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Objective To evaluate the quality of the evidence on the incidence of sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in athletes and military members and estimate the annual incidence of SCA and SCD. Data Sources We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, BIOSIS, Scopus, SPORTDiscus, PEDro, and ClinicalTrials.gov from inception to dates between February 21 and July 29, 2019. Study Selection Studies in which the incidence of SCA, SCD, or both in athletes or military members aged Data Extraction Risk of bias (ROB) was assessed using a validated, customized tool for prevalence studies. Twelve had a low ROB, while the remaining 28 had a moderate or high ROB. Data were extracted for narrative review and meta-analysis. Data Synthesis Random-effects meta-analysis was performed in studies judged to have a low ROB in 2 categories: (1) 5 studies of regional- or national-level data, including athletes at all levels and both sexes, demonstrated 130 SCD events with a total of 11 272 560 athlete-years, showing a cumulative incidence rate of 0.98 (95% CI = 0.62, 1.53) per 100 000 athlete-years and high heterogeneity (I2 = 78%) and (2) 3 studies of competitive athletes aged 14 to 25 years were combined for a total of 183 events and 17 798 758 athlete-years, showing an incidence rate of 1.91 (95% CI = 0.71, 5.14) per 100 000 athlete-years and high heterogeneity (I2 = 97%). The remaining low-ROB studies involved military members and were not synthesized. Conclusions The worldwide incidence of SCD is rare. Low-ROB studies indicated the incidence was PROSPERO Registration CRD42019125560

Objectives The aim of this study was to conduct an economic evaluation for the treatment of subjective tinnitus using different modalities of cognitive behavioral therapy (CBT) in Australia. Design A decision tree model was used to conduct a cost-utility analysis for CBT to determine the cost effectiveness for tinnitus treatments, in terms of cost per responder and cost per quality-adjusted life-year (QALY), from a health system perspective using a 2-year time horizon. Meta-analysis was used to differentiate the levels of effectiveness between three delivery methods for CBT: individual face-to-face care (fCBT), group sessions (gCBT), and a supported internet program (iCBT). One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) explored the uncertainty surrounding model inputs and outcomes. Results were presented as incremental cost-effectiveness ratios compared with no treatment, and as net monetary benefit at a $50,000 willingness-to-pay threshold. Results Compared with no treatment, the incremental cost per responder was $700 for gCBT, $871 for iCBT, and $1380 for fCBT. The base case incremental cost-effectiveness ratio was $35,363 per QALY for fCBT, $17,935 per QALY for gCBT, and $22,321 per QALY for iCBT compared with no treatment, although there was substantial uncertainty around the QALY gain for responders. Net monetary benefit was $356 (fCBT), $555 (gCBT), and $487 (iCBT), indicating the treatments were cost effective compared with no treatment. One-way sensitivity analysis revealed the results were most sensitive to the probability of a positive response to treatment and treatment length. The PSA found the probability of being cost effective compared with no treatment for gCBT was 99.8%, iCBT 98.4%, and fCBT 71.5% at a willingness-to-pay of $50,000 per QALY, although QALY gain remained at a fixed value in the PSA. Conclusions CBT for tinnitus was likely to be cost effective compared with no treatment regardless of treatment modality, assuming they are not mutually exclusive. Of the interventions, gCBT was the lowest cost per responder and lowest cost per QALY. Internet CBT obtained comparable economic outcomes due to similar treatment effectiveness and cost. Group CBT and iCBT warrant greater adoption in clinical practice for the treatment of subjective tinnitus. Further research on preference-based utility measures for varying levels of tinnitus severity and the durability of treatment effect is required to enhance the quality of economic evaluation in this field.

Objective To determine the effect of electrocardiogram (ECG) screening on the prevention of sudden cardiac arrest and death in young athletes and military members. Data Sources MEDLINE, Embase, CENTRAL, Web of Science, BIOSIS, Scopus, SPORTDiscus, PEDro, and ClinicalTrials.gov were searched from inception to dates between February 21 and July 29, 2019. Study Selection Randomized and nonrandomized controlled trials in which preparticipation examination including ECG was the primary intervention used to screen athletes or military members aged ≤40 years. Acceptable control groups were those receiving no screening, usual care, or preparticipation examination without ECG. Three published studies and 1 conference abstract were identified for inclusion. Data Extraction In all 4 studies, risk of bias was assessed using the Cochrane risk-of-bias tool and was found to be generally high. Two studies had data extracted for random effects meta-analysis, and the remaining study and conference abstract were included in the narrative review. The overall quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Data Synthesis We included 4 nonrandomized studies (11 689 172 participants), of which all had a high risk of bias. Pooled data from 2 studies (n = 3 869 274; very low-quality evidence) showed an inconclusive 42% relative decrease in risk of sudden cardiac death (relative risk = 0.58; 95% CI = 0.23, 1.45), equating to an absolute risk reduction of 0.0016%. The findings were consistent with a potential 77% relative decreased risk to a 45% relative increased risk in participants screened using ECG. Heterogeneity was found to be high, as measured using I2 statistic (71%). Data from the remaining study and abstract were similarly inconclusive. Conclusions Existing evidence for the effect of ECG screening is inconclusive and of very low quality. In our meta-analysis, we observed that screening ECG may result in a considerable benefit or harm to participants. Higher-quality studies are needed to reduce this uncertainty.

