CRASH was an online cross-sectional survey conducted across eight countries. PWD with self-reported type 1 (T1D) or insulin-treated type 2 (T2D) diabetes were aged≥18 years and had experienced one or more SHEs in the past 3 years; CGs were non-medical professionals aged ≥18 years, caring for PWD meeting all the above criteria except for PWD age (≥4 rather than ≥18 years). The present report is a descriptive analysis of data from France.Among PWD who had ever discussed SHEs with an HCP, 38.9% of T1D PWD and 50.0% of T2D PWD reported that SHEs were discussed at every consultation; 26.3% and 8.8%, respectively, had not discussed the most recent SHE with an HCP. In total, 35.7% of T1D PWD and 53.8% of T2D PWD reported that glucagon was not available to them at the time of their most recent SHE. Only 16.9% of T1D PWD and 6.5% of T2D PWD who had discussed their most recent SHE with an HCP reported that the HCP recommended obtaining a glucagon kit or asked them to confirm that they already had one. High proportions of PWD and CGs reported that the most recent SHE had made them feel unprepared, scared and helpless and had affected mood, emotional state and activities.CRASH survey data from France identify a need for greater discussion about SHEs between HCPs and PWD and the CGs of such people, and reveal gaps in the diabetes education of PWDs and CGs.

Background and Objectives Lilly insulin glargine (LY IGlar; Basaglar®) and the reference insulin glargine product (IGlar; Lantus®) are basal insulin glargine analogs with identical amino acid sequence and similar pharmacological profiles. ELEMENT 5, a Phase 3, prospective, randomized, multinational, two-arm, active-controlled, open-label, parallel-design study in type 2 diabetes mellitus (T2DM) patients (N = 493) showed similar efficacy and safety profiles with LY IGlar and IGlar. This study reports results from India (N = 100) and East Asia (N = 134) subpopulations. Methods Patients from India and East Asia (Korea and Taiwan) with T2DM who were insulin naïve (glycated hemoglobin (HbA1c) ≥ 7.0% and ≤ 11.0%) or on basal insulin (HbA1c ≤ 11.0%) were randomized to receive LY IGlar or IGlar along with oral antihyperglycemic medications (OAMs) for 24 weeks. Patients were instructed to self-titrate from the starting dose by 1 unit/day until fasting blood glucose (FBG) ≤ 5.6 mmol/L (100 mg/dL) was achieved. The key outcome was HbA1c change from baseline to Week 24. Results Within-group least-squares mean (LSM) decrease (baseline to Week 24) in HbA1c was similar between treatments. The upper limit of confidence interval (CI) for treatment difference was below the defined 0.4% noninferiority margin in India (LY IGlar: − 0.83%; IGlar: − 0.62%; difference [95% CI] − 0.21 [− 0.70, 0.28]) and East Asia (LY IGlar: − 1.28%; IGlar: − 1.26%; difference [95% CI] − 0.02 [− 0.34, 0.30]) subpopulations. Results of other efficacy and safety endpoints at Week 24 were similar between treatments in both subpopulations. LSM self-monitored FBG levels were similar between treatments at all visits in both subpopulations except at Week 24 in the India subpopulation (LY IGlar: 5.65 [0.10] mmol/L or 101.8 [1.86] mg/dL; IGlar: 5.18 [0.10] mmol/L or 93.3 [1.75] mg/dL; p = 0.002). Conclusion Efficacy and safety profiles of LY IGlar and IGlar, in combination with OAMs, were similar in India and East Asia subpopulations. This was consistent with the ELEMENT 5 total population. Clinical Trial Registration NCT02302716. Electronic supplementary material The online version of this article (10.1007/s40261-019-00798-1) contains supplementary material, which is available to authorized users.

Objectives: The Conversations and Reactions Around Severe Hypoglycemia cross-sectional study was conducted to better understand the severe hypoglycemia experiences in persons with diabetes (PWD) and their caregivers (CGs). Methods: Adults with type 1 or type 2 diabetes and CGs were recruited in 8 countries; Canadian cohort data are reported in this study. Insulin-treated PWD who reported a severe hypoglycemic event within the past 3 years and CGs who care for PWD ≥4 years old and who met the criteria were eligible for the study. Participants completed an online survey about their experience with severe hypoglycemia, its treatment and actions during and after severe hypoglycemia. Results: Of the 324 respondents, 139 (43%) reported discussions about severe hypoglycemia with a health-care provider (HCP) at every visit. During the most recent severe hypoglycemic event, the most common actions taken included ingestion of oral carbohydrates and calling emergency medical services; glucagon was rarely used. Despite many respondents (67%) feeling scared because of the most recent severe hypoglycemic event, only 55% (51% with type 1 and 61% with type 2) discussed this event with an HCP. The event affected the mood/emotional status, physical activities and sleep of PWD and CGs. Conclusions: Severe hypoglycemia impacts the emotional and physical status of PWD and CGs. Despite this, many respondents did not report discussions about the most recent severe hypoglycemic event with HCPs. Furthermore

Background A global cross-sectional survey (CRASH) was designed to provide information about the experiences of people with diabetes (PWD) and their caregivers in relation to severe hypoglycaemic events. Methods Adults with type 1 diabetes or insulin-treated type 2 diabetes who had experienced one or more severe hypoglycaemic events within the past 3 years, and adult caregivers for such people, were recruited from medical research panels using purposive sampling. We present here results from Germany. Results Approximately 100 individuals in each of the four participant groups completed a 30-minute online survey. Survey results indicated that the most recent severe hypoglycaemic event made many participants feel scared (80.4%), unprepared (70.4%), and/or helpless (66.5%). Severe hypoglycaemia was discussed by healthcare professionals at every visit with only 20.2% of participants who had ever had this conversation, and 53.5% of participants indicated that their insulin regimen had not changed following their most recent event. 37.1% of PWD/people with diabetes cared for by caregivers owned a glucagon kit at the time of survey completion. Conclusions The survey identified areas for improvement in the prevention and management of severe hypoglycaemic events. For healthcare professionals, these include enquiring more frequently about severe hypoglycaemia and adjusting blood glucose-lowering medication after a severe hypoglycaemic event. For individuals with diabetes and their caregivers, potential improvements include ensuring availability of glucagon at all times. Changes in these areas could lead not only to improved patient wellbeing but also to reduced use of emergency services/hospitalisation and, consequently, lower healthcare costs.

