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Background Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilization, survival and function. Methods We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥2+ on dipstick testing, on kidney utilization, early graft function, graft failure and estimated glomerular filtration rate (eGFR). Results Eighteen percent (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% versus 82%; odds ratio 0.70, 95% confidence interval 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (hazard ratio 0.91, 95% confidence interval 0.74 to 1.11). There was also no association with delayed graft function, patient survival or eGFR at 1 or 3 years. Conclusions Our study suggests reluctance in the UK to utilize kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilization without negatively impacting transplant outcomes.

Differentiated thyroid cancer (DTC) affects thousands of lives worldwide every year. Typically, DTC is a treatable disease with a good prognosis. Yet, some patients are subjected to partial or total thyroidectomy and radioiodine therapy to prevent local disease recurrence and metastasis. Unfortunately, thyroidectomy and/or radioiodine therapy often worsen(s) the quality of life and might be unnecessary in indolent DTC cases. This clinical setting highlights the unmet need for a precise molecular diagnosis of DTC, which should dictate appropriate therapy. Here we propose a differential multi-omics model approach to distinguish normal gland from thyroid tumor and to indicate potential metastatic diseases in papillary thyroid cancer (PTC), a sub-class of DTC. Based on PTC patient samples, our data suggest that elevated nuclear and mitochondrial DNA mutational burden, intratumor heterogeneity, shortened telomere length, and altered metabolic profile reflect the potential for metastatic disease. Specifically, normal and tumor thyroid tissues from these patients had a distinct yet well-defined metabolic profile with high levels of anabolic metabolites and/or other metabolites associated with the energy maintenance of tumor cells. Altogether, this work indicates that a differential and integrated multi-omics approach might improve DTC management, perhaps preventing unnecessary thyroid gland removal and/or radioiodine therapy. Well-designed, prospective translational clinical trials will ultimately show the value of this targeted molecular approach.TRANSLATIONAL RELEVANCEIn this article, we propose a new integrated metabolic, genomic, and cytopathologic methods to diagnose Differentiated Thyroid Cancer when the conventional methods failed. Moreover, we suggest metabolic and genomic markers to help predict high-risk Papillary Thyroid Cancer. Both might be important tools to avoid unnecessary surgery and/or radioiodine therapy that can worsen the quality of life of the patients more than living with an indolent Thyroid nodule.Graphical Abstract

There are concerns that simultaneous pancreas-kidney (SPK) transplants from donation after circulatory death (DCD) donors have a higher risk of graft failure than those from donation after brain death (DBD) donors. A UK registry analysis of SPK transplants between 2005 and 2018 was performed. Pancreas survivals of those receiving organs from DCD or DBD donors were compared. Multivariable analyses were used to adjust for baseline differences between the two groups and to identify factors associated with pancreas graft loss. A total of 2228 SPK transplants were implanted; 403 (18.1%) were from DCD donors. DCD donors were generally younger, slimmer, less likely to have stroke as a cause of death, with lower terminal creatinines and shorter pancreas cold ischemic times than DBD donors. Median (IQR) follow-up was 4.2 (1.6-8.1) years. On univariable analysis, there were no statistically significant differences in 5-year death-censored pancreas graft survival between the two donor types (79.5% versus 80.4%; p = .86). Multivariable analysis showed no statistically significant differences in 5-year pancreas graft loss between transplants from DCD (n = 343) and DBD (n = 1492) donors (hazard ratio 1.26, 95% CI 0.76-1.23; p = .12). The findings from this study support the increased use of SPK transplants from DCD donors.

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF 7 days, 576 (31·2%) had DGF 7-14 days, and 345 (18·7%) had DGF14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF14 days is a novel early biomarker for significantly worse longer-term outcomes.