Objective To report the epidemiology of Women's National Professional Fast-Pitch (NPF) softball injuries during the 2017 season. The secondary objective was to evaluate risk factors for pitching injuries. Design/setting Prospective injury data were collected from the primary clinical care of 6 professional softball teams. Participants The NPF study population consisted of 153 players. Independent variables Data collection included the following: number of practices each week, diagnosis of the injury, game or practice injury, position played when sustaining the injury, treatment for the injury, number of missed practices and/or games as a result of the injury, and total days until return to play. Main outcome measures Injury rate (IR) overall, IR in position players, and IR in pitchers. Secondary outcomes included risk assessment for injury in pitchers; descriptive statistics on the injuries recorded in all players. Results Pitchers reported both upper extremity and lower extremity injuries equally, whereas positional players reported more lower extremity injuries. Pitchers were also most likely to be injured during a practice than a game. Overall, there were 3.26 reported game injuries per 1000 athlete exposures (AE) and 4.79 practice injuries per 1000 AE. Pitchers specifically had 1.88 reported game injuries per 1000 AE and 5.66 practice injuries per 1000 AE. Conclusions In contrast to previous data, our study showed an increased IR in practice as compared to games in both position players and pitchers. Significant injuries were relatively rare, and most injuries seemed minor, usually with less than 7 days missed, suggesting a relative safety associated with this sport.

Objective: We report a case of Streptococcus intermedius splenic abscess and review of relevant literature. Design: A retrospective report and review of the English literature concerning splenic abscess cause by Streptococcus intermedius via PubMed was conducted. Results: An 8-year-old boy, who presented with fever, abdominal pain, and vomiting, was found to have a large splenic fluid collection. He underwent ultrasound-guided aspiration of the abscess, and the culture grew Streptococcus intermedius. His symptoms and radiographic findings resolved after completion of antibiotics. Isolated splenic abscesses are rare, and this represents the second case in the literature of splenic abscess caused by Streptococcus intermedius. Conclusion: Streptococcus intermedius is a rare cause of splenic abscess. Isolated splenic abscess requires drainage for both diagnostic and therapeutic purposes.

Document is the main proof for showing identity of a person and nowadays there has been many cases related to document tampering. Most of the documents like marksheet, birth certificate, identity card, etc. can be easily tampered and produced, sometimes the tampered document looks much more real and it becomes difficult for the organization or the verifier to verify the document. This research paper will try to overcome the issues with the help of blockchain technology. Blockchain is a decentralized peer-to-peer mechanism that provides protection, trustworthiness, legitimacy, immutability, and transparency. In this proposed system hashing technique is used for encryption. By using this technology people can request for the necessary documents and verifier can easily verify the documents using hash value.

