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Introduction: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare entity with no standard of care and high mortality, despite the use of plasma exchange. Methods: Using specific search terms, all cases having TA-TMA treated with eculizumab and indexed in MEDLINE (English language only) by November 2014 were reviewed. Results: A total of 26 cases, 53% men, had a median age of 33 years (range 2-61). Transplant-associated thrombotic microangiopathy occurred after stem-cell transplant (35%) or solid-organ transplant (65%), frequently associated with the use of cyclosporine or tacrolimus (96%). A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS 13) level was always >10%. After TA-TMA diagnosis, the following drug adjustments were made: discontinuation of cyclosporine or tacrolimus in 45%, dose reduction in another 27%, continuation of the drugs in 23%, and switch from cyclosporine to tacrolimus in remaining 5%. Plasma exchange was performed in ∼43%. The median interval between transplant and initiation of eculizumab was 63 days (range 11-512). A median of 5.5 doses (range 2-21) of eculizumab was utilized with 92% response occurring after a median of 2 doses (range 1-18). At a median follow-up of 52 weeks (range 3-113), the survivors (92%) were doing well. Conclusion: Within the limits of this retrospective analysis, our study demonstrates that eculizumab use may result in high response rate and 1-year survival in patients with TA-TMA refractory to discontinuation of calcineurin inhibitor and plasma exchange.

Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss. Although minor bleed may be managed with discontinuation of anticoagulant, major bleed may require transfusion of blood products and use of specific antidote. The residual effects of each anticoagulant may be monitored with distinct coagulation assay. Intravenous or oral vitamin K can reverse the effect of warfarin within 24 to 48 hours and is indicated for any bleeding, international normalized ratio of >10 or 4.5 to 10 in patients with other risk factors for bleeding. Fresh frozen plasma or prothrombin complex concentrate (PCC) may be necessary in major bleeding related to warfarin. Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially. Idarucizumab has recently been approved in United States for dabigatran reversal, whereas andexanet alfa is expected to get approved in the near future for reversal of oral factor Xa inhibitors. The PCC may reverse the effect of rivaroxaban to some extent, but no data are available regarding reversal of apixaban and edoxaban. Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase.

Background To evaluate if United States Medical Licensing Examination (USMLE) Step 1, USMLE Step 2 CK, USMLE Step 3, and residency third-year in-service training exam (ITE) scores predict the results of American Board of Internal Medicine Certifying Exam (ABIM-CE). Methods We performed a retrospective review of USMLE Step 1, USMLE Step 2 CK, USMLE Step 3, third-year residency ITE scores and ABIM-CE results of IM residents at our residency program from 2004 through 2017. Statistical analysis was perfrormed using Pearson correlation coefficient, and logistic regression to assess the relationship between USMLE Step 1, USMLE Step 2CK, USMLE Step 3, 3rd year ITE scores and ABIM-CE results. We used Multivariate logistic regression to predict pass or fail results in ABIM-CE based on USMLE and third-year ITE test scores controlling for other covariates. Results Among 114 Internal Medicine MD residents included in the study, 92% ( n  = 105) passed the ABIM-CE. The OR of passing ABIM-CE was 2.70 (95% CI = 1.38–5.29), 2.31 (95% CI = 1.33–4.01), and 1.63 (95% CI = 0.81–3.29) with a ten-point increase in USMLE Step 1, USMLE Step 2 CK and USMLE Step 3 scores respectively. The OR of ABIM-CE passing chance was 2.96 (95% CI = 0.95–9.20), with a ten-point increase in the average score of the above three exams. A 5 % increase in ITE percentage raised the likelihood of passing ABIM-CE (OR 2.92, 95% CI 1.15–7.38). All residents who failed ABIM-CE had Step 1 scores < 220. Among 31 residents with Step 2 CK score < 220, 20% ( n  = 6) failed ABIM. Similarly, 9% of residents with USMLE Step 3 score < 220 failed ABIM-CE; all residents who failed had scored < 220. The probability curve predicted that the chance of passing ABIM- CE was around 80% with USMLE scores greater than 200 and increased to almost 100% with USMLE scores of 250 or more. Conclusion USMLE Step 1, USMLE Step 2 CK, and third-year ITE scores can predict the chances of passing ABIM-CE. The third-year ITE score has a higher preditive value compared to USMLE Step 1 and USMLE Step 2 scores. USMLE Step 1 scores more predictive of ABIM-CE results compared to USMLE Step 2CK scores. Thus, residency programs can identify internal medicine residents at risk of failing ABIM-CE and formulate interventions at an early stage during residency training. Measures such as enrolling them in question banks or board review courses can be helpful in improving their chances of passing ABIM-CE.