Maria Ibrahim, a kidney doctor in training, explains the vital role of statistics and statistical analysis in transplant medicine: from matching donor organs to patients, to helping doctors and patients discuss the risks and benefits of a life-changing operation

Macroautophagy (hereafter autophagy) degrades and recycles intracellular components to sustain metabolism and survival during starvation. Host autophagy promotes tumor growth by providing essential tumor nutrients. Autophagy also regulates immune cell homeostasis and function and suppresses inflammation. Although host autophagy does not promote a T-cell antitumor immune response in tumors with low tumor mutational burden (TMB), whether this was the case in tumors with high TMB was not known. Here we show that autophagy, especially in the liver, promotes tumor immune tolerance by enabling regulatory T-cell function and limiting stimulator of interferon genes, T-cell response and interferon-γ, which enables growth of high-TMB tumors. We have designated this as hepatic autophagy immune tolerance. Autophagy thereby promotes tumor growth through both metabolic and immune mechanisms depending on mutational load and autophagy inhibition is an effective means to promote an antitumor T-cell response in high-TMB tumors. White and colleagues identify a role for host autophagy in restraining T-cell-dependent immune responses, specifically against tumors with high mutational burden.

The two erythropoietin (EPO) receptor forms mediate different cellular responses to erythropoietin. While hematopoiesis is mediated via the homodimeric EPO receptor (EPOR), tissue protection is conferred via a heteromer composed of EPOR and CD131. In the skeletal system, EPO stimulates osteoclast precursors and induces bone loss. However, the underlying molecular mechanisms are still elusive. Here, we evaluated the role of the heteromeric complex in bone metabolism in vivo and in vitro by using Cibinetide (CIB), a non-erythropoietic EPO analogue that exclusively binds the heteromeric receptor. CIB is administered either alone or in combination with EPO. One month of CIB treatment significantly increased the cortical (~5.8%) and trabecular (~5.2%) bone mineral density in C57BL/6J WT female mice. Similarly, administration of CIB for five consecutive days to female mice that concurrently received EPO on days one and four, reduced the number of osteoclast progenitors, defined by flow cytometry as Lin−CD11b−Ly6Chi CD115+, by 42.8% compared to treatment with EPO alone. In addition, CIB alone or in combination with EPO inhibited osteoclastogenesis in vitro. Our findings introduce CIB either as a stand-alone treatment, or in combination with EPO, as an appealing candidate for the treatment of the bone loss that accompanies EPO treatment.

Donor-transmitted cancer (DTC) has major implications for the affected patient as well as other recipients of organs from the same donor. Unlike heterotopic transplant recipients, there may be limited treatment options for orthotopic transplant recipients with DTC. We systematically reviewed the evidence on DTC in orthotopic solid organ transplant recipients (SOTRs). We searched MEDLINE, EMBASE, PubMed, Scopus, and Web of Science in January 2020. We included cases where the outcome was reported and excluded donor-derived cancers. We assessed study quality using published checklists. Our domains of interest were presentation, time to diagnosis, cancer extent, management, and survival. There were 73 DTC cases in liver (n = 51), heart (n = 10), lung (n = 10) and multi-organ (n = 2) recipients from 58 publications. Study quality was variable. Median time to diagnosis was 8 months; 42% were widespread at diagnosis. Of 13 cases that underwent re-transplantation, three tumours recurred. Mortality was 75%; median survival 7 months. Survival was worst in transmitted melanoma and central nervous system tumours. The prognosis of DTC in orthotopic SOTRs is poor. Although re-transplantation offers the best chance of cure, some tumours still recur. Publication bias and clinical heterogeneity limit the available evidence. From our findings, we suggest refinements to clinical practice.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020165001, Prospero Registration Number: CRD42020165001.

This article briefly discusses the topic of digitization in the banking industry, consumer behavior when purchasing financial services and the importance of digitization for the delivery of customer services. In this research work the authors focused on the theories of consumer behavior, digitization as a financial innovation in order to answer the following problem: Does digitization satisfy the customers of financial institutions and would it replace one day the employees in their work and the services rendered? In order to collect and analyze the data, a questionnaire was sent to the clients of several Lebanese commercial banks, a quantitative methodology is used to process and analyze the responses through the IBM SPSS version 24 software. Finally, from the results, the researchers can conclude that customers are encouraged to use digitization especially in times of crisis or when there is no access to financial institutions, as is currently the case in lockdowns due to the pandemic such as Covid-19 but still prefer human contact in ordinary moments for greater interaction with the customer advisor.

