[Effect of Plasmafiltration and Adsorption in Cocaine Abuse: A Case Report].

Rhabdomyolysis is one of the principal causes of acute kidney disease. Multiple endogenous and exogenous causes could start this process: cocaine addiction, a social phenomenon present in our Country among young adults, is one exogenous causes. Natural stimulating alkaloid cocaine has toxic action on multiple systems, principally central nervous system and cardiovascular system. Etiopathogenesis is related either to changes in local and systemic hemodynamics, or to direct damage caused by myofibril accumulation, or to immunological events leading to vasculitis or thrombotic microangiopathies. Scientific evidences describe different therapeutic approaches: supportive therapy, extracorporeal treatments and possible removal of the pathogenic noxa, and the therapeutic apheresis plays a role yet to be confirmed in this field. We describe the case of a 52-year-old man, hospitalized in the Cardiological Intensive Care Unit of our hospital, due to serious alterations in the indices of myocardiocytonecrosis and liver function, following cocaine abuse. During hospitalization, renal function indices worsened associated to diuresis contraction and onset of metabolic acidosis, not responsive to medical therapy. Also in consideration of myoglobin high circulating levels, related to rhabdomyolysis, the patient went under a cycle of selective apheresis using adsorption with a TR350 cartridge associated to hemodialysis: after two adsorption sessions, the patient resumed spontaneous diuresis with progressive normalization of the blood indices.

Cell throughput and performance ratio as quality indicators on hematopoietic stem cell apheresis: A single-center experience.

BACKGROUND: Benchmarking in CD34+ cell apheresis is crucial for optimizing resources, ensuring consistent collection performance, and ultimately, decision-making algorithms to improve donor safety. Key performance indicators such as the "performance ratio" (PR) are applied routinely in some apheresis centers, whereas this report identifies the "cell throughput" (CT) as another quality indicator in apheresis. MATERIAL AND METHODS: This single-center study includes retrospective data from 117 aphereses. CT and PR were calculated based on the mononuclear cell collection (MNC) or continuous mononuclear cell collection (cMNC) protocols of the Spectra Optia® apheresis system, types of venous access, transplant settings, and mobilization regimens. RESULTS: CTs (× 106 CD34+ cells/min) were found to be greater in cMNC compared to MNC protocols (1.4 vs. 1.0, p = 0.0037), in allogeneic versus autologous (1.3 vs. 1.1, p = 0.0274), and in the mobilization regimen of G-CSF alone versus the G-CSF combined (1.3 vs. 1.0, p = 0.0249). In contrast, PR (%) was only statistically significant in favor of the cMNC protocol (213.0 vs. 186.8 for MNC). CONCLUSIONS: CT and PR are feasible quality indicators on CD34+ cell apheresis, are easy to calculate and implement, and have clinical and administrative implications. Analyzing CT and PR may strengthen the institutional criteria for selecting cMNC or MNC protocols; they may also be used to evaluate the performance of new personnel or cell separator devices or, eventually, trigger investigations for those aphereses under-collected by specific thresholds.

The practical use of artificial intelligence in Transfusion Medicine and Apheresis.

BACKGROUND: Blood and plasma volume calculations are a daily part of practice for many Transfusion Medicine and Apheresis practitioners. Though many formulas exist, each facility may have their own modifications to consider. ChatGPT (Generative Pre-trained Transformer) provides a new and exciting pathway for those with no programming experience to create personalized programs to meet the demands of daily practice. Additionally, this pathway creates computer programs that provide accurate and reproducible outputs. Herein, we aimed to create a step-by-step process for clinicians to create customized computer programs for use in everyday practice. METHODS: We created a process of inputs to ChatGPT-40, which generated computer programming code. This code was copied and pasted into Notepad (and saved as a Python file) and Google Colaboratory to verify functionality. We validated the durability of our process by repeating it over a 5-day timeframe and by recruiting volunteers to reproduce our outputs using the suggested process. RESULTS: Computer code generated by ChatGPT-40 in response to our common language inputs was accurate and durable over time. The code was fully functional in both Python and Colaboratory. Volunteers reproduced our process and outputs with minimal assistance. CONCLUSION: We analyzed the practical application of ChatGPT-40 and artificial intelligence (AI) to perform daily calculations encountered in Transfusion Medicine. Our results provide a proof of concept that people with no programming experience can create customizable solutions for their own facilities. Our future work will expand to the creation of comprehensive and customizable websites designed for each individual user.

