IV Sodium Ferric Gluconate Complex in Patients Hospitalized Due to Acute Decompensated Heart Failure and Iron Deficiency

Background: Patients suffering from heart failure (HF) and iron deficiency (ID) have worse outcomes. Treatment with intra-venous (IV) ferric carboxymaltose has been shown to reduce HF rehospitalizations and to improve functional capacity and symptoms in patients with HF and reduced ejection fraction (HFrEF). However, IV ferric carboxymaltose is significantly more expensive than IV sodium ferric gluconate complex (SFGC) limiting its availability to most HF patients around the globe. Methods: A retrospective analysis comparing patients admitted to internal medicine or cardiology departments between January 2013 to December 2018 due to acute decompensated HF (ADHF) and treated with or without IV SFGC on top of standard medical therapy. Results: During the study period, a total of 1863 patients were hospitalized due to ADHF with either HFrEF or HF with preserved ejection fraction (HFpEF). Among them, 840 patients had laboratory evidence of iron deficiency (absolute or functional) and met the inclusion criteria. One hundred twenty-two of them (14.5%) were treated with IV SFGC during the index hospitalization. Patients treated with IV iron were more likely to have history of ischemic heart disease, atrial fibrillation, and chronic kidney disease. The rate of readmissions due to ADHF was similar between the groups at 30 days, 3 months, and 1 year. Conclusion: High risk patient hospitalized to ADHF and treated with IV SFGC showed comparable ADHF readmission rates, compared to those who did not receive iron supplementation.

Recent Advances in Bedside Device-Based Early Detection of Sepsis

Early detection of sepsis is challenging to achieve with current diagnostic methods, leading to expenditures of $27 billion annually in the United States with significant associated mortality. Various scoring systems have been proposed such as the sequential organ failure assessment (SOFA) and systemic inflammatory response syndrome (SIRS) criteria for identification of sepsis, but their sensitivities range from 60% to 70% when used in the emergency department triage. Other methods for the recognition of sepsis may rely on laboratory work, in addition to vitals monitoring, and are often outpaced by the development of sepsis. Automated alerts have not shown any reduction in mortality thus far. New technology may fill a critical gap in the early detection of sepsis. The ideal bedside screening device for would demonstrate rapid time to result, high portability, and high sensitivity to not miss cases, but also reasonable specificity to prevent provider fatigue from excessive false alerts. Non-invasive end-organ perfusion devices analyzing lactate and capillary refill time (CRT) tend to perform well in speed and portability, but may be less sensitive. Biomarker devices demonstrate a wider array of performance metrics. Those analyzing a single biomarker tend to be more sensitive but are less specific to the diagnosis of sepsis than technologies that assess multiple biomarkers, which in turn have lower sensitivity. Additionally, biomarker devices are generally invasive requiring blood samples, which may or may not be feasible in all patients especially when serial draws are needed. Sepsis is a complex disease process and most likely will require a combination of improved technology in addition to vital signs and high-risk patient history for better recognition. This review examines recent advances in the device-based early detection of sepsis between 2017 and 2020 with emphasis on bedside diagnostics, divided into markers of perfusion and biomarkers commonly implicated in sepsis.

Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients

Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled. TCR αβ/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1 × 106 CD34+ cells/kg and 14.2 × 103 TCRαβ+ T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCRαβ/CD19-depleted grafts represents a viable treatment option.

Effect of haemodynamics on the risk of ischaemic stroke in patients with severe vertebral artery stenosis

