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BACKGROUND Throughout the COVID-19 pandemic, multiple policies and guidelines were issued and updated for healthcare personnel (HCP) COVID-19 testing and return-to-work (RTW) after reporting symptoms, exposures, or positive COVID-19 tests. The relatively high frequency of changes and complexity of the policies made it difficult for HCP to understand when they needed testing and were eligible to return to work, therefore calls to occupational health services (OHS) hotlines rapidly increased creating a need for other tools to guide HCP return to work. OBJECTIVE We aim to describe the development of the Return-to-Work Chatbot, and report its impact on demand for OHS support services during the first omicron surge. METHODS This study was conducted at Mass General Brigham, an integrated healthcare delivery system. RTW Chatbot was developed using agile design methodology. We mapped the RTW policy into a unified flow diagram that included all required questions and recommendations. We obtained chatbot data and OHS call data from December 10, 2021 to February 17, 2022. We compared use of OHS resources before and after the deployment of the RTW Chatbot. RESULTS In the 5 weeks post-deployment, a total of 5575 users used the RTW Chatbot. During the total of 10 weeks, the median number of daily calls that OHS received before and after deployment of the chatbot were 633 (IQR 251-934) and 115 (IQR 62-167), respectively. (p < 0.001). The median time from dialing the OHS phone number to hanging up the call decreased from 28 minutes and 22 seconds to 6 minutes and 25 seconds after the deployment of the chatbot (p CONCLUSIONS Using agile methodology, a chatbot can be rapidly designed and deployed to enable employees to efficiently receive guidance regarding returning to work that faithfully complies with the complex and shifting return-to-work policies which may reduce the utilization of OHS resources.

Vitamin D deficiency has emerged as another potential risk factor for coronavirus disease (COVID-19) due to the immunomodulatory effects of 25 hydroxyvitamin D [25 (OH)D]. Vitamin D receptor (VDR) gene polymorphisms such as Fok I, Bsm I, Apa I, and Taq I are also associated with different courses of viral infections. This study aimed to evaluate the association between the VDR gene polymorphism at Fok I, Taq I, Bsm I, and Apa I genotypes and the prognosis of COVID-19 in respect to vitamin D deficiency.Two-hundred ninety-seven patients with COVID-19 were enrolled. Serum 25 (OH)D levels were measured. Four variant regions of the VDR gene, FokI, BsmI, ApaI, and TaqI were determined.Eighty-three percent of subjects had vitamin D deficiency, and 40.7% of the whole group had severe deficiency. Median 25 (OH)D level was 11.97 ng/ml. Vitamin D levels were not related to inflammatory markers, disease severity, admission to intensive care unit (ICU), and mortality. While disease severity was related to Fok I Ff genotype, it was Taq TT genotype for ICU admission. Moreover, the ApaI aa genotype was common among the patients who were died. None of the deceased subjects had the Fok I FF genotype.25 (OH)D levels were not related to the severity and mortality of COVID-19. VDR gene polymorphisms are independently associated with the severity of COVID-19 and the survival of patients.

Background To facilitate evidence-based medicine (EBM) on an individual level, it may be important for clinical practice guidelines (CPGs) to incorporate the performance parameters of diagnostic studies and therapeutic interventions (such as likelihood ratio and absolute benefit or harm), and to incorporate relevant patient contexts that may influence decision-making. We sought to determine the extent to which heart failure CPGs currently incorporate this information. Methods We reviewed the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013 Heart Failure CPG, the 2017 ACCF/AHA/HFSA update, and European Society of Cardiology (ESC) 2016 Heart Failure CPG. We abstracted variables for each CPG recommendation from the following domains: quality of evidence, strength of recommendation, diagnostic and therapeutic performance parameters, and patient context. Results We examined 169 recommendations from the ACCF/AHA 2013 CPGs and 2017 update and 187 recommendations from the 2016 ESC CPGs. Performance parameters for diagnostic studies (2013 ACCF/AHA: 13%; 2017 ACCF/AHA/HFSA update: 0%; 2016 ESC: 0%) and therapeutic interventions (2013 ACCF/AHA: 65%; 2017 ACCF/AHA/HFSA update: 64%; 2016 ESC: 16%) were not commonly included in CPGs. Patient context was included in about half of ACCF/AHA recommendations and a quarter of ESC recommendations. Conclusions The majority of recommendations from heart failure CPGs lack information on diagnostic and therapeutic performance parameters and patient context. Given the importance of these components to effectively implement EBM, particularly for a heterogeneous heart failure population, innovative strategies are needed to optimize CPGs so they provide comprehensive yet succinct recommendations that can improve population-level outcomes and ensure optimal patient-centered care.