Performance and safety of therapeutic erythrocytapheresis in polycythemia and hemochromatosis treatment: single centre experience.

INTRODUCTION: Therapeutic erythrocytapheresis has some advantages over therapeutic phlebotomy, the standard treatment for cytoreduction in polycythemia and hemochromatosis. Erythrocytapheresis can be performed on different cell separators, each with its own characteristics. We present our experience of therapeutic erythrocytapheresis in the treatment of polycythemia and hemochromatosis with an analysis of the performance of cytoreduction, and a comparison between the characteristics of intermittent- and continuous-flow cell separators. MATERIAL AND METHODS: During a 20-year period, 1731 procedures were performed in 125 patients, 1634 (94.4%) with a Haemonetics MCS+ separator and 97 (5.6%) with a Spectra Optia system device. The performance of cytoreduction using the Haemonetics MCS+ separator was analysed in 442 procedures performed in 56 patients and the performance of the two apheresis devices was compared. RESULTS: Haemoglobin (Hb) and haematocrit (Hct) values were significantly reduced after erythrocytapheresis with the Haemonetics MCS+ device (Hb: 18.69%; Hct: 18.73%; p-values both <0.001). The reductions of Hb and Hct were significantly higher in the Haemonetics MCS+ procedure (p-value <0.001), but the Spectra Optia procedure depleted a significantly higher RBC volume (495 mL versus 442 mL) in a shorter time (18 min versus 36 min). CONCLUSION: Both the Haemonetics MCS+ and Spectra Optia systems proved to be highly efficient and safe in RBC cytoreduction with short procedure times. Erythrocytapheresis reduces the frequency of necessary procedures thereby justifying its therapeutic use especially in eligible patients of working age.

Selective red blood cell depletion by apheresis in sheep causes severe normovolemic anemia.

BACKGROUND: The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4-6 g dL-1 using apheresis in sheep. METHODS: In vitro experiments were performed first to establish the apheresis protocol. In vivo, anesthetized ewes underwent a sham protocol without apheresis (n = 5) or apheresis (n = 4). Both groups were observed for the following six hours at a defined starting point (BE0) to compare Hgb, hematocrit (Hct), coagulation and clinical parameters. For statistical analysis, unpaired t-test with Welch`s correction was used. RESULTS: Hgb levels were effectively decreased by 51 % to mean Hgb of 4.4 g dL-1 in the apheresis group compared to 9.1 g dL-1 in sham (*p < 0.0001). Hct (11.2% vs 25.1 %, *p = 0.01) and RBCs (3.7 vs 8.2 × 106/µl, *p = 0.003) also decreased. The relative number of platelets compared to baseline was different (55.6 ± 10.6% vs. 100 ± 0 %, *p = 0.004), but no hemorrhage was observed. White blood cells (WBCs), lactate, prothrombin ratio and activated partial thromboplastin time (aPTT) remained within similar ranges. CONCLUSIONS: Critical normovolemic anemia without bleeding complications was successfully reached by selective RBC depletion in sheep. Investigations of physiological adaptations to severe anemia and pharmaceutical testing can be performed in large animals with depleted RBCs.

Planning Split-Apheresis Designs for Demonstrating Comparability of Cellular and Gene Therapy Products.

A recent FDA draft guidance discusses statistical considerations for demonstrating comparability of cell and gene therapy products and processes. One experimental study described in the guidance is the split-apheresis design. The FDA draft guidance recommends a paired data analysis for such a design. This paper demonstrates that the paired analysis is under powered for some quality attributes for practical sample sizes of three to five donors unless a significant portion of variability is attributed to donor. Addition of historic lots from the pre-change process can increase the power for these attributes. This paper provides appropriate statistical methods for including this information.

Label-Free Microfluidic Apheresis of Circulating Tumor Cell Clusters.

