Which Parameter Influences Local Disease-Free Survival after Radiation Therapy due to Osteolytic Metastasis? A Retrospective Study with Pre- and Post-Radiation Therapy MRI including Diffusion-Weighted Images

Although radiation therapy (RT) plays an important role in the palliation of localized bone metastases, there is no consensus on a reliable method for evaluating treatment response. Therefore, we retrospectively evaluated the potential of magnetic resonance imaging (MRI) using apparent diffusion coefficient (ADC) maps and conventional images in whole-tumor volumetric analysis of texture features for assessing treatment response after RT. For this purpose, 28 patients who received RT for osteolytic bone metastasis and underwent both pre- and post-RT MRI were enrolled. Volumetric ADC histograms and conventional parameters were compared. Cox regression analyses were used to determine whether the change ratio in these parameters was associated with local disease progression-free survival (LDPFS). The ADCmaximum, ADCmean, ADCmedian, ADCSD, maximum diameter, and volume of the target lesions after RT significantly increased. Change ratios of ADCmean < 1.41, tumor diameter ≥ 1.17, and tumor volume ≥ 1.55 were significant predictors of poor LDPFS. Whole-tumor volumetric ADC analysis might be utilized for monitoring patient response to RT and potentially useful in predicting clinical outcomes.

Minimal complications observed with a modified surgical approach for treatment of canine anal sac neoplasia

OBJECTIVE To describe a modified approach to closed anal sacculectomy and report the short-term outcomes of dogs that underwent the procedure for treatment of neoplasia. ANIMALS 16 client-owned dogs. PROCEDURES Medical records of 1 referral hospital were reviewed to identify dogs that underwent modified closed anal sacculectomy for treatment of anal sac neoplasia between January 2018 and September 2020. Data collected included signalment, examination and diagnostic imaging findings, surgical details, intraoperative and postoperative complications, cytologic and histologic findings, adjuvant treatments, duration of follow-up, and short-term outcome. RESULTS 15 dogs had apocrine gland anal sac adenocarcinoma, and 1 had a collision tumor. No dogs had intraoperative complications; 1 dog had a minor postoperative complication (paraparesis) that resolved. The median duration of postoperative follow-up was 286 days (range, 67 to 777 days). One dog had confirmed local disease recurrence 290 days after surgery, and 1 had suspected local disease recurrence 203 days after surgery and was euthanized because of systemic disease progression. CONCLUSIONS AND CLINICAL RELEVANCE The modified closed anal sacculectomy was well tolerated in this sample of dogs, with minimal short-term complications. This study provided evidence to justify evaluation of the procedure in a larger number of dogs and assessment of the effects of procedural modifications on postoperative complication rates and time to local recurrence.

Enrolment in clinical research at UCLH and geographically distributed indices of deprivation

Healthcare should be judged by its equity as well as its quality. Both aspects depend not only on the characteristics of service delivery but also on the research and innovation that ultimately shape them. Conducting a fully-inclusive evaluation of the relationship between enrolment in primary research studies at University College London Hospitals NHS Trust and indices of deprivation, here we demonstrate a quantitative approach to evaluating equity in healthcare research and innovation. We surveyed the geographical locations, aggregated into Lower Layer Super Output Areas (LSOAs), of all England-resident UCLH patients registered as enrolled in primary clinical research studies. We compared the distributions of ten established indices of deprivation across enrolled and non-enrolled areas within Greater London and within a distance-matched subset across England. Bayesian Poisson regression models were used to examine the relation between deprivation and the volume of enrolment standardized by population density and local disease prevalence. A total of 54593 enrolments covered 4401 LSOAs in Greater London and 10150 in England, revealing wide geographical reach. The distributions of deprivation indices were similar between enrolled and non-enrolled areas, exhibiting median differences from 0.26% to 8.73%. Across Greater London, enrolled areas were significantly more deprived on most indices, including the Index of Multiple Deprivation; across England, a more balanced relationship to deprivation emerged. Regression analyses of enrolment volumes yielded weak biases, in favour of greater deprivation for most indices, with little modulation by local disease prevalence. Primary clinical research at UCLH has wide geographical reach. Areas with enrolled patients show similar distributions of established indices of deprivation to those without, both within Greater London, and across distance-matched areas of England. We illustrate a robust approach to quantifying an important aspect of equity in clinical research and provide a flexible set of tools for replicating it across other institutions.

