Development of a Uniform Apheresis Case Report Form for Standardized Collection of Apheresis Data.

Apheresis is performed worldwide for an increasing number of indications. The development of common data elements (CDE) for apheresis related areas may facilitate conduct of new research, enhance quality initiatives including benchmarking, and improve patient care. This report describes the systematic development of the Uniform Apheresis Case Report Form (UACRF) as part of the Apheresis in the United States (ApheresUS) program. A consensus panel of 17 diverse experts in apheresis, related specialties, and electronic case report form (eCRF), and database development was assembled. The panel met via online conferencing from November 17, 2020 to December 1, 2021. A draft document was posted online for public comment from October 11, 2021 to November 10, 2021. Feedback was collected using an online survey tool. The consensus panel revised the UACRF. This version was converted to an eCRF with additional changes made to improve usability in this format. The final version of the UACRF was created on August 24, 2023. The UACRF contains 16 modules: procedure and subject eligibility, patient demographics, general procedure information, laboratory parameters, vascular access, common procedure elements, eight procedure specific modules (mononuclear cell collection and seven therapeutic modalities), outcomes, and site information. A total of 137 data elements were created, including 57 with one or more subelements. The UACRF is the first systematic attempt to develop CDE for therapeutic apheresis and white blood cell collections. Further validation of the UACRF is necessary to confirm the tool's ability to collect the relevant data elements and determine the usability of the form.

The seasonal distribution of immune thrombotic thrombocytopenic purpura is influenced by geography: Epidemiologic findings from a multi-center analysis of 719 disease episodes.

Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5-year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere-winter (December-February); spring (March-May); summer (June-August); autumn (September-November) and Southern Hemisphere-winter (June-August); spring (September-November); summer (December-February); autumn (March-May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%-31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization.

Progress on the role of LIN28A/B in tumor development and progression.

LIN28A and its homolog LIN28B are highly conserved RNA-binding proteins that play important roles in early embryonic development, somatic cell reprogramming, metabolism and tumorigenesis. LIN28A/B are highly expressed in a variety of malignant tumors such as breast cancer. They play important roles in the initiation, maintenance, and metastasis of tumors and are associated with poor prognosis. Previous studies have shown that the main regulatory mechanisms of LIN28A/B include let-7s dependent ways and let-7s independent ways, such as directly targeting mRNA. In this review, we summarize the function and molecular regulatory mechanisms of LIN28A/B in malignant tumors such as liver cancer, breast cancer and colorectal cancer, in order to provide references for further exploring the function and mechanism of LIN28A/B and their possible roles in clinical applications.

Advances in Human Leukocyte Antigen Testing Technologies and Management Strategies for Platelet Transfusion Refractoriness.

CONTEXT.­: The blood bank is often consulted for transfusion support of patients with suspected platelet transfusion refractoriness (PTR). The workup is complex because testing includes specialized assays that are uncommonly ordered with limited availability. Add to this the variety of possible products-crossmatched platelets, human leukocyte antigen (HLA)-matched platelets, HLA antigen-negative platelets-and the approach to PTR can be overwhelming. Moreover, most literature on the subject is published in transfusion medicine journals aimed at transfusion medicine physicians and blood bank specialists in academic settings. Resources tailored to community hospital blood banks are lacking. OBJECTIVE.­: To provide pathologists who may not have subspecialized training in transfusion medicine and who direct blood banks algorithmic workflows based on clinical scenario and test availability to provide appropriate transfusion support for patients with PTR. DATA SOURCES.­: This review is a comprehensive overview of terminology, HLA testing procedures, interpretations, and practical recommendations for managing PTR in various scenarios based on expert opinion as well as relevant medical literature published from 2007 to 2022. CONCLUSIONS.­: Consultation on PTR is complicated and encompasses many clinical and laboratory aspects. The lack of guidelines derived from high-quality prospective studies poses challenges in the workup and management of PTR. Hindering the process further are limited test availability, unfamiliarity with the technical assays, and the various specialized platelet products. The clinical evaluation algorithm presented herein along with the workflow pathways offer pathologists user-friendly and best-practice guidelines with different options based on the clinical scenario and the tests available.

