Retrieval Augmented Generation Enabled Generative Pre-Trained Transformer 4 (GPT-4) Performance for Clinical Trial Screening.

Background: Subject screening is a key aspect of all clinical trials; however, traditionally, it is a labor-intensive and error-prone task, demanding significant time and resources. With the advent of large language models (LLMs) and related technologies, a paradigm shift in natural language processing capabilities offers a promising avenue for increasing both quality and efficiency of screening efforts. This study aimed to test the Retrieval-Augmented Generation (RAG) process enabled Generative Pretrained Transformer Version 4 (GPT-4) to accurately identify and report on inclusion and exclusion criteria for a clinical trial. Methods: The Co-Operative Program for Implementation of Optimal Therapy in Heart Failure (COPILOT-HF) trial aims to recruit patients with symptomatic heart failure. As part of the screening process, a list of potentially eligible patients is created through an electronic health record (EHR) query. Currently, structured data in the EHR can only be used to determine 5 out of 6 inclusion and 5 out of 17 exclusion criteria. Trained, but non-licensed, study staff complete manual chart review to determine patient eligibility and record their assessment of the inclusion and exclusion criteria. We obtained the structured assessments completed by the study staff and clinical notes for the past two years and developed a workflow of clinical note-based question answering system powered by RAG architecture and GPT-4 that we named RECTIFIER (RAG-Enabled Clinical Trial Infrastructure for Inclusion Exclusion Review). We used notes from 100 patients as a development dataset, 282 patients as a validation dataset, and 1894 patients as a test set. An expert clinician completed a blinded review of patients' charts to answer the eligibility questions and determine the "gold standard" answers. We calculated the sensitivity, specificity, accuracy, and Matthews correlation coefficient (MCC) for each question and screening method. We also performed bootstrapping to calculate the confidence intervals for each statistic. Results: Both RECTIFIER and study staff answers closely aligned with the expert clinician answers across criteria with accuracy ranging between 97.9% and 100% (MCC 0.837 and 1) for RECTIFIER and 91.7% and 100% (MCC 0.644 and 1) for study staff. RECTIFIER performed better than study staff to determine the inclusion criteria of "symptomatic heart failure" with an accuracy of 97.9% vs 91.7% and an MCC of 0.924 vs 0.721, respectively. Overall, the sensitivity and specificity of determining eligibility for the RECTIFIER was 92.3% (CI) and 93.9% (CI), and study staff was 90.1% (CI) and 83.6% (CI), respectively. Conclusion: GPT-4 based solutions have the potential to improve efficiency and reduce costs in clinical trial screening. When incorporating new tools such as RECTIFIER, it is important to consider the potential hazards of automating the screening process and set up appropriate mitigation strategies such as final clinician review before patient engagement.

Machine Learning in Invasive and Noninvasive Coronary Angiography.

PURPOSE OF REVIEW: The objective of this review is to shed light on the transformative potential of machine learning (ML) in coronary angiography. We aim to understand existing developments in using ML for coronary angiography and discuss broader implications for the future of coronary angiography and cardiovascular medicine. RECENT FINDINGS: The developments in invasive and noninvasive imaging have revolutionized diagnosis and treatment of coronary artery disease (CAD). However, CAD remains underdiagnosed and undertreated. ML has emerged as a powerful tool to further improve image analysis, hemodynamic assessment, lesion detection, and predictive modeling. These advancements have enabled more accurate identification of CAD, streamlined workflows, reduced the need for invasive diagnostic procedures, and improved the diagnostic value of invasive procedures when they are needed. Further integration of ML with coronary angiography will advance the prevention, diagnosis, and treatment of CAD. The integration of ML with coronary angiography is ushering in a new era in cardiovascular medicine. We highlight five use cases to leverage ML in coronary angiography: (1) improvement of quality and efficacy, (2) characterization of plaque, (3) hemodynamic assessment, (4) prediction of future outcomes, and (5) diagnosis of non-atherosclerotic coronary disease.

Virtual Care Team Guided Management of Patients With Heart Failure During Hospitalization.

BACKGROUND: Scalable and safe approaches for heart failure guideline-directed medical therapy (GDMT) optimization are needed. OBJECTIVES: The authors assessed the safety and effectiveness of a virtual care team guided strategy on GDMT optimization in hospitalized patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In a multicenter implementation trial, we allocated 252 hospital encounters in patients with left ventricular ejection fraction ≤40% to a virtual care team guided strategy (107 encounters among 83 patients) or usual care (145 encounters among 115 patients) across 3 centers in an integrated health system. In the virtual care team group, clinicians received up to 1 daily GDMT optimization suggestion from a physician-pharmacist team. The primary effectiveness outcome was in-hospital change in GDMT optimization score (+2 initiations, +1 dose up-titrations, -1 dose down-titrations, -2 discontinuations summed across classes). In-hospital safety outcomes were adjudicated by an independent clinical events committee. RESULTS: Among 252 encounters, the mean age was 69 ± 14 years, 85 (34%) were women, 35 (14%) were Black, and 43 (17%) were Hispanic. The virtual care team strategy significantly improved GDMT optimization scores vs usual care (adjusted difference: +1.2; 95% CI: 0.7-1.8; P < 0.001). New initiations (44% vs 23%; absolute difference: +21%; P = 0.001) and net intensifications (44% vs 24%; absolute difference: +20%; P = 0.002) during hospitalization were higher in the virtual care team group, translating to a number needed to intervene of 5 encounters. Overall, 23 (21%) in the virtual care team group and 40 (28%) in usual care experienced 1 or more adverse events (P = 0.30). Acute kidney injury, bradycardia, hypotension, hyperkalemia, and hospital length of stay were similar between groups. CONCLUSIONS: Among patients hospitalized with HFrEF, a virtual care team guided strategy for GDMT optimization was safe and improved GDMT across multiple hospitals in an integrated health system. Virtual teams represent a centralized and scalable approach to optimize GDMT.