Erythropoietin (EPO) is a key regulator of erythropoiesis. However, EPO receptors (EPO-Rs) are also expressed on non-erythroid cell types, including myeloid and bone cells. Immune cells also participate in bone homeostasis. B cells produce receptor activator of nuclear factor kappa-Β ligand (RANKL) and osteoprotegerin (OPG), two pivotal regulators of bone metabolism. Here we explored the ability of B cells to transdifferentiate into functional osteoclasts and examined the role of EPO in this process in a murine model. Methods: We have combined specifically-designed experimental mouse models and in vitro based osteoclastogenesis assays, as well as PCR analysis of gene expression. Results: (i) EPO treatment in vivo increased RANKL expression in bone marrow (BM) B cells, suggesting a paracrine effect on osteoclastogenesis; (ii) B cell-derived osteoclastogenesis occured in vivo and in vitro, as demonstrated by B cell lineage tracing in murine models; (iii) B-cell-derived osteoclastogenesis in vitro was restricted to Pro-B cells expressing CD115/CSF1-R and is enhanced by EPO; (iv) EPO treatment increased the number of B-cell-derived preosteoclasts (β3+CD115+), suggesting a physiological rationale for B cell derived osteoclastogenesis; (v) finally, mice with conditional EPO-R knockdown in the B cell lineage (cKD) displayed a higher cortical and trabecular bone mass. Moreover, cKD displayed attenuated EPO-driven trabecular bone loss, an effect that was observed despite the fact that cKD mice attained higher hemoglobin levels following EPO treatment. Conclusions: Our work highlights B cells as an important extra-erythropoietic target of EPO-EPO-R signaling and suggests their involvement in the regulation of bone homeostasis and possibly in EPO-stimulated erythropoietic response. Importantly, we present here for the first time, histological evidence for B cell-derived osteoclastogenesis in vivo.

BACKGROUND AND OBJECTIVES: Kidneys from elderly deceased donors are often discarded after procurement if the expected outcomes from single kidney transplantation are considered unacceptable. An alternative is to consider them for dual kidney transplantation. We aimed to examine the utilization of kidneys from donors aged ≥60 years in the United Kingdom and compare clinical outcomes of dual versus single kidney transplant recipients.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the United Kingdom Transplant Registry from 2005 to 2017 were analyzed. We examined utilization rates of kidneys retrieved from deceased donors aged ≥60 years, and 5-year patient and death-censored graft survival of recipients of dual and single kidney transplants. Secondary outcomes included eGFR. Multivariable analyses and propensity score analysis were used to correct for differences between the groups.RESULTS: During the study period, 7841 kidneys were procured from deceased donors aged ≥60 years, of which 1338 (17%) were discarded; 356 dual and 5032 single kidneys were transplanted. Donors of dual transplants were older (median, 73 versus 66 years; PCONCLUSIONS: Recipients of kidneys from donors aged ≥60 years have similar 5-year graft survival and better graft function at 12 months with dual compared with single deceased donor kidney transplants.

