Blood Demand Forecasting and Supply Management: An Analytical Assessment of Key Studies Utilizing Novel Computational Techniques.

Use of data-driven methodologies in enhancing blood transfusion practices is rising, leveraging big data, machine learning, and optimization techniques to improve demand forecasting and supply chain management. This review used a narrative approach to identify, evaluate, and synthesize key studies that considered novel computational techniques for blood demand forecasting and inventory management through a search of PubMed and Web of Sciences databases for studies published from January 01, 2016, to March 30, 2023. The studies were analyzed for their utilization of various techniques, and their strengths, limitations, and areas for improvement. Seven key studies were identified. The studies focused on different blood components using various computational methods, such as regression, machine learning, hybrid models, and time series models, across different locations and time periods. Key variables used for demand forecasting were largely derived from electronic health record data, including clinical related predictors such as laboratory test results and hospital census by location. Each study offered unique strengths and valuable insights into the use of data-driven methods in blood bank management. Common limitations were unknown generalizability to other healthcare settings or blood components, need for field-specific performance measures, lack of ABO compatibility consideration, and ethical challenges in resource allocation. While data-driven research in blood demand forecasting and management has progressed, limitations persist and further exploration is needed. Understanding these innovative, interdisciplinary methods and their complexities can help refine inventory strategies and address healthcare challenges more effectively, leading to more robust, accurate models to enhance blood management across diverse healthcare scenarios.

Increased serum pro-B-type natriuretic peptide in hematopoietic progenitor cell donors stimulated with G-CSF.

Hematopoietic stem cells (HPCs) donors mobilized by granulocyte-colony-stimulating factor (G-CSF) can develop various signs and symptoms. proBNP (pro-B-type natriuretic peptide) is a serum marker of heart failure. A donor who developed severe adverse reactions after G-CSF mobilization was found to have high serum proBNP levels. We followed additional donors who received identical mobilization regimen to investigate the prevalence of this phenomenon. Eighteen healthy donors underwent a mobilization regimen of 10 µg/Kg G-CSF daily for 5 days prior to allogeneic HPC collection using Spectra Optia between January 2016 and February 2017 were included in this study. Serum proBNP levels were measured before and after G-CSF stimulation and immediately after apheresis. Apheresis collection parameters and other laboratory results were also reviewed. The majority of donors (86.7%) had post-G-CSF elevation of serum proBNP. Seven of those had elevated proBNP above upper normal range (124 pg/ml). The subgroup of donors with normal proBNP is younger (median age of 37 vs 42 years), with majority being male (90.9% vs 28.6%) and with smaller processed blood volume (2.2 vs 3 × total blood volume). This case series demonstrates an increase of serum proBNP can be common in HPC donors stimulated with 5 days of 10 mcg/kg G-CSF. This is an adverse reaction that has not been described before. The temporary elevation of proBNP in these donors is not associated with ventricular dysfunction of the heart. The risk factors for marked elevation of proBNP post-G-CSF should be further investigated.

Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project.

BACKGROUND: The 1000 Genomes Project provides a database of genomic variants from whole genome sequencing of 2504 individuals across five continental superpopulations. This database can enrich our background knowledge of worldwide blood group variant geographic distribution and identify novel variants of potential clinical significance. STUDY DESIGN AND METHODS: The 1000 Genomes database was analyzed to 1) expand knowledge about continental distributions of known blood group variants, 2) identify novel variants with antigenic potential and their geographic association, and 3) establish a baseline scaffold of chromosomal coordinates to translate next-generation sequencing output files into a predicted red blood cell (RBC) phenotype. RESULTS: Forty-two genes were investigated. A total of 604 known variants were mapped to the GRCh37 assembly; 120 of these were reported by 1000 Genomes in at least one superpopulation. All queried variants, including the ACKR1 promoter silencing mutation, are located within exon pull-down boundaries. The analysis yielded 41 novel population distributions for 34 known variants, as well as 12 novel blood group variants that warrant further validation and study. Four prediction algorithms collectively flagged 79 of 109 (72%) known antigenic or enzymatically detrimental blood group variants, while 4 of 12 variants that do not result in an altered RBC phenotype were flagged as deleterious. CONCLUSION: Next-generation sequencing has known potential for high-throughput and extended RBC phenotype prediction; a database of GRCh37 and GRCh38 chromosomal coordinates for 120 worldwide blood group variants is provided as a basis for this clinical application.