Background: Prior work has shown that fibrinogen, a well-known inflammatory marker, is associated with cardiovascular (CV) events. While it is known that physical activity (PA) imparts CV health benefits, there remains a knowledge gap on the interactions of PA with systemic inflammation on risk of CV death among American Indians. Hypothesis: To investigate the relationship between PA, inflammation, and CV death, we tested the hypotheses that: (i) PA is associated with lower risk of CV death, and (ii) the CV benefit of PA is mediated via an inflammatory pathway. Methods: We examined the association between PA (leisure-time plus occupational as METs[Metabolic Equivalent of Task]-hours per week via a validated questionnaire) and CV death among 3,135 adults (mean age 56 ± 8) without baseline CV disease in Strong Heart Study (1989-1991), a longitudinal study among American Indians. Preacher and Hayes bootstrap method was used for the model assessing mediation by fibrinogen. Results: During 26 years (mean 17.3 ± 8 years) of follow-up, there were 378 CV deaths. Compared to participants with minimal activity, subjects with higher levels of PA had a lower risk of CV death. Odds ratios were 0.91 (95% confidence interval [CI]: 0.65-1.21), 0.69 (95% CI: 0.51-0.92), and 0.56 (95% CI: 0.39-0.71) (p-trend=0.003), for increasing quartile of activity compared to the lowest, after adjustment for age, sex, study site, education, smoking, diabetes, hypertension, BMI, LDL cholesterol, and urine albumin-creatinine ratio. Mediation analysis showed the effect of PA on CV death was fully mediated via fibrinogen level (correlation coefficient: 0.998, 95% CI 0.995-0.999; Sobel test z= -3.11, p=0.03) (Figure). Conclusion: In a population-based study of American Indians, PA compared to inactivity, was associated with lower risk of CV death. This study highlights that PA is associated with improved CV outcomes and this effect is largely driven by inflammation.

Background: Despite potential harm that can result from polypharmacy, real-world data on polypharmacy in the setting of heart failure (HF) are limited. We sought to address this knowledge gap by studying older adults hospitalized for HF derived from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Methods: We examined 558 older adults aged ≥65 years with adjudicated HF hospitalizations from 380 hospitals across the United States. We collected and examined data from the REGARDS baseline assessment, medical charts from HF-adjudicated hospitalizations, the American Hospital Association annual survey database, and Medicare’s Hospital Compare website. We counted the number of medications taken at hospital admission and discharge; and classified each medication as HF-related, non-HF cardiovascular-related, or noncardiovascular-related. Results: The vast majority of participants (84% at admission and 95% at discharge) took ≥5 medications; and 42% at admission and 55% at discharge took ≥10 medications. The prevalence of taking ≥10 medications (polypharmacy) increased over the study period. As the number of total medications increased, the number of noncardiovascular medications increased more rapidly than the number of HF-related or non-HF cardiovascular medications. Conclusions: Defining polypharmacy as taking ≥10 medications might be more ideal in the HF population as most patients already take ≥5 medications. Polypharmacy is common both at admission and hospital discharge, and its prevalence is rising over time. The majority of medications taken by older adults with HF are noncardiovascular medications. There is a need to develop strategies that can mitigate the negative effects of polypharmacy among older adults with HF.

Patients with aortic disease should have regular imaging surveillance. The goal of this review is to provide an overview of the etiologies of aortic disease as well as provide information on available imaging modalities including ones that are under investigation. As routine imaging is required for surveillance of aortic disease, many concerns come up including cumulative radiation and contrast exposure, as well as limitations, availability, and cost of imaging modalities. Novel hybrid imaging modalities hold promise for the prediction of complications related to aortic disease. A variety of etiologies can lead to aortic disease which can cause fatal complications if not monitored regularly and intervened when appropriate. Therefore, routine imaging surveillance is critical in patients with aortic disease, especially in high-risk groups. Understanding of advantages and limitations of each imaging technique is important in choosing the right modality.

Objective Although systemic lupus erythematosus (SLE) is the most common autoimmune disease associated with antiphospholipid antibodies (aPL), limited data exist regarding the impact of SLE on the clinical phenotype of aPL-positive patients. The primary objective of this study was to compare the clinical, laboratory, and treatment characteristics of aPL-positive patients with SLE with those of aPL-positive patients without SLE. Methods A secure web-based data capture system was used to store patient demographic characteristics and aPL-related clinical and laboratory characteristics. Inclusion criteria included positive aPL according to the updated Sapporo classification criteria. Antiphospholipid antibody-positive patients fulfilling the American College of Rheumatology criteria for the classification of SLE ("aPL with SLE") and those with no other autoimmune diseases ("aPL only") were included in the analysis. Results Six hundred seventy-two aPL-positive patients were recruited from 24 international centers; 426 of these patients did not have other autoimmune disease, and 197 had SLE. The frequency of thrombocytopenia, hemolytic anemia, low complement levels, and IgA anti-β2 -glycoprotein I (anti-β2 GPI) antibodies was higher in the aPL-positive patients with SLE, whereas the frequency of cognitive dysfunction and IgG anti-β2 GPI antibodies was higher in the aPL-only group. The frequency of arterial and venous thromboses (including recurrent) as well as pregnancy morbidity was similar in the 2 groups. The prevalence of cardiovascular disease risk factors at the time of entry into the registry entry did not differ between the 2 groups, with the exception of current smoking, which was more frequent in aPL-positive patients with SLE. Conclusion Although the frequencies of thrombosis and pregnancy morbidity are similar in aPL-positive patients with and those without SLE, the diagnosis of SLE in patients with persistently positive aPL is associated with an increased frequency of thrombocytopenia, hemolytic anemia, low complement levels, and positive IgA anti-β2 GPI antibodies.