Screening liters of blood (i.e., apheresis) represents a generalized approach to promote the reliable access to circulating tumor cell clusters (CTCCs), which are known to be highly metastasis-competent, yet ultrarare. However, no existing CTCC sorting technology has demonstrated high throughput, high yield, low shear stress, and minimal blood dilution simultaneously as required in apheresis. Here, a label-free method is introduced termed Precision Apheresis for Non-invasive Debulking of cell Aggregates (PANDA) to continuously isolate CTCCs from undiluted blood to clean buffer through size sorting, processing 1.4 billion cells per second. The cell focusing is optimized within whole blood leveraging secondary transverse flow and margination. The PANDA chip recovers >90% of spiked ≈24 rare HeLa cell clusters from 100 mL undiluted blood samples (equivalent to ≈500 billion blood cells) at 1 L h-1 throughput, with ≤20s device residence time, ≤15 Pa shear stress, and >99.9% return of blood components. The technology lays the groundwork for future routine isolation to increase the recovery of these ultrarare yet clinically significant tumor cell populations from large volumes of blood to advance cancer research, early detection, and treatment.

Characteristics of HPC(A) product obtained from a donor with SARS-CoV-2 infection and outcome of autologous transplant.

Collection of hematopoietic progenitor cell products [HPC(A)] is deferred if the donor is symptomatic and tests positive for Covid-19. However, donor questionnaires are subjective and may miss minimally symptomatic donors. Alternatively, myalgia associated with Covid-19 infection can be falsely dismissed as an adverse effect of granulocyte stimulating factor (Filgrastim) administered prior to product collection. The likelihood of donors with an underlying acute but minimally symptomatic infection undergoing successful product collection is significant. In these circumstances, it is less known whether Covid-19 infection results in product viremia or alters the clinical outcome of transplant. We aimed to evaluate the above question by studying a donor whose product was collected during acute Covid-19 infection. Aliquots of the product tested negative for SARS-CoV-2 RNA by reverse-transcriptase polymerase chain reaction assay (RT-PCR). Importantly, the donor received an autologous stem cell transplant using the product collected at the time of infection, and their case will be described in this report. We describe one of the very few reports of successful transplant of HPC(A) product collected during acute Covid-19 infection.

Evaluating hydrogen ion mobilization during hemodialysis using only predialysis and postdialysis blood bicarbonate concentrations.

INTRODUCTION: The hydrogen ion (H+) mobilization model has been previously shown to provide a quantitative description of intradialytic changes in blood bicarbonate (HCO3) concentration during hemodialysis (HD). The current study evaluated the accuracy of different methods for estimating the H+ mobilization parameter (Hm) from this model. METHODS: The study compared estimates of the H+ mobilization parameter using predialysis, hourly during the HD treatment, and postdialysis blood HCO3 concentrations (Hm-full2) with those determined using only predialysis and postdialysis blood HCO3 concentrations assuming steady state conditions (Hm-SS2) during the midweek treatment in 24 chronic HD patients treated thrice weekly. RESULTS: Estimated Hm-full2 values (0.163 ± 0.079 L/min [mean ± standard deviation]) were higher than, but not statistically different (p = 0.067) from, those of Hm-SS2 (0.152 ± 0.065 L/min); the values of Hm-full2 and Hm-SS2 were highly correlated with a correlation coefficient of 0.948 and a mean difference that was small (0.011 L/min). Further, the H+ mobilization parameter values calculated using only predialysis and postdialysis blood HCO3 concentrations during the first and third HD treatments of the week were not different from those calculated during the midweek treatment. CONCLUSIONS: The H+ mobilization model can be used to provide estimates of the H+ mobilization parameter without the need to measure hourly intradialytic blood HCO3 concentrations.

Autologous peripheral blood stem cell harvest timing by absolute neutrophil count in children and young adult patients: Single-institute experience.

BACKGROUND: Myeloablative, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) improves outcome in some high-risk malignant solid tumors and lymphomas in children and young adults. METHODS: We performed 16 peripheral blood stem cell (PBSC) harvests in 12 children and 2 young adult patients with a high-risk malignant solid tumor or refractory/relapsed Hodgkin's lymphoma from August 2015 to December 2020. In our chemotherapy mobilization protocol, we used an absolute neutrophil count (ANC) of >1 × 109/L following the nadir after chemotherapy as the criterion for undertaking the apheresis. RESULTS: The median CD34+ cell count per kg body weight of the 33 apheresis products was 4.92 × 106 cells/kg (range, 0.34-22.53 × 106 cells/kg). Thirteen of the 14 patients (93%) had successful PBSC collections that met their goals for PBSCT. Three patients did not receive PBSCT due to disease progression prior to transplantation. Prompt engraftment occurred in all the remaining 11 patients with 17 PBSCTs. CONCLUSION: Our data suggest that ANC can be helpful as a surrogate parameter in clinical decision-making when the peripheral blood CD34+ count is unavailable.