Successful salvage chemotherapy and allogeneic transplantation of an acute myeloid leukemia patient with disseminated Fusarium solani infection.

Disseminated Fusarium infection is associated with high mortality in immunocompromised patients. Patients with acute myeloid leukemia (AML) often have an extended duration of neutropenia during intensive induction chemotherapy, consolidation chemotherapy, and hematopoietic stem cell transplantation (SCT). There is no consensus regarding management of invasive disseminated Fusarium infections in the setting of prolonged neutropenia (Tortorano et al., 2014) [1]. We report a case of disseminated Fusarium in a patient with relapsed AML who underwent successful chemotherapy and haplo-identical allogeneic SCT with administration of granulocyte colony stimulating factor (G-CSF) and granulocyte infusions.

Encapsulated follicular variant of papillary thyroid cancer: are these tumors really benign?

BACKGROUND: Recent studies suggest that the encapsulated form of follicular variant of papillary thyroid cancer (eFVPTC) behaves more similarly to benign lesions and can be treated with thyroid lobectomy alone instead of total thyroidectomy. To distinguish aggressive cancers from more benign lesions more clearly, the objective of this study was to determine if the eFVPTC behaves less aggressively than the nonencapsulated variant (neFVPTC). METHODS: A prospectively collected endocrine surgery database in our institution was reviewed for all patients with FVPTC on surgical pathology from 1999 to 2012. Samples were rereviewed to determine if the tumor was eFVPTC or neFVPTC, which were correlated with patient outcomes. RESULTS: Of the 68 patients, 59 (87%) had eFVPTC and 9 (13%) had neFVPTC. The mean age was 48 y and 63% were female. Fifty-four of 64 patients (84%) who had a total thyroidectomy received radioactive iodine. The eFVPTC group had lower rates of cervical LN involvement (5% versus 22%, P = 0.2504). The median follow-up time was 3 y (0-13 y) and only two patients had recurrence, one with eFVPTC and one with neFVPTC. None of the patients had distant metastasis or died of their disease. CONCLUSIONS: eFVPTCs appear to have a lower rate of cervical lymph node metastases compared with neFVPTCs, but recurrent disease may be seen in both subtypes. These findings suggest eFVPTC can be managed more conservatively.

Acquired RhD mosaicism identifies fibrotic transformation of thrombopoietin receptor-mutated essential thrombocythemia.

BACKGROUND: Acquired copy-neutral loss of heterozygosity has been described in myeloid malignant progression with an otherwise normal karyotype. CASE REPORT: A 65-year-old woman with MPL-mutated essential thrombocythemia and progression to myelofibrosis was noted upon routine pretransplant testing to have mixed field reactivity with anti-D and an historic discrepancy in RhD type. The patient had never received transfusions or transplantation. RESULTS: Gel immunoagglutination revealed group A red blood cells and a mixed-field reaction for the D phenotype, with a predominant D-negative population and a small subset of circulating red blood cells carrying the D antigen. Subsequent genomic microarray single nucleotide polymorphism profiling revealed copy-neutral loss of heterozygosity of chromosome 1 p36.33-p34.2, a known molecular mechanism underlying fibrotic progression of MPL-mutated essential thrombocythemia. The chromosomal region affected by this copy-neutral loss of heterozygosity encompassed the RHD, RHCE, and MPL genes. We propose a model of chronological molecular events that is supported by RHD zygosity assays in peripheral lymphoid and myeloid-derived cells. CONCLUSION: Copy-neutral loss of heterozygosity events that lead to clonal selection and myeloid malignant progression may also affect the expression of adjacent unrelated genes, including those encoding for blood group antigens. Detection of mixed-field reactions and investigation of discrepant blood typing results are important for proper transfusion support of these patients and can provide useful surrogate markers of myeloproliferative disease progression.

Dysadherin specific drug conjugates for the treatment of thyroid cancers with aggressive phenotypes.