Background According to criteria for the classification of Systemic Lupus Erythematosus (SLE), autoimmune hemolytic anemia is one of the disease-defining hematologic disorders together with thrombocytopenia. Since the recognition of Antiphospholipid Syndrome (APS), hemolytic anemia was frequently reported but several studies yielded contradictory results on the association between antiphospholipid antibodies (aPL) and hemolytic anemia. Therefore, we evaluated the association of aPL and autoimmune hemolytic anemia in SLE patients by conducting a systematic review and meta-analysis of available literature. Methods MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference lists of eligible studies were searched from 1987 to 2020. Studies were selected if they included SLE patients with descriptions of exposure to aPL and occurrence of hemolytic anemia. Three reviewers extracted study characteristics and association data from published reports. Risk estimates were pooled using random effects models and sensitivity analyses. We followed the PRISMA guidelines for all stages of the meta-analysis (Supplemental Table). PROSPERO registration number: CRD42015027376. Results From 3555 articles identified, 38 studies met inclusion criteria and included 8286 SLE patients. 20.5% of aPL-positive SLE patients had hemolytic anemia compared to 8.7% in aPL-negative SLE patients. The overall pooled Odds Ratio (OR) for hemolytic anemia in aPL positive patients was 2.83 (95% CI; 2.12–3.79). Among aPL subtypes, the risk of hemolytic anemia was highest for lupus anticoagulant (OR = 3.37 [95% CI; 2.26–5.04]) and, antiβ2Glycoprotein I antibodies (OR = 3.21 [95% CI; 1.54–6.72]), especially IgM antiβ2Glycoprotein I (OR = 3.01 [95% CI; 1.26, 7.24]). Conclusions The occurrence of hemolytic anemia was strongly associated with presence of aPL in SLE patients. Interestingly, IgM isotypes indicate an increased risk of hemolytic anemia in SLE.

Introduction Renal dysfunction is a prognostic factor in morbidity and mortality after left ventricular assist device (LVAD) placement. As a result, poor renal function often affects a patient's eligibility for LVAD implantation. However, in some, cardiac output augmentation following LVAD placement may improve renal perfusion. The extent of change in renal function and predictors of long-term renal function post-LVAD implantation have not been well studied. Methods This retrospective cohort included consecutive patients who underwent LVAD implantation (HeartMate[HM] II and HM3) between 2008-2018 at a single center for both bridge-to-transplant and destination therapy (DT) indications. We examined the relationship of clinical parameters with changes in renal function 6 months post-LVAD. Glomerular filtration rate (GFR) was calculated using Modification of Diet in Renal Disease Study equation. We performed multivariable logistic regression analyses to determine predictors of decreased renal function. Results We examined 91 patients (mean age 59.7± 13.2, female 11%, HM II 89%, DT 68%). Post-LVAD, 52 patients (57.1%) improved and 39 (42.9%) had deterioration in renal function (Table). Among all patients, 16 (17.6%) had more than 25% reduction in GFR, 6 (6.6%) had a post-LVAD GFR of less than 30 mL/min/1.73 m2, and 2 (2.2%) developed end stage renal disease (ESRD) requiring dialysis. Of those patients who had improved GFR post-LVAD, 30 (57.7%) had more than 25% improvement in their GFR. Among patients who had a GFR 25% reduction in GFR (OR: 3.96, 95% CI 1.4 - 13.8), p=0.03). None of the other clinical parameters listed in the Table were associated with worse renal outcomes. Pre-LVAD GFR was also not predictive of >25% post-implant GFR reduction or the development of ESRD. Conclusion Renal function may improve after LVAD placement. In patients with long-term decreased renal function post-LVAD, the reduction in GFR was rarely severe. Elevated RA pressure, a marker of right ventricular dysfunction and volume overload, is potential predictor of poor renal outcomes after LVAD placement.

Background Direct oral anticoagulants (DOACs) are effective alternatives to warfarin for stroke prevention in patients with atrial fibrillation (AF) including patients with CKD III. However, data on patient outcomes with DOACs for advanced CKD are limited, while warfarin use is controversial. Methods A retrospective study of patients with AF using DOACs and CKD stages III-V was conducted. The primary outcomes were stroke or systemic embolism and major bleeding while on DOAC therapy among CKD IV and V patients. Rates of outcomes from the DOAC trials and from previous studies of warfarin in CKD were referenced. Results Of 316 patients reviewed, 152 were included with mean CrCl of 38.8 mL/min. Stroke and systemic embolism occurred at a rate of 1.17 per 100 person-years, with no significant difference between CKD IV/V and CKD III (P = .567). Rates were comparable to DOAC use from the DOAC trials, and lower than rates in studies of warfarin in CKD IV/V patients. There was a nonstatistically significant trend toward increased major bleeding in CKD IV/V patients. Rates of major bleeding in CKD III to V subjects were comparable to published rates for warfarin users with similar levels of renal impairment. Conclusions In our study, DOACs appeared to be as efficacious and safe in CKD IV and V as in CKD III. In addition, DOACs appeared to be more effective than, and as safe as warfarin when compared with reference studies of patients with advanced CKD. Our findings support the use of DOACs for thromboembolism prevention in patients with advanced CKD and AF.