Purpose Some classes of glucose-lowering medications, including sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1-receptor agonists (GLP1-RAs) have cardio-protective benefit, but it is unclear whether this influences prescribing in the United Kingdom (UK). This study aims to describe class-level prescribing in adults with type 2 diabetes mellitus (T2DM) by cardiovascular disease (CVD) history using the Clinical Practice Research Datalink (CPRD). Methods Four cross-sections of people with T2DM aged 18–90 and registered with their general practice for >1 year on 1st January 2017 (n = 166,012), 1st January 2018 (n = 155,290), 1st January 2019 (n = 152,602) and 31st December 2019 (n = 143,373) were identified. Age-standardised proportions for class use through time were calculated separately in those with and without CVD history and by total number of medications prescribed (one, two, three, four+). An analysis by UK country was also performed. Findings Around 31% of patients had CVD history at each cross-section. Metformin was the most common treatment (>70% of those with and without CVD had prescriptions across all treatment lines). Overall use of SGLT2is and GLP1-RAs was low, with slightly less use in patients with CVD (SGLT2i: 9.8% and 13.8% in those with and without CVD respectively; GLP1-RA: 4.3% and 4.9%, December 2019). Use of SGLT2is as part of dual therapy was low but rose throughout the study. In January 2017, estimated use was 8.0% (95% CI 6.9–9.1%) and 8.9% (8.6–9.3%) in those with and without CVD. By December 2019 this reached 18.3% (17.0–19.5%) and 21.2% (20.6–21.7%) for those with and without CVD respectively. SGLT2i use as triple therapy increased: 22.7% (21.0–24.4%) and 25.9% (25.2–26.6%) in January 2017 to 41.3% (39.5–43.0%) and 45.5% (44.7–46.3%) in December 2019. GLP1-RA use also increased, but observed usage remained lower than SGLT2 inhibitors. Insulin use remained stable throughout, with higher use observed in those with CVD (16% vs 9.7% Dec 2019). Time trends in England, Wales, Scotland and Northern Ireland were similar, although class prevalence varied. Implications Although use of SGLT2is and GLP1-RAs has increased, overall usage remains low with slightly lower use in those with CVD history, suggesting there is opportunity to optimise use of these medicines in T2DM patients to manage CVD risk. Insulin use was substantially more prevalent in those with CVD despite no evidence of CVD benefit. Further investigation of factors influencing this finding may highlight strategies to improve patient access to the most appropriate treatments, including those with evidence of cardiovascular benefit.

Objectives The goals of this review are to evaluate the quality of the evidence on the incidence of sudden cardiac arrest and death (SCA/D) in athletes and military members; and to estimate annual incidence of SCA/D. Data Sources MEDLINE, Embase, Cochrane CENTRAL, Web of Science, BIOSIS, Scopus, SPORT discus, PEDro, and clinicaltrials.gov were searched from inception to dates between 2/21/19 and 7/29/19. Study Selection Studies which reported incidence of SCA/D or both in athletes, or military members under age 40 were eligible for inclusion. 40 studies were identified for inclusion Data Extraction Risk of bias was assessed using a validated, customized tool for prevalence studies in all included studies. 12 were found to be low ROB, with the remaining 28 moderate or high ROB. Data was extracted for narrative review, and meta-analysis. Data Synthesis Random-effects meta-analysis was performed in studies judged to be low risk of bias in two separate categories: 5 studies on regional or national level data including athletes at all levels, and both sexes included 130 events of SCD, with a total of 11,272,560 athlete years showing a cumulative incidence rate of 0.98 [95%CI: 0.62, 1.53] per 100,000 athlete years, with high heterogeneity with I2 of 78%; 3 Studies focusing on competitive athletes between the ages of 14 and 25 were combined, and included 183 events, and 17,798758 athlete years showing an incidence rate of 1.91[95%CI: 0.71; 5.14] per 100,000 athlete years with high heterogeneity with I2 of 97%. Conclusion The worldwide incidence of SCD is a rare event. Low risk of bias studies indicate levels of SCD to be below 2 per 100,000 athlete years. Overall, the quality of the evidence available on the subject of SCA/D is low, but there are high quality individual studies to inform the question of incidence levels. PROSPERO Registration CRD42019125560 Key Points There are several published articles which give a clear picture on the estimate of sudden cardiac arrest and death in athletes and military members, but the overall state of the literature has substantial risk of bias, with only 12 of 40 included articles at low risk of bias. Meta-analysis of sudden cardiac death was shown to be rare overall in athletes, with high quality, large population level studies synthesized to show a rate of 0.98 [95%CI: 0.62, 1.53] per 100,000 athlete years, and more focused studies on competitive younger athletes synthesized to show a rate 1.91[95%CI: 0.71; 5.14] per 100,000 athlete years. There was high heterogeneity present in both meta-analyses.

The peritonitis caused by gram-negative organisms is a serious complication encountered in patients undergoing peritoneal dialysis, often causing high morbidity and mortality. There has been recognition of peritonitis caused by uncommon organisms because of improved microbiological detection techniques. The healthcare providers involved in the management of these patients should be very vigilant. We report a rare case of peritonitis caused by Citrobacter freundii. A 42-year-old male on peritoneal dialysis for five years presented with abdominal pain and cloudy effluent. The peritoneal fluid analysis was consistent with peritonitis, and peritoneal fluid culture grew Citrobacter freundii. The patient was treated with two courses of double antibiotic coverage with intraperitoneal ceftazidime and oral ciprofloxacin, which failed to resolve the infection and hence resulted in the removal the peritoneal dialysis catheter and dialysis modality change.