Cognitive impairment, neuroimaging abnormalities, and their correlations in myotonic dystrophy: a comprehensive review.

Myotonic dystrophy (DM) encompasses a spectrum of neuromuscular diseases characterized by myotonia, muscle weakness, and wasting. Recent research has led to the recognition of DM as a neurological disorder. Cognitive impairment is a central nervous system condition that has been observed in various forms of DM. Neuroimaging studies have increasingly linked DM to alterations in white matter (WM) integrity and highlighted the relationship between cognitive impairment and abnormalities in WM structure. This review aims to summarize investigations into cognitive impairment and brain abnormalities in individuals with DM and to elucidate the correlation between these factors and the potential underlying mechanisms contributing to these abnormalities.

Comprehensive multiparameter evaluation of platelet function using a highly sensitive membrane capacitance sensor.

An accurate and comprehensive assessment of platelet function is essential for managing patients who receive antiplatelet therapies or require platelet transfusion either for treating active bleeding or for prophylaxis. Platelets contribute to clotting by undergoing a series of highly regulated functional responses including adhesion, spreading, granular secretion, aggregation, and cytoskeletal contraction. However, current platelet function assays evaluate only partial aspects of this intricate process and often under non-physiological testing conditions. Herein, we describe the development of a new approach to measure multiple key platelet function-related parameters, in a more physiologically relevant ex vivo semi-rigid microenvironment using a membrane capacitance sensor (MCS). MCS response to clotting provided three sensing parameters with sensitivities towards platelet counts, stimulation strengths, and activation pathways. Live confocal fluorescent imaging of stimulated platelets on MCS suggests that the presented system can readily and accurately convert the dynamics of cytoskeletal reorganization into analyzable electrical signals. Together, this new completely electrical sensing platform can be a promising diagnostic venue to recognize the impairment of primary hemostatic functions, evaluate the efficacy of therapeutic interventions, and gain further insights into the mechanisms of platelets in hemostasis and thrombosis.

Clinical Efficacy of Minocycline Hydrochloride for the Treatment of Peri-Implant Disease: A Systematic Review With Meta-Analysis of Randomized Controlled Trials.

This systematic review aimed to assess the clinical efficacy of the local application of minocycline hydrochloride for treating peri-implantitis. Four databases-PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure-were searched from their inception through December 2020. English and Chinese randomized controlled trials (RCTs) that compared minocycline hydrochloride with control regimes, including negative control, iodine solution or glycerin, and chlorhexidine, for patients with peri-implant diseases were retrieved. Three outcomes-plaque index (PLI), probing depth (PD), and sulcus bleeding index (SBI)-were assessed using meta-analysis based on the random-effects model. Fifteen RCTs were included in the present meta-analysis, and results suggested that minocycline hydrochloride significantly affected PLI, PD, or SBI reduction regardless of the type of comparator regime. However, subgroup analyses suggested that minocycline hydrochloride was not superior to chlorhexidine in terms of reduction of PLI (1 week: MD = -0.18, 95% CI = -0.55 to 0.20, P = .36; 4 weeks: MD = -0.08, 95% CI = -0.23 to 0.07, P = .28; 8 weeks: MD = -0.01, 95% CI = -0.18 to 0.16, P = .91) and PD (1 week: MD = 0.07, 95% CI = -0.27 to 0.41, P = .68; 4 weeks: MD = -0.10, 95% CI = -0.43 to 0.24, P = .58; 8 weeks: MD = -0.30, 95% CI = -0.68 to 0.08, P = .12), and minocycline hydrochloride was also not better than chlorhexidine regarding reduction of SBI at 1 week after treatment (MD = -0.10; 95% CI = -0.21 to 0.01; P = .08). This study concludes that minocycline hydrochloride as adjuvant therapy of nonsurgical treatment enhances the clinical results when compared to control regimes. However, the difference between minocycline hydrochloride and chlorhexidine should be further investigated by designing additional high-quality studies with large sample sizes.

Cold stored platelets - Increasing understanding and acceptance.