Introduction:A Belgian predictive medical resource tool, Plan Risk Manifestations (PRIMA), for the prediction of the number of patient encounters at mass gatherings (MGs) has recently been developed, in addition to the existing models of Arbon and Hartman. This study presents the results of the validation process for the PRIMA model for music MGs.Methods:A retrospective study was conducted using data gathered from music MGs in the province of Antwerp (Belgium) during the period of 2012-2016. Data from 87 music MGs were used for the study. The forecast of medical resources for these events was determined by entering the characteristics of individual events into the Arbon, Hartman, and PRIMA models. In order to determine if the PRIMA model is under- or over-predictive, the data gathered were retrospectively compared to the predicted number of resources needed using the aforementioned models. Statistical analysis included means, medians, and interquartile ranges (IQRs). Nonparametric related samples test (Wilcoxon Samples Signed Rank Test) for comparison of the median in deviations in predictions of patient presentation rates (PPRs) was performed using SPSS version 23 (IBM Corp.; Armonk, New York USA). Confidence interval levels were set at 95% and results were deemed statistically significant at P Results:All three models had an acceptable rate of over-prediction of number of patient encounters ([Arbon 25.29%; 95% CI, 30.91-43.74]; [Hartman 29.89%; 95% CI, 57.10-68.90]; and [PRIMA 19.54%; 95% CI, 57.80-76.20]). But all models also had a high rate of under-prediction of number of patient encounters ([Arbon 74.71%; 95% CI, 453.31-752.52]; [Hartman 70.11%; 95% CI, 546.90-873.77]; and [PRIMA 78.16%; 95% CI, 288.91-464.89]). Only the PRIMA model succeeded in the correct prediction of the number of patient encounters on two occasions (2.3%).Conclusion:Results of this study are in-line with existing literature. When comparing the predicted patient encounters, all three models had high rates of under-prediction and moderate rates of over-prediction. When comparing mean deviations, the PRIMA model had the lowest mean deviation of all predicted PPRs. Belgian events of the types included in the presented data may use the PRIMA model with confidence to predict PPRs and estimate the in-event health services (IEHS) requirements.

Introduction:Mass gatherings (MGs) grow in frequency around the world. With the intrinsic potential for significant health risks for all involved, MGs pose a challenge for those responsible for the provision of on-site medical care. Belgian law obliges local governments to identify and analyze the risks involving a MG. Though medical risk factors are long known, all too often, resourcing for in-event health services is based on anecdotal and previous experiences.Problem:Despite the fast-evolving science on MGs, the lack of reliable tools – based on empirical and analytical approaches – to predict patient presentation rates (PPRs) at MGs remains.Methods:A two-step method was followed to develop, update, and support a Plan Risk Manifestation (PRIMA) program. First, a continuous systematic literature review was conducted. Once developed, the model was run using data obtained from Belgian Federal Public Service (FPS; Brussels, Belgium) Health, Food Chain Safety, and Environment (HFCSE); event organizers; and municipalities.Results:In total, 231 studies and documents were included to form the program. With the data provided, three variables were computed to run the calculation model to predict the PPR. Three medical risk axes were defined for this model: (1) isolation risk; (2) population risk; and (3) risk at illness. A combined dataset was derived from the prediction of the PRIMA program combined with the actual data obtained after the MG. This proved a solid basis for the calculation model of the PRIMA program.Conclusion:Despite that validation is needed, the PRIMA program and its prediction model for PPRs at MGs carries the promise of a general, applicable prediction and risk analysis tool for a multitude of events.

BACKGROUND The microparticle content (MP%) of apheresis platelets-a marker of platelet activation-is influenced by donor factors and by external stressors during collection and storage. This study assessed the impact of apheresis technology and other factors on the activation status (MP%) of single-donor apheresis platelets. STUDY DESIGN AND METHODS Data from six US hospitals that screened platelets by measuring MP% through dynamic light scattering (ThromboLUX) were retrospectively analyzed. Relative risks (RRs) were derived from univariate and multivariable regression models, with activation rate (MP% ≥15% for plasma-stored platelets; ≥10% for platelet additive solution [PAS]-stored platelets) and MP% as outcomes. Apheresis platform (Trima Accel vs Amicus), storage medium (plasma vs PAS), pathogen reduction, storage time, and testing location were used as predictors. RESULTS Data were obtained from 7511 platelet units collected using Trima (from 16 suppliers, all stored in plasma, 20.0% were pathogen-reduced) and 2456 collected using Amicus (from four different collection facilities of one supplier, 65.0% plasma-stored, 35.0% PAS-stored, none pathogen-reduced). Overall, 30.0% of Trima platelets were activated compared to 45.6% of Amicus platelets (P

In cases of chronic instability of the lateral ligament complex following an ankle sprain, operative stabilization should be considered when conservative treatment fails. The purpose of this study is to determine the outcome of a percutaneous stabilization of the lateral ligament complex with a gracilis tendon auto-graft, after an adjuvant arthroscopy of the ankle joint. We retrospectively reviewed the medical files of patients who underwent this surgery performed by the senior author. Between 2012 and 2015, 18 ankles were stabilized. Clinical results were assessed at final follow-up at a mean post-operative period of 25 months (range, 10-42 months). The mean post-operative AOFAS ankle-hindfoot score was 90 points (range, 48-100 points). The mean Karlsson Ankle Functional Score was 85 points (range, 37-100 points). The mean VAS score was 1.2 (range, 0-7). Concomitant procedures were performed on 14 out of 18 ankles. In conclusion, we state that this arthroscopically assisted percutaneous technique is a viable treatment option for chronic lateral ankle instability. It offers an alternative for the modified Broström procedure when tissue quality is poor and carries all the advantages of a minimally invasive procedure.

Patients with Down syndrome are at increased risk of respiratory syncytial virus- and H1N1-related death. Literature on COVID-19 in Down syndrome patients is unavailable thus far. We describe the clinical course of 4 patients with Down syndrome during an outbreak of COVID-19. In all four patients, disease course was severe, warranting hospital care in three patients, with fatal outcome in one patient. Another patient receives supportive care in our institution. Our case series is the first report on probable increased risk of life-threatening disease course of COVID-19 in patients with Down syndrome. Proper surveillance, the adherence of social distancing, and the use of personal protective equipment will be essential in reducing morbidity and mortality in our patients.

Objective: A severe hypoglycemia (SH) episode is an acute, high-stress moment for the caregivers of persons with diabetes (PWD). We compared the success rates of nasal glucagon (NG) and injectable glucagon (IG) administration for PWD-trained and untrained users in treating simulated SH episodes. Methods: Thirty-two PWD-trained users and 33 untrained users administered NG and IG to high-fidelity manikins simulating treatment of an SH emergency. Simulation rooms resembled common locations with typical diabetic supplies and stressor elements mimicking real-life SH environments. Success rate and time to administer glucagon were measured. Results: Of all the PWD-trained and untrained users, 58/64 (90.6%) could successfully deliver NG, while 5/63 (7.9%) could successfully deliver IG. For NG simulations, 28/31 (90.3%) PWD-trained users and 30/33 (90.9%) untrained users could successfully administer the dose (mean time 47.3 seconds and 44.5 seconds, respectively). For IG simulations, 5/32 (15.6%) PWD-trained users successfully injected IG (mean time 81.8 seconds), whereas none (0/31 [0%]) of the untrained users were successful. Reasons for unsuccessful administration of NG included oral administration and incomplete pushing of the device plunger. For IG, inability to perform reconstitution steps, partial dose delivery, and injection at an inappropriate site were the causes for failure. Conclusion: With or without training, the success rate for administering NG was 90.6%, whereas it was only 7.9% for IG. NG was easily and quickly administered even by untrained users, whereas training was necessary for successful administration of IG. NG may expand the community of caregivers who can help PWD during an SH episode. Abbreviations: IG = injectable glucagon; NG = nasal glucagon; PWD = person with diabetes; SH = severe hypoglycemia; T1D = type 1 diabetes; T2D = type 2 diabetes.