Objective iBook on Antiphospholipid Syndrome (APS) did not exist before our work, and hence the utility of an Apple iBook as a teaching method in APS for medical students has never been assessed. Our objective was to evaluate medical students' improvement of knowledge and satisfaction with an interactive APS iBook, in comparison with conventional teaching methods. Methods An iBook designer with the guidance of a medical team developed the APS iBook in both French and English. Second-year medical students, naive of APS knowledge, were enrolled from two institutions. For the "teaching intervention", participants were randomly assigned to three groups: a) APS iBook with interactive capability; b) printed copy of the APS iBook material; and c) classroom lecture presentation of the APS iBook material by a physician-scientist experienced in APS. The participants filled a standardized medical questionnaire about APS before and after teaching interventions to determine the relative change of knowledge. Participants were asked to fill out a standardized satisfaction survey. After 20 weeks of the intervention, recall capability of students was tested. Results A total of 233 second-year medical students were enrolled (iBook group: 73; print group: 79, and lecture group: 81). Relative change of knowledge was not different between the iBook group and the printed material group; additionally, it was significantly higher in the lecture group than the two other methods. Satisfaction was significantly higher in both the lecture and the iBook groups than the print group, on several dimensions including overall quantitative satisfaction, subjective enhanced knowledge, interactivity, quality of content, comprehensibility, and pleasure of learning. Recall capability of students (n=109, 47%) was not significantly different among groups. Conclusion The APS iBook is as effective as printed material in improving medical student's knowledge, although a classroom lecture was the most effective method when compared to self-learning methods. Among self-learning methods, medical students are more satisfied with the APS iBook, whereas the recall capability was not different among groups. These results suggest that the APS iBook will help medical students in their curriculum and increase the awareness of APS among the community.

Background Iron chelation therapy is one of the mainstays of the management of the patients with β-thalassemia (BT) major. Deferasirox is an oral active iron chelating agent. Proteinuria is one of the potential renal adverse effects of deferasirox, and monthly follow-up for proteinuria is suggested by Food and Drug Administration and European Medicine Agency. Methods We aimed to investigate the necessity for monthly monitoring for proteinuria among patients with BT on deferasirox. A retrospective laboratory and clinic data review was performed for patients with BT major or intermedia who were treated with deferasirox chelation therapy. All patients were monitored for proteinuria for every 3 or 4 weeks after the initiation of deferasirox with serum creatinine and spot urine protein/creatinine ratios. Results The median follow-up time of the 37 (36 BT major and one BT intermedia) patients was 44 months. Seven patients (18.9%) developed significant proteinuria (ratio ≥0.8). Of the 1490 measurements, 12 tests (0.8%) were proteinuric. Urine proteinuria resolved in all of the patients during the follow-up. The risk of proteinuria was higher at ages below a cut-off point of 23 years (p = 0.019). Patients, who were on deferasirox at doses above a cut-off dose of 29 mg/kg/day, were found to have higher risk of proteinuria development (p = 0.004). Conclusion Proteinuria resolves without any complication or major intervention according to our results. Potentially more risky groups (age below 23 years old and receivers above a dose of 29 mg/kg/day) might be suggested to be followed monthly, besides monitoring all of the patients.

Objective: To clarify the patient characteristics associated with seeking medical help for insomnia. Methods: A consecutive sample (n = 700) of adults attending a nonurgent primary care appointment was screened for sleep problems. A follow-up mailed survey then assessed insomnia symptoms, daytime impairment, beliefs about sleep, medication use, sleepiness and fatigue, and medical help-seeking. Results: Fifty-two percent of patients with probable insomnia reported discussing this with a physician. Multivariate logistic regression analyses indicated that discussing one’s probable insomnia with a physician was independently associated with having a greater number of medical conditions (OR, 2.19 [95% CI, 1.13 to 4.22]), being more highly educated (1.67 [95% CI, 1.11 to 2.51]), sleeping less per night (OR, 0.71 [95% CI, 0.52 to 0.96]), and greater perceived daytime impairment due to insomnia (OR, 2.07 [95% CI, 1.06 to 4.03]). Conclusions: Primary care patients often seek medical help when they experience insomnia. Clinical treatment ought to especially target poor sleepers presenting with significant insomnia-related impairment, medical morbidity, or both. Future research should further clarify the role of medical and psychiatric comorbidities and determine whether resolution of insomnia and its consequences improves the outcomes of common medical conditions.

Introduction To apply evidence-based medicine (EBM) to individual patients and implement shared decision-making, it is necessary for clinical practice guidelines (CPGs) to incorporate performance metrics for diagnostic studies and therapeutic interventions, as well as relevant patient contexts. This is especially important in heart failure (HF), which is a highly heterogeneous population with a high prevalence of multimorbidity, and impairments in other domains (e.g. function and cognition) that can significantly impact the value of diagnostic studies and therapeutic interventions. We sought to determine the extent to which performance metrics and patient context are incorporated into major HF CPGs. Methods We reviewed the main and supplementary documents of 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) CPG, 2017 ACCF/AHA/HFSA update, and 2016 European Society of Cardiology (ESC) CPG. We assessed the following domains from each recommendation: performance metrics including sensitivity/specificity, positive/negative predictive value, number needed to treat, absolute benefit/harm, and time horizon to benefit; and patient context, including comorbidity, socio-personal milieu, personal preferences, and life expectancy. Results We examined 169 recommendations from the 2013 ACCF/AHA CPG and 2017 update, and 187 recommendations from the 2016 ESC CPG. Performance metrics for diagnostic studies were rarely included; metrics for therapeutic interventions were included to a varying degree depending on the CPG (Figure). Sensitivity/specificity, time horizon to benefit, and absolute benefits were mentioned in 7%, 13%, and 30% of all recommendations, respectively. Patient context was included in over 60% of ACCF/AHA/HFSA CPG recommendations but only included in 25% of the ESC CPG recommendations (Figure). Conclusion The majority of recommendations from HF CPGs lack granular information on diagnostic and therapeutic performance metrics. Contextual patient factors are also inconsistently included. These findings indicate that while HF CPGs may be evidence-based, they are not yet patient-centered. Given their importance to effectively implement EBM and shared decision-making among the complex and heterogeneous HF population, future CPGs should explicitly incorporate these aspects.