Platelet transfusions decreased the risk of morbidity and mortality secondary to thrombocytopenia. This therapy not only ameliorates platelet loss in bleeding patients,but also those with acquired dysfunction of platelets. The current standard of practice worldwide is to provide room temperature platelets (RTPs); however, there are many disadvantages to the use of RTPs such that alternative approaches have been explored. One potential approach is the integration and use of cold stored platelets (CSP), which are platelets stored at 1-6 °C, in clinical settings. CSP research studies show equivalent hemostasis and platelet dysfunction restoration compared to RTPs. In addition, publications have demonstrated advantages of CSP such as reduced bacterial contamination and wastage. Despite its benefits, the production of CSP by blood centers (BCs) and uptake and use of CSP by hospitals has remained relatively low. This review highlights the rationale for CSP production and strategies for overcoming the implementation challenges faced by BCs based on a literature review.Experiences of Consortium for Blood Availability members to integrate CSP in their BCs and clinical practices by providing variance applications are reviewed in this paper. Also, demonstrated in this manuscript are the current indications and opportunities for CSP utilization by healthcare providers.

Considerations for immune effector cell therapy collections: a white paper from the American Society for Apheresis.

BACKGROUND AIMS: This white paper was developed to provide leukapheresis guidance for the collection of mononuclear cells from adult and pediatric patients who are destined for immune effector cell (IEC) therapies for commercial and research applications. Currently, there is considerable variability in leukapheresis processes and limited published information regarding best practices relevant to new cellular therapies, especially IECs. Herein the authors address critical leukapheresis questions in five domains to help guide consistent collection processes and ensure high-quality products. The first four domains are onboarding, pre-collection, collection and post-collection, with protocol feasibility, preparation, care and follow-up of the patient/donor at each step, respectively, and technical considerations during collection. The fifth domain of quality assurance focuses on ensuring product potency, purity, safety and auditing. METHODS: The American Society for Apheresis (ASFA) Clinical Applications Committee (IEC Therapy Subcommittee) was charged by the society's board of directors with working collaboratively with other ASFA committees and organizations, including the Foundation for the Accreditation of Cellular Therapy, Association for the Advancement of Blood and Biotherapies, American Society for Transplantation and Cellular Therapy, National Marrow Donor Program and International Society for Cell & Gene Therapy, to develop guidelines regarding leukapheresis collection of cells destined for the manufacture of IEC therapies. After a review of the literature and discussion with members of the involved committees and various institutions, a draft guidance was created and circulated for comment and revision. RESULTS: Critical aspects of apheresis that could affect the quality and quantity of the leukapheresis product were identified. These areas were then discussed and reviewed. After consensus, the best practice guidelines were proposed and accepted. CONCLUSIONS: In the current era of rapid growth of IEC therapies, it is important to address critical leukapheresis steps to provide high-quality products and more consistent practices and to eliminate redundant efforts.

Therapeutic plasma exchange in a patient with acute motor axonal neuropathy subtype of Guillain-Barre syndrome and systemic lupus erythematosus.

A young female in her early 20s with a history of systemic lupus erythematosus presented to the emergency department due to 4 days of progressive bilateral extremity weakness and numbness. The patient reported flu-like symptoms that had spontaneously recovered 2 weeks prior to her presentation. She was 10 weeks pregnant at presentation. Lumbar puncture study and electrical muscle stimulation (EMS) were consistent with acute motor axonal neuropathy subtype of Guillain-Barre syndrome (GBS). Patient also had increased proteinuria and renal biopsy performed that was consistent with lupus nephritis. Despite treatment with pulse dose corticosteroids and IVIG, the patient had minimal neurological improvement and with continued decline required intubation. Her pregnancy was terminated at this point and a course of therapeutic plasma exchange (TPE) was started. Patient was also treated with cyclophosphamide. The patient responded to the combination of therapy and had slow but gradual neurologic recovery as well as improvement of proteinuria. Here we describe a case of an acute motor axonal neuropathy (AMAN) subtype of GBS in a young woman with active SLE and current pregnancy at the time of the presentation. Concurrent GBS and active SLE in the setting of pregnancy may be more treatment resistant, and combination therapy including TPE, immunosuppression, and termination of pregnancy may be indicated.

CUGBP1, a crucial factor for heart regeneration in mice.