Background and aims: Erythropoietin (EPO) is a pleiotropic cytokine, which besides its classical role in driving erythropoiesis, displays tissue protective and immunomodulatory activities. EPO also induces bone loss. While hematopoiesis is mediated via the homodimeric EPO receptor (EPOR), tissue protection is conferred via a heteromer composed of EPOR and CD131. Cibinetide (CIB), a non-erythropoietic analogue of EPO, specifically binds to the heteromeric receptor and confers tissue protection. Our published findings that EPO stimulates osteoclast precursors and entrains a decrease in bone density, raise questions regarding the underlying molecular mechanisms. Here, we evaluated the role of the heteromeric complex in bone metabolism using CIB alone and in combination with EPO in vivo and in vitro. Results: CIB injections to 12-week-old female mice (120 µg/kg thrice weekly for 4 weeks) resulted in a significant increase in tissue mineral density in cortical bone by 5.8% (1416.4±39.27 vs 1338.74±16.56 mgHA/cm 3) and in trabecular bone by 5.2% (1056.52±30.94 vs 1004.13±16.91 mg HA/cm 3) (n=10 in each group, p< 0.05 versus saline-injected controls), as measured by microCT (Figure 1A). To evaluate the capacity of CIB to attenuate EPO mediated bone loss, we administered CIB (300 µg/kg) for 5 consecutive days, to 13-week-old female mice that also received 2 injections of 120U EPO on days 1 and 4. Flow cytometry analysis revealed a 1.8-fold reduction in the number of osteoclast progenitors, defined as Lin -CD11b −CD115 +Ly6C hi, in the EPO + CIB injected mice, compared to the mice injected with EPO alone (n=7 in each group, p< 0.05). Hemoglobin levels and TER119 + bone marrow (BM) erythroid progenitors were similar in both groups. In vitro, EPO administration to BM-derived macrophages (BMDM) enhanced osteoclastogenesis, whereas CIB had an opposite, dose-dependent effect. Combining CIB with EPO inhibited osteoclastogenesis in BMDM, suggesting that CIB overrides the pro-osteoclastogenic effect of EPO (Figure 1B). Conclusions: Our findings highlight the increasing complexity of EPOR signaling in bone and pave the way for clinical translation through potential combination therapy of EPO and CIB in anemic and in cancer patients. Adjunctive administration of CIB may prevent or attenuate bone loss while preserving the erythropoietic actions of EPO. This study was supported by a grant from the Dotan Hemato-oncology Fund, the Cancer Biology Research Center, Tel Aviv University to DN and YG. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction Faecal Immunohistochemistry Testing (FIT) is recommended as an adjunct to guide referrals from Primary Care for individuals without rectal bleeding, who do not meet the suspected cancer pathway referral guidelines. It has largely replaced Faecal Occult Blood Testing. Aims To assess the specificity of FIT. To understand the characteristics of FIT negative cancer patients and whether they have predominantly right sided cancers. Evaluating the efficacy of FIT and Iron deficiency anaemia in combination to capture patients with colorectal cancers. Methods A study of 1000 symptomatic patients, undergoing FIT by Clinicians during the ‘Digital rectal examination’. Inclusion criteria; all patients referred via our cancer referral pathway. FIT positivity was set at 10 μg g of faeces. Results There were 7 FIT negative cancers in this cohort; 1 was a lymphoma and the other 6 were caecal adenocarcinomas. 5 were anaemic. The positive predictive value of IDA was 34% compared with ‘other symptoms’; 18%. The negative predictive value of FIT was 99.05% in this cohort. Specificity for FIT was 86.9% (CI 96%). Conclusion Two separate referral pathways for IDA and FIT positive tests, would have captured all patients except 2; the lymphoma and 1 advanced caecal adenocarcinoma. FIT is an excellent triage tool prior to colonoscopy however capturing right sided disease remains a weak point. Multivariate analysis of patients in addition to IDA and FIT should improve capture of this subgroup.

In transplant, meaningful international comparisons in organ utilization are needed. This collaborative study between the United Kingdom (UK) and the United States (US) aimed to develop a kidney utilization metric allowing for legitimate intercountry comparisons. Data from the UK and US transplant registries, including all deceased donor kidneys recovered from 2006 to 2017, were analyzed. To identify a potentially comparable kidney utilization rate (UR), several denominators were assessed. We discovered that the proportion of transplanted kidneys from elderly donors in the UK (10.7%) was 18 times greater than that in the US (0.6%). Conversely, en bloc pediatric kidney transplant was more common in the US. Donation after circulatory death utilization has risen in both countries but is twice as prevalent in the UK (39% of transplants) vs the US (20%). In addition, US and UK URs are not directly comparable due to fundamental system differences. However, using a suite of URs revealed practice areas likely to yield the most benefit if improved, such as efforts to increase kidney offer acceptance in the US and to reduce postacceptance discard in the UK. Methods used in this study, including novel intracountry risk-adjusted UR trend logistic regression analyses, can be translated to other international transplant registries in pursuit of further global learning opportunities.