Background Post-transplant lymphoproliferative disorder is a well-recognized but rare complication of hematopoietic stem cell and solid organ transplant. Due to rarity of this disease, retrospective studies from major transplant centers has been the main source to provide treatment guidelines, which are still in evolution. The sample size of this study is among one of the largest study on PTLD till date reported throughout the world. Methods This study was performed at University of Florida which is one of the largest transplant center in South East United States. We performed treatment and survival analysis along with univariate and multivariate analysis to identify prognostic factors. Results We reviewed 141 patients diagnosed with PTLD over last 22 years with median follow-up of 2.4 years. The estimated median overall survival of the entire group was 15.0 years. Sub group analysis showed that 5-year overall survival rates of pediatric population were 88% (median not reached). For adults, median OS was 5.35 years while for elderly patients it was 1.32 years. The estimated median OS of patients with monomorphic PTLD was 9.0 years while in polymorphic PTLD was 19.3 years. Univariate analysis identified gender, age at transplant and PTLD diagnosis, performance status, IPI score, allograft type, recipient EBV status, multiple acute rejections prior to PTLD diagnosis, PTLD sub-type, extra-nodal site involvement, immunosuppressive drug regimen at diagnosis, initial treatment best response were statistically significant prognostic factors (p

Aim To compare different variables among (S)CID patients diagnosed in the USA and Kuwait. Methods Review of patients registered in The US Immune Deficiency Network registry or Kuwait National PID Registry between 2004 and 2014. Results Totals of 98 and 69 (S)CID patients were registered during the study period in the USIDNET registry and the KNPIDR, respectively. The average annual incidence rate for the period 2004–2014 of (S)CID in children in Kuwait was 13.01/100,000 children, with an estimated occurrence of 1/7500 live births. There were differences between the two countries in the following variables: age at onset and diagnosis, family history of (S)CID, parental consanguinity, and outcome. More than 14% of (S)CID patients from USIDNET registry were diagnosed through newborn screening. Conclusions Patients' characteristics and molecular causes of S(CID) are different between USA and Kuwait. NBS for SCID should be started in countries where the incidence of (S)CID is high.

Lymphomas are the second most common gastric malignancy following gastric adenocarcinoma. The majority of gastric lymphomas are either mucosa-associated lymphoid tissue lymphomas or diffuse large B-cell lymphomas. Primary gastric Burkitt lymphoma is a subtype of non-Hodgkin's lymphoma and represents an aggressive and rare malignancy with only a small number of cases reported worldwide. Clinical and radiological presentation is non-specific and mimics other gastric lymphomas. Diagnosis is established with pathological evaluation. Due to the paucity of cases, treatment of this condition is not well studied and is extrapolated from paediatric and adult literature of Burkitt lymphoma not isolated to the stomach. We present the case of a male patient with primary gastric Burkitt lymphoma who initially presented with life-threatening haematemesis, later achieving complete remission with treatment. We discuss the epidemiology, presentation and management of gastric Burkitt lymphoma.

Biliptysis is an important clinical feature to recognize as it is associated with bronchobiliary fistula, a rare entity. Bronchobiliary fistulas have been diagnosed with planar cholescintigraphy. However, cholescintigraphy with single-photon emission computed tomography (SPECT) can better spatially localize a bronchobiliary fistula as compared to planar cholescintigraphy alone, and is useful for preoperative planning if surgical treatment is required. Here, we present the case of a 23-year-old male who developed a bronchobiliary fistula in the setting of posttraumatic and postsurgical infection, which was diagnosed and localized by cholescintigraphy with SPECT.

The windmill softball pitch generates considerable forces about the athlete's shoulder and elbow. The injury pattern of softball pitchers seems to be primarily overuse injury, and they seem not to suffer the same volume of injury that baseball pitchers do. This article will explore softball pitching techniques, kinetics and kinematics of the windmill pitch, epidemiology of softball pitchers, and discuss possible etiologies of softball pitching injuries.

Vaccine refusal has an impact on public health, and the human pappillomavirus (HPV) vaccine is particularly underutilized. Research suggests that it may be difficult to change vaccine-related attitudes, and there is currently no good evidence to recommend any particular intervention strategy. One reason for vaccine hesitancy is lack of trust that vaccine harms are adequately documented and reported, yet few communication strategies have explicitly attempted to improve this trust. This study tested the possibility that data from the vaccine adverse event reporting system (VAERS) can be used to increase trust that vaccine harms are adequately researched and that potential harms are disclosed to the public, and thereby improve perceptions of vaccines. In the study, participants were randomly assigned to one of three communication interventions. All participants read the Centers for Disease Control (CDC) vaccine information statement (VIS) for the HPV vaccine. Two other groups were exposed to additional information about VAERS, either summary data or full detailed reports of serious adverse events from 2013. Results showed that the CDC's VIS alone significantly increased perceptions of vaccine benefits and decreased perceived risks. Participants who were also educated about VAERS and given summary data about the serious adverse events displayed more trust in the CDC and greater HPV vaccine acceptance relative to the VIS alone. However, exposure to the detailed VAERS reports significantly reduced trust in the CDC and vaccine acceptance. Hence, general information about the VAERS data slightly increased trust in the CDC and improved vaccine acceptance, but the specific VAERS reports negatively influenced both trust and acceptance. Implications for communicating about vaccines are discussed.