The mammalian heart is capable of achieving perfect regeneration following cardiac injury through sustained cardiomyocyte proliferation during the early period after birth. However, this regenerative capacity is lost by postnatal day 7 and throughout adulthood. CUGBP1 is critical for normal cardiac development but its role in heart regeneration remains unclear. Cardiac CUGBP1 levels are high in the early postnatal period and soon downregulate to adult levels within 1 week following birth in mice. The simultaneously diminished regenerative capacity and CUGBP1 levels by postnatal day lead us to hypothesize that CUGBP1 may be beneficial in heart regeneration. In this study, the function of CUGBP1 in heart regeneration was tested by a heart apex resection mouse model. We demonstrate that cardiac inactivation of CUGBP1 impairs neonatal heart regeneration at P1, in turn, replenishment of CUGBP1 levels prolong regenerative potential at P8 and P14. Furthermore, our results imply that the Wnt/ß-catenin signaling and GATA4 involve in the CUGBP1 modulated neonatal heart regeneration. Altogether, our findings support CUGBP1 as a key factor promoting post-injury heart regeneration and provide a potential therapeutic method for heart disease.

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial.

Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures: The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results: Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance: In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration: ClinicalTrials.gov Identifier: NCT04364737.

Effect of bedside filtration on aggregates from cold-stored whole blood-derived platelet-rich plasma and apheresis platelet concentrates.

BACKGROUND: The current approach to manufacture cold-stored platelets (CSP) replicates that of room temperature-stored platelets (RSP). However, this production method is associated with aggregate formation in CSP, a major pitfall that leads to significant wastage. We hypothesized that isolating platelets from whole blood as platelet-rich plasma (PRP) and storing them at a lower concentration reduces aggregates and that conventional bedside transfusion filtration removes CSP aggregates. METHODS: We collected platelets from healthy humans by apheresis (AP) and by phlebotomy, from which we generated platelet-rich plasma (PRP). We split each AP and PRP platelets into two equal aliquots, storing one at 22°C (RT-PRP and RT-AP) and the other at 4°C (4C-PRP and 4C-AP). We evaluated platelets on day 0 and day 7 of storage. After storage, we measured platelet counts, aggregates, and other key characteristics before and after filtration by a bedside filter. RESULTS: After storage, the 4C-AP platelet counts decreased significantly. 4C-PRP preserved glucose better and prevented a significant increase in lactate contrary to 4C-AP. Filtration led to significantly lower platelet counts in both 4C-PRP and 4C-AP but not in their RT counterparts. Post filtration, we observed 50% fewer aggregates only in 4C-AP, whereas 4C-PRP showed an unexpected but significant increase in aggregates. Testing confirmed activation during storage but filtration did not further activate platelets. CONCLUSION: We provide evidence that 4C-PRP is an alternative to 4C-AP and that bedside filters reduce aggregates from 4C-AP. Further studies are needed to evaluate the hemostatic potential of 4C-PRP and the management of aggregates.

Simultaneous multiparameter whole blood hemostasis assessment using a carbon nanotube-paper composite capacitance sensor.

Rapid and accurate clinical assessment of hemostasis is essential for managing patients who undergo invasive procedures, experience hemorrhages, or receive antithrombotic therapies. Hemostasis encompasses an ensemble of interactions between the cellular and non-cellular blood components, but current devices assess only partial aspects of this complex process. In this work, we describe the development of a new approach to simultaneously evaluate coagulation function, platelet count or function, and hematocrit using a carbon nanotube-paper composite (CPC) capacitance sensor. CPC capacitance response to blood clotting at 1.3 MHz provided three sensing parameters with distinctive sensitivities towards multiple clotting elements. Whole blood-based hemostasis assessments were conducted to demonstrate the potential utility of the developed sensor for various hemostatic conditions, including pathological conditions, such as hemophilia and thrombocytopenia. Results showed good agreements when compared to a conventional thromboelastography. Overall, the presented CPC capacitance sensor is a promising new biomedical device for convenient non-contact whole-blood based comprehensive hemostasis evaluation.