Background and aims: Immunotherapy with anti-CD20-specific antibodies (e.g. rituximab), has become the standard of care for B cell lymphoproliferative disorders and many autoimmune diseases. Despite previously demonstrated role for B cells in bone metabolism, the effect of anti-CD20-mediated B cell depletion on bone mass in human patients has not been thoroughly studied. For example, in rheumatological patients the effect of rituximab on bone mass yielded conflicting results, while in lymphoma patients it has not yet been described. Here, we describe the effect of treatment with anti-CD20-specific antibodies on bone mass in a cohort of patients with follicular lymphoma and propose a plausible mechanism using murine model. Methods: To assess the effect of rituximab on bone mass in lymphoma patients, we retrospectively studied the bone mass in patients with follicular lymphoma (FL) during the maintenance phase of chemoimunotherapy, i.e. when rituximab is administered as monotherapy. FL patients on no maintenance (historical controls) or patients with marginal zone lymphoma were include as a control group. Cross-sectional X-ray imaging (CT/PET-CT), performed at the completion of the induction phase and 6-12 months thereafter, were used to serially assess bone density. Wild-type female C57BL/6J mice and mouse anti-mouse CD20 antibody (Genentech) were used for the animal experimental system. Murine bone structure was assessed by the microCT method. Immunophenotyping of the bone marrow (BM), spleen and peripheral blood cells was performed. ELISA and "real-time" quantitative PCR were used to measure the levels of key mediators of bone remodeling, e.g. RANKL, OPG and TNFα. Standard osteoclastogenic assay was used to assesses the osteoclastogenic potential of BM cells. Results: Rituximab treatment prevented the decline in bone mass observed in patients who did not receive active maintenance therapy, both in the lumbar spine (-2.6% vs -8%) and femoral head (-0.5% vs -5.1%) (n=12 patients in each group, p Conclusions: While many lymphoma patients may suffer from bone loss due to advanced age and glucocorticoid administration, our data suggest additional favorable effect of anti-CD20 treatment in bone preservation. Importantly, our murine studies indicate that B cell depletion has a direct effect on bone remodeling, primarily by reducing the osteoclastogenic signals, thus potentially diminishing bone resorption. This novel unrecognized effect should be taken into consideration when maintenance treatment is considered. MM and DN contributed equally to this work. Figure Disclosures No relevant conflicts of interest to declare.

Background Autologous stem cell transplantation (ASCT) and novel therapies have improved the prognosis for patients with multiple myeloma (MM). For those who undergo ASCT while on dialysis, a similar survival compared with the overall MM population has been reported. Therefore, for patients achieving remission following ASCT, kidney transplantation is an attractive option, offering an improved quality of life and significant economic advantage. Method This case series investigates the outcome of five patients who underwent an ASCT for MM with subsequent kidney transplantation between 2006 and 2012. Results Four patients presented with end-stage renal disease (ESRD) and one progressed to ESRD shortly after diagnosis. Induction chemotherapy regimens with novel agents including thalidomide and bortezomib were utilized. Following attainment of very good partial remission or complete remission, high-dose melphalan ASCTs were performed after a median of 10 months. Kidney transplantation (living donor n = 3, deceased donor n = 2) with tacrolimus-based immunosuppression regimens was completed at a median of 27 months after ASCT. Patients 1 and 3 experienced relapse of myeloma at 6 and 16 months after kidney transplantation. Patients 2, 4 and 5 remain alive at 55 months (median) after kidney transplantation with no evidence of relapse. Conclusion Forty percent of our cohort experienced a relapse in MM within 2 years of kidney transplantation. Death-censored graft survival and patient survival were 80% at 4 years. Our study adds to the growing literature supporting kidney transplantation following successful ASCT for MM and is useful when counselling patients regarding renal and haematological outcomes.