Improving cellular therapy operations through pre-harvest measurement of peripheral CD34-positive cell counts in allogeneic stem cell harvest.

INTRODUCTION: Previously, our institution measured peripheral blood CD34 cell counts both pre- and post-peripheral blood stem cell harvest (PBSCH), with both samples analyzed simultaneously post-PBSCH. Since 2021, we have measured pre-CD34 cell counts during PBSCH, adjusting the processed blood volume based on these results. We retrospectively evaluated how this change impacted cellular therapy. METHODS: Related healthy donors were included and divided into 1-day and 2-day harvest cohorts. Donors with CD34 cell counts measured post- and during PBSCH were categorized into the previous and current sub-cohorts, respectively. RESULTS: Regarding the 1-day cohort (n = 212), the current sub-cohort had a significantly shorter average harvest duration (151 [standard deviation, SD = 45.1] vs. 180 [SD = 27.8] minutes, respectively) and higher average infusion rates (87.6% [SD = 21.1] vs. 78.1% [SD = 25.7], respectively) than the previous sub-cohort. CONCLUSION: Adjusting the processed blood volume based on pre-PBSCH CD34 cell counts measured during the harvest may reduce donor burden and enhance workflow efficiency.

Prediction of CD34+ hematopoietic stem cells in healthy allogeneic stem cell donors on the Optia cell separator based on CE2: Which formula is more correlated with actual CD34+?

BACKGROUND: Peripheral blood-derived hematopoietic stem cells (HSCs) are widely used for various adult stem cell transplants. To obtain sufficient HSCs from healthy volunteer donors during the apheresis process and ensure that the donors are exposed to fewer apheresis-related side effects, calculation methods have been developed for the prediction of processed blood volume or CD34+ count. However, there is no consensus on a formula to predict the volume of blood to be processed or the number of stem cells to be obtained. OBJECTIVE: This study aimed to estimate the predicted blood volume and CD34+ cell counts using collection efficiency (CE)-based formulas and evaluate their accuracy compared to the actual CD34+ cell counts. It also seeks to identify the factors that affect CE. METHODS: Data from 397 healthy, unrelated stem cell donors were retrospectively analyzed. An algorithm using four different CE2 metrics (1st quartile, mean, 3rd quartile, and median) was developed to predict the volume of blood to be processed using the Spectra Optia continuous mononuclear cell collection procedure. RESULTS: When employing the mean CE2 algorithm, the results revealed a strong correlation (r = .894, p < .001) between predicted and actual CD34+ values. The study also identified strong associations between pre-apheresis CD34+, pre-apheresis leukocyte count, the use of two doses of G-CSF, and low CE2. CONCLUSION: These findings suggest that the mean CE2 algorithm could be a potent, straightforward, and accurate tool for predicting CD34+ stem cell counts in healthy allogeneic stem cell donors and potentially optimizing stem cell collection procedures.

Case Report: C-reactive protein apheresis in non-ST-elevation ACS-case series from the C-reactive protein apheresis in Acute Myocardial Infarction Registry.

C-reactive protein (CRP) apheresis has been introduced in ST-elevation myocardial infarction and cardiogenic shock. Here, we describe a first-in-man application in non-ST-elevation acute coronary syndrome (NSTE-ACS). Seven NSTE-ACS patients with high CRP levels (range 14.2-154 mg/L) were treated with CRP apheresis. Treatment was well-tolerated. Patients were discharged in good clinical condition.

Use of a novel configuration of ports for patients needing intermittent long-term apheresis.

PURPOSE: In patients with a need for frequent but intermittent apheresis, vascular access can prove challenging. We describe the migration of the use of a Vortex LP dual lumen port (Angiodynamics, Latham, NY) to one Powerflow and one ClearVUE power injectable port (Becton Dickinson, Franklin Lakes, NJ) in a series of patients undergoing intermittent apheresis. MATERIALS AND METHODS: All patients had a need for long-term intermittent apheresis. Eight had double lumen Vortex port (pre) and were exchanged for one Powerflow port and one conventional subcutaneous venous port with 90° needle entry (post) while 12 did not have any port in place and received the same configuration. IRB approval was granted. We recorded the treatment time, flow rate, and tissue plasminogen activator (tPA) use for five treatment sessions after placement. When available, we compared five treatments with the Vortex port and the new configuration. RESULTS: The mean treatment time is reduced with the new configuration (P = 0.0033). The predicted mean treatment time, adjusting for gender, race, BMI and age and accounting for correlations within a patient is 91.18 min pre and 77.96 min post. The flow rate is higher with the new configuration (P < 0.0001). The predicted mean flow rate in mL/min is 61.59 for the Vortex port and 71.89 for the new configuration. tPA use was eliminated in the population converted from Vortex ports and had a 48% reduction when compared to all other configurations in the study. CONCLUSION: The introduction of a novel device configuration of venous access ports for intermittent apheresis resulted in higher flow rates and less total time for treatment. Use of tPA was greatly reduced. These results suggest that the new configuration could result in less expense for the hospital and better throughput in a busy pheresis practice. Clinical trial registration with ClinicalTrials.gov: NCT04846374.

