bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial adenomatous polyposis gene MUTYH mutations are identified in anaplastic thyroid carcinoma
Authors: Kovalenko M , Xiaoming Z , Jansen S , Hammer R , Pavlick D C , Hiemenz M , Dougherty K C , Dooley L M , Chen N 
Published: October 2024

Abstract

Introduction/Objective
Anaplastic thyroid carcinoma (ATC) is a rare aggressive disease unresponsive to treatment. Next-Generation Sequencing (NGS) allows identification of targets for precision therapies, such as BRAF, with implications in treating ATC. Our prior work identified ATC clusters with characteristic gene mutations and multiple previously unreported mutations. One of these is MUTYH, which is associated with colon (CRC), ovarian, breast, bladder, and duodenal carcinomas in MUTYH-associated polyposis (MAP). Its association with ATC is not defined.

Methods/Case Report
Exploratory analysis of pathogenic mutations in 727 ATC cases using a 324-gene panel (FoundationOneCDx) and an interactive visualization of association rules was conducted for informative maximal frequent patterns among mutated gene combinations to identify gene clusters including genes not commonly associated with ATC. TCGA database was reviewed for frequency of MUTYH mutations. My Cancer Genome and the Drug-Gene Interaction Database were used to identify potential targeted drugs for MUTYH gene-mutated cancers.

Results (if a Case Study enter NA)
NGS showed MUTYH short-variant mutations in 17 cases (2.34%). Germline MUTYH variants incidence is 1.43% in normal samples. 5 cases harbored only Y165C and 7 had only G382D, with 1 case having both Y165C and G382D. The other 4 cases contained sporadic truncating events in MUTYH. All instances of Y165C and G382D were predicted to be germline. 6 patients (35%) had BRAF co-mutations, correlating with expected frequency of ATC thought to transform from papillary carcinoma (PC). One case had only MUTYH mutation while a second had MUTYH with TERT and TP53. TCGA database contained 6(0.2%) cases of PC with MUTYH mutations (total 2871 MUTYH-mutated carcinomas), but no cases of ATC or other thyroid tumors were described.

Conclusion
MUTYH is a DNA repair enzyme linked to CRC and other cancers. MUTYH mutations occur in 6.7% of MAP patients and 1–2.2% of sporadic CRC cases that are mutually exclusive of BRAF mutations. While MAP increases the lifetime risk of CRC by over 60%, the link of MUTYH mutations to PC has only been observed in MAP and not been described outside of it. To our knowledge this is the first description of MUTYH mutations in ATC, especially without concurrent BRAF mutation (11 cases), suggesting MUTYH may independently contribute to pathogenesis of ATC. PARP inhibitors, PD-1/PD-L1 inhibitors, and ATR inhibitors demonstrate promising results in clinical trials of MUTYH-mutated cancers, warranting further research.
Development of drug resistance in cancer cells
Authors: Farrell C , Caswell-Rios H 
Published: October 2024

Abstract

Introduction/Objective
The purpose of this study was to evaluate omeprazole treament in cancer cells.

Methods/Case Report
The colorectal cancer cell line, CACO2, was treated with omeprazole at two different concentrations and methotrexate as a positive control for 3-4 months. Using exon-spanning primers for the ABCG2 and ABCB1 genes, qPCR was used to monitor changes in mRNA expression of the efflux pumps, Breast Cancer Resistant Protein (BCRP) and P-glycoprotein (Pgp). Upregulation of BCRP and Pgp was observed through the western blot assay. Once overexpression of BCRP was confirmed, the omeprazole-treated and methotrexate-treated cells were tested for chemotherapy-resistance using the Prestoblue proliferation assay and were compared to the untreated cells. The omeprazole treatments were repeated for reproducibility using two esophageal cancer cell lines. The treated cells were also studied for expression changes of possible drug resistant and cancer genes using RNASeq analysis.

Results (if a Case Study enter NA)
N/A

Conclusion
Esophageal cancer patients, who are treated for acid reflux, may be at higher risk for developing chemotherapy-resistant/multidrug resistance (MDR) tumor cells prior to chemotherapy treatment. Esophageal cancer patients with MDR tumors will have lower chance of survival compared to patients who are responsive to chemotherapy treatment. By identifying the overexpression of BCRP in the tumor cells of cancer, oncologists will be able to use a better treatment plan with more effective chemotherapy drugs.
Sevelamer Treatment for Hyperphosphatemia in a Saudi Arabian Chronic Renal Disease Patient
Authors: Abdelmonem M , Wasim H , Hammad A , Abdelmageed M , Abdelhai A , Abdelmonem M , Hemdan A , Abo Amer S 
Published: October 2024

Abstract

Introduction/Objective
Introduction: Patients with advanced chronic kidney disease (CKD) often require phosphate binders to manage elevated serum phosphorus levels due to phosphorus-restricted diets being insufficient. This study aimed to assess the safety and efficacy of sevelamer in lowering serum phosphorus and improving the serum lipid profile in a hemodialysis patient.

Methods/Case Report
A prospective study was conducted on a 59-year-old hemodialysis man with CKD. Sevelamer was administered orally as 800 mg tablets, with the dosage adjusted based on washout serum phosphorus levels (WSPL). Blood samples were collected every two weeks before dialysis, and all samples were analyzed using standard clinical laboratory methods.
Sevelamer treatment resulted in a significant reduction in serum phosphorus levels from 6.9 mmol/l to 4.3 mmol/l. No major adverse events were observed during the trial period, and there was no evidence of negative consequences associated with sevelamer therapy. Additionally, sevelamer treatment led to a decrease in hemoglobin levels to 10.5 g/dl and a substantial reduction in total cholesterol concentration from 5.22 mmol/l to 4.26 mmol/l.