Bone marrow derived-mesenchymal stem cell improves diabetes-associated fatty liver via mitochondria transformation in mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a global epidemic disease. Its incidence is associated with type 2 diabetes mellitus (T2DM). Presently, there is no approved pharmacological agents specially developed for NAFLD. One promising disease-modifying strategy is the transplantation of stem cells to promote metabolic regulation and repair of injury. METHOD: In this study, a T2DM model was established through 28-week high-fat diet (HFD) feeding resulting in T2DM-associated NAFLD, followed by the injection of bone marrow mesenchymal stem cells (BMSCs). The morphology, function, and transfer of hepatocyte mitochondria were evaluated in both vivo and in vitro. RESULTS: BMSC implantation resulted in the considerable recovery of increasing weight, HFD-induced steatosis, liver function, and disordered glucose and lipid metabolism. The treatment with BMSC transplantation was accompanied by reduced fat accumulation. Moreover, mitochondrial transfer was observed in both vivo and vitro studies. And the mitochondria-recipient steatotic cells exhibited significantly enhanced OXPHOS activity, ATP production, and mitochondrial membrane potential, and reduced reactive oxygen species levels, which were not achieved by the blocking of mitochondrial transfer. CONCLUSION: Mitochondrial transfer from BMSCs is a feasible process to combat NAFLD via rescuing dysfunction mitochondria, and has a promising therapeutic effect on metabolism-related diseases.

Rapid development of a de novo convalescent plasma program in response to a global pandemic: A large southeastern U.S. blood center's experience.

BACKGROUND: During the pandemic in the spring of 2020 with no vaccine or treatment for SARS-CoV-2 and its associated disease, COVID-19, convalescent plasma from recovered COVID-19 (CCP) patients offered a potential therapy. In March 2020, the United States (U.S.) Food and Drug Administration (FDA) authorized CCP under emergency Investigational New Drug (eIND) exemption and an IRB-approved Expanded Access Program (EAP) to treat severe COVID-19. Hospital demand grew rapidly in the Southeastern U.S., resulting in backlogs of CCP orders. We describe a large U.S. blood center's (BC) rapid implementation of a CCP program in response to community needs. STUDY DESIGN AND METHODS: From April 2 to May 17, 2020, CCP was collected by whole blood or apheresis. Initial manual approaches to donor intake, collection, and distribution were rapidly replaced with automated processes. All CCP donors and products underwent FDA-required screening and testing. RESULTS: A total of 619 CCP donors (299 females, 320 males) presented for CCP donation (161 [25.7%] whole blood, 466 [74.3%] plasmapheresis) resulting in 1219 CCP units. Production of CCP increased as processes were automated and streamlined, from a mean of 11 donors collected/day for the first month to a mean of 25 donors collected/day in the subsequent 2 weeks. Backlogged orders were cleared, and inventory began to accumulate 4 weeks after project initiation. CONCLUSION: The BC was able to implement an effective de novo CCP collection program within 6 weeks in response to a community need in a global pandemic. Documentation of the experience may inform preparedness for future pandemics.

Autologous fat transplantation for the treatment of abdominal wall scar adhesions after cesarean section.

Cesarean section results in scarring, which usually leads to adhesion between the subcutaneous fat and the abdominal wall muscle. The present study aimed to evaluate the therapeutic effect of autologous fat grafting on scar adhesion to the abdominal wall after cesarean section. Thirty-six patients with scar adhesion to the abdominal wall after cesarean section were recruited and treated between October 2013 and December 2015. The adhesion between the subcutaneous fat and the abdominal wall muscle was carefully separated through a small incision in the original scar to form multiple subcutaneous tunnels. Aspirated fat was injected into the scar lesion and subcutaneous tunnels, and the wound was then sutured. The clinical outcome was evaluated by comparing the pretreatment and 1-year posttreatment photographs and Patient and Observer Scar Assessment Scale (POSAS) scores. All patients had a marked improvement in the appearance, texture, and depression of the scar during 12 months of follow-up. The 1-year posttreatment POSAS scores for the color, pain, pruritus, hardness, fullness, mobility, and appearance of the scar were significantly decreased compared with the pretreatment scores. Hematoxylin-eosin staining revealed adipocyte-like cells in treated scar tissue specimens obtained 1 year after treatment. None of the patients reported severe adverse reactions. Autologous fat grafting combined with adhesion release may be a good treatment option for abdominal wall scarring after cesarean section. This method is minimally invasive and effective in achieving good functional and esthetic outcomes.