Psoriasis is a systemic disease: A proposed approach for inflammation scale calculation

Background: Psoriasis is a skin disease affecting 2.3% of the Iraqi population and begins as a local disease with subsequent systemic comorbidities. Aim: The aim was to clarify whether psoriasis is a local or systemic disease. Materials and Methods: A total of 211 subjects with psoriasis and 163 sex- and age-matched controls were included in the study. Serum adiponectin, interleukin-6, interleukin-8, interleukin-10 (IL-10), interleukin-23 (IL-23), interleukin-18 (IL-18), paraoxonase, lipoprotein (a), osteopontin, chemerin, tumor necrosis factor-a (TNF-a), high-sensitivity C- reactive protein (hs-CRP), bilirubin, D-dimer, and creatinine were determined using commercial kits. Results: There was no significant difference in the mean age and BMI between psoriasis and the control groups. However, there was significantly higher mean serum values of IL-6, IL-8, IL-10, IL-23, lipoprotein (a), chemerin, TNF-a, hs-CRP, osteopontin, D-dimer, troponin I, creatinine, bilirubin, and platelet counts in psoriatic patients than in the controls. Meanwhile, the serum mean values of adiponectin, paraoxonase, and cortisol were significantly lower in psoriasis subjects than in the controls. The mathematical model was proposed to clarify whether psoriasis is a systemic or local disease. The application of the model to our data of biomarkers indicated the presence of systemic inflammation in psoriasis. Conclusion: The present study finding suggests that psoriasis is a systemic disease rather than a local skin disease. However, there is a need for the application of the model in a large-scale study.

The Impacts of Remote Learning in Secondary Education: Evidence from Brazil during the Pandemic

The goal of this paper is to document the pedagogic impacts of the remote learning strategy used by an state department of education in Brazil during the pandemic. We found that dropout risk increased by 365% under remote learning. While risk increased with local disease activity, most of it can be attributed directly to the absence of in-person classes: we estimate that dropout risk increased by no less than 247% across the State, even at the low end of the distribution of per capita Covid-19 cases. Average standardized test scores decreased by 0.32 standard deviation, as if students had only learned 27.5% of the in-person equivalent under remote learning. Learning losses did not systematically increase with local disease activity, attesting that they are in fact the outcome of remote learning, rather than a consequence of other health or economic impacts of Covid-19. Authorizing schools to partially reopen for in-person classes increased high-school students test scores by 20% relative to the control group.

POS0249 THE EFFECT OF NASAL STAPHYLOCOCCUS AUREUS COLONIZATION ON DISEASE ACTIVITY AND THE EFFECT OF ANTIBIOTIC TREATMENT IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS; A RETROSPECTIVE COHORT STUDY

Background:Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis, predominantly affecting small or medium vessels with few or no immune deposits. Ear, nose and throat (ENT) involvement in AAV is frequently present. AAV has a relapsing-remitting disease course. A factor that has been associated with induction of relapses is nasal Staphylococcus aureus (S. aureus) colonization. This alleged association between nasal colonization and induction of relapses has resulted in the use of antibiotics. However, the effect of antibiotic treatment on disease activity remains controversial. Some studies showed a beneficial effect of antibiotic treatment whereas other studies found no effect of antibiotic treatment on disease activity.Objectives:The aim of this study was to identify the role of nasal S. aureus colonization and the effect of systemic or local antibiotic treatment on disease activity in patients with AAV.Methods:Clinical, laboratory and histological data from all AAV patients with ENT involvement, diagnosed in two medical centers between 1981 and 2020, were retrospectively collected. Nasal S. aureus colonization was defined as at least one positive nasal swab during follow-up. Data on systemic (cotrimoxazole and azithromycin) and local antibiotics (mupirocin) use was collected. Disease activity was divided into systemic and local disease activity. Systemic disease activity consisted of history of relapses, relapse number per patient years and Birmingham vasculitis activity score version 3 (BVAS3) at last visit. Local disease activity included history of ENT relapses, development of saddle nose deformity or subglottic stenosis during follow-up.Results:Two-hundred and thirteen patients were included in the analysis. Median follow-up time was 8 (IQR 3 -17) years. S. aureus colonization was tested in 100 (46.9%) cases of which 44 patients tested positive. Only one patient developed a subglottic stenosis, and 13 patients developed a saddle nose deformity during follow-up. Systemic and local disease activity at baseline and at last visit were comparable between patients with and without and S. aureus colonization. Regression analysis showed no difference in relapse number per patient year between AAV patients colonized with S. aureus versus non-colonized patients (RR 2.03; 95%CI, 0.97 – 4.26, p=0.06). This also accounted for local ENT relapses (OR 0.134; 95%CI 0.06-1.47, p=0.14) and saddle nose deformity (OR 0.61; 95%CI 0.04-10.68, p=0.74). Twenty-eight (13.1%) S. aureus positive patients received antibiotics aimed at eradication of S. aureus. Twenty-two (10.3%) received cotrimoxazole, 2 (0.9%) received azithromycin and 17 (8.0%) patients received mupirocin ointment. No significant difference was found between the treated versus non-treated group with regard to systemic and local disease activity.Conclusion:Nasal S. aureus colonization does not influence systemic or local disease activity. Antibiotic eradication treatment did not modify disease activity in this study.Table 1.Effect of AB treatment on disease activity of 40 AAV patients with ENT involvement and S. aureus colonizationDisease activityAntibiotic treatmentP-valueYes (n=28)No (n=12)Systemic symptomsHistory of one or more relapses, n (%)18 (47.4%)4 (10.5%)0.635Relapse number per patient years, median (IQR) *0.11 (0-0.18)0.17 (0.02 – 0.26)0.346BVAS3 last visit, median (IQR)1 (0-4)1 (0-4)0.932Local symptomsHistory of one or more ENT relapses, n(%) *9 (33.3%)3 (11.1%)0.438Development of saddle nose deformity during follow-up, n (%) *4 (12.1%)0 (0%)0.367Values are median (interquartile range IQR) or n (%). BVAS3: Birmingham Vasculitis Activity Score version 3; ANCA: Anti-Neutrophilic Cytoplasmic Autoantibody; AAV: ANCA associated vasculitis; ENT: ear, nose and throat. * More than 10% missings in analysis. For an overview of the number of included patients per analysis, see supplementary table B.Disclosure of Interests:None declared