To understand physicians’ reasons for prescribing Insulin Lispro 200 units/ml (IL200) and their experience with IL200 treatment in Germany. The survey consisted of 28 questions on physician’s profile, average IL200 patients’ characteristics and rationales for prescribing IL200. Questions were rated on a scale of 0 (‘not at all important’/‘strongly disagree’) to 4 (‘absolutely important’/‘strongly agree’). The surveyed physicians had a mean (SD) experience of 18.1 (7.0) years managing diabetes, consulted an average of 226.8 patients with diabetes/month and prescribed IL200 to 56.1% of their patients on mealtime insulin (MTI). About 80.0% of IL200 patients had type 2 diabetes mellitus, were overweight/obese, and received >20 units/day of MTI. More than 70.0% of physicians rated patient’s insulin dose, pattern of self-measured glucose levels, hemoglobin A1c (HbA1c) (clinical); adherence, hypoglycemia knowledge, motivation to improve lifestyle, desire to reduce injection volume and emotional struggle with controlling HbA1c (behavioral) as ‘very important’/‘absolutely important’ factors when prescribing IL200. Physicians considered IL200 a promising treatment option that reduces the injection burden for patients on MTI. Physicians adopted a patient-centered perspective by aligning IL200 prescribing decisions with each patient’s medical needs and non-clinical preferences, with an aim to encourage treatment adherence through resorting to IL200’s advantageous attributes.

Aims We evaluated risk factors for clinically relevant hypoglycaemia (blood glucose 8.5%) at Week 12 (titration period) and at Week 24 (overall study), and by subgroups of age (

Aims To describe the characteristics and fasting experience of a subgroup of patients in the VISION study who initiated insulin therapy and chose to fast during Ramadan, and to discuss the VISION Ramadan substudy data in the context of previous Ramadan studies. Methods The VISION study was a prospective, non-interventional, observational study of adult patients with Type 2 diabetes mellitus in 6 countries in the Western Pacific, Middle East and North Africa, receiving insulin injection therapy for the first time. In this VISION Ramadan substudy, fasting data was collected during Ramadan 2014 and 2015. Results Of 1617 patients in the VISION study, data was collected for 357 patients who chose to fast during Ramadan. At baseline, mean HbA1c was 10.1%, duration of diabetes was 8.8 years, and mean BMI was 30 kg/m2. All patients with non-missing data (n = 169) received advice on fasting during Ramadan. The majority of patients fasted for the full month of Ramadan, and around one-third of patients fasted outside Ramadan. Conclusions Here we provide an update on the characteristics and Ramadan experience of patients with Type 2 diabetes mellitus who initiated insulin therapy and chose to fast during Ramadan. There is still a need to explore patient’s experience during fasting, and identify and address methods to better help manage those patients.

BACKGROUND: The Hopkins criteria were introduced for nodal response evaluation after therapy in head and neck cancer, but its superiority over quantification is not yet confirmed.METHODS: SUVbody weight thresholds and lesion-to-background ratios were explored in a prospective multicenter study of standardized FDG-PET/CT 12 weeks after CRT in newly diagnosed locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients (ECLYPS). Reference standard was histology, negative FDG-PET/CT at 12 months after treatment or ≥ 2 years of negative follow-up. Area under the receiver operator characteristics curves (AUROC) were estimated and obtained thresholds were validated in an independent cohort of HNSCC patients (n = 127).RESULTS: In ECLYPS, 124 patients were available for quantification. With a median follow-up of 20.4 months, 23 (18.5%) nodal neck recurrences were observed. A SUV70 threshold of 2.2 (AUROC = 0.89; sensitivity = 79.7%; specificity = 80.8%) was identified as optimal metric to identify nodal recurrence within 1 year after therapy. For lesion-to-background ratios, an SUV50/SUVliver threshold of 0.96 (AUROC = 0.89; sensitivity = 79.7%; specificity = 82.8%) had the best performance. Compared with Hopkins criteria (AUROC = 0.81), SUV70 and SUV50/SUVliver provided a borderline significant (p = 0.040 and p = 0.094, respectively) improvement. Validation of thresholds yielded similar AUROC values (SUV70 = 0.93, SUV50/SUVliver = 0.95), and were comparable to the Hopkins score (AUROC = 0.91; not statistically significant).CONCLUSION: FDG quantification detects nodal relapse in LAHNSCC patients. When using EARL standardized PET acquisitions and reconstruction, absolute SUV metrics (SUV70 threshold 2.2) prove robust, yet ratios (SUV50/SUVliver, threshold 0.96) may be more useful in routine clinical care. In this setting, the diagnostic value of quantification is comparable to the Hopkins criteria.TRIAL REGISTRATION: US National Library for Medicine, NCT01179360. Registered 11 August 2010, https://clinicaltrials.gov/ct2/show/NCT01179360.

Current and future estimates of the burden of diabetes in the Middle East and North Africa (MENA) region are among the highest in the world. VISION, an 18-month observational study, explored patterns of insulin initiation and intensification in T2DM patients in the MENA region.1192 patients aged ≥18 years were enrolled from Algeria, Egypt, Saudi Arabia and the UAE. Treating physicians recorded participants' data. Patient-reported outcomes (PROs) were assessed using questionnaires completed by participants.67.6% patients had HbA1c ≥9% at insulin initiation, with a mean HbA1c of 9.9%, despite 68.3% patients being on ≥2 oral anti-diabetics, indicating a significant delay in insulin initiation. Basal insulin was initiated in 50.6% and premixed insulin in 46.3% patients. After 18 months, changes in insulin therapy were observed in 33.7% patients, while 39.6% patients achieved HbA1c levels of7.5%. The proportion of patients completely satisfied with their insulin treatment, and the QoL increased over the study course.Results support that timely initiation and early intensification of insulin therapy are necessary in the region to achieve adequate and timely glycemic control and to prevent diabetic complications.

Purpose: To evaluate the efficacy and safety of transarterial chemoembolization with polyethylene glycol (PEG) drug-eluting embolic agents in the treatment of hepatocellular carcinoma (HCC). Materials and methods: A single-center retrospective study of 302 patients (258 men; 85.4%) with HCC treated during a 20-month period was conducted. The mean patient age was 66 years ± 10; 142 (47%) had Barcelona Clinic Liver Cancer stage A disease and 134 had (44.4%) stage B disease; 174 (57.6%) had a single HCC tumor, 65 (21.5%) had 2, and 62 (20.9%) had 3 or more. Mean index tumor size was 36.6 mm ± 24.8. One-month follow-up computed tomography (CT) response per modified Response Evaluation Criteria In Solid Tumors and clinical and biochemical safety were analyzed. Progression-free and overall survival were calculated by Kaplan-Meier method. Results: Median follow-up time was 11.9 months (95% confidence interval, 11.0-13.0 mo). One-month follow-up CT revealed complete response in 179 patients (63.2%), partial response in 63 (22.3%), stable disease in 16 (5.7%), and progressive disease in 25 (8.8%). The most frequent complications were postembolization syndrome in 18 patients (6%), liver abscess in 5 (1.7%), and puncture-site hematoma in 3 (1%). Biochemical toxicities occurred in 57 patients (11.6%). Survival analysis at 12 months showed a progression-free survival rate of 65.9% and overall survival rate of 93.5%. Patients who received transplants showed a 57.7% rate of complete pathologic response. Conclusions: Chemoembolization with PEG embolic agents for HCC is safe and effective, achieving an objective response rate of 85.5%. info:eu-repo/semantics/publishedVersion

A patient with extensive multisystem overgrowth caused by a somatic gain of function PIK3CA-mutation is described. This case is an example of the clinical diversity of the PIK3CA-Related Overgrowth Spectrum (PROS) as the patient had overlapping features of Congenital Lipomatous Overgrowth Vascular malformations Epidermal nevi and Skeletal abnormalities (CLOVES) syndrome and Megalencephaly-Capillary malformation Polymicrogyria (MCAP) syndrome and underlines the utility of this umbrella term.

