In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

New England Journal of Medicine

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Journal of the American College of Cardiology

Cardiac arrest is a serious condition frequently managed in the emergency department (ED). Medications are a component of cardiac arrest management.

This paper evaluates key evidence-based updates concerning medications used for patients in cardiac arrest.

Several medications have been evaluated for use in cardiac arrest. Routes of administration may include intravenous (IV) and intraosseous (IO). IV administration is recommended, though if an attempt at IV access is unsuccessful, IO access can be utilized. Epinephrine is a core component of guidelines, which recommend 1&#xa0;mg in those with shockable rhythms if initial CPR and defibrillation are unsuccessful, while in nonshockable rhythms, guidelines recommend that epinephrine 1&#xa0;mg be administered as soon as feasible. While epinephrine may improve rates of ROSC, it is not associated with improved survival with a favorable neurologic outcome. Evidence suggests the combination of vasopressin, steroids, and epinephrine may improve ROSC among those with in-hospital cardiac arrest, but there is no improvement in survival to discharge and survival with a favorable neurologic outcome. Antiarrhythmics (e.g., amiodarone, lidocaine, procainamide) likely do not improve short-term or long-term survival or neurologic outcomes, though guidelines state that amiodarone may be used in those with cardiac arrest and refractory pulseless ventricular tachycardia (pVT)/ventricular fibrillation (VF). Calcium and sodium bicarbonate should not be routinely administered in those with cardiac arrest. Beta-blockers may be considered in those with shock-resistant pVT/VF.

An understanding of literature updates concerning medication use in cardiac can improve the ED care of these patients.

Emergency medicine updates: Cardiac arrest medications.

American Journal of Emergency Medicine

To review the key updates in the 2024 KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease (CKD) and highlight the essential role of pharmacists in implementing these recommendations.

The updated guideline introduces significant changes in CKD management, including the use of validated equations for estimating glomerular filtration rate (GFR) for drug dosing, with incorporation of serum cystatin C into GFR estimates for specific patient populations, and an emphasis on a comprehensive approach to delay disease progression. The guideline recommends sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy for kidney disease with proteinuria, with or without diabetes, renin-angiotensin-aldosterone system inhibitors (RAASi) blood pressure control and proteinuria management, and statins to reduce the risk of atherosclerotic cardiovascular disease. New evidence supports the use of finerenone in patients with type 2 diabetes and CKD, and GLP-1 receptor agonists for their kidney-protective effects. The guidelines also emphasize the importance of nephrotoxin stewardship and prevention of acute kidney injury through patient education on sick day medication management.

Pharmacists play a crucial role in implementing these updated guidelines through comprehensive medication management, nephrotoxin stewardship, drug dosing adjustments, and patient education. Their involvement in interprofessional care teams is essential for optimizing health outcomes in patients with CKD.

KDIGO 2024 clinical practice guideline on evaluation and management of chronic kidney disease: A primer on what pharmacists need to know.

American Journal of Health-system Pharmacy : AJHP

Accurate measurements of the platelet count are necessary to diagnose thrombocytosis or thrombocytopenia correctly, gauge the severity of the clinical risk and identify the most appropriate therapeutic intervention. Despite increased diagnostic accuracy with the electronic counters, it is still unsatisfactory in rare situations. Conditions causing spurious thrombocytopenia include the following. 1) Pre-analytical errors, such as difficult venipunctures, over-/under-filling of blood collection tubes, insufficient mixing of blood with the anticoagulant (EDTA), which may cause fibrin formation; 2) EDTA-induced, temperature- and time-dependent, antibody-mediated in vitro platelet agglutination, with consequent reduction in the number of single platelets in the sample; the condition, referred to as Pseudothrombocytopenia, is benign and does not need follow-up or medical interventions; the use of alternative in vitro anticoagulants does not prevent agglutinates formation in all samples; accurate platelet counts could be obtained by testing EDTAsamples immediately after blood collection. 3) EDTA-induced in vitro platelet adherence to leukocytes (Platelet Satellitism), caused by bridging IgG antibodies binding to GPIIb-IIIa on platelets and the Fc receptor-III on leukocytes; occasionally, leukocytes may phagocytose platelets and/or form platelets/leukocytes clumps. 4) Presence of large/giant platelets (commonly from patients with congenital or acquired thrombocytopenia) that are not recognized as such by electronic counters, which distinguish platelets from other cells based on their smaller size. 5) Blood from patients with type 2B von Willebrand Disease, which may display large/giant platelets and platelet agglutinates. All the above conditions are easily identifiable by microscopic examination of anticoagulated peripheral blood smears, which is an indispensable diagnostic procedure in hematology.

Pseudothrombocytopenia and other conditions associated with spuriously low platelet counts.