Background and aim Iatrogenic perforation of the gut during endoscopy remains an uncommon but critical complication with significant morbidity and probable mortality than usual surgical treatment. Some authors have adopted a non-surgical closure method in chosen cases and, since 1993, endoclips have been used to close perforation in the stomach. The endoscopic practice of endoclips has been commonly used in the gut for hemostasis. Currently, the use of endoscopic techniques is increasing for the closure of endoscopic submucosal dissection or endoscopic mucosal resection. Endoscopic perforations that improved with endoscopic closure in the literature prior to 2008 have been previously described. In the present article, we present a descriptive review of cases with iatrogenic perforation in the gut treated with endoclips between 2008 and 2014. Methods Comprehensive literature screening and a systematic review using PubMed and Medline was done for all reports published between January 2008 and December 2014 using the endoclip technique in the closure of iatrogenic perforations. Results A total of 47 studies published between 2008 and 2014 using endoclips for the closure of iatrogenic perforations of the gut (nine esophagus, 11 stomach, 15 duodenum, 12 colon and rectum) were found. All studies were explained briefly and summarized in a table. Conclusions There is strong evidence to show the efficacy of endoclips in the management of iatrogenic perforations, especially when recognized early. Limitations of endoclipping such as inefficiency against large perforations may be overcome by improving novel techniques in the future.

Objective To investigate trends in Internet search volumes linked to Antiphospholipid Syndrome (APS), using Big Data monitoring and data mining. Methods Based on the large amount of data generated by Google Trends and scientific search tools (SCOPUS, Medline/Pubmed, and ClinicalTrails.gov), we performed a longitudinal analysis based on the term "antiphospholipid" in a 5-year web-based research. Results Google Trends captured that APS-related digital interest was generally steady in the study period (Relative Search Volume [RSV] mean value 71.1±9.3% [95%CI 55.6-89.4], median 72.0), with no significant peak based on different seasons (e.g. winter vs. summer time). When comparing the APS-related digital interest with search volumes generated in the same time period for Inherited Thrombophilias (IT) and Systemic Lupus Erythematosus (SLE), we found a digital interest 35-times higher for APS than for IT (RSV mean value 71.1±9.3% [95%CI 55.6-89.4] vs. 2±3.2% [95%CI 0.7-7.4]). When compared to SLE, APS reached a similar RSV, showing a comparable digital interest (RSV mean value 71.1±9.3% [95%CI 55.6-89.4] vs. 87±11.8% [95%CI 60.7-107.9]). When adjusting for relative search volumes of Google Trends, we found a relative prevalence of search volumes of 35.5% in Europe, 12.3% in the United States, 11.5% in South America, 11.2% in Australia, 9.2% in Canada, 9.2% in Japan, and 5.1% in India. We observed an overall similar distribution of search volumes from Google Trends compared to results from Medline/Pubmed, SCOPUS, and ClinicalTrials.gov. In brief, the United States and Europe (mainly Italy, the United Kingdom, Spain, France, and Germany) presented the higher RSV. Similarly, these countries showed a higher number of research publications and on-going trials in the field of APS. Conclusion In this study, we demonstrated that the interest in APS is not equally distributed globally. Thus, geopolitical differences might represent a challenge when attempting to estimate the prevalence of APS or designing worldwide investigations in APS. Combining the expanding framework of infodemiology with scientific networking collaborative efforts, such as AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION), will help better define the syndrome in terms of prevalence, event occurrence ratios, and thrombosis risk assessment.

Objective The objective of this study was to determine the efficacy of hydroxychloroquine (HCQ) in the primary thrombosis prevention of antiphospholipid antibody (aPL)-positive patients with no other systemic autoimmune diseases. Methods Under the auspices of Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking, a multicenter, international, randomized controlled trial (RCT) was initiated, in which persistently aPL-positive but thrombosis-free patients without systemic autoimmune diseases were randomized to receive HCQ or no treatment in addition to their standard regimen. The primary objective was the efficacy of HCQ in preventing the first thrombosis. The secondary objectives were the thrombosis incidence rate, and the effects of HCQ on aPL profile and mortality rate. Patients were risk-stratified based on antiplatelet agent use. The goal was to follow patients every 6 months for 5 years. Results We recruited 20 persistently aPL-positive patients (female: 19, mean age: 46.6 ± 9.9 years, and baseline antiplatelet medication: 14); 9/20 were randomized to HCQ. During the mean follow-up of 1.7 years, no patients developed thrombosis or a serious adverse event. The study was terminated early due to the low recruitment rate, exacerbated by the prolonged manufacturing shortage and significant price increase of HCQ in the United States. Conclusion Given that a small number of patients with a relatively short follow-up were enrolled in our RCT, and no patients developed thrombosis, we cannot accurately assess the effectiveness of HCQ for primary thrombosis prevention in persistently aPL-positive patients with no other systemic autoimmune diseases. Our experience suggests that conducting an international RCT, especially without pharmaceutical support, is an extremely challenging undertaking.