Before learning the cardinal principle (knowing that the last word reached when counting a set represents the size of the whole set), children do not use number words accurately to label most set sizes. However, it remains unclear whether this difficulty reflects a general inability to conceptualize and communicate about number, or a specific problem with number words. We hypothesized that children's gestures might reflect knowledge of number concepts that they cannot yet express in speech, particularly for numbers they do not use accurately in speech (numbers above their knower-level). Number gestures are iconic in the sense that they are item-based (i.e., each finger maps onto one item in a set) and therefore may be easier to map onto sets of objects than number words, whose forms do not map transparently onto the number of items in a set and, in this sense, are arbitrary. In addition, learners in transition with respect to a concept often produce gestures that convey different information than the accompanying speech. We examined the number words and gestures 3- to 5-year-olds used to label small set sizes exactly (1-4) and larger set sizes approximately (5-10). Children who had not yet learned the cardinal principle were more than twice as accurate when labeling sets of 2 and 3 items with gestures than with words, particularly if the values were above their knower-level. They were also better at approximating set sizes 5-10 with gestures than with words. Further, gesture was more accurate when it differed from the accompanying speech (i.e., a gesture-speech mismatch). These results show that children convey numerical information in gesture that they cannot yet convey in speech, and raise the possibility that number gestures play a functional role in children's development of number concepts.

Co-morbidities have typically been considered as prevalent cardiovascular risk factors and cardiovascular diseases rather than systematic measures of general co-morbidity burden in patients who underwent percutaneous coronary intervention (PCI). Charlson co-morbidity index (CCI) is a measure of co-morbidity burden providing a means of quantifying the prognostic impact of 22 co-morbid conditions on the basis of their number and prognostic impact. The study evaluated the impact of the CCI on cardiac mortality and major adverse cardiovascular events (MACE) after PCI through analysis of the Nobori-2 study. The prognostic impact of CCI was studied in 3,067 patients who underwent PCI in 4,479 lesions across 125 centers worldwide on 30-day and 1- and 5-year cardiac mortality and MACE. Data were adjusted for potential confounders using stepwise logistic regression; 2,280 of 3,067 patients (74.4%) had ≥1 co-morbid conditions. CCI (per unit increase) was independently associated with an increase in both cardiac death (odds ratio [OR] 1.47 95% confidence interval [CI] 1.20 to 1.80, p = 0.0002) and MACE (OR 1.29 95% CI 1.14 to 1.47, p ≤0.0011) at 30 days, with similar observations recorded at 1 and 5 years. CCI score ≥2 was independently associated with increased 30-day cardiac death (OR 4.25, 95% CI 1.24 to 14.56, p = 0.02) at 1 month, and this increased risk was also observed at 1 and 5 years. In conclusion, co-morbid burden, as measured using CCI, is an independent predictor of adverse outcomes in the short, medium, and long term. Co-morbidity should be considered in the decision-making process when counseling patients regarding the periprocedural risks associated with PCI, in conjunction with traditional risk factors.

Approximate number word knowledge—understanding the relation between the count words and the approximate magnitudes of sets—is a critical piece of knowledge that predicts later math achievement. However, researchers disagree about when children first show evidence of approximate number word knowledge—before, or only after, they have learned the cardinal principle. In two studies, children who had not yet learned the cardinal principle (subset-knowers) produced sets in response to number words (verbal comprehension task) and produced number words in response to set sizes (verbal production task). As evidence of approximate number word knowledge, we examined whether children’s numerical responses increased with increasing numerosity of the stimulus. In Study 1, subset-knowers (ages 3.0–4.2 years) showed approximate number word knowledge above their knower-level on both tasks, but this effect did not extend to numbers above 4. In Study 2, we collected data from a broader age range of subset-knowers (ages 3.1–5.6 years). In this sample, children showed approximate number word knowledge on the verbal production task even when only examining set sizes above 4. Across studies, children’s age predicted approximate number word knowledge (above 4) on the verbal production task when controlling for their knower-level, study (1 or 2), and parents’ education, none of which predicted approximation ability. Thus, children can develop approximate knowledge of number words up to 10 before learning the cardinal principle. Furthermore, approximate number word knowledge increases with age and might not be closely related to the development of exact number word knowledge.

PURPOSE: Adductor longus injuries are complex. The conflict between views in the recent literature and various nineteenth-century anatomy books regarding symphyseal and perisymphyseal anatomy can lead to difficulties in MRI interpretation and treatment decisions. The aim of the study is to systematically investigate the pyramidalis muscle and its anatomical connections with adductor longus and rectus abdominis, to elucidate injury patterns occurring with adductor avulsions.METHODS: A layered dissection of the soft tissues of the anterior symphyseal area was performed on seven fresh-frozen male cadavers. The dimensions of the pyramidalis muscle were measured and anatomical connections with adductor longus, rectus abdominis and aponeuroses examined.RESULTS: The pyramidalis is the only abdominal muscle anterior to the pubic bone and was found bilaterally in all specimens. It arises from the pubic crest and anterior pubic ligament and attaches to the linea alba on the medial border. The proximal adductor longus attaches to the pubic crest and anterior pubic ligament. The anterior pubic ligament is also a fascial anchor point connecting the lower anterior abdominal aponeurosis and fascia lata. The rectus abdominis, however, is not attached to the adductor longus; its lateral tendon attaches to the cranial border of the pubis; and its slender internal tendon attaches inferiorly to the symphysis with fascia lata and gracilis.CONCLUSION: The study demonstrates a strong direct connection between the pyramidalis muscle and adductor longus tendon via the anterior pubic ligament, and it introduces the new anatomical concept of the pyramidalis-anterior pubic ligament-adductor longus complex (PLAC). Knowledge of these anatomical relationships should be employed to aid in image interpretation and treatment planning with proximal adductor avulsions. In particular, MRI imaging should be employed for all proximal adductor longus avulsions to assess the integrity of the PLAC.