Improved biomarkers are needed for prostate cancer, as the current gold standards have poor predictive value. Tests for circulating prostate-specific antigen (PSA) levels are susceptible to various noncancer comorbidities in the prostate and do not provide prognostic information, whereas physical biopsies are invasive, must be performed repeatedly, and only sample a fraction of the prostate. Injectable biosensors may provide a new paradigm for prostate cancer biomarkers by querying the status of the prostate via a noninvasive readout. Proteases are an important class of enzymes that play a role in every hallmark of cancer; their activities could be leveraged as biomarkers. We identified a panel of prostate cancer proteases through transcriptomic and proteomic analysis. Using this panel, we developed a nanosensor library that measures protease activity in vitro using fluorescence and in vivo using urinary readouts. In xenograft mouse models, we applied this nanosensor library to classify aggressive prostate cancer and to select predictive substrates. Last, we coformulated a subset of nanosensors with integrin-targeting ligands to increase sensitivity. These targeted nanosensors robustly classified prostate cancer aggressiveness and outperformed PSA. This activity-based nanosensor library could be useful throughout clinical management of prostate cancer, with both diagnostic and prognostic utility.

Brown tumours affecting the cervical spine are a rare but recognised complication of renal failure-related secondary hyperparathyroidism. We present a case of a 26 year-old female with radiculopathy who was managed successfully with 360° cervical spine fixation and parathyroidectomy.

Background and aims: Erythropoietin (EPO) is the key regulator of red blood cell production, commonly used in clinical practice to treat certain forms of anemia. Our studies and those of others have demonstrated that EPO administration induces substantial trabecular bone loss. We proposed that EPO-induced bone loss is partially mediated by subsets of bone marrow (BM) B cells that express EPO-R. Mechanistically, EPO upregulates the surface expression of RANKL by BM B cells and augments B cell-derived osteoclastogenesis in vitro. We showed that the latter is likely mediated by pro-B cells expressing the MCS-F receptor (CD115) and capable of transdifferentiation to osteoclasts (Abstract # 1007, EHA 2017). Here we address the role of B cell-specific EPO-R in EPO-induced bone loss (i.e. at supra-physiological EPO levels). Moreover, we demonstrate, for the first time, the occurrence of B cell-derived osteoclastogenesis in vivo, a finding of critical importance in the field of osteohematology. Methods: In order to trace the B cell lineage from its earliest precursors, we used the MB1-Cre mouse line combined with either the R26R-EYFP or the EPO-Rfl/fl mice for lineage tracing and B cell-specific EPO-R knockdown, respectively. Sequential fluorescence and light microscopy were used for the demonstration of B cell-derived osteoclastogenesis in vivo. Human recombinant EPO was administered in vivo at a dose of 180IU thrice weekly for two weeks. Immunophenotyping of BM B cell populations was assessed by multi-color flow cytometry. Results: Using female MB1-Cre; EPO-Rfl/fl (cKD) mice, we found that B cell-specific EPO-R knockdown attenuated the profound EPO-induced trabecular bone loss in the proximal part of the femoral distal metaphysis (proximal BV/TV 0.034±0.012% vs 0.007±0.003% in the cKD vs control mice, p Using the MB1-Cre;R26R-EYFP murine model for B cell lineage tracing, we could demonstrate that some of the TRAP+/ β3 integrin+ bone lining cells were also positive for EYFP (Figure 2). This demonstrates the B cell origin of some of the osteoclasts in vivo. Conclusions: Our work highlights B cells as an important extra-erythropoietic target of EPO-EPO-R signaling that regulates bone homeostasis and might also indirectly affect EPO-stimulated erythropoietic response. The relevance and the mechanisms of the latter phenomenon merits further investigation. Importantly, we present here, for the first time, histological evidence for B cell-derived osteoclastogenesis in vivo, thus opening novel research avenues. DN and YG Equal contribution Funded by the German Israel Foundation, Grant # 01021017 to YG, DN, MR and BW and by the Israel Science Foundation (ISF) Grant No. 343/17 to DN. Disclosures Mittelman: Novartis: Honoraria, Research Funding, Speakers Bureau.