The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The purpose of this study was to investigate the effect of inflammatory markers on prognosis in patients with metastatic breast cancer.This study was conducted on 81 patients with metastatic breast cancer who have been followed up at the Department of Medical Oncology, Hacettepe University Institute of Oncology, between December, 2009 and March, 2014. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value0.05 was considered statistically significant.Median follow-up time was 26 months. There were 38 deaths due to disease progression during the follow up. The levels of serum albumin, and erythrocyte sedimentation rate (ESR) were not associated with a significant effect on overall survival (OS). Among patients with a higher serum C-reactive protein (CRP), the estimated mean survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p=0.032). When patients with higher and normal lactate dehydrogenase (LDH) levels were compared, their 2-year OS survival rates were 68.2 and 87.7%, respectively (p=0.034). Among patients with higher serum ferritin levels, the estimated mean survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p=0.01). Among patients with higher serum beta-2 microglobulin (β2-M), the estimated mean OS survival was 28±8 months, compared to 84±57 months for those with normal levels (p0.01).Serum CRP, ferritin and β2-M can be useful prognostic factors for OS in patients with metastatic breast cancer.

Although there are studies that investigate different risk factors and clinicopathological features of breast cancer in women at different age groups and menopausal status, there is a need for studies with larger study populations due to controversial findings. We conducted this study to identify demographic parameters in breast cancer patients and histopathological features of the tumors for different age groups and compare them to demonstrate significant differences, if any.3325 women diagnosed with breast cancer in Hacettepe University Oncology Hospital Outpatient Clinic between January 1994 and March 2014 were included in this study.Postmenopausal women who were older than 65 were found to have higher number of children, higher rates of oral contraceptive use, greater age at menarche, and have higher rates of first full-time pregnancy before the age of 30. On the other hand, higher rates of grade 3 tumors, advanced lymph node stage, lymphovascular invasion, and triple negative breast cancers were more frequently seen in premenopausal women below the age of 35. Since earlier age at the time of diagnosis is associated with bad prognosis, early diagnosis of breast cancer gains importance in younger women.Implementing targeted screening programs of breast cancer for younger women may become a need in the future. Meanwhile, well-education on risks of breast cancer and regular self-examination for early diagnosis need to be emphasized for the prevention of breast cancer and related diseases in young ages.

Myriad factors can lead to a high number of medications in older adults with heart failure (HF) which is concerning as taking at least 10 medications is associated with adverse outcomes. We aimed to examine patterns of polypharmacy among older adults hospitalized with HF. We examined adults aged

Catastrophic antiphospholipid syndrome (CAPS) is a potentially lethal disease that presents with rapidly progressive multiple organ thromboses. Anticoagulation, corticosteroids, intravenous immunoglobulin, and plasma exchange are the most commonly used treatments for CAPS patients. However, the high mortality despite these medications necessitates new treatment strategies. Following a brief review of current diagnostic and management strategies, we discuss the candidate therapies, i.e., hydroxychloroquine, rituximab, eculizumab, sirolimus, and defibrotide, that can be considered in CAPS patients refractory to traditional treatment.

Accurate definition and epidemiology of a disease are the first steps to understand clinical and global burden of a disease. Although antiphospholipid syndrome (APS) has a clear definition for classification of patients with a limited spectrum of clinical and laboratory criteria, a broader spectrum of clinical manifestations exists, and thrombosis may be multifactorial. A standard definition of APS is challenging. Although data on epidemiology of APS are limited, being based on small scale studies or studies with methodological limitations, this chapter gives the best synthesis possible today.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the production of antiphospholipid antibodies (aPL) resulting in clinical complications such as blood clots and pregnancy complications. The purpose of this chapter is to provide a general review of APS for patients and those who are interested in learning more about aPL/APS. Detailed information about aPL-related pregnancy problems can be found in Chapter 20.

Obesity is an epidemic leading to high morbidity, mortality, and therefore health-related costs. Thus, there is a huge need for development of safe and effective treatments. Even though success rates of conservative methods are highly limited, the surgical approaches lead to major complications in as many as 25% of the patients. In this study, we aimed to review the currently available, less-invasive, endoscopic bariatric techniques which provides an option to reduce the risks of the patients and the medical costs.A systematic literature review through Pubmed and Medline was performed to find the studies on this topic, and all controlled clinical trials, case reports, and case series were reviewed.Endoluminal bariatric interventions include restrictive, malabsorptive approaches, and other techniques including transpyloric shuttle, botulinum toxin, gastric pacing and vagal nerve stimulation. Restrictive procedures act by limiting the gastric volume and leading to early satiety, while malabsorptive procedures create a malabsorption state. Transpyloric shuttle is a device decreasing the rate of gastric emptying. Botox injection causes a delay in gastric emptying, and vagal nerve stimulation modulates eating behavior.Endoluminal bariatric techniques can become the primary choice of therapy in the near future for bariatric care.

