Successful application of eculizumab in typical haemolytic uraemic syndrome.

A woman in her 40s with no medical history presented on hospital day #0 with 3 days of epigastric pain, nausea, vomiting and bloody diarrhoea. Initial blood work demonstrated acute kidney injury with metabolic acidosis with an elevated anion gap, thrombocytopenia, an elevated lactate dehydrogenase, and an undetectable haptoglobin. She was quickly diagnosed with haemolytic uraemic syndrome from Shiga toxin-producing O157:H7 Escherichia coli Her microangiopathic haemolytic anaemia and renal failure progressively worsened and only improved after the initiation of eculizumab, a monoclonal antibody directed against complement component C5. We report a case of Shiga toxin-producing E. coli-haemolytic uraemia syndrome with a complement-mediated component.

Detection and margin assessment of thyroid carcinoma with microscopic hyperspectral imaging using transformer networks.

Significance: Hyperspectral imaging (HSI) is an emerging imaging modality for oncological applications and can improve cancer detection with digital pathology. Aim: The study aims to highlight the increased accuracy and sensitivity of detecting the margin of thyroid carcinoma in hematoxylin and eosin (H&E)-stained histological slides using HSI and data augmentation methods. Approach: Using an automated microscopic imaging system, we captured 2599 hyperspectral images from 65 H&E-stained human thyroid slides. Images were then preprocessed into 153,906 image patches of dimension 250 × 250 × 84 pixels . We modified the TimeSformer network architecture, which used alternating spectral attention and spatial attention layers. We implemented several data augmentation methods for HSI based on the RandAugment algorithm. We compared the performances of TimeSformer on HSI against the performances of pretrained ConvNext and pretrained vision transformers (ViT) networks on red, green, and blue (RGB) images. Finally, we applied attention unrolling techniques on the trained TimeSformer network to identify the biological features to which the network paid attention. Results: In the testing dataset, TimeSformer achieved an accuracy of 90.87%, a weighted F 1 score of 89.79%, a sensitivity of 91.50%, and an area under the receiving operator characteristic curve (AU-ROC) score of 97.04%. Additionally, TimeSformer produced thyroid carcinoma tumor margins with an average Jaccard score of 0.76 mm. Without data augmentation, TimeSformer achieved an accuracy of 88.23%, a weighted F 1 score of 86.46%, a sensitivity of 85.53%, and an AU-ROC score of 94.94%. In comparison, the ViT network achieved an 89.98% accuracy, an 88.14% weighted F 1 score, an 84.77% sensitivity, and a 96.17% AU-ROC. Our visualization results showed that the network paid attention to biological features. Conclusions: The TimeSformer model trained with hyperspectral histological data consistently outperformed conventional RGB-based models, highlighting the superiority of HSI in this context. Our proposed augmentation methods improved the accuracy, the F 1 score, and the sensitivity score.

Eculizumab for Shiga-toxin-induced hemolytic uremic syndrome in adults with neurological involvement.

The role of eculizumab in treating Shiga-toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) patients with neurological involvement remains unclear. We describe two distinctly different STEC-HUS patients with neurologic involvement successfully managed with eculizumab, and perform a literature review of all published cases. Both patients had complete resolution of neurological symptoms after initiation of eculizumab. Eighty patients with STEC-HUS treated with eculizumab were identified in the literature, 68.7% had complete resolution of neurological symptoms. Based on our experience and literature review, three prevailing themes were noted: 1) Early eculizumab administration optimized neurological outcomes, 2) Symptom resolution may not be immediate, neurological symptoms may initially worsen before improvement, and 3) Plasma exchange yielded no benefit. Early administration of eculizumab may reverse neurotoxicity in patients with STEC-HUS.

Nerve Detection and Visualization Using Hyperspectral Imaging for Surgical Guidance.