Accurate interpretation of thyroid dysfunction during pregnancy: should we continue to use published guidelines instead of population-based gestation-specific reference intervals for the thyroid-stimulating hormone (TSH)?

BACKGROUND: Considering the changes in thyroid physiology associated with pregnancy and poor outcomes related to abnormal maternal thyroid function, international guidelines recommend using population-based trimester-specific reference intervals (RIs) for thyroid testing. If these RIs are not available in the laboratory, implementing recommended fixed cut-off values globally is still controversial. To address this issue, we aimed to establish appropriate RI of thyroid-stimulating hormone (TSH) in pregnant Turkish women for our laboratory and compare the prevalence of thyroid dysfunction based on the established and recommended criteria. METHODS: Of 2638 pregnant women, 1777 women followed in the obstetric outpatient were enrolled in the reference interval study after applying exclusion criteria related to medical and prenatal history. A retrospective study was conducted by collecting data from July 2016 to March 2019. Serum TSH was measured by UniCel DxI 800 Immunoassay System (Beckman Coulter Inc., Brea, CA, USA). The study design relied on two approaches in order to classify pregnant women: trimester-specific and subgroup-specific; the latter involved dividing each trimester into two subgroups: T1a, T1b, T2a, T2b, T3a, T3b. The lower and upper limits of the RIs were derived by the parametric method after normalizing the data distribution using the modified Box-Cox power transformation method. RESULTS: The lowest TSH value was detected at 8-12 weeks in early pregnancy, and the median value of TSH in the T1b subgroup was significantly lower than the T1a subgroup (P < 0.05). TSH levels showed a gradual trend of increase along with the pregnancy and increased significantly in the T2a, T2b, and T3b subgroups compared to the preceding subgroups (P < 0.05). Compared to the diagnostic criteria recommended by American Thyroid Association (ATA), the prevalence of thyroid dysfunction was significantly different from the established trimester- and subgroup-specific RIs throughout the pregnancy (P < 0.001). CONCLUSIONS: We conclude that establishing gestation- and laboratory-specific RIs, especially for TSH, is essential for diagnosing thyroid disorders in pregnancy, and the recommended universal cut-off values, which may contribute to the risk of a misdiagnosis or a missed diagnosis, should be taken with caution in the clinical setting. However, regarding the fluctuation of thyroid function tests throughout pregnancy, trimester-specific RIs are insufficient, and implementing split phases is required.

Antiphospholipid antibodies and the risk of autoimmune hemolytic anemia in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

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, antiß2Glycoprotein I antibodies (OR = 3.21 [95% CI; 1.54-6.72]), especially IgM antiß2Glycoprotein 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.

Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID-19.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Inclusion of Performance Parameters and Patient Context in the Clinical Practice Guidelines for Heart Failure.

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.

Polypharmacy in Older Adults Hospitalized for Heart Failure.

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.

Impact of antiphospholipid syndrome iBook on medical students' improvement of knowledge: An international randomized controlled study.

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, naïve 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.

Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease.

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.

The Impact of Systemic Lupus Erythematosus on the Clinical Phenotype of Antiphospholipid Antibody-Positive Patients: Results From the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Clinical Database and Repository.

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-ß2 -glycoprotein I (anti-ß2 GPI) antibodies was higher in the aPL-positive patients with SLE, whereas the frequency of cognitive dysfunction and IgG anti-ß2 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-ß2 GPI antibodies.

Infodemiology of antiphospholipid syndrome: Merging informatics and epidemiology.

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.

Prognostic role of inflammatory biomarkers in metastatic breast cancer.

PURPOSE: 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. METHODS: 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 value < 0.05 was considered statistically significant. RESULTS: 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 (ß2-M), the estimated mean OS survival was 28±8 months, compared to 84±57 months for those with normal levels (p<0.01). CONCLUSION: Serum CRP, ferritin and ß2-M can be useful prognostic factors for OS in patients with metastatic breast cancer.

Risk factors and histopathological features of breast cancer among women with different menopausal status and age at diagnosis.

PURPOSE: 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. METHODS: 3325 women diagnosed with breast cancer in Hacettepe University Oncology Hospital Outpatient Clinic between January 1994 and March 2014 were included in this study. RESULTS: 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. CONCLUSION: 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.

Catastrophic Antiphospholipid Syndrome: Candidate Therapies for a Potentially Lethal Disease.

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.