BACKGROUND: EDC1 is a novel type of antibody-drug conjugate which binds and inhibits the Na,K-ATPase on the surface of cancer cells expressing dysadherin. The purpose of this study was to determine the expression of dysadherin in different types of thyroid carcinoma, and evaluate the therapeutic potential of EDC1 for thyroid carcinomas. METHODS: Thyroid tissues from 158 patients were examined for dysadherin expression and correlation with clinicopathological features. Thyroid cancer cell lines were examined for the expression of dysadherin and effective dose range of EDC1. RESULTS: One in 53 benign thyroid tissues and 62% of thyroid cancers expressed dysadherin. All anaplastic and a majority of papillary thyroid cancers overexpressed dysadherin, while 25% of follicular thyroid cancers was found to be positive for dysadherin. Dysadherin expression significantly correlated with extrathyroidal extension and lymph node metastases in papillary thyroid cancer. Five of six human thyroid cancer cell lines analyzed expressed high levels of dysadherin. Of those cells lines sensitive to EDC1, half maximal effective concentrations (EC50) were observed to be between 0.125 nM and 1 nM. CONCLUSIONS: EDC1 showed selective inhibition of growth in thyroid cancer cells with moderate to high expression of dysadherin, thus could be a specific and effective treatment.

In Situ Hybridization Analysis of miR-146b-5p and miR-21 in Thyroid Nodules: Diagnostic Implications.

Some thyroid nodules such as follicular adenomas (FAs), follicular variant of papillary thyroid carcinomas (FVPTCs), and follicular thyroid carcinomas (FTCs) exhibit similar clinical presentations and gross morphologic appearances. The differential diagnosis of these lesions is sometimes difficult based on morphologic, cytologic, or clinical features alone. miR-146b-5p and miR-21 deregulation has been associated with progression and metastasis of thyroid cancers. However, the utility of in situ hybridization (ISH) to determine the cellular localization, diagnostic, and prognostic significance of miR-146b-5p and miR-21 expression in thyroid tumors has not been extensively analyzed. In order to examine the expression of miR-146b-5p and miR-21 in benign and malignant thyroid tissues and to determine if these microRNAs could be assigned to distinct histomorphological types of thyroid nodules, we analyzed miR-146b-5p and miR-21 expression in thyroid nodules on tissue microarrays (TMAs) with 193 thyroid specimens by ISH. miR-146b-5p and miR-21 expression in thyroid tissues was also analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). miR-146b-5p was highly expressed (89%) in papillary thyroid carcinomas (PTCs) and 41% of FVPTC. The expression of miR-146b-5p was not expressed in most FTCs, anaplastic thyroid carcinomas (ATCs), poorly differentiated thyroid carcinomas (PDTCs), or FAs (7, 8, 0, and 0%, respectively). MiR-21 was overexpressed in 83% of ATCs, 79 % of PTCs, 34% of FVPTCs, and 19% of PDTCs. The expression of miR-21 was not expressed in most FAs (9%) or FTCs (4%). Normal thyroid tissues and most benign goiters were negative for miR-146b-5p and miR-21. qRT-PCR analysis supported the ISH findings. PTC cases with positive expression of miR-146b-5p and miR-21 had significantly poorer disease-free survival rates. Immunohistochemical staining for HBME-1 showed positive staining in PTCs (100 %) and FVPTCs (92 %) with a subset of FTC (40%) staining positive, while all FAs were negative. Since miR-146b-5p was mainly expressed in PTC including FVPTC and was not expressed in most FTC, PDTC, or ATC, it may serve as a useful diagnostic marker for PTC. ISH is a useful method to analyze microRNA expression in formalin-fixed paraffin-embedded thyroid tissues.

Role of percutaneous needle core biopsy in diagnosis and clinical management of renal masses.

Percutaneous needle core biopsies are routinely performed for renal mass diagnosis in some institutions. Because of limited tissue availability, accurate diagnosis can be challenging, and the role of needle core biopsy (NCB) remains debatable in kidney tumor management. In the present study, we reported our experience in diagnosing renal masses via percutaneous NCB and the role it plays in clinical management of these masses. We studied 301 consecutive cases of percutaneous NCBs performed for 280 renal masses from 269 patients between year 2008 and 2011 by reviewing final pathology diagnosis, hematoxylin and eosin slides, and ancillary studies. Diagnostic accuracy was determined by comparing biopsy and nephrectomy diagnoses in a subset of renal masses. Clinical data including demographic information, clinical presentation, radiographic findings, and treatment information were reviewed subsequently if available. The size of renal masses in our study cohort ranged from 0.5 to 24 cm, and 78% of them were small renal masses. Definite diagnoses were rendered in 89% of the renal masses by NCBs, and 23% of them were benign. Renal mass NCB was 100% accurate in diagnosing primary renal malignancy and 93% accurate in determining histologic subtypes. Clinical management was analyzed for 180 renal masses. There was significant difference in clinical management between different diagnostic groups. We conclude that percutaneous NCB is a powerful tool not only for definite tissue diagnosis of renal masses before treatment but also plays an important role in guiding patient management and obtaining material for future molecular studies for targeted therapies.