Endoscopic retrograde cholangiopancreatography (ERCP) is a state of the art diagnostic and therapeutic procedure for various pancreatic and biliary problems. In spite of the well-established safety of the procedure, there is still a risk of complications such as pancreatitis, cholangitis, bleeding and perforation. Air leak syndrome has rarely been reported in association with ERCP and the optimal management of this serious condition can be difficult to establish. Our group successfully managed a case of air leak syndrome following ERCP which was caused by a 3cm Stapfer type I perforation in the posterolateral aspect of the second part of the duodenum and was repaired surgically. Hereby, we describe the presentation and subsequent therapeutic approach.

Iatrogenic perforation of the gut during endoscopy remains an uncommon but critical complication with significant morbidity and probable mortality than usual surgical treatment. Some authors have adopted a non-surgical closure method in chosen cases and, since 1993, endoclips have been used to close perforation in the stomach. The endoscopic practice of endoclips has been commonly used in the gut for hemostasis. Currently, the use of endoscopic techniques is increasing for the closure of endoscopic submucosal dissection or endoscopic mucosal resection. Endoscopic perforations that improved with endoscopic closure in the literature prior to 2008 have been previously described. In the present article, we present a descriptive review of cases with iatrogenic perforation in the gut treated with endoclips between 2008 and 2014.Comprehensive literature screening and a systematic review using PubMed and Medline was done for all reports published between January 2008 and December 2014 using the endoclip technique in the closure of iatrogenic perforations.A total of 47 studies published between 2008 and 2014 using endoclips for the closure of iatrogenic perforations of the gut (nine esophagus, 11 stomach, 15 duodenum, 12 colon and rectum) were found. All studies were explained briefly and summarized in a table.There is strong evidence to show the efficacy of endoclips in the management of iatrogenic perforations, especially when recognized early. Limitations of endoclipping such as inefficiency against large perforations may be overcome by improving novel techniques in the future.

Background: The current management for patients with antiphospholipid syndrome (APS) presenting with arterial thrombosis (AT) remains controversial. There are no prospective data demonstrating the superiority of high over moderate intensity anticoagulation with vitamin K antagonists (VKA) over antiplatelet agents. The Antiphospholipid Antibodies and Stroke Study (APASS showed that the lupus anticoagulant (LA) or anticardiolipin antibodies (aCL) among patients with ischemic stroke did not predict either increased risk for subsequent vascular occlusive events over 2 years or a distinct response to aspirin or VKA. The purpose of our study was to evaluate recurrent thrombosis in patients with APS presenting with AT treated with either antiplatelet and/or anticoagulant therapy. Methods: Using the two antiphospholipid antibody databases (single center [New York Presbyterian Hospital]; and multicenter [APS Alliance for Clinical Trials and International Networking - APS ACTION]), we retrospectively collected the demographic and clinical data of patients with APS who presented with AT. These included gender, age, ethnicity, cardiovascular (CV) risk factors (hypertension, smoking, hyperlipidemia, diabetes and family history of early CV disease), type of antiphospholipid antibodies (aPLs), and treatment modalities (antiplatelet and/or anticoagulant). CV risk factors were only available for patients seen at New York Presbyterian Hospital. The primary outcome was time to thrombosis recurrence and the secondary outcome was any bleeding event while receiving antiplatelet and/or anticoagulant therapy. Kaplan Meier Curves were used to estimate the time at which we expected one fifth of patients to have had a second thrombosis. Results: We identified 139 patients, 92 (66.2%) were females. The median age was 42 years (range 18-84). Majority of patients 85 (61.2%) were Caucasian, 19 (13.7%) Hispanic, 13 (9.4%) Asian, 6 (4.3%) Black, and 1 (0.7%) Middle Eastern and the ethnicity of 15 (10.8%) patients were not recorded. Median follow-up time from initial thrombosis was 4.24 years. Thirty-seven (27.3%) patients were treated with anticoagulants, 43 (30.9%) with antiplatelets, and 58 (41.7%) with both combined. Median age at initial thrombosis was 37, 46, and 42 for the anticoagulant, antiplatelet and combined therapies, respectively. Median number of CV risk factors was 2 in the anticoagulant group, 1 in the antiplatelet group, and 1.5 in the combined therapy group. There were 12 (31.6%), 17 (39.5%) and 21 (36.2%) patients with triple positivity in the anticoagulant, antiplatelet, and combined therapy groups respectively. LA was positive in 30 (78.9%) of patients in the anticoagulant group, 30 (69.8%) in the antiplatelet group, and 47 (81.0%) in the combined therapy group see Table 1. Initial thromboses were observed in cardiac, cerebral, and other arteries. The only major difference across groups was with patients presenting with coronary artery events, who were more likely on antiplatelet agents. Nine (23.7%) patients in the anticoagulant group, 16 (37.2%) in the antiplatelet group and 4 (6.9%) in the combined therapy group experienced a recurrent thrombotic event. Overall, we estimate that 20% of patients will have had a recurrent thrombotic event within 7.3 years of the initial event. Figure 1 This time varies by treatment, with 7.3, 3.4, and 16.3, years until 20% experience a recurrent event in anticoagulants, antiplatelets, and combined therapy groups, respectively. Compared to those on anticoagulants, patients on antiplatelets have a 2.1-fold increase in the hazard ratio, though due to low power the difference was marginally significant (95% CI 0.90, 4.7, p=0.09). Those on combined therapy had a 70% lower hazard of a recurrent event (HR 0.30, 95% CI (0.08, 0.83, p Bleeding was seen in only one of 26 patients for whom data was available. Conclusion: Our results suggest that combined antiplatelet and anticoagulation therapy for APS patients presenting with arterial events, compared to antiplatelet or anticoagulant therapy alone, significantly decreases time to thrombosis recurrence and overall recurrence. These results should be confirmed with prospective randomized controlled trials. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Liver transplantation (LT) is a widely-accepted, definitive therapy of irreversible liver diseases including hepatitis C, alcoholic liver disease and metabolic liver disease. After transplantation, patients generally use a variety of immunosuppressive medications for the rest of their lives to prevent rejection of transplanted liver. Mortality after LT is mainly caused by recurrence of alcoholic hepatitis which is mostly seen in the patients who resume heavy drinking. On the other hand, de-novo malignancies after LT are not seldom. Skin cancers make up 13.5% of the de-novo malignancies seen in these patients. Malignancies tend to affect survival earlier in the course with a 53% risk of death at 5 years after diagnosis. We aimed to report a case who underwent LT secondary to alcoholic liver disease and developed squamous cell carcinoma of the skin eighteen years after transplantation. In summary, transplant recipients are recommended to be educated on self examination for skin cancer; health care providers should be further suspicious during routine dermatological examinations of the transplant patients and biopsies of possible lesions for skin cancer is warranted even many years after transplantation.