e19048 Background: The outcome and prognostic factors of post-transplant lymphoproliferative disorder (PTLD) varies in currently reported literature. We present one of the largest single institution retrospective analysis from University of Florida. Methods: Patient population was identified from EMR and charts were reviewed to collect data. Primary outcome was Overall survival (OS) and secondary outcome was identification of prognostic factors. Results: We identified 138 patients with PTLD from Sept 1994 to Feb 2016 (liver 34%, Kidney 23%, heart 21%, lungs 12%, kidney-pancreas 2% and BMT 6%). After survival analysis, 131 patients were further followed for secondary outcomes. 36% (n = 47) were less than 18 years of age, 60% (n = 83) were males. The median age of PTLD diagnosis was 44 years and the median duration from transplant to PTLD was 4.4 years. Pathology was early lesion 6% (n = 8), polymorphic 17% (n = 23), Monomorphic 71% (n = 93), Hodgkin/like 4.5% (n = 6). Extra-nodal site involvement was 61% (n = 80), most common being GI tract. Ann-Arbor stage distribution was stage I/II 50% (n = 65), stage III/IV 46% (n = 60). Initial treatment was immunosuppression (IS) reduction alone in 24% (n = 31), Rituximab (R) 24% (n = 31), chemotherapy (+/- R) 46% (n = 60). Most common chemo regimen was CHOP (+/-R) 27% (N = 36). After first line, 48% patients had complete remission (CR), 18% partial remission (PR) and 15% progressive disease (PD). Second line treatment was required in 33% (n = 44) and 10% (n = 13) patients required 3rdline treatment. Final analysis showed 61% (n = 80) achieved CR, 17% (n = 22) had PD, 56% (n = 74) patients were alive and 49% (n = 64) are alive without PTLD. Median OS was 14.99 years. Multivariate analysis identified transplant age, organ transplant recipients, PTLD diagnosis age, performance status, IPI score, graft rejection, history of malignancy and recipient EBV status as prognostic factors (p < .05). Conclusions: This study from a leading regional transplant center shows notable OS which is likely from improved immunosuppressive regimens, treatment modalities and large pediatric population. We identified various prognostic factors affecting survival and propose validation to generate prognostic score.

Introduction The objective of this study was to evaluate the antimicrobial effects of photodynamic therapy (PDT) on infected human teeth ex vivo . Methods Fifty-two freshly extracted teeth with pulpal necrosis and associated periradicular radiolucencies were obtained from 34 subjects. Twenty-six teeth with 49 canals received chemomechanical debridement (CMD) with 6% NaOCl, and 26 teeth with 52 canals received CMD plus PDT. For PDT, root canal systems were incubated with methylene blue (MB) at concentration of 50 μg/mL for 5 minutes, followed by exposure to red light at 665 nm with an energy fluence of 30 J/cm 2 . The contents of root canals were sampled by flushing the canals at baseline and after CMD alone or CMD+PDT and were serially diluted and cultured on blood agar. Survival fractions were calculated by counting colony-forming units (CFUs). Partial characterization of root canal species at baseline and after CMD alone or CMD+PDT was performed by using DNA probes to a panel of 39 endodontic species in the checkerboard assay. Results The Mantel-Haenszel χ 2 test for treatment effects demonstrated the better performance of CMD+PDT over CMD ( P = .026). CMD+PDT significantly reduced the frequency of positive canals relative to CMD alone ( P = .0003). After CMD+PDT, 45 of 52 canals (86.5%) had no CFUs as compared with 24 of 49 canals (49%) treated with CMD (canal flush samples). The CFU reductions were similar when teeth or canals were treated as independent entities. Post-treatment detection levels for all species were markedly lower for canals treated by CMD+PDT than they were for those treated by CMD alone. Bacterial species within dentinal tubules were detected in 17 of 22 (77.3%) and 15 of 29 (51.7%) canals in the CMD and CMD+PDT groups, respectively ( P = .034). Conclusions Data indicate that PDT significantly reduces residual bacteria within the root canal system, and that PDT, if further enhanced by technical improvements, holds substantial promise as an adjunct to CMD.

e19561Background: Post-transplant lymphoproliferative disorder (PTLD), is a very rare complication following transplant (solid organ or allogeneic) due to proliferation of lymphoid cells in immunos...