COVID-19: Learning from Past Funding Initiatives and their Dismissal in Southeast Asia

This article examines philanthropic funding of past efforts to control emerging infectious diseases in Southeast Asia and China. The recount, based on personal insights as a foundation professional and a review of both published and unpublished material, shows that American foundations and other like-minded donors identified the risks associated with zoonotic infections early on – including from the same coronavirus family that is causing the current COVID-19 pandemic – and were later followed by bilateral and multilateral donors investing greater resources. At the cusp of the 2000s, foundations played a leadership and catalyst role in advancing a transdisciplinary agenda to better understand and respond to new emerging threats and in building the necessary individual and institutional capacities for regional and local disease surveillance. For more than a decade, this concentration of resources and approaches was recognised as having contributed to better preparedness. Gradually, however, funding initiatives declined in value and intensity due to several internal and external factors. This article argues that COVID-19 arrives in the midst of an unfinished donor agenda and that it is important to reflect on why philanthropic foundations, and the development aid community more generally, found themselves unprepared for the pandemic in order to draw lessons for addressing today’s crisis – and future outbreaks of emerging infectious diseases.

Clinical Phase I/II Study: Local Disease Control and Survival in Locally Advanced Pancreatic Cancer Treated with Electrochemotherapy

Objective. To assess local disease control rates (LDCR) and overall survival (OS) in locally advanced pancreatic cancer (LAPC) treated with electrochemotherapy (ECT). Methods. Electrochemotherapy with bleomycin was performed in 25 LAPC patients who underwent baseline Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) and Position Emission Tomography (PET) scans before ECT and 1 and 6 months post ECT. LDCR were assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Choi criteria. Needle electrodes with fixed linear (N-30-4B) or fixed hexagonal configurations (N-30-HG or I-40-HG or H-30-ST) or variable geometry (VGD1230 or VGD1240) (IGEA S.p.A., Carpi, Italy) were used to apply electric pulses. Pain evaluation was performed pre-ECT, after 1 month and after 6 months with ECT. Overall survival estimates were calculated by means of a Kaplan-Meier analysis. Results. At 1 month after ECT, 76% of patients were in partial response (PR) and 20% in stable disease (SD). Six months after ECT, 44.0% patients were still in PR and 12.0% in SD. A LDCR of 56.0% was reached six months after ECT: 13 patients treated with fixed geometry had a LDCR of 46.1%, while for the 12 patients treated with variable geometry, the LDCR was 66.7%. The overall survival median value was 11.5 months: for patients treated with fixed geometry the OS was 6 months, while for patients treated with variable geometry it was 12 months. Electrochemotherapy was well-tolerated and abdominal pain was rapidly resolved. Conclusions. Electrochemotherapy obtained good results in terms of LDCR and OS in LAPC. Multiple needle insertion in a variable geometry configuration optimized by pre-treatment planning determined an increase in LDCR and OS compared to a fixed geometry configuration.