During surgery of delicate regions, differentiation between nerve and surrounding tissue is crucial. Hyperspectral imaging (HSI) techniques can enhance the contrast between types of tissue beyond what the human eye can differentiate. Whereas an RGB image captures 3 bands within the visible light range (e.g., 400 nm to 700 nm), HSI can acquire many bands in wavelength increments that highlight regions of an image across a wavelength spectrum. We developed a workflow to identify nerve tissues from other similar tissues such as fat, bone, and muscle. Our workflow uses spectral angle mapper (SAM) and endmember selection. The method is robust for different types of environment and lighting conditions. We validated our workflow on two samples of human tissues. We used a compact HSI system that can image from 400 to 1700 nm to produce HSI of the samples. On these two samples, we achieved an intersection-over-union (IoU) segmentation score of 84.15% and 76.73%, respectively. We showed that our workflow identifies nerve segments that are not easily seen in RGB images. This method is fast, does not rely on special hardware, and can be applied in real time. The hyperspectral imaging and nerve detection approach may provide a powerful tool for image-guided surgery.

A High-Resolution Hyperspectral Imaging System for the Retina.

In this study, we developed an imaging system that can acquire and produce high-resolution hyperspectral images of the retina. Our system combines the view from a high-resolution RGB camera and a snapshot hyperspectral camera together. The method is fast and can be constructed into a compact imaging device. We tested our system by imaging a calibrated color chart, biological tissues ex vivo, and a phantom of the human retina. By using image pansharpening methods, we were able to produce a high-resolution hyperspectral image. The images from the hyperspectral camera alone have a spatial resolution of 0.2 mm/pixel, whereas the pansharpened images have a spatial resolution of 0.1 mm/pixel, a 2x increase in spatial resolution. Our method has the potential to capture images of the retina rapidly. Our method preserves both the spatial and spectral fidelity, as shown by comparing the original hyperspectral images with the pansharpened images. The high-resolution hyperspectral imaging device can have a variety of applications in retina examinations.

Challenges to Laboratory Monitoring of Direct Oral Anticoagulants.

Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though DOACs are characterized by fixed-dose prescribing and generally do not require routine laboratory drug-level monitoring (DLM), circumstances may arise where the DLM may aid in clinical decision-making, including DOAC dose adjustment, anticoagulant class change, or decisions to withhold or administer reversal agents. We review the current literature that describes high-risk patient groups in which DLM may be beneficial for improved patient anticoagulation management and stewardship. The review also summarizes the limitations of conventional coagulation testing and discuss the emerging utility of quantitative methods for routine and rapid emergent evaluation of DOAC drug levels-in particular, the Anti-Xa activity to detect Factor Xa Inhibitors (rivaroxaban, apixaban, and edoxaban). Both technical and regulatory barriers to widespread DLM implementation are limiting factors to further clinical research that must be overcome, in order to propose universal DOAC DLM strategies and provide clinical-laboratory correlation to formally classify high-risk patient groups.

Peripheral blood stem cell collection: Are midline catheters a viable alternative to central venous catheters?

BACKGROUND: Vascular access is a rate-limiting step for peripheral blood stem cell collection. In the absence of readily accessible superficial veins, placement of tunnelled or non-tunnelled central venous catheters (CVCs) is common. These invasive access routes create medical risks for patients and are associated with logistical challenges, thus prompting a search for alternatives. One such option is the off-label use of midline catheters. STUDY DESIGN AND METHODS: We carried out a literature search for published experience with the use of midline catheters for peripheral blood stem cell collection. Data extracted included whether collections were allogeneic or autologous, donor sex, age and weight, inlet flow rate, total blood volumes (TBV) processed, collection duration, number of collections per donor, and achievement of collection targets. RESULTS: The search produced three reports (one in abstract form) comprising 19 patients and 26 collection events. Donor sex and status were provided for 18 patients; 10 were female, 8 were male, 12 were allogeneic, and 6 autologous. Median (range) for: donor age was 28 (12-59); donor body weight (kg) was 77.5 (45.4-113.4); inlet flow rate (in mL/min) was 66 (28-80); TBV processed (in mL) was 15,880 (6178-21,871); collection duration (in hours) was 5.0 (3.2-7.0); and CD34 × 106/kg collection yield was 5.9 (3.6-23.0). Target CD34 yields were achieved in 14/19 (74%) of donors with 7/19 (37%) requiring two collections days. DISCUSSION: Peripheral blood stem cell collection does appear to be viable via midline-based catheter access, particularly for allogeneic donors and shorter collection courses. Development of institution-specific guidelines and care pathways are recommended.