Unexpected Death of a Sickle Cell Disease Patient: A Case Report and Literature Review.

Sickle cell disease (SCD) is an autosomal recessive genetic disorder characterized by the abnormal formation of sickle hemoglobin (HbS). Under conditions of deoxygenation, HbS undergoes polymerization, resulting in microvascular occlusion, tissue hypoxia, and infarction. The elevated mortality rate associated with SCD is primarily attributed to complications such as sepsis, acute chest syndrome, stroke, acute multiorgan failure, and pulmonary hypertension. Despite advancements in awareness and treatments, preventing mortality in young individuals with SCD remains a formidable challenge. In an effort to shed light on these challenges, we present a case of unexpected death associated with SCD to emphasize the pressing need for continued research and intervention strategies to improve patient outcomes.

A study on beneficial impact of the use of medium-molecular-weight hydroxyethyl starch in granulocyte apheresis using continuous-flow cell separator Spectra Optia: A retrospective single-center study at a tertiary care oncology center.

INTRODUCTION: Granulocyte transfusion is one of the best therapeutic modalities in prolonged neutropenic patients with severe bacterial/fungal infections. Granulocyte harvest using conventional acid citrate dextrose (ACD) anticoagulant (ACD-A) by apheresis is not satisfactory in comparison to the use of hydroxyethyl starch (HES), but the latter is associated with various adverse events, especially with high-molecular-weight HES. AIMS AND OBJECTIVE: This study aimed to assess the beneficial impact of the use of medium-molecular-weight (MMW)-HES and trisodium citrate combination over ACD-A in granulocyte apheresis when using Spectra Optia. MATERIALS AND METHODS: This was a retrospective study comparing granulocyte harvest results with the use of ACD or HES and trisodium citrate combination. All the donors in both the groups received single 600 µg of granulocyte colony-stimulating factor subcutaneous injection followed by 8 mg of dexamethasone tablet 10-12 h and omnacortil 60 mg orally 3 h before harvest. A number of adverse incidents, if any, were observed and noted. Donor/procedure parameters were compared using Mann-Whitney U-test/unpaired t-test. RESULTS: Granulocyte yield (mean: 3.29 × 1010/unit vs. 4.5 × 1010/unit in the ACD and HES groups, respectively, P ≤ 0.0001) was significantly better in the HES group. The collection efficiency was also better in the HES group (mean: 15.86% vs. 26.70% in the ACD and HES groups, respectively, P ≤ 0.0001) in the ACD and HES groups, respectively. There was no significant adverse event noted in any of these two groups. CONCLUSION: In our study, granulocytes with optimum yield can be easily harvested with Spectra Optia cell separator using 6% HES (MMW) and trisodium citrate combination with standard 12-h interval gap between mobilization and harvest. This strategy can also have no or minimal extra cost burden to patients.

Estimation of serum calcium levels in apheresis platelet donors.