Lesser celandine, also known as Ranunculus ficaria, is a herbaceous perennial plant that commonly utilizes piles and is taken either internally or used externally. The causality assessment of several reports provided evidence for the existence of Greater Celandine hepatotoxicity. However, there hasn’t been any case report published thus far, about lesser celandine induced liver injury. Here, we present a case of 36-year-old woman admitted to the hospital with acute hepatitis and jaundice on her sclera with no history of drug abuse or alcohol consumption. However, the patient had a recent history of lesser celandine extract consumption for hemorrhoids, for about 10 d, prior to the admission. Viral hepatitis, autoimmune hepatitis, and drug induced toxic hepatitis were ruled out by further imaging studies and laboratory analysis. Using the Council for International Organizations of Medical Sciences scale, the type of liver injury was assumed as hepatocellular and was scored as 7 which shows probable causality. Immediate discontinuation of lesser celandine extract resulted in rapid decrease of the elevated enzymes. Herbs have been reported to cause liver injury and therefore should be suspected in the case of acute hepatitis with an unknown etiology. This case is important to be the first to explain hepatotoxicity caused by lesser celandine. Physicians should consider lesser celandine as a causative agent for hepatotoxicity.

e11544 Background: Identification of simple and measurable prognostic factors is an important issue in treatment evaluation of breast cancer. Although various markers are considered while making a decision to treatment modality, clinicians investigate for new prognostic factors for reason of highly variable responses of individuals. Therefore, this study estimates the survival probability of the neutrophil to lymphocyte ratio (NLR) for patients with metastatic breast cancer. Methods: We included the patients with metastatic breast carcinoma who were treated for metastasis. NLR were calculated and patients were divided into four quartiles (25th, 50th and 75th NLR; the lowest being the 1st quartile, the highest being 4th quartile ). Survival status was retrieved from our cancer registry. Survival analysis, stratified by NLR quartiles, was used to evaluate the predictive value of NLR. Results: Eighty-one patients with metastatic breast cancer were included in this study. Median age of diagnosis of the patients was 47 (26-83), the majority of them had grade II (%37) and grade III (%29.6) tumors and were metastatic at the time of their initial diagnosis. ER (+), PR (+) and HER2 (+) percentages were confirmed as 82%, 73% and 24% ,respectively. Ten percent of the patients were triple negative. Median follow-up time was 26 months and 29 patients died during the follow up period. We analyzed the overall survival among NLR quartiles. When we compared the quartiles with the highest and lowest NLR values, the quartile with the lowest NLR values had longer median overall survival than the quartile with the highest NLR values (212 vs. 27 months; p=0.01). The second and third quartiles, however, showed no statistically significant difference of overall survival between four quartiles. Conclusions: NLR can be a prognostic factor for overall survival in metastatic breast cancer patients.

Educational status may be an important parameter in assessing breast cancer risk and prognosis. The purpose of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor (ER) status, tumor size, axillary lymph node involvement and metastasis.The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis as follows: low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6-12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated.In all patient, a significant relationship was found between educational status and T stages (p0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age and were less likely to have axillary lymph node involvement (p=0.001) or metastasis (p=0.001). A significant correlation was found between educational status and ER positivity in patients over 50 years of age (p=0.03). When the patients of all ages were evaluated, no statistically significant correlation was shown (p=0.27) between educational status and ER positivity. A significant relationship was found between educational status and HER-2 status (p=0.003), regardless of the patients' age. HER-2 positivity increased in patients with low educational status, however this significance was lost in patients over the age of 50 (p=0.1).The relationship between educational status and biological factors in breast cancer are not conclusive as yet, but this particular study revealed that educational status played a major influence in each of the five breast cancer prognostic factors: ER status, HER-2 status, tumor size, lymph node status and metastasis.