Therapeutic Plasma Exchange Versus FcRn Inhibition in Autoimmune Disease.

Therapeutic plasma exchange (TPE or PLEX) is used in a broad range of autoimmune diseases, with the goal of removing autoantibodies from the circulation. A newer approach for the selective removal of immunoglobulin G (IgG) antibodies is the use of therapeutic molecules targeting the neonatal Fc receptor (FcRn). FcRn regulates IgG recycling, and its inhibition results in a marked decrease in circulating autoantibodies of the IgG subtype. The difference between FcRn inhibition and PLEX is often questioned. With anti-FcRn monoclonal antibodies (mAbs) and fragments only recently entering this space, limited data are available regarding long-term efficacy and safety. However, the biology of FcRn is well understood, and mounting evidence regarding the efficacy, safety, and potential differences among compounds in development is available, allowing us to compare against nonselective plasma protein depletion methods such as PLEX. FcRn inhibitors may have distinct advantages and disadvantages over PLEX in certain scenarios. Use of PLEX is preferred over FcRn inhibition where removal of antibodies other than IgG or when concomitant repletion of missing plasma proteins is needed for therapeutic benefit. Also, FcRn targeting has not yet been studied for use in acute flares or crisis states of IgG-mediated diseases. Compared with PLEX, FcRn inhibition is associated with less invasive access requirements, more specific removal of IgG versus other immunoglobulins without a broad impact on circulating proteins, and any impacts on other therapeutic drug levels are restricted to other mAbs. In addition, the degree of IgG reduction is similar with FcRn inhibitors compared with that afforded by PLEX. Here we describe the scientific literature regarding the use of PLEX and FcRn inhibitors in autoimmune diseases and provide an expert discussion around the potential benefits of these options in varying clinical conditions and scenarios.

Liquid Storage of Peripheral Blood Stem Cell Products: Effects of Time and Temperature on Product Quality.

Unrelated donor peripheral blood stem cell (PBSC) products often require transport to distant locations, which may take up to 72 hours. Temperature is an important variable that can be controlled during PBSC storage or transport; therefore, we studied the impact of temperature on prolonged storage of clinical-grade, mobilized PBSC products. PBSC products were collected by apheresis from 3 granulocyte colony-stimulating factor-mobilized donors, split into 2 PVC blood bags of equal volume, and stored at room temperature (RT) (18°C to 25 ºC) or 4 °C (2°C to 8 ºC) for 96 hours. Samples were obtained at 24-hour intervals for pH, cell counts, flow cytometry phenotyping and viability (7AAD), and hematopoietic colony-forming units (CFU). Starting PBSC products contained 52, 65, and 38 × 109 total nucleated cells (TNCs), with cell concentrations of 125, 263, and 94.6 × 106 TNCs/mL, respectively. Product pH dropped during storage, with significantly lower values for RT stored products than for 4 ºC stored products, and was greatest in the product with the highest TNC count. The percent recovery of viable CD34+ progenitor cells, CD3+ T cells, CD4+ T helper cells, CD8+ cytotoxic T cells, CD19+ B cells, CD15+ granulocytes, CD14+ monocytes, and CD16+/56+ natural killer (NK) cells all decreased over 96 hours but decreased more dramatically in the RT group. Cell recovery differences were statistically significant at most time points for all cell populations except CD15+ granulocytes. For CD34+ cells stored at 4 °C, mean recovery from prestorage values were 97 ± 3% at 24 hours, 87 ± 4% at 48 hours, 88 ± 10% at 72 hours, and 78 ± 1% at 96 hours, compared to RT product values of 45 ± 11%, 19 ± 19%, 2 ± 2%, and 0 ± 0%, respectively. CFUs were well preserved through 96 hours at 4 ºC but not at RT. During PBSC storage, pH and content of viable CD34+ cells, T cells, B cells, monocytes, NK cells, and CFU all declined. However, at 4 ºC, viable cell recoveries are relatively well preserved, even at 72 hours, whereas RT storage resulted in rapid product deterioration. PBSC products requiring prolonged liquid storage or transport before cryopreservation or infusion should be maintained at 4 ºC.

Thrombotic microangiopathy - the importance of a multidisciplinary approach.

PURPOSE OF REVIEW: The purpose of this review is to highlight the importance of a multidisciplinary thrombotic microangiopathies (TMA) Team. This goal will be accomplished through review of the complement system, discuss various causes of thrombotic microangiopathies (TMA), and aspects of their diagnosis and management. In so doing, readers will gain an appreciation for the complexity of this family of disorders and realize the benefit of a dedicated multidisciplinary TMA Team. RECENT FINDINGS: TMA causes derive from multiple specialty areas, are difficult to timely recognize, pose complex challenges, and require multidisciplinary management. Hematopoietic stem cell transplant-associated TMA (TA-TMA) and TA-TMA related multiorgan dysfunction syndrome (TA-TMA MODS) are areas of burgeoning research; use of complement testing and eculizumab precision-dosing has been found to better suppress complement activity in TA-TMA than standard eculizumab dosing. Newer tests are available to risk-stratify obstetric patients at risk for severe pre-eclampsia, whose features resemble those of TA-TMA MODS. Numerous disorders may produce TMA-like findings, and a systematic approach aids in their identification. TMA Teams elevate institutional awareness of increasingly recognized TMAs, will help expedite diagnostic and therapeutic interventions, and create pathways to future TMA-related research and facilitate access to clinical trials. SUMMARY: Establishment of a TMA-Team is valuable in developing the necessary institutional expertise needed to promptly recognize and appropriately manage patients with TMA.

Updates on the mobilization pipeline for hematopoietic stem cell collection.

Hematopoetic Stem Cell Transplantation is a life saving procedure which requires mobilization of stem cells for apheresis procedure. In this review we aimed to examine mobilizing agents that are in use and under investigation. Apheresis practitioners who oversee stem cell collections should be familiar with the recent advances in mobilization agents to utilize most up-to-date information for better patient outcomes.

Effect of erythropoietin on perioperative blood transfusions in primary total hip arthroplasty: A systematic review.

BACKGROUND: Primary total hip arthroplasty (THA) often requires blood transfusion. Transfusions are undesirable due to risks of infectious and noninfectious complications. This systematic review therefore studied the effectiveness of erythropoietin (EPO) in reducing allogeneic transfusion rate during THA. METHODS: Using the MESH terms "Erythropoietin" AND "Total Hip" with restrictions to 'Randomized Controlled Trial', 'Clinical Trial', 'Humans', and 'English', a literature search was performed in PubMed and CINAHL. Articles were scanned by both authors and retained for further review if eligibility was met according to the inclusion criteria defined by the PICOS (population, intervention, comparator, outcomes, study design) configuration. Risk of bias was assessed using the Cochrane risk of bias criteria. Data extracted include patient demographics, intervention versus comparator arm, outcomes, laboratory data, and individual study characteristics. The primary outcome of focus was rate or amount of allogeneic blood transfusions intra- or postoperatively. In 6/8 studies, data permitted calculations of absolute risk reduction (ARR) in transfusion rate (%) and number needed to treat (NNT) to evade transfusions. RESULTS: A total of 8 studies met all eligibility criteria and were retained for data extraction; risk of bias was low-moderate in 7/8 and high in 1/8. Allogeneic transfusion exposure was lowered by the intervention in 7/8 studies with ARR from 9.6% to 33.5% and NNT from 4 to 10. CONCLUSIONS: In the blood conservation systems described, the addition of EPO was effective in reducing allogeneic transfusions. The studies included spanned a nearly 30-year period. Earlier studies incorporated preoperative autologous donation, a now outdated modality.

Caplacizumab as rescue therapy in refractory TTP involving neurologic features.

BACKGROUND: The role of caplacizumab in the routine treatment of immune thrombotic thrombocytopenic purpura (iTTP) remains to be established. CASE SUMMARY: A 56-year-old woman was transferred to our center with iTTP and neurologic features. At the outside hospital, she was initially diagnosed and managed as Immune Thrombocytopenia (ITP). Upon transfer to our center, daily plasma exchange, steroids, and rituximab were initiated. After an initial improvement, refractoriness became evident with a decline in platelet count and continued neurologic abnormalities. Initiation of caplacizumab resulted in rapid hematologic and clinical responses. CONCLUSION: Caplacizumab is a valuable treatment modality in iTTP, particularly in cases associated with refractoriness or neurologic features.

Therapeutic modalities in thrombotic thrombocytopenic purpura management among Jehovah's Witness patients: A review of reported cases.

INTRODUCTION: Devout members of the Jehovah's Witness faith flatly refuse transfusions of white blood cells, red blood cells, platelets, and plasma. The latter agent is a mainstay in the treatment of thrombotic thrombocytopenic purpura (TTP). Alternative treatment options for Jehovah's Witness patients are needed and reviewed herein. METHODS: Cases of TTP treatment among Jehovah's Witnesses were obtained from the published literature. Key baseline and clinical data were extracted and summarized. RESULTS: A total of 13 reports spanning a 23-year period and 15 TTP episodes were identified. Median (IQR) age was 45.5 (29.0-57.5) and 12/13 (93%) patients were female. Neurologic symptoms were present in 7/15 (47%) episodes at presentation. Disease confirmation with ADAMTS13 testing was present in 11/15 (73%) of episodes. Corticosteroids and rituximab were employed in 13/15 (87%) and 12/15 (80%) of cases, respectively, with apheresis-based therapy employed in 9/15 (60%) episodes. For eligible cases, caplacizumab was used in 4/5 (80%) episodes; average time to platelet response was shortest in these cases. Sources of exogenous ADAMTS13 accepted by patients in this series included cryo-poor plasma, FVIII concentrate, and cryoprecipitate. CONCLUSIONS: Successful management of TTP within the boundaries of the Jehovah's Witness faith is possible.

An automatic whole-slide hyperspectral imaging microscope.

Whole slide imaging (WSI) is a common step used in histopathology to quickly digitize stained histological slides. Digital whole-slide images not only improve the efficiency of labeling but also open the door for computer-aided diagnosis, specifically machine learning-based methods. Hyperspectral imaging (HSI) is an imaging modality that captures data in various wavelengths, some beyond the range of visible lights. In this study, we developed and implemented an automated microscopy system that can acquire hyperspectral whole slide images (HWSI). The system is robust since it consists of parts that can be swapped and bought from different manufacturers. We used the automated system and built a database of 49 HWSI of thyroid cancer. The automatic whole-slide hyperspectral imaging microscope can have many potential applications in biological and medical areas.

A Video Transformer Network for Thyroid Cancer Detection on Hyperspectral Histologic Images.

Hyperspectral imaging is a label-free and non-invasive imaging modality that seeks to capture images in different wavelengths. In this study, we used a vision transformer that was pre-trained from video data to detect thyroid cancer on hyperspectral images. We built a dataset of 49 whole slide hyperspectral images (WS-HSI) of thyroid cancer. To improve training, we introduced 5 new data augmentation methods that transform spectra. We achieved an F-1 score of 88.1% and an accuracy of 89.64% on our test dataset. The transformer network and the whole slide hyperspectral imaging technique can have many applications in digital pathology.

"Plasma exchange in a bottle": An overview of efgartigimod for apheresis practitioners.

Efgartigimod represents a first-in-class immunomodulatory agent that is comparable to TPE in reducing immunoglobulin levels. This translates to reductions in Myasthenia Gravis symptom scores with maximal effect following the fourth weekly efgartigimod dose. Efgartigimod received FDA approval in December of 2021 and may be an alternative particularly for patients on long-term TPE regimens of weekly or less frequent. Apheresis practitioners, especially those managing long-term apheresis in seropositive individuals, may therefore see some of their patients transitioned from plasma exchange to efgartigimod. Long-term experience with efgartigimod remains lacking and studies are needed to establish the role of efgartigimod in the acute setting.