ObjectivesEndovascular treatment strategies to optimise individualised care for patients with vertebral artery (VA) stenosis need to be revisited. This study aimed to investigate the relationship between net VA flow volume (NVAFV) and the risk of posterior circulation infarction (PCI) in a high-risk patient population.MethodsWe screened 1239 patients with extracranial VA stenosis, of whom 321 patients with severe VA V1 segment stenosis (≥70%) were enrolled in our study. We restratified the patients based on NVAFV and contralateral VA stenosis grades to analyse the proportion of each PCI mechanism—large artery atherosclerosis and branch artery occlusive disease. Furthermore, we estimated the incidence of recurrent ischaemic stroke between groups with different NVAFV over a follow-up period of 2 years.ResultsNVAFV was lower in the PCI group. Multiple logistic regression analysis showed that NVAFV is an independent risk factor for PCI and that the OR for PCI for the lowest NVAFV (<112.8 mL/min) was 4.19 (1.76 to 9.95, p=0.001). In patients with severe carotid artery disease, the OR for the lowest NVAFV was 14.03 (3.18 to 61.92, p<0.001). The lower NVAFV group had a higher incidence of recurrent ischaemic stroke events than the higher NVAFV group (HR 2.978, 95% CIs 1.414 to 6.272).ConclusionOur study demonstrated that NVAFV, as estimated by colour duplex ultrasonography, was associated with the incidence of PCI and subsequent ischaemic events and that a high-risk population could be identified for further posterior circulation revascularisation.

Safety & efficacy of antibiotic de-escalation and discontinuation in high-risk haematological patients with febrile neutropenia: a single-centre experience

Background There is currently no consensus on optimal duration of antibiotic treatment in febrile neutropenia. We report on the clinical impact of implementation of antibiotic de-escalation and discontinuation strategies based on the 4th European Conference on Infections in Leukaemia (ECIL-4) recommendations in high-risk haematological patients. Methods We studied 446 admissions after introduction of an ECIL-4 based protocol (= ECIL-4 group) in comparison to a historic cohort of 512 admissions. Primary clinical endpoints were the incidence of infectious complications including septic shock, infection-related intensive care unit (ICU) admission and overall mortality. Secondary endpoints included the incidence of recurrent fever, bacteraemia and antibiotic consumption. Results Bacteraemia occurred more frequently in the ECIL-4 group [46.9% (209/446) vs 30.5% (156/512); p&lt;0.001], without an associated increase in septic shock [4.7% (21/446) vs 4.5% (23/512); p=0.878] or infection-related ICU admission [4.9% (22/446) vs 4.1% (21/512); p=0.424]. Overall mortality was significantly lower in the ECIL-4 group [0.7% (3/446) vs 2.7% (14/512); p=0.016], resulting mainly from a decrease in infection-related mortality [0.4% (2/446) vs 1.8% (9/512); p=0.058]. Antibiotic consumption was significantly reduced by a median of 2 days on antibiotic therapy (12 versus 14; p=0.001) and 7 daily antibiotic doses (17 versus 24; p&lt;0.001) per admission period. Conclusions Our results support implementation of ECIL-4 recommendations to be both safe and effective based on real world data in a large high-risk patient population. We found no increase in infectious complications and total antibiotic exposure was significantly reduced.

Improving the Safety of the Manchester Triage System for Children with Congenital Heart Disease

This study is a prospective evaluation of the validity of a Manchester Triage System (MTS) modification for detecting under-triaged pediatric patients with congenital heart disease (CHD). Children with CHD visiting the emergency unit of the Department of Pediatrics and Adolescent Medicine, Vienna General Hospital, in 2014 were included. The MTS modification updated the prioritization of patients with complex syndromic diseases, specific symptoms related to chronic diseases, decreased general condition (DGC), profound language impairment, unknown medical history, or special needs. A four-level outcome severity index based on diagnostic and therapeutic interventions, admission to hospital, and follow-up strategies, was defined as a reference standard for the correct clinical classification of the MTS urgency level. Of the 19,264 included children, 940 had CHD. Of this group, 266 fulfilled the inclusion criteria for the modified triage method. The MTS modification was significantly more often applied in under-triaged (65.9%) than correctly or over-triaged (25%) children with CHD (p-value χ²test <0.0001, OR 5.848 95% CI: 3.636-9.6).Conclusion: The MTS urgency level upgrade modification could reduce under-triage in children with CHD. Applying a safety strategy concept to the MTS could mitigate under-triage in such a high-risk patient group.