Background The current revascularization treatment recommendation is different according to lesion location and a higher recommendation is given to surgery for proximal LAD (pLAD) lesions over PCI. This is based on previous studies and expert opinion. We aimed to investigate whether indeed there is a difference in outcome with respect to LAD lesion location while using a drug eluting stent (DES). Methods The NOBORI-2 trial, enrolled 3067 consecutive patients in 125 centers who were treated with DES for single and multivessel disease. We compared 834 [27.2%] patients who underwent PCI of the pLAD as part of their revascularization, to 2203 [71.8%] patients in which stenting to other lesion(s) but not the pLAD was performed. Results The pLAD group had lower incidence of hypertension, peripheral vascular disease, prior PCI and CABG, but had more lesions treated [1.55 ± 0.8 vs. 1.35 ± 0.6], more stents implanted [1.98 ± 1.2 vs. 1.66 ± 1.0] and longer overall stent length [31.8 ± 20.2 vs. 28.2 ± 17.8 mm]. There was no difference in the occurrence of the primary endpoint [cardiac death, myocardial infarction and target lesion revascularization] at 1 or 2 years of follow up between the pLAD and non pLAD [6.0% vs. 4.6%, p = 0.14 and 7.7% vs. 6.6%; p = 0.22, respectively]. The relief from anginal symptoms was similar. Multivariate analysis showed that pLAD location was not a variable that predicted MACE or TLF. Stent thrombosis rate was similar. Conclusion When considering PCI with DES, there is no difference in outcome between patients with and without proximal LAD lesions.

Internationally, hospital readmissions have a great appeal as an indicator of hospital quality. Since possibilities in prevention and control exist, reducing rates of hospital readmission has attracted attention of policymakers as a way to improve quality of care while simultaneously reducing costs. Therefore reducing the number of readmissions is considered to be a pillar of more cost-effective hospital care. The goal of this study was to estimate the cost of hospital readmissions at a national level, describe differences in readmission rates between hospitals and to calculate the potential monetary savings of reducing excess readmissions.Stays data were obtained from the Minimum Basic Data Set 2008 in a sample of 45 hospitals representing 16,141 beds. Readmissions were identified as a second admission for the same patient with the same APR-DRG code within 1 month or 3 months after discharge. Hospital type, diagnosis-related group, age and gender were used as matching factors in comparing readmission rates. Specific types of readmissions that occur naturally in each other's proximity due to the repeating nature of the therapy were excluded from the analysis. The costs per readmission were then calculated by linking the stays data with the cost data per APR-DRG and per severity index using the 2008 national feedback. The results of our sample were then extrapolated to all Belgian hospitals in order to calculate the total cost of readmissions. By means of a sensitivity analysis we estimated potential monetary savings when a reduction in the incidence of readmissions in hospitals having a higher readmission rate in comparison to other hospitals would be realized.In our sample 1.5% readmissions within 1 month after discharge and 2.1% within 3 months after discharge were identified. The additional weighted mean cost of these readmissions was Euro 3,495.58 within 1 month and Euro 3,572.20 within 3 months. The total financial burden, as extrapolated to the Belgian setting, is estimated at Euro 280,091,471.The wide variability between hospitals in incidence of readmissions (1.17-6.40%) indicates a potential for improvement. For instance, if all Belgian hospitals having a higher readmission rate improve their rate to the level of the hospital corresponding to percentile 75 (= 2.4% readmissions) savings would amount to Euro 14,118,509.The observed incidence of readmissions is associated with important additional healthcare costs. Although not all readmissions can be prevented, there is clearly a potential to increase cost-effectiveness of hosp tal care delivery.

When asked to explain their solutions to a problem, children often gesture and, at times, these gestures convey information that is different from the information conveyed in speech. Children who produce these gesture-speech "mismatches" on a particular task have been found to profit from instruction on that task. We have recently found that some children produce gesture-speech mismatches when identifying numbers at the cusp of their knowledge, for example, a child incorrectly labels a set of two objects with the word "three" and simultaneously holds up two fingers. These mismatches differ from previously studied mismatches (where the information conveyed in gesture has the potential to be integrated with the information conveyed in speech) in that the gestured response contradicts the spoken response. Here, we ask whether these contradictory number mismatches predict which learners will profit from number-word instruction. We used the Give-a-Number task to measure number knowledge in 47 children (Mage = 4.1 years, SD = 0.58), and used the What's on this Card task to assess whether children produced gesture-speech mismatches above their knower level. Children who were early in their number learning trajectories ("one-knowers" and "two-knowers") were then randomly assigned, within knower level, to one of two training conditions: a Counting condition in which children practiced counting objects; or an Enriched Number Talk condition containing counting, labeling set sizes, spatial alignment of neighboring sets, and comparison of these sets. Controlling for counting ability, we found that children were more likely to learn the meaning of new number words in the Enriched Number Talk condition than in the Counting condition, but only if they had produced gesture-speech mismatches at pretest. The findings suggest that numerical gesture-speech mismatches are a reliable signal that a child is ready to profit from rich number instruction and provide evidence, for the first time, that cardinal number gestures have a role to play in number-learning.

Learning the cardinal principle (the last word reached when counting a set represents the size of the whole set) is a major milestone in early mathematics. But researchers disagree about the relationship between cardinal principle knowledge and other concepts, including how counting implements the successor function (for each number word N representing a cardinal value, the next word in the count list represents the cardinal value N + 1) and exact ordering (cardinal values can be ordered such that each is one more than the value before it and one less than the value after it). No studies have investigated acquisition of the successor principle and exact ordering over time, and in relation to cardinal principle knowledge. An open question thus remains: Is the cardinal principle a “gatekeeper” concept children must acquire before learning about succession and exact ordering, or can these concepts develop separately? Preschoolers (N = 127) who knew the cardinal principle (CP-knowers) or who knew the cardinal meanings of number words up to “three” or “four” (3–4-knowers) completed succession and exact ordering tasks at pretest and posttest. In between, children completed one of two trainings: counting only versus counting, cardinal labeling, and comparison. CP-knowers started out better than 3–4-knowers on succession and exact ordering. Controlling for this disparity, we found that CP-knowers improved over time on succession and exact ordering; 3–4-knowers did not. Improvement did not differ between the two training conditions. We conclude that children can learn the cardinal principle without understanding succession or exact ordering and hypothesize that children must understand the cardinal principle before learning these concepts.

Giant cell granuloma (GCG) of the jaw is a rare, well-known feature of neurofibromatosis type 1 (NF1), an inborn multisystem disorder. Recently, the development of GCG in NF1 was attributed to second hit mutations in the NF1 gene. The treatment of GCG is pragmatic with a preference for local curettage of lytic osseous areas. This report describes the surgical therapy of an NF1-affected female with multilocular mandibular GCG and hypodontia who additionally suffered from a brain tumour and Hashimoto's thyroiditis. Although local recurrence of GCG was noted, augmentation of the curetted cavities with a bone substitute in successive interventions successfully restored the extensive periradicular local defects and stabilised the teeth. A meticulous in vitro study of the GCG specimen revealed a second hit mutation in the NF1 gene in the GCG spindle-cells. This study contributes to the increasing knowledge of the molecular basis for GCG in the jaw of NF1 patients, indicating that it is a neoplasm.