BACKGROUND: cerebrovascular disease (CVD) during childhood is a rare condition; its short, medium and long-term characteristics deserve further investigation. The application of behavioral techniques may improve clinical characterization, thus rendering more efficient therapeutic planning and control. AIM: to describe the audiological manifestations in a child with CVD in two distinct moments of clinical follow-up. METHOD: the child, with a confirmed diagnosis of a single and unilateral episode of CVD, presenting satisfactory cognition and language skills, was submitted to a battery of conventional and auditory processing tests, which included a simplified evaluation as well as monotic, dichotic, and temporal processing tests. The obtained data was paired with those of a normal right-handed child, of the same gender, age and socio-cultural level. RESULTS: results indicate impairments in auditory memory as well as in selective attention during binaural separation and integration tasks for verbal and non-verbal stimuli. CONCLUSION: clinical development, although favorable, was below the average expected for the same age when compared to the control. The prospective evaluation of a child with DCV permitted the characterization of the auditory behavior, the definition of its parameters as well as the development of the audiological characteristics.

Barotrauma is a physical injury that results from ambient pressure changes during flying, diving or hyperbaric oxygen therapy. The aim of this study was to assess the prevalence of oro-facial barotrauma among a sample of scuba divers in Jeddah, Saudi Arabia.Data for the study were collected through a self-reported questionnaire that was distributed to 166 divers. The questionnaire was divided into two parts, in which the first part contained demographic data and the second part consists of multiple choice questions and a few open-ended questions discussing the different signs and symptoms of orofacial barotraumas.One-hundred-and-sixty-three divers responded. The most frequent symptoms during diving were dry mouth (51.9%), followed by clenching (32.5%) and temporomandibular joint (TMJ) pain (19.5%), while the most frequent symptoms after diving were dry mouth (22.7%) followed by clenching and facial pain (16.9%).Clenching and dry mouth were common findings but are temporary in nature and do not warrant any dental intervention. TMJ and facial pain were also reported but were temporary. The use of commercial mouthpieces during diving may be related to more symptoms when compared with customized types.

TEMA: na infância a doença cerebrovascular (DCV) constitui condição rara em que a evolução a curto, médio e longo prazo tem merecido esclarecimentos. Neste sentido, a aplicação de técnicas comportamentais pode possibilitar melhor caracterização clínica, visando o planejamento e controle terapêutico eficientes. OBJETIVO: descrever em uma criança com DCV as manifestações audiológicas em dois momentos distintos da evolução clínica. MÉTODO: a criança, com diagnóstico comprovado de episódio único e unilateral de DCV, apresentando habilidades de linguagem e cognição satisfatórias, foi submetida a conjunto de testes convencionais e de processamento auditivo, incluindo a avaliação simplificada e as categorias de testes monóticos, dicóticos e de processamento temporal. Os dados obtidos foram pareados com criança normal destra, de mesmo sexo, idade e nível sócio-cultural. RESULTADOS: foi constatado comprometimento nas habilidades de memória auditiva e atenção seletiva em tarefas de integração e separação binaural para estímulos verbais e não-verbais. CONCLUSÃO: a evolução, embora favorável, se mostrou abaixo do esperado para a idade, quando comparado com seu par. A avaliação prospectiva da criança acometida por DCV possibilitou caracterizar o comportamento auditivo, definir seus parâmetros e a evolução do quadro audiológico. BACKGROUND: cerebrovascular disease (CVD) during childhood is a rare condition; its short, medium and long-term characteristics deserve further investigation. The application of behavioral techniques may improve clinical characterization, thus rendering more efficient therapeutic planning and control. AIM: to describe the audiological manifestations in a child with CVD in two distinct moments of clinical follow-up. METHOD: the child, with a confirmed diagnosis of a single and unilateral episode of CVD, presenting satisfactory cognition and language skills, was submitted to a battery of conventional and auditory processing tests, which included a simplified evaluation as well as monotic, dichotic, and temporal processing tests. The obtained data was paired with those of a normal right-handed child, of the same gender, age and socio-cultural level. RESULTS: results indicate impairments in auditory memory as well as in selective attention during binaural separation and integration tasks for verbal and non-verbal stimuli. CONCLUSION: clinical development, although favorable, was below the average expected for the same age when compared to the control. The prospective evaluation of a child with DCV permitted the characterization of the auditory behavior, the definition of its parameters as well as the development of the audiological characteristics.