e19047 Background: Post transplant lymphoproliferative disorder (PTLD) is a rare, but potentially fatal complication of transplantation and therapeutic immunosuppression (IS). The cornerstone of PTLD management is reduction of IS, which carries the risk of allograft rejection. Methods: Retrospective analysis of patients diagnosed with PTLD after solid organ (SOT) or allogeneic stem cell transplant (HSCT) at the University of Florida were identified through a review of individual EMR charts. This analysis focused on rates of allograft rejection and graft failure with RI. Results: Of 138 patients diagnosed with PTLD between 1994 and 2016, 15% (n = 20) experienced allograft rejection during PTLD treatment. The primary organ of transplant and rejection included liver (35%), lung (25%), heart (10%), HSCT (15%) and kidney (15%). Median age at PTLD diagnosis was 14.5 years (range 2-59), males (50%) and median time from transplant to PTLD diagnosis was 25 months (range 0-173). RI was a documented as a component of initial PTLD treatment in 19/20 (95%) patients, with 2/20 (10%) undergoing complete withdrawal of immunosuppression, 13/20 (65%) partial RI (withdraw of one or more drugs) and 3/20 (10%) dose reductions of their established IS regimen. One lung recipient (5%) was transitioned to an alternative agent, and one patient had no documented records of IS adjustment. Treatment for acute rejection included observation 2/20 (10%), pulse steroids 11/29 (55%) or IS increase 12/20 (60%). 7/20 (35%) received combination steroids and increased IS. Allograft failure developed in 5/20 (25%) (1 kidney, 1 lung, 1 heart, 1 liver, 1 BMT). Allograft failure was not shown to correlate with RPI score at diagnosis, organ transplanted, induction therapy at transplant or 3-year OS. Of note 5/5 (100%) of patients received Rituximab as part of initial treatment, versus 5/15 patients whose grafts survived. Conclusions: RI for PTLD is associated with moderate rates of response, however acute graft rejection is common and is associated with high rates of graft failure. PTLD may still have favorable outcomes when combining partial RI with chemotherapy and Rituximab.

Photodynamic therapy (PDT) is based on the synergism of a photosensitive drug (a photosensitizer) and visible light to destroy target cells (e.g., malignant, premalignant, or bacterial cells). The aim of this study was to investigate the response of normal rat tongue mucosa to PDT following the topical application of hematoporphyrin derivative (Photogem®), Photodithazine®, methylene blue (MB), and poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MB. One hundred and thirty three rats were randomly divided in various groups: the PDT groups were treated with the photosensitizers for 10 min followed by exposure to red light. Those in control groups received neither photosensitizer nor light, and they were subjected to light exposure alone or to photosensitizer alone. Fluorescent signals were obtained from tongue tissue immediately after the topical application of photosensitizers and 24 h following PDT. Histological changes were evaluated at baseline and at 1, 3, 7, and 15 days post-PDT treatment. Fluorescence was detected immediately after the application of the photosensitizers, but not 24 h following PDT. Histology revealed intact mucosa in all experimental groups at all evaluation time points. The results suggest that there is a therapeutic window where PDT with Photogem®, Photodithazine®, MB, and MB-loaded PLGA nanoparticles could safely target oral pathogenic bacteria without damaging normal oral tissue.

Autoimmune limbic encephalitis (ALE) is a severe, but treatable, neuropsychiatric disorder that is difficult to diagnose clinically. With the goal of improving diagnosis of this disorder, we retrospectively evaluated the cerebral FDG PET pattern in a group of patients with ALE.Nine adult patients with subacute cognitive decline were eventually diagnosed with ALE based on clinical presentation, cerebrospinal fluid inflammatory markers, and response to immunosuppressive therapy. All patients received FDG PET brain scanning during their diagnostic evaluation, which were retrospectively reviewed for this study.Our patients' scans fell into 2 readily separable patterns. Five younger patients had a mixed metabolic pattern most easily recognized by pronounced occipital hypometabolism, accentuated by hypermetabolism in the temporal and orbitofrontal cortex. Other, milder findings were also present. Once this unusual pattern was established as corresponding to ALE, it helped lead to the correct clinical diagnosis in the last 2 patients. Four older patients had scans that closely resembled diffuse neurodegenerative disease.We found 2 different PET scan patterns in patients with ALE. One is an easily recognizable mixture of hyper- and hypometabolism that has also been described in a few recent case reports and is potentially specific for ALE. The other is indistinguishable from neurodegenerative disease. We propose that awareness of these patterns may contribute to the diagnosis of this elusive, but treatable, neurologic disorder.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is neuroprotective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the central nervous system (CNS), when delivered peripherally, is limited due to the blood-brain barrier (BBB). We have developed a means of delivering BDNF into the CNS using genetically engineered bone marrow stem cells (BMSCs) as a vehicle, and have explored the clinical effects of BDNF on outcomes in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). BDNF-engineered-BMSCs were transplanted (i.v.) into irradiated 2-week-old SJL/J female mice. Eight weeks after transplantation, mice were immunized with a peptide of proteolipid protein (PLP(139-151)). Mice, which had received BDNFengineered BMSCs, showed a significant delay in EAE onset and a reduction in overall clinical severity compared to mice receiving BMSC transfected with an empty vector lacking the BDNF gene. In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination. Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group. These results support the use of BMSCs as vehicles to deliver BDNF into the CNS of EAE animals. This is a potentially novel therapeutic approach that might be used to deliver BDNF gene or genes for other therapeutic proteins into the CNS in MS or in other diseases of the CNS in which accessibility of therapeutic proteins is limited due to the BBB.

Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) which includes a neurodegenerative component. Brain derived neurotrophic factor (BDNF) is a neuroprotective agent which might be useful in preventing neurodegeneration but its application has been limited because the blood brain barrier restricts its access to the CNS. We have developed a novel delivery system for BDNF using transformed bone marrow stem cells (BMSC) and undertook studies of EAE to determine whether the delivery of BDNF could reduce inflammation and apoptosis. Mice receiving BDNF producing BMSC had reduced clinical impairment compared to control mice receiving BMSC that did not produce BDNF. Pathological examination of brain and spinal cord showed a reduction in inflammatory infiltrating cells in treated compared to control mice. Apoptosis was reduced in brain and spinal cord based on TUNEL and cleaved Caspase-3 staining. Consistent with the known mechanism of action of BDNF on apoptosis, Bcl-2 and Akt were increased in treated mice. Further studies suggested that these increases could be mediated by inhibition of both caspase dependent and caspase independent pathways. These results suggest that the BDNF delivered by the transformed bone marrow stem cells reduced clinical severity, inflammation and apoptosis in this model.

To compare the mechanical effectiveness of three different techniques for stabilization of transverse fractures of the patella.Cadaveric knees were used to model acute fractures of the patella. To test three treatment techniques in pairs of knees, specimen pairs were assigned randomly to a set of predetermined treatment pairs so as to provide equal numbers of paired and unpaired data sets. Results then were analyzed using a two-way analysis of variance.The treatment techniques used are widely applicable in the clinical setting for the treatment of transverse fractures of the patella. No specialized equipment or training is required for the general or subspecialized orthopaedic surgeon.None.Fractures were created in eighteen knees (nine pairs) and repaired by one of three techniques: (a) modified tension band (AO technique); (b) two parallel 4.5-millimeter interfragmentary lag screws; or (c) a new technique using four-millimeter cannulated lag screws with a tension band wired through the screws.In mechanical testing, the amount of interfragmentary separation in simulated knee extension and the maximum load to failure at 45 degrees of flexion were measured.Fractures stabilized with a modified tension band were found to displace significantly more than those fixed with screws alone or screws plus a tension band in simulated knee extensions (p0.05). The fractures fixed with the cannulated screws plus the tension band failed at higher loads (mean = 732 newtons) than those stabilized with screws alone (mean = 554 newtons, p = 0.06) or those with a modified tension band (mean = 395 newtons, p0.05).Combining interfragmentary screw fixation with the tension band principle appears to provide improved stability over the modified tension band or screws alone for transverse patella fractures. Cannulated screws allow for simple, reliable addition of a tension band to screw fixation.

Objective: To raise awareness of two distinct metabolic patterns on FDG PET associated with autoimmune limbic encephalitis (ALE), a potentially reversible neuropsychiatric disorder. Background ALE can present as rapid cognitive deterioration and bizarre behavior. Recent publications indicate that ALE is more common than previously estimated, but is difficult to diagnose clinically. However, if recognized early, it is reversible with treatment. Conventional neuroimaging is usually unremarkable. We tested the hypothesis that ALE can produce distinctive patterns on FDG PET. Design/Methods: The diagnosis of non-paraneoplastic ALE was based on clinical presentation, CSF inflammatory markers, and response to immunosuppressive therapy. We performed 18-FDG brain PET scan on nine patients diagnosed with non-paraneoplastic ALE during the course of their illness and the results were retrospectively reviewed. Results: Five patients who were younger had a mixed metabolic pattern most easily recognized by pronounced occipital hypometabolism and hypermetabolism in the temporal and orbitofrontal cortex. Other milder findings were also present. Four older patients had scans that closely resembled diffuse neurodegenerative disease. Mild or improving PET scan findings predicted an excellent clinical recovery in two patients. Conclusions: We found two distinct PET scan patterns in patients with ALE. One may be specific for the disorder, while the other could easily be confused with neurodegenerative disease. Our results suggest 18-FDG PET can be useful in the early recognition ALE, but the interpreting physician must be aware of the specific scan patterns. Disclosure: Dr. Lai has received personal compensation for activities with Forest Pharmaceuticals, Allergan, Pfizer, and Novartis Pharmaceuticals as a speaker and consultant. Dr. Lai has received research support from Medtronic and Allergan. Dr. Schulz has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Fisher has nothing to disclose.