Rescaling generic models is the most frequently applied approach in generating biomechanical models for inverse kinematics. Nevertheless it is well known that this procedure introduces errors in calculated gait kinematics due to: (1) errors associated with palpation of anatomical landmarks, (2) inaccuracies in the definition of joint coordinate systems. Based on magnetic resonance (MR) images, more accurate, subject-specific kinematic models can be built that are significantly less sensitive to both error types. We studied the difference between the two modelling techniques by quantifying differences in calculated hip and knee joint kinematics during gait. In a clinically relevant patient group of 7 pediatric cerebral palsy (CP) subjects with increased femoral anteversion, gait kinematic were calculated using (1) rescaled generic kinematic models and (2) subject-specific MR-based models. In addition, both sets of kinematics were compared to those obtained using the standard clinical data processing workflow. Inverse kinematics, calculated using rescaled generic models or the standard clinical workflow, differed largely compared to kinematics calculated using subject-specific MR-based kinematic models. The kinematic differences were most pronounced in the sagittal and transverse planes (hip and knee flexion, hip rotation). This study shows that MR-based kinematic models improve the reliability of gait kinematics, compared to generic models based on normal subjects. This is the case especially in CP subjects where bony deformations may alter the relative configuration of joint coordinate systems. Whilst high cost impedes the implementation of this modeling technique, our results demonstrate that efforts should be made to improve the level of subject-specific detail in the joint axes determination.

Summary Background: Work-related musculoskeletal disorders (MSD) of the neck and the shoulders are a growing problem in society. An interesting pattern of spontaneous muscle activity, the firing of a single motor unit, in the trapezius muscle is observed during a laboratory study in a rest state or a state with a mental load. Objective: In this study, we report on the finding of the single motor unit firing and we present a detection algorithm to localize these single motor unit firings. Methods: A spike train detection algorithm, using a nonlinear energy operator and correlation, is presented to detect burst of highly correlated, high energetic spike-like segments. Results: This single motor unit was visible in 65% of the test subjects on one or both trapezius muscles although there was no change in posture of the test subjects. All the segments in the data that were determined as single motor unit firings were detected by the algorithm. Discussion: The physiological meaning of this firing pattern is a very low and subconscious contraction of the muscle. A long-term contraction could lead to the exhaustion of the muscle fibers, thus resulting in musculoskeletal disorders. The detection algorithm is able to localize this phenomenon in a sEMG measurement. The ability of detecting these firings is helpful in the research of its origin. Conclusion: The detection algorithm can be used to gain insight in the physiological origin of this phenomenon. In addition, the algorithm can also be used in a biofeedback system to warn the user for this undesired contraction to prevent MSD.

Musculoskeletal loading is an important factor affecting the development of osteoarthritis, bone remodelling and primary fixation of total hip replacement (THR). In this study, we analyzed the relation between muscular force, gait kinematics and kinetics and hip loading in 20 patients before and six weeks after THR. Hip contact forces were calculated from gait analysis data using musculoskeletal modelling, inverse dynamics and static optimization. We found aberrant pelvis and hip kinematics and kinetics before and six weeks after surgery, confirming previous findings in literature. Furthermore, we found a decrease in the total contact force and its vertical component. These changes result in a decrease of the associated inclination angles of the total hip contact force in the sagittal and transverse planes, changing the orientation towards more vertical implant loading after THR. These changes in hip loading were related to observed gait kinematics and kinetics. Most importantly, excessive pelvic obliquity and associated hip adduction related to impaired implant loading. We concluded, therefore, that physical therapy in the early post-operative phase should primarily focus on stretching of anterior and medial structures and strengthening of hip flexors and abductors to achieve normalization of the hip and pelvis kinematics and consequently normalize hip loading.

Research has raised a growing concern about the accuracy of rescaled generic musculoskeletal models for estimating a subject's musculoskeletal geometry. Information extracted from magnetic resonance (MR) images can improve the subject-specific detail and accuracy of musculoskeletal models. Nevertheless, methods that allow efficient, automated definition of subject-specific muscular models for use in biomechanical analysis of gait have not yet been published to the best of our knowledge. We report a novel method for automated definition of subject-specific muscle paths using non-rigid image registration between an atlas image and the subject's MR images. We validated this approach quantitatively by measuring the distance between automatically and manually defined coordinates of muscle attachment sites. Data was collected for 34 muscles in each lower limb of 5 paediatric subjects diagnosed with diplegic cerebral palsy and presenting varying degrees of increased femoral anteversion. Distances showed an overall median Euclidean error of 6.1mm: 2.0mm along the medio-lateral direction, 1.8mm along the anterior-posterior direction and 3.8mm along the superior-inferior direction. A qualitative validation between automatically defined muscle points and the muscular geometry observed in the subject's medical image data corroborated the quantitative validation. This automated approach followed by visual inspection and, if needed, correction to the muscle paths, reduced the time required for defining 34 lower-limb muscle paths from around 3.5 to 1h. Furthermore, the method was also applicable to aberrant skeletal geometry. Using the proposed method, defining MR-based musculoskeletal models becomes a time efficient and more accurate alternative to rescaling generic models.

Advanced biomechanical analysis of muscle function during gait relies on the use of a musculoskeletal model. In clinical practice, personalization of the model is usually limited to rescaling a generic model to approximate the patient's anthropometry, even in the presence of bony deformities, as in the case of cerebral palsy (CP). However, the current state of the art in biomechanics allows highly detailed subject-specific models to be built based on magnetic resonance (MR) images. We hypothesized that moment arm length (MAL) calculations from MR-based models would be more accurate than those from rescaled generic musculoskeletal models. Our study compared hip muscle MAL estimated by (1) a personalized model based on full-leg MR scans and (2) a rescaled generic model of both lower limbs in six children presenting with increased femoral anteversion. Personalized MR-based models were created using a custom-built workflow. Rescaled generic models were created based on three-dimensional positions of anatomical markers measured during a standing trial. For all 12 lower limb models, the hip flexion, adduction and rotation MAL of 13 major muscles were analyzed over a physiological range of hip motion using Software for interactive musculoskeletal modelling (SIMM) (Motion Analysis Corporation, USA). Our results showed that rescaled generic models, which do not take into account the subject's femoral geometry, overestimate MAL for hip flexion, extension, adduction, abduction and external rotation, but underestimate MAL for hip internal rotation. The differences in MAL introduced by taking the aberrant femoral geometry into account in the MR-based model were consistent with major gait characteristics presented in CP patients.

Non-insulin-dependent diabetes mellitus has been recognized to be heterogeneous in etiology, with multiple subgroups. Several genes or chromosomal regions have been implicated in the development of the disease. In this study the association of HLA class II alleles and genotypes and the association of CD4 and CD3 polymorphisms were assessed in a large number of Belgian non-insulin-dependent diabetes mellitus patients. Furthermore, the importance of the DQ alpha 1Arg52/DQ alpha 1Arg52 and the DQ beta 1Asp57/DQ beta 1Asp57 genotypes and the combination of both genotypes were examined. Our results show that in the HLA class II genes only the DQ alpha 1Arg52+/DQ alpha 1Arg52+ genotype was significantly associated with non-insulin-dependent diabetes mellitus compared with controls (p = 0.011, RR = 2.02). We also observed that the frequency of the CD4*A4/*A8 genotype and the CD4*A7 allele was significantly increased and decreased respectively in non-insulin-dependent diabetes mellitus patients as compared with the controls (p = 0.018, RR = 2.16 and p = 0.0003, RR = 0.49 respectively). These results therefore suggest that HLA class II and CD4 genes might independently contribute to the susceptibility for non-insulin-dependent diabetes mellitus and that these alleles and genotypes might identify subgroups of patients with different susceptibilities.