INTRODUCTION: Apheresis is practiced widely to collect single donor platelets (SDPs). This procedure utilizes an anticoagulant acid citrate dextrose to prevent clotting of blood in the extracorporeal circuit which chelates divalent ions like calcium. This alters the calcium homeostasis resulting in hypocalcemia causing acute adverse events. AIM: The study aimed to know the calcium homeostasis in apheresis platelet donors. MATERIALS AND METHODS: This cross-sectional study was conducted from January 2020 to December 2020 in the department of transfusion medicine. The sample size was 50. Donors who walk in for voluntary SDP donation were selected. Total and ionized calcium, pH, and serum albumin for all the donors at baseline and ionic calcium at the end of the procedure and 30 min after the procedure were measured. RESULTS: According to statistical analysis of the ionic calcium level at pre procedure, immediate post procedure and 30 minutes post procedure, there was decrease in the value immediate post procedure and values returned to baseline within 30 minutes. The levels of pH change were analyzed. On comparing the preprocedure and immediate postprocedure values, there was a significant lowering of pH value from the baseline (P = 0.5), indicating acute lowering of pH immediate postprocedure. Hence, most of the citrate metabolism can be achieved within 30 min after completion of the apheresis procedure. CONCLUSION: SDP collection is essentially a safe procedure with minimal adverse effects. Toxicity of citrate is not much pronounced. Recovery of calcium levels is within 30 min of completion of plateletpheresis.

Real-world experience of long-term efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia treated and not treating with lipoprotein apheresis.

BACKGROUND: Evinacumab is an inhibitor of angiopoietin-like 3 protein (ANGPTL3) that offers a new approach for correcting high low-density lipoprotein-cholesterol (LDL-C) and may reduce the need or frequency for lipoprotein apheresis (LA) in patients with homozygous familial hypercholesterolemia (HoFH). OBJECTIVE: We aimed to investigate the long-term efficacy and safety of evinacumab in patients with HoFH aged between 14 and 63 years on and off LA in real-world clinical practice. METHODS: Evinacumab was administrated intravenously (15 mg /kg Q4W) for the first 24 months in 7 patients with genetically confirmed HoFH, receiving best standard of lipid-lowering treatment and LA, followed by a subsequent compassionate extension period of approximately 12-month treatment with evinacumab without LA. Patient experience of evinacumab and health-related EuroQol (EQ-5D-3L) quality of life questionnaire were also assessed. RESULTS: Compared with baseline, evinacumab resulted in a sustained reduction in plasma LDL-C concentration of -43.4 % and -54.2 % at 30 and 36 months, respectively. All 7 HoFH patients achieved an LDL-C reduction >30 % with 3 patients having on-treatment LDL-C level < 2.5 mmol/L (96 mg/dL). Evinacumab was well-tolerated, with no major adverse reported or significant changes in liver enzyme concentrations. All FH patients agreed that evinacumab was acceptable and less physically demanding than LA. The mean utility score and EQ- visual analogue scale scores were 0.966 and 78.6, respectively, which are comparable to the Italian general population. CONCLUSIONS: Our findings suggest that evinacumab is a safe and effective treatment for high LDL-cholesterol that is acceptable to HoFH patients receiving and not receiving LA.

The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies.

Atherosclerotic cardiovascular disease poses a significant global health issue, with dyslipidemia standing out as a major risk factor. In recent decades, lipid-lowering therapies have evolved significantly, with statins emerging as the cornerstone treatment. These interventions play a crucial role in both primary and secondary prevention by effectively reducing cardiovascular risk through lipid profile enhancements. Beyond their primary lipid-lowering effects, extensive research indicates that these therapies exhibit pleiotropic actions, offering additional health benefits. These include anti-inflammatory properties, improvements in vascular health and glucose metabolism, and potential implications in cancer management. While statins and ezetimibe have been extensively studied, newer lipid-lowering agents also demonstrate similar pleiotropic effects, even in the absence of direct cardiovascular benefits. This narrative review explores the diverse pleiotropic properties of lipid-modifying therapies, emphasizing their non-lipid effects that contribute to reducing cardiovascular burden and exploring emerging benefits for non-cardiovascular conditions. Mechanistic insights into these actions are discussed alongside their potential therapeutic implications.

Small but mighty: Case report and practical guidance for peripheral blood stem cell collection in small infants.

Modern apheresis devices, with increased procedural precision, automation, and monitoring, have been shown to allow for safe delivery of apheresis therapies in young children. Medical advances are increasing demand for apheresis procedures like mononuclear cell collection in infants <10 kg, including stem-cell supported chemotherapy, cell collection for chimeric antigen receptor T cell development, and now ex vivo gene therapies for rare genetic diseases. Nevertheless, safe delivery in small infants involves a range of unique considerations and challenges, beyond just size, and experience will vary between centers. In this case report we describe our experience performing mononuclear cell collection in our smallest patient to date and outline a practice guideline developed following a literature review and discussion with both international experts and device representatives. This case may help to inform other clinicians aiming to provide apheresis care to very small infants in their own centers.