Objective: To analyze accuracy and reliability of visual assessment of I-123 ioflupane DaTscan (GE Healthcare, Princeton, NJ) in the diagnosis of movement disorders and to propose a rating scale for image interpretation. Background Since approval by the Food and Drug Administration (FDA), DaTscan has been increasingly used in the evaluation of patients with parkinsonism. Visual assessment, a mainly descriptive technique based on Benamer9s criteria (Benamer, Mov Disord 2000; 15:503-10) for grading abnormal patterns of striatal radiotracer uptake, remains the main interpretation method of the images. The diagnostic accuracy of DaTscan since its FDA approval has not been previously reported. Design/Methods: 9 raters experienced in movement disorders or nuclear medicine, blinded to the clinical diagnosis, interpreted 21 DaTscans individually and in consensus. Raters interpreted scans according to Benamer9s criteria and commented on asymmetry of striatal uptake. The consensus interpretation was compared to clinical diagnosis: Parkinson9s disease (PD) (N=14), essential tremor (ET) (N=1), healthy controls (N=6). The mean symptom duration among PD patients was 4.0 years (SD ±2.22, range 1- 9 years), mean UPDRS III score was 15.15; (SD ±13.46, range 1-42). The sensitivity, specificity, positive and negative predictive values of the consensus, and the inter-rater reliability of individual visual interpretations were calculated. Results: Sensitivity of identifying abnormal scans was 1.0 for consensus review. Specificity was 0.714, negative predictive value 1.0, positive predictive value 0.875. Two subjects had false-positive images (1 healthy control, 1 ET). Inter-rater reliability was 0.948 for identifying abnormal scans, 0.896 for grading abnormal scans, 0.790 for detecting asymmetry of decreased uptake. Conclusions: Visual assessment of DaTscan images has high sensitivity and inter-rater reliability in detecting abnormal scans, but its clinical utility may be enhanced by reliable recognition of altered patterns of striatal uptake. A new rating scale for visual assessment is proposed that may increase reliability of the image interpretation. Disclosure: Dr. Waln has nothing to disclose. Dr. Jimenez-Shahed has received personal compensation for activities with Teva Neuroscienece, Allergan, Inc., Merz Pharma, Medtronic, Inc., and Lundbeck Research USA, Inc. Dr. Wendt has nothing to disclose. Dr. York has nothing to disclose. Dr. Baizabal Carvallo has nothing to disclose. Dr. Mehanna has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Hunter has received personal compensation for activities with Lundbeck Research USA, Inc. as a consultant. Dr. Van has nothing to disclose. Dr. Jankovic has received personal compensation for activities with Allergan, Inc., Chelsea Therapeutics, Serono Inc., Merz Pharma, Lundbeck Research USA, Inc, Teva Neuroscience as a consultant. Dr. Jankovic has received personal compensation in an editorial capacity for Medlink: Neurology in Clinical Practice. Dr. Jankovic has received research support from Allergan, Inc, Allon Therapeutics, Ceregene, Inc., Chelsea Therapeutics; Diana Helis Henry Medical Research Foundation, Serono Inc., Huntington9s Disease Society of America, Huntington Study Group, Impax Pharmaceuticals, Ipsen Limited, Lundbeck Research USA, Inc.

Abstract: The use of 3D printed models created using cone beam computed tomography (CBCT) is a new addition to the field of dentistry. 3D printed models are easier for the patients to understand and serve as an effective treatment planning tool for the clinician. This case describes 3D printing as a technique which not only aids in visualization of the complex anatomy but serves as a great motivational and educational tool. A tooth with dens invaginatus and chronic apical periodontitis requiring surgical intervention was printed and used for patient motivation and three-dimensional visualization, which improved the accuracy of diagnosis, treatment planning, predictability of procedures and final outcome. CPD/Clinical Relevance: 3D printed models can be utilized as a patient education tool for motivating patients who are not convinced by the surgical treatment modality.