Infants as young as 5 months of age view familiar actions such as reaching as goal-directed (Woodward, 1998), but how do they construe the goal of an actor's reach? Six experiments investigated whether 12-month-old infants represent reaching actions as directed to a particular individual object, to a narrowly defined object category (e.g., an orange dump truck), or to a more broadly defined object category (e.g., any truck, vehicle, artifact, or inanimate object). The experiments provide evidence that infants are predisposed to represent reaching actions as directed to categories of objects at least as broad as the basic level, both when the objects represent artifacts (trucks) and when they represent people (dolls). Infants do not use either narrower category information or spatiotemporal information to specify goal objects. Because spatiotemporal information is central to infants' representations of inanimate object motions and interactions, the findings are discussed in relation to the development of object knowledge and action representations.

Until recently, response assessment in patients with lymphoma was primarily performed by computed tomography (CT). Based on CT, International Workshop Criteria (IWC) were developed and widely used. Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a more sensitive and specific imaging technique for the detection of residual disease in lymphoma, and Revised Integrated International Workshop Criteria (IWC + PET) were recently proposed by the members of the International Harmonization Project (IHP), which combine both imaging techniques. We determined whether these new IWC + PET-criteria, can more accurately predict outcome compared to IWC-criteria in aggressive and indolent non-Hodgkin's lymphoma (NHL), and therefore correlated IWC and IWC + PET response with time-to-next-treatment (TNT) in 69 patients with NHL. We demonstrated that IWC + PET-guidelines are highly recommended over IWC-guidelines for patients with potentially-curable and routinely FDG-avid lymphoma. In contrast, no additional value of IWC + PET was demonstrated in a small group of patients with incurable histological subtypes.

Microsatellite instability (MSI) accounts for 15% of all colorectal tumours. Several specific clinicopathologicals (e.g. preference for the proximal colon over the distal colon, improved prognosis and altered response to chemotherapeutics) are described for this subset of tumours. This study aimed to analyse morphological, inflammatory and angiogenic features of MSI vs microsatellite stable (MSS) tumours., SCOPUS: ar.j, info:eu-repo/semantics/published

A 58-year-old man presented with transient vertigo and pulsatile tinnitus.High-resolution computed tomography, magnetic resonance imaging, excision, and subsequent immunohistochemical assays were performed.Imaging showed a soft tissue mass in the epitympanum and mastoid with bone erosion of the tegmen tympani and a dural tail sign, suggesting meningioma. Subsequently, because of signs of clinical progression, a canal-wall-up attico-antromastoidectomy was performed, with near-complete removal of a granulomatous, ossifying, haemorrhagic mass.Radiological imaging was critical in determining the extent of the mass and excluding other pathologies. Due to the atypical clinical and radiological signs, the final diagnosis of capillary haemangioma of the middle ear and temporal bone was made only after surgical resection and histopathological examination with immunohistochemistry, which excluded meningioma. The contiguous occurrence of cutaneous capillary haemangioma of the lateral face and neck was an important clue to the diagnosis.

Background Keratinocytic epidermal nevus syndrome (KENS) is a complex disorder not only characterized by the presence of epidermal nevi but also by abnormalities in the internal organ systems. A small number of cases with KENS are molecularly characterized and reported in the literature with somatic activating RAS, FGFR3 and PIK3CA mutations. Case presentation In this study we present a patient with hyper- and hypopigmented regions, verrucous pigmented skin lesions and a paravertebral conglomerate tumour at the level of the cervical and thoracic spine. A large lipomatous dumbbell tumour caused atrophy of the spinal cord with progressive paraparesis. We identified a mosaic c.35G > A (p.Gly12Asp) KRAS mutation in the pigmented verrucous epidermal nevus tissue, the intraneural schwann cells and the lipoma. The c.35G > A (p.Gly12Asp) KRAS mutation was absent in the peripheral blood leukocytes. Conclusion We conclude that KENS, the intraneural Schwann cell proliferation and the lipoma in this individual were caused by a postzygotic and mosaic activating c.35G > A (p.Gly12Asp) KRAS mutation.

Background: Hereditary nonpolyposis colon cancer (HNPCC-Lynch syndrome) is caused by mutations in genes involved in DNA mismatch repair (MMR), mostly in the hMLH1 and hMSH2 genes. The mutation spectrum in the Belgian population is still poorly documented. Aim: To report our experience on the mutation screening in Belgian familial colorectal cancer (CRC) patients, including the investigation of the pathogenicity of the missense and splice mutations. To increase the mutation detection rate by selecting the target population. Methods: Two hundred and twenty five Belgian patients with familial clustering of CRC were genetically tested. Point mutations in the hMLH1 and hMSH2 genes were screened by denaturing gradient gel electrophoresis (DGGE) followed by direct sequencing. Genomic deletions and duplications were assessed by multiplex ligase dependent probe amplification (MLPA) and multiplex PCR. Missense mutations were examined for pathogenicity by means of cosegregation of the mutation with the disease, microsatellite instability (MSI) in tumors, immunohistochemical staining of tumors and determination of the population frequency of the particular mutation. Results: Twenty five pathogenic mutations were identified from which 16 were novel: 7 frameshifts, one in frame deletion, 5 genomic deletions, 5 splice defects, 4 nonsense (stop) mutations and 3 missense mutations which were classified as pathogenic (out of 10 missense mutations). In retrospect, a mutation detection rate of 71% was obtained if MSI was used as a supplementary selection criterion in addition to familial clustering. Conclusion: Different types of pathogenic mutations in the hMLH1 and hMSH2 genes were identified in a Belgian CRC group with familial clustering. The mutation detection yield drastically increased by preliminar selection of those familial CRC patients with a microsatellite instable tumor. Considerable attention went to the assessment of the pathogenicity of the missense mutations. In practice, the cosegregation with the disease was the most relevant criterion.