Introduction Syncope accounts for up to 6% of admissions annually. 1 In the over 65 age group, 23% will have an episode of syncope over a 10 year period with a 30% recurrence rate over two years. 2 Up to 60% of patients presenting to A&E with syncope are admitted, however only 50% will have syncope specific investigations and only 50% will receive a final diagnosis. 2 Financial restraints and bed pressures in the UK have increased the need for effective management of syncope. We aimed to assess the management of syncope on the acute medical take. Method An audit was devised to evaluate the management of patients referred to the medical team over a 50-day period. The medical notes of patients meeting the inclusion criteria were sourced, retrospectively analysed and compared with current NICE guidelines. The project was extended to assess whether development of a pathway with same day syncope services would impact hospital bed stays. Results Of 190 patients, 77 randomly sourced notes were analysed; 35 patients were identified as having had a syncopal event. 63% were female and the average age was 85 years (67–98). 11% of patients had a full history recorded and only 3% had a complete initial assessment including history, ECG and postural blood pressure recording. 51% of patients had CT brain imaging of which 74% were not indicated. 34% of patients had 24 h ECG monitoring of which none were indicated and no significant result identified. 29% of patients did not have an inpatient echocardiogram and 34% of patients did not have an inpatient cardiology review despite indications. 37% of patients were discharged with no diagnosis. 29% of all patients had previously been admitted with a similar presentation. 46% of patients admitted could have been discharged on the same day had rapid ECHO, cardiology review and injectable loop recorder services been available. This accounts for 160 days of inappropriate hospital stay and with extrapolation, 1168 days in one year. Thus, 3.2 extra beds could be made available at our DGH. Conclusion The initial assessment of syncope is inadequate and investigations are inappropriately requested or not considered. A proportion of patients do not receive a diagnosis and are unnecessarily admitted. A considerable number of bed days could be prevented with a clear syncope pathway including same day ECHO, cardiology review and injectable loop recorder service, thus relieving pressures on acute medical beds and accident and emergency services. This problem is not unique to our trust and represents a pattern currently prevalent across the UK and further afield. References Shen WK, Decker WW, Smars PA, et al . Syncope Evaluation in the Emergency Department Study (SEEDS): a multidisciplinary approach to syncope management. Circulation 2004;110(24):3636-45 Lipsitz L, Wei JY, Rowe JW. Syncope in an elderly, institutionalised population: prevalence, incidence, and associated risk. Q J Med. 1985;55(216):45-54

cerebrovascular disease (CVD) during childhood is a rare condition; its short, medium and long-term characteristics deserve further investigation. The application of behavioral techniques may improve clinical characterization, thus rendering more efficient therapeutic planning and control.to describe the audiological manifestations in a child with CVD in two distinct moments of clinical follow-up.the child, with a confirmed diagnosis of a single and unilateral episode of CVD, presenting satisfactory cognition and language skills, was submitted to a battery of conventional and auditory processing tests, which included a simplified evaluation as well as monotic, dichotic, and temporal processing tests. The obtained data was paired with those of a normal right-handed child, of the same gender, age and socio-cultural level.results indicate impairments in auditory memory as well as in selective attention during binaural separation and integration tasks for verbal and non-verbal stimuli.clinical development, although favorable, was below the average expected for the same age when compared to the control. The prospective evaluation of a child with DCV permitted the characterization of the auditory behavior, the definition of its parameters as well as the development of the audiological characteristics.