Early and Long Term Results of Our Open Heart Surgical Operations in the Presence of Active Oncological Diseases

Objectives: Active cancer and heart disease, which share similar environmental and biological characteristics, can occur concomitantly. Open heart surgery may be required for these patients when indicated. The aim of this study is to demonstrate the early and long-term results and discuss the intervention strategy in patients with different types of active malignancies, who underwent open heart surgery. Patients and Methods: Between January 2012 and May 2020, open heart surgery was performed on 10 patients with active malignancies. The mean age was 65.5 (52–77), and 4 of the patients were female. 2 patients were operated emergently due to advanced pleural effusion. AVR+CABG, CABG, CABG+left upper lobectomy and AVR+MVR were performed in 4 patients with lung cancer; AVR+CABG were performed in 1 patient with colon cancer; CABG was performed in 4 patients each with one of the following conditions: lymphoma, breast cancer, essential thrombocytosis, meningioma); and mass resection operation from the left atrium and left ventricle was performed in one patient with osteosarcoma. Results: 8 patients were discharged and 2 patients died in the early postoperative period. Postoperative left hemiparesis developed in 1 patient. 6-month, 1-year and 5-year survival rates were 79%, 37.5% and 25%, respectively. Conclusion: Open heart surgery can be successfully performed with acceptable mortality and morbidity rates on the high-risk patient group with active cancer. We believe that, where percutaneous coronary intervention and/or TAVI are not considered or deemed appropriate, surgical intervention should be performed with careful patient selection in patients with multi-vessel coronary artery disease, coronary artery stenosis +aortic stenosis, and in cases requiring double valve replacement.

Kinesin Family Member C1 (KIFC1/HSET): A Potential Actionable Biomarker of Early Stage Breast Tumorigenesis and Progression of High-Risk Lesions

The enigma of why some premalignant or pre-invasive breast lesions transform and progress while others do not remains poorly understood. Currently, no radiologic or molecular biomarkers exist in the clinic that can successfully risk-stratify high-risk lesions for malignant transformation or tumor progression as well as serve as a minimally cytotoxic actionable target for at-risk subpopulations. Breast carcinogenesis involves a series of key molecular deregulatory events that prompt normal cells to bypass tumor-suppressive senescence barriers. Kinesin family member C1 (KIFC1/HSET), which confers survival of cancer cells burdened with extra centrosomes, has been observed in premalignant and pre-invasive lesions, and its expression has been shown to correlate with increasing neoplastic progression. Additionally, KIFC1 has been associated with aggressive breast tumor molecular subtypes, such as basal-like and triple-negative breast cancers. However, the role of KIFC1 in malignant transformation and its potential as a predictive biomarker of neoplastic progression remain elusive. Herein, we review compelling evidence suggesting the involvement of KIFC1 in enabling pre-neoplastic cells to bypass senescence barriers necessary to become immortalized and malignant. We also discuss evidence inferring that KIFC1 levels may be higher in premalignant lesions with a greater inclination to transform and acquire aggressive tumor intrinsic subtypes. Collectively, this evidence provides a strong impetus for further investigation into KIFC1 as a potential risk-stratifying biomarker and minimally cytotoxic actionable target for high-risk patient subpopulations.

Invasive Fungal Infections and Targeted Therapies in Hematological Malignancies

The use of targeted biologic therapies for hematological malignancies has greatly expanded in recent years. These agents act upon specific molecular pathways in order to target malignant cells but frequently have broader effects involving both innate and adaptive immunity. Patients with hematological malignancies have unique risk factors for infection, including immune dysregulation related to their underlying disease and sequelae of prior treatment regimens. Determining the individual risk of infection related to any novel agent is challenging in this setting. Invasive fungal infections (IFIs) represent one of the most morbid infectious complications observed in hematological malignancy. In recent years, growing evidence suggests that certain small molecule inhibitors, such as BTK inhibitors and PI3K inhibitors, may cause an increased risk of IFI in certain patients. It is imperative to better understand the impact that novel targeted therapies might have on the development of IFIs in this high-risk patient population.