Inappropriate activity of M. rectus femoris (RF) during swing is believed to contribute to stiff knee gait in cerebral palsy. This study used musculoskeletal modeling techniques to analyze rectus femoris musculo-tendon (MT) length and lengthening velocity during stiff knee gait in 35 children with diplegic cerebral palsy (CP). Duncan Ely test scores were used to categorize the patients into four groups with increasing levels of rectus femoris spasticity. Knee kinematics confirmed a significant reduction and delay of maximal peak knee flexion during swing in the patient groups compared to reference values. Maximal musculo-tendon length of M. rectus femoris was reduced and occurred prematurely in swing. Musculo-tendon lengthening velocity was significantly reduced and the timing of the maximal lengthening velocity was shifted into stance phase. The present study demonstrates altered dynamic behavior of the M. rectus femoris in stiff knee gait and the results indicate that maximal knee flexion in swing was not a valid reference for the MT length of the M. rectus femoris. Furthermore, in the patient group maximal musculo-tendon lengthening velocity of the muscle related to the stance phase rather than the stance-swing transition. ispartof: Gait & posture vol:23 issue:2 pages:222-229 ispartof: location:England status: published

Contains fulltext : 50538.pdf (Publisher’s version ) (Closed access) BACKGROUND AND PURPOSE: Because the locoregional control for HNSCC is still disappointing, research efforts focus on the exploration of new molecular markers located in both tumour and microenvironment, which could help stratify patients. The aim of the present work was therefore first to assess microsatellite alterations and hypoxia in HNSCC as possible molecular markers. Second, a relation between both was investigated, as hypoxia is known to select for genetic alterations. MATERIAL AND METHODS: Forty-eight patients with advanced HNSCC treated by surgery+/-radiotherapy were included. MSI and LOH were investigated with microsatellite markers using automatic fragment analysis. The presence of hypoxia was assessed by immunohistochemistry for pimonidazole, CA IX and GLUT-1. The mutual relationship between MSI/LOH and hypoxia was evaluated. RESULTS: No MSI was detected in this patient group. LOH occurred mostly on chromosomal arms 3p, 5q, 9p, 17p and 17q. Patients with LOH at D17S799, located in the near environment of p53, showed a higher CA IX expression (p=0.01). CONCLUSIONS: LOH is a possible molecular marker in HNSCC. The positive correlation between LOH at D17S799 and CA IX is in full concordance with previous publications linking hypoxia to selective pressure on the p53 gene.

Background. Although health-related benefits of fitness training in older men are well established, it is not clear yet which mode and intensity of a exercise program is most effective. This study addresses whether the combination of endurance (ED) and resistance training in older men have supplementary health-related benefits in addition to profits attained through endurance training alone. Additionally, effects of moderate- and low-intensity resistance training are compared. Methods. Men, 55–75 years of age, were randomly assigned to a control group (N = 13) or one of three exercise groups (20 weeks, two to three times per week): endurance plus moderate resistance (MR) training (N = 22), endurance plus low resistance (LR) training (N = 22) and endurance training only (N = 22). Cardiovascular (CV) risk factors, muscular fitness and postural control were assessed before and after training. Results. All exercise groups revealed significant (P < 0.05) improvements in resting heart rate, work capacity and recovery, waist girth, insulin response and knee-extensor strength with no differences among groups. Body composition, resting metabolic rate (RMR), VO2peak and postural control did not change in exercise groups. Conclusion. In older men, a fitness program consisting of 20 weeks endurance training combined with resistance training is equally effective as endurance training alone. Moderate vs. low resistance training added to endurance training yields similar health-related benefits.

Sleep-related phenomena or disorders, including snoring and tooth grinding, can be investigated using polysomnography. This method, however, generates large amounts of synchronically recorded data that are often analyzed visually with subjective interpretation. The purpose of this study was to minimize the need for subjective evaluation by developing a computer program for analysis of EMG data linked with polysomnographic recordings in a standardized and semi-automatic way. The selected algorithm differs from the Root Mean Square (RMS) method by being based on the theory of "differentiated EMG" (DIFEMG), which relies on two principles. The first says that the activation of a larger number of motor units results in a greater force production. The second principle says that the force production will continue for some time after the muscle is no longer stimulated. After a visual check for artifacts in the basic EMG recordings, the computer program is used to analyze the corrected basic EMG signal. The results were that both methods yield identical results as far as the detected number of events is concerned. There is, however, a significant difference when the duration of the events is considered, because the start and end of an event can be more accurately determined with the new method presented here. The computer program described will make comparison of data from different studies easier.

Objective. Whether different muscle-loading patterns with the same mean load have a similar influence on the resultant muscle fatigue is still unknown. This study investigated the influence of two intermittent exercise protocols, with equal mean muscle loading, on the mechanical and myoelectrical signs of fatigue in the elbow flexor muscles. Design. Ten subjects performed two 20-min long intermittent isometric elbow flexion tasks. The exercise period load for the low force intermittent test was 25% of the maximum voluntary contraction, with a work-cycle time of 20 s and a duty cycle of 0.5. The high force intermittent exercise protocol had an exercise period load of 50% maximum voluntary contraction, a cycle time of 20 s and a duty cycle of 0.25. Methods . Muscle fatigue was quantified both by measuring the maximal voluntary contraction torque before and after the intermittent exercises, and also by the temporal changes observed in the electromyography signal. Results. Both muscle-loading patterns induced a 15% decrease in maximum voluntary contraction. However, the electromyographic spectral changes during the intermittent static contractions varied between the two protocols. Conclusions. Variation in muscle load without loss in productivity can affect the physiological responses. The results also showed that different methods to assess muscle fatigue sometimes provide different information on the resultant fatigue. Relevance. Indications of muscle fatigue are required to understand work-related musculoskeletal injuries and improve working practices. Results of this study are applicable to comparisons of repetitive tasks with varying intensities and frequencies.

The study assessed the prognostic value of fluorine 18-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) after salvage chemotherapy before high-dose chemotherapy with stem cell transplantation (HDT/SCT) in patients with induction failure or relapsing chemosensitive lymphoma. Retrospective analysis of the clinical and conventional imaging data of 60 patients scheduled for HDT/SCT was performed in parallel with the analysis of the [18F]FDG-PET results. To determine the ability of [18F]FDG-PET to predict clinical outcome, PET images were reread without knowledge of conventional imaging and clinical history. Presence or absence of abnormal [18F]FDG uptake was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. Thirty patients showed a negative [18F]FDG-PET scan before HDT/SCT; 25 of those remained in complete remission, with a median follow-up of 1510 days. Two patients died due to a treatment-related mortality but without evidence of recurrent disease at that time (228-462 days). Only 3 patients had a relapse (median PFS, 1083 days) after a negative [18F]FDG-PET scan. Persistent abnormal [18F]FDG uptake was seen in 30 patients and 26 progressed (median PFS, 402 days); of these 26, 16 died from progressive disease (median OS, 408 days). Four patients are still in complete remission after a positive scan. Comparison between groups indicated a statistically significant association between [18F]FDG-PET findings and PFS (P < .000001) and OS (P < .00002). [18F]FDG-PET has an important prognostic role in the pretransplantation evaluation of patients with lymphoma and enlarges the concept of chemosensitivity used to select patients for HDT/SCT. (Blood. 2003;102:53-59)

This paper focuses on the contributions of the gluteus maximus, biceps femoris, gastrocnemius and soleus in maintaining the stability of the stance limb in the sagittal plane during the mid-stance phase of gait. In the absence of any one of these muscles, the potential compensatory changes in muscle activation are explored, the aim being to restore stability to the stance limb. The investigation was carried out by integrating musculoskeletal modelling, forward simulation and optimization techniques. We concluded that maintenance of stance limb stability requires a subtle interplay of muscle activations. Weakness in a single muscle is unlikely to be adequately compensated for by increasing or decreasing the activation of one muscle alone.