Haematologica

Background : Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by persistent antiphospholipid antibodies (aPL) in combination with recurrent thrombosis in the veins and/or arteries, obstetric morbidity, and various non-thrombotic associated complications. APS can be primary, as an isolated condition, or secondary in the context of another autoimmune disease, especially systemic lupus erythematosus. This comprehensive clinical review aims to summarize the current understanding of APS pathogenesis, diagnostic approaches, and treatment strategies for this unique clinical entity. Methods : A comprehensive review of the existing literature on APS was conducted, focusing on pathophysiological mechanisms, current diagnostic criteria, and therapeutic approaches. Results : APS pathogenesis involves complex interactions between aPL, phospholipid-binding proteins, and the coagulation cascade. Apart from the cardinal features of thrombosis and APS-related obstetric morbidity, APS is associated with a wide spectrum of clinical manifestations. Diagnosis remains challenging due to overlapping symptoms with other conditions, and clinicians should maintain a high index of suspicion in order to set the diagnosis. The recently published 2023 ACR/EULAR criteria although not definitive for clinical decision-making, these criteria offer clinicians a valuable tool to aid in determining whether further investigation for APS is warranted. Continued refinement of these criteria through ongoing feedback and updates is anticipated. Treatment strategies center on anticoagulation, but individualized approaches are necessary. Conclusions : Early diagnosis and multidisciplinary management of APS are critical to reducing morbidity and improving outcomes. Moreover, familiarization with the 2023 ACR/EULAR criteria is encouraged, recognizing that ongoing feedback and updates will contribute to their ongoing refinement and improvement. While VKAs remain the mainstay of treatment for most APS patients further research is needed to optimize treatment strategies and deepen our understanding of APS's underlying disease mechanisms.

Antiphospholipid Syndrome: A Comprehensive Clinical Review.

Journal of Clinical Medicine

At the 10th European Conference on Infections in Leukaemia (ECIL), the guidelines for antifungal prophylaxis in pediatric and adult patients with hematological malignancies (HM) were updated and some changes introduced. Regarding acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients undergoing remission induction chemotherapy, a B-II grading has been assigned to isavuconazole, micafungin, and caspofungin, based on non-randomized studies that have shown efficacy in preventing invasive fungal diseases (IFD). Regarding high-risk MDS patients treated with azacytidine, prophylaxis with posaconazole during the first four cycles of treatment is supported in the literature. Prophylaxis is not indicated in patients treated for myeloproliferative neoplasms (NPM), acute lymphoid leukemia (ALL), and Hodgkin lymphoma (HL). For patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), prophylaxis is not generally indicated. For patients with multiple myeloma (MM), prophylaxis is not indicated and the limited epidemiological data available do not support the use of prophylaxis in subjects treated with bispecific antibodies. For patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), no substantial changes were made, apart from the addition of isavuconazole with grading B-II in the post-engraftment period. In patients undergoing auto-HSCT, antifungal prophylaxis is not indicated. Previous ECIL guidelines did not include CAR-T cells. The expert panel proposes to endorse the use of anti-mold prophylaxis in high-risk patients during pre-infusion and post-infusion, while in low-risk patients, anti-yeast prophylaxis can be recommended (B-II). For pediatric hematology patients, based on newly published data, caspofungin received a B-I grading as mold-active prophylaxis. Moreover, patients with ALL with insufficient treatment response during induction therapy, and children older than 12&#x2009;y.o are now considered at high risk for IFD and are recommended to receive antifungal prophylaxis.

Primary antifungal prophylaxis in hematological malignancies. Updated clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL).

Leukemia

Whether the choice of ventilator mode affects outcomes for critically ill patients is unknown.

What are the effects of three common ventilator modes (volume control vs pressure control vs adaptive pressure control) on death and duration of mechanical ventilation among critically ill adults?

We conducted a pragmatic, cluster-randomized, crossover pilot trial among adults receiving invasive mechanical ventilation in a medical intensive care unit between November 1, 2022 and July 31, 2023. Each month, patients in the participating unit were assigned to receive volume control, pressure control, or adaptive pressure control during continuous mandatory ventilation. The primary outcome was ventilator-free days through 28 days.

Among 566 patients included in the primary analysis, the median proportion of ventilator mode assessments in the assigned mode during the first 72 hours was 100% in each group. The median number of ventilator-free days was 23 [IQR, 0-26] in the volume control group, 22 [0-26] in the pressure control group, and 24 [0-26] in the adaptive pressure control group (P=0.60). The median tidal volume was similar in the three groups, but the percentage of breaths larger than 8mL/kg of predicted body weight differed between volume control (median, 4.0%; IQR, 0.0-14.1), pressure control (10.6%; 0.0-31.5), and adaptive pressure control (4.7%; 0.0-19.2).

This pilot trial establishes the feasibility of conducting a cluster-randomized, crossover trial of ventilator mode among critically ill adults receiving invasive mechanical ventilation and demonstrates differences in intermediate outcomes that warrant further investigation in a larger trial.

Effect of Ventilator Mode on Ventilator-Free Days in Critically Ill Adults: A Randomized Clinical Trial.

Chest

Pancreatic cancer is frequently a lethal disease with an aggressive tumour biology often presenting with non-specific symptoms. Median survival is approximately 4 months with a 5-year survival of 13%. Surveillance is recommended in individuals with familial pancreatic cancer, specific mutations, and high-risk intraductal papillary mucinous neoplasm, as they are at high risk of developing pancreatic cancer. Chemotherapy combined with surgical resection remains the cornerstone of treatment. However, only a small subset of patients are candidates for surgery. Multi-agent chemotherapy has improved survival in the palliative setting for patients with metastatic disease, as (neo)adjuvant and induction therapy have in patients with borderline resectable and locally advanced pancreatic. Given that pancreatic cancer is predicted to become the second leading cause of cancer-related death by 2030, novel therapies are urgently needed.

Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

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