Ever since the association between cancer and thrombosis was reported by Jean-Baptiste Bouillaud in the early 19th century, cancer-associated thrombosis has remained a challenging domain of cancer management. Thrombosis can at times be a lead to cancer diagnosis, while it often complicates medical situations as a coexisting disorder. In this handbook, the contributors have compiled comprehensive information on the subject to provide the reader a comprehensive review of current medical literature and guidelines for cancer-associated thrombosis. Key Features -clinically oriented text for application in healthcare settings -current, evidence-based literature reviews and references -includes guidelines on VTE prophylaxis, heparin effects and more -includes information about special cases Thrombosis in Cancer: A Medical Professional's Guide to Cancer Associated Thrombosis is an informative handbook for a broad range of readers in medicine, including generalists, residents, and graduate-level trainees.

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal, multifactorial disorder, which may present with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. The pathogenesis of TA-TMA is complex and includes multiple risk factors such as certain conditioning regimens, calcineurin inhibitors (CNIs), graft-versus-host disease (GVHD), human leukocyte antigen mismatch, and opportunistic infections. The end result of these insults is endothelial injury in the kidney and other organs. Recent studies also indicate a role of complement activation in tissue damage. The lack of sensitive and specific diagnostic tests for TA-TMA often results in delayed diagnosis. Biopsy is not always possible for diagnosis because of the risk of complications such as bleeding. Recently, an emerging role of renal-centered screening approach has been demonstrated, which utilize the monitoring of blood pressure, urine protein, serum lactate dehydrogenase and hemogram for early detection. Therapeutic options are limited, and plasma exchange plays a minor role. Withdrawal of offending agent such as CNIs and the use of rituximab can be effective in some patients. However, the current treatment strategy is suboptimal and associated with high mortality rate. Recently, eculizumab has been utilized in a few patients with good outcomes. Patients, who develop TA-TMA, are also at an increased risk of GVHD, infection, renal, cardiovascular, and other complications, which can contribute to high mortality. Better understanding of molecular pathogenesis, improvement in posttransplant management, leading to early diagnosis, and management of TA-TMA are required to improve outcomes of this fatal entity.

We report a rare case of congenital toxoplasmosis in a 2‐month‐old female infant from rural Nepal, born to a primigravida mother without prenatal care. The infant presented with progressive lethargy, feeding difficulties, intermittent fever, and progressive macrocephaly. Neuroimaging revealed obstructive hydrocephalus and multiple cerebral ring‐enhancing lesions without intracranial calcifications. Ophthalmologic examination demonstrated bilateral chorioretinitis. Serologic testing confirmed congenital toxoplasmosis. Despite initiation of standard therapy with pyrimethamine, sulfadiazine, and folinic acid, the infant experienced clinical deterioration prior to planned neurosurgical intervention. This case highlights the clinical and radiologic variability of congenital toxoplasmosis, the diagnostic challenges in resource‐limited settings, and the importance of recognizing atypical imaging patterns to guide timely management.

Non-vitamin K antagonist oral anticoagulants (NOACs) include thrombin inhibitor dabigatran and coagulation factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and betrixaban. NOACs have several benefits over warfarin, including faster time to the achieve effect, rapid onset of action, fewer documented food and drug interactions, lack of need for routine INR monitoring, and improved patient satisfaction. Local hemostatic measures, supportive care, and withholding the next NOAC dose are usually sufficient to achieve hemostasis among patients presenting with minor bleeding. The administration of reversal agents should be considered in patients on NOAC's with major bleeding manifestations (life-threatening bleeding, or major uncontrolled bleeding), or those who require rapid anticoagulant reversal for an emergent surgical procedure. The Food and Drug Administration (FDA) has approved two reversal agents for NOACs: idarucizumab for dabigatran and andexanet alfa for apixaban and rivaroxaban. The American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) have released an updated guideline for the management of patients with atrial fibrillation that provides indications for the use of these reversal agents. In addition, the final results of the ANNEXA-4 study that evaluated the efficacy and safety of andexanet alfa were recently published. Several agents are in different phases of clinical trials, and among them, ciraparantag has shown promising results. However, their higher cost and limited availability remains a concern. Here, we provide a brief review of the available reversal agents for NOACs (nonspecific and specific), recent updates on reversal strategies, lab parameters (including point-of-care tests), NOAC resumption, and agents in development.