Results (if a Case Study enter NA)
NA

Conclusion
Conclusion: Sevelamer, a non-absorbable aluminum and calcium-free phosphate binder, effectively lowered serum phosphorus levels in dialysis patients while improving lipid profiles. It was well tolerated with no instances of hypercalcemia and resulted in significant reductions in intact parathyroid hormone (PTH) and total and LDL cholesterol. Sevelamer may serve as a valuable therapeutic option for managing hyperphosphatemia in patients with CKD.
Implementation of CPOE, ERBI, and ePPID in Critical Care Operating Rooms at a Tertiary Care Academic Center
Authors: Grewal A , Anders M , Rock P , Williams N A , Fontaine M , Lokhandwala P 
Published: October 2024

Abstract

Introduction/Objective
Blood transfusion in operating rooms (ORs) is a critical and complex process, often complicated by issues such as paper-based orders, lack of guidelines, and delays in blood delivery. In response, a multidisciplinary task force developed a quality improvement plan. This study assesses the impact of implementing an electronic positive patient identification (ePPID) system, standardized computer provider order entry (CPOE), and electronic remote blood issue (ERBI) process in a critical care OR setting at our institution.

Methods/Case Report
The team initially implemented ePPID in cardiac surgery ORs before expanding hospital-wide. CPOE was developed in collaboration with the laboratory information systems (LIS) and hospital information technology (IT). ERBI required cross-departmental coordination to establish a bi-directional interface between LIS and ERBI software. Staff received training through a train-the-trainer approach, interactive sessions, videos, and surveys. CPOE focused on order set development and creating the Maximum Surgical Blood Order Schedule (MSBOS). ePPID began with a pilot program and expanded with training sessions. Data collection tracked blood ordering, ERBI workflow, and transfusion data for compliance and utilization rates.

Results (if a Case Study enter NA)
The implementation of ePPID saw a rise in compliance rates from 71% to 98%, with 60 completed cases and 233 blood products transfused by 24 clinicians. ePPID’s utilization for blood products increased from 60% to 98% within 90 days. ERBI lowered RBC return rates from 30% to 15% and plasma return rates from 45% to 35% over a 2.5 year span. ERBI utilization rates reached 81% at 24 months post-implementation.

Conclusion
The implementation of ePPID, CPOE, and ERBI in critical care ORs was well-received among clinicians. Significant improvements in compliance and utilization rates for blood products following ePPID implementation were evident. ERBI implementation also led to substantial reductions in return rates of blood products allocated to ORs. The steady increase in ERBI utilization indicates successful integration into OR workflows.
Lost in the Ds: Unexplained Loss of Rh(D) Antigen Expression By Serological Testing In Two Patients
Authors: Carmichael G , Lee E S , Tormey C , Yurtsever N , Shah B , Bizzario L 
Published: October 2024

Abstract

Introduction/Objective
While the loss of ABOH antigens has been well documented, reduced-to-absent expression of the RHD antigen is comparatively rare. Here, we describe two cases with D antigen loss presenting associated clinical settings, smear results, and red blood cell (RBC) genotyping findings to elucidate this unusual phenomenon.

Methods/Case Report
Cases (n=2) were retrospectively reviewed based on discovery during routine serological testing in our Blood Bank. RhD blood typing was performed via gel methods [Grifols, Los Angeles, CA]. Clinical information and laboratory data were extracted via the electronic medical record.
Case 1 is a 79-year-old female with metastatic breast cancer. She initially typed as D positive (4+) in at least two separate analyses, but her D front type progressively became weaker until turning entirely negative after several weeks. Spherocytes and stomatocytes were present on her peripheral blood smear. This patient received 10 D+ red blood cell (RBC) units without anti-D formation. RBC genotyping revealed traditional “dce” by standard polymerase chain reaction (PCR).
Case 2 is a 61-year-old male with a history of pre-B acute lymphocytic leukemia post-stem cell transplant, myelodysplastic syndrome, and progressive loss of D antigen expression (4+ to 0). Standard RBC genotyping revealed “Dce” by PCR. The peripheral blood smear was significant for RBC anisopoikilocytosis with increased stomatocytes, spherocytes, and ovalocytes.

Results (if a Case Study enter NA)
NA

Conclusion
The disappearance of the D antigen is rare, and our experience suggests an association between malignancies (both hematopoietic and non-hematopoietic) and D antigenic loss. Beyond these disease associations, however, loss of RhD is not otherwise readily explained in either case. Further analysis to test for other RHAG and RHCE mutational variants is an ongoing area of investigation in these cases, as more sensitive testing may reconcile the traditional PCR results with our initial detection of the D antigen.
Quality Improvement Assessment of Massive Transfusion Protocol (MTP) Utilization and Blood Component Return to Blood Bank in a Level 1 Trauma Center
Authors: Poonam F , Makuria A , Causey B , Ballengee S , Duncan H , Steffee C , Fallon J 
Published: October 2024

Abstract

Introduction/Objective
The goal of MTP in management of patients with hemorrhage is to restore coagulation factors, oxygen carrying capacity, and platelets by transfusing equal amount of plasma, RBC, and platelets. Upon activation of MTP, blood components are released in rounds until deactivation. This quality improvement study was initiated to assess blood products transfused versus returned during MTP activation at our Level1 Trauma Medical Center.

Methods/Case Report
Upon MTP activation, the Blood Bank (BB) prepares first round of cooler with components at 5:5:1 ratio of plasma, RBC, apheresis platelets. We reviewed retrospective MTP data of eleven-month, from 10/2022- 08/2023. We analyzed patterns of blood component usage