The roles of the epithelial-mesenchymal transition marker PRRX1 and miR-146b-5p in papillary thyroid carcinoma progression.

Thyroid carcinoma is the most common endocrine malignancy, and papillary thyroid carcinoma represents the most common thyroid cancer. Papillary thyroid carcinomas that invade locally or metastasize are associated with a poor prognosis. We found that, during epithelial-mesenchymal transition (EMT) induced by transforming growth factor-ß1 (TGF-ß1), papillary thyroid carcinoma cells acquired increased cancer stem cell-like features and the transcription factor paired-related homeobox protein 1 (PRRX1; alias PRX-1), a newly identified EMT inducer, was markedly up-regulated. miR-146b-5p was also transiently up-regulated during EMT, and in siRNA experiments miR-146b-5p had an inhibitory role on cell proliferation and invasion during TGF-ß1-induced EMT. We conclude that papillary thyroid carcinoma tumor cells exhibit increased cancer stem cell-like features during TGF-ß1-induced EMT, that miR-146b-5p has a role in cell proliferation and invasion, and that PRRX1 plays an important role in papillary thyroid carcinoma EMT and disease progression.

The role of epithelial mesenchymal transition markers in thyroid carcinoma progression.

Understanding the molecular mechanisms involved in thyroid cancer progression may provide targets for more effective treatment of aggressive thyroid cancers. Epithelial mesenchymal transition (EMT) is a major pathologic mechanism in tumor progression and is linked to the acquisition of stem-like properties of cancer cells. We examined expression of ZEB1 which activates EMT by binding to the E-box elements in the E-cadherin promoter, and expression of E-cadherin in normal and neoplastic thyroid tissues in a tissue microarray which included 127 neoplasms and 10 normal thyroid specimens. Thyroid follicular adenomas (n = 32), follicular thyroid carcinomas (n = 28), and papillary thyroid carcinomas (n = 57) all expressed E-cadherin and were mostly negative for ZEB1 while most anaplastic thyroid carcinomas (ATC, n = 10) were negative for E-cadherin, but positive for ZEB1. A validation set of 10 whole sections of ATCs showed 90 % of cases positive for ZEB1 and all cases were negative for E-cadherin. Analysis of three cell lines (normal thyroid, NTHY-OR13-1; PTC, TPC-1, and ATC, THJ-21T) showed that the ATC cell line expressed the highest levels of ZEB1 while the normal thyroid cell line expressed the highest levels of E-Cadherin. Quantitative RT-PCR analyses showed that Smad7 mRNA was significantly higher in ATC than in any other group (p < 0.05). These results indicate that ATCs show evidence of EMT including decreased expression of E-cadherin and increased expression of ZEB1 compared to well-differentiated thyroid carcinomas and that increased expression of Smad7 may be associated with thyroid tumor progression.

Thyroid cancer stem-like cells and epithelial-mesenchymal transition in thyroid cancers.

Cancer stem-like cells are a subpopulation of self-renewing stem cells in cancers that are more resistant to chemotherapy and radiation therapy. Evidence supporting the existence of cancer stem-like cells in thyroid and in many other solid tissue cancers is rapidly accumulating. These cells have been studied using specific biomarkers such as CD133, CD44, and aldehyde dehydrogenase enzymes. Putative cancer stem-like cells can be studied in vitro using serum-free media supplemented with basic fibroblast growth factor and epidermal growth factor grown in nonadherent culture (ultra-low attachment plates) or in extracellular matrix leading to cell spheres formation in vitro. Cancer stem-like cells can also be separated by fluorescent cell sorting and used for in vitro or in vivo studies. Injection of enriched populations of cancer stem-like cells (also referred to as tumor initiating cells) into immunodeficient mice often results in rapid growth of xenografts, which express cancer stem-like cell biomarkers. Human cancer stem-like cells have been identified in thyroid cancer cell lines including papillary, follicular, medullary, and anaplastic carcinoma cell lines. They have also been identified in primary thyroid cancers and have been shown to have similar properties as the cancer stem-like cells in thyroid cancer cell lines. Immunohistochemical staining with CD133 and other biomarkers has been used to characterize thyroid cancer stem-like cells in paraffin sections of thyroid cancers. Recent studies of epithelial-mesenchymal transition in which cells lose their epithelial features and acquire mesenchymal phenotypes have shown that these changes are present in thyroid cancers. Biomarkers used to characterize epithelial-mesenchymal transition have also been studied in primary thyroid cancers. A close relationship between epithelial-mesenchymal transition and stem cell features of cancers has been identified in recent studies. New discoveries in this field may lead to more effective therapies for highly aggressive and lethal thyroid cancers.

Stem cells and cancer stem-like cells in endocrine tissues.

Cancer stem-like cells are a subpopulation of self-renewing cells that are more resistant to chemotherapy and radiation therapy than the other surrounding cancer cells. The cancer stem cell model predicts that only a subset of cancer cells possess the ability to self-renew and produce progenitor cells that can reconstitute and sustain tumor growth. Evidence supporting the existence of cancer stem-like cells in the thyroid, pituitary, and in other endocrine tissues is rapidly accumulating. These cells have been studied using specific biomarkers including: CD133, CD44, Nestin, Nanog, and aldehyde dehydrogenase enzyme. Putative cancer stem-like cells can be studied in vitro using serum-free media supplemented with basic fibroblast growth factor and epidermal growth factor grown in low attachment plates or in extracellular matrix leading to sphere formation in vitro. Cancer stem-like cells can also be separated by fluorescent cell sorting and used for in vitro or in vivo studies. Injection of enriched populations of cancer stem-like cells (also referred to as tumor initiating cells) into immunodeficient mice results in growth of xenografts which express cancer stem-like biomarkers. Human cancer stem-like cells have been identified in thyroid cancer cell lines, in primary thyroid cancers, in normal pituitary, and in pituitary tumors. Other recent studies suggest the existence of stem cells and cancer stem-like cells in endocrine tumors of the gastrointestinal tract, pancreas, lungs, adrenal, parathyroid, and skin. New discoveries in this field may lead to more effective therapies for highly aggressive and lethal endocrine cancers.

Expression of epithelial-mesenchymal transition regulators SNAI2 and TWIST1 in thyroid carcinomas.

Epithelial-mesenchymal transition is an important mechanism of epithelial tumor progression, local invasion and metastasis. The E-cadherin (CDH1) repressor SLUG (SNAI2) and the basic helix-loop-helix transcription factor TWIST1 inhibit CDH1 expression in poorly differentiated malignancies as inducers of epithelial-mesenchymal transition. Epithelial-mesenchymal transition has been implicated in progression from well to poorly differentiated/anaplastic thyroid carcinoma but the expression of SNAI2 and TWIST1 proteins and their phenotypic association in human thyroid cancers has not been extensively studied. We examined the expression of SNAI2, TWIST1 and CDH1 by immunohistochemistry in a panel of well-differentiated and anaplastic thyroid cancers and by qRT-PCR in thyroid cell lines. Ten normal thyroids, 33 follicular adenomas, 56 papillary thyroid carcinomas including 28 follicular variants, 27 follicular carcinomas and 10 anaplastic thyroid carcinomas were assembled on a tissue microarray and immunostained for SNAI2, TWIST1 and CDH1. Most (8/10) anaplastic thyroid carcinomas demonstrated strong nuclear immunoreactivity for SNAI2 with associated absence of CDH1 in 6/8 cases (75%). TWIST1 was expressed in 5/10 anaplastic thyroid carcinomas with absence of CDH1 in 3/5 (60%) cases. These findings were confirmed in whole sections of all anaplastic thyroid carcinomas and in a separate validation set of 10 additional anaplastic thyroid carcinomas. All normal thyroids, follicular adenomas, papillary and follicular thyroid carcinomas were negative for SNAI2 and TWIST1 (P<0.0001) and all showed strong diffuse immunoreactivity for CDH1 (P=0.026). Expression of SNAI2, TWIST1 and CDH1 mRNA varied in a normal thyroid, papillary carcinoma and two anaplastic thyroid carcinoma cell lines tested, but the highest levels of CDH1 mRNA were detected in the normal thyroid cell line while the anaplastic thyroid carcinoma cell line demonstrated the highest levels of SNAI2 and TWIST1 mRNA. Our findings support the role of epithelial-mesenchymal transition in the development of anaplastic thyroid carcinoma.