The global demand for concrete, driven by rapid industrialization and urbanization, has led to significant depletion of natural aggregates and increased environmental concerns. Natural aggregates, which constitute about 70%–80% of concrete mix volume, are essential for concrete production, but their extraction, processing, and transport contribute to considerable environmental degradation. The extensive demolition of old infrastructure due to urban growth generates massive construction and demolition waste (CDW), exacerbating landfill shortages and leading to contamination of groundwater and ecosystems. This paper explores the use of recycled aggregate concrete (RAC) derived from CDW as an alternative to natural aggregates, offering a sustainable solution to reduce waste, conserve natural resources, and minimize environmental impact. It examines the structural and environmental implications of RCA in concrete, particularly focusing on challenges such as high porosity, elevated water absorption, and reduced mechanical and durability performance. Strategies to overcome these limitations, such as incorporating supplementary cementitious materials (fly ash, silica fume), advanced mixing techniques like the Two‐Stage Mixing Approach (TSMA), and fiber reinforcement, are critically discussed. The review also emphasizes the role of numerical models and machine learning in optimizing RAC mix designs and predicting its behavior, offering valuable insights for sustainable construction practices. Furthermore, the study incorporates Life Cycle Assessment (LCA) to quantify environmental benefits and assesses real‐world applications and current codal provisions. The conclusions drawn suggest that RAC, if optimized with appropriate mix designs and processing methods, can significantly contribute to sustainable construction. However, more research is needed to standardize RCA processing methods and conduct long‐term field validations to further enhance its mechanical and durability properties. RAC not only presents an environmentally beneficial alternative to traditional concrete, but also supports a circular economy by reducing CDW and minimizing reliance on natural resources. Methodology flowchart.

Objectives: Patients with a history of heparin-induced thrombocytopenia (HIT), who require subsequent anticoagulation, have limited options. Rechallenge with unfractionated heparin (UFH) has been reported but may be associated with a risk of recurrence of HIT. The objective of this study was to determine the safety of heparin reexposure in patients with a history of HIT. Methods: Using several search terms, all cases of heparin reexposure in patients with HIT indexed in MEDLINE (English language only) by June 2014 were reviewed. The bibliography of each relevant article was searched for additional reports. In cases of multiple reexposures, each reexposure was identified as a separate instance of reexposure during analysis. Results: A total of 136 patients with a history of HIT had 141 instances of heparin reexposure. Cardiac (76%) and vascular surgeries (11%) were the most common indications. Antiplatelet factor 4/heparin antibodies were positive in 63% of evaluable cases before reexposure. Preexposure plasma exchange (11%) and postexposure nonheparin anticoagulants (63%) were frequently utilized. Complications with heparin reexposure included recurrence of HIT (2.1%, 95% confidence interval 0.73%-6.07%) and bleeding (2.1%). Conclusion: Intraoperative heparin reexposure in patients with a history of HIT has a small risk of developing HIT recurrence. The use of preexposure plasma exchange in patients with positive antiplatelet factor 4/heparin antibody and postexposure nonheparin anticoagulants arguably may have reduced the risk of recurrence of HIT.

This study aimed to identify predictors of venous thromboembolism (VTE) in hospitalized cancer patients and develop a predictive model using demographic, clinical, and laboratory data. Our analysis showed that patient groups categorized under a very high risk, and high risk, patients with low hemoglobin levels and renal disease were at a significantly increased risk of developing VTE. We developed a VTE risk-assessment model (RAM) with moderate discriminatory performance, high specificity, and negative predictive value, indicating its potential utility in identifying patients without VTE risk. However, the model's positive predictive value and sensitivity were low due to the low prevalence of VTE within the analyzed population. Future studies are needed to analyze additional predictive factors, and to validate the effectiveness of our VTE RAM to safely rule out VTE, compare it with other VTE RAMs in hospitalized cancer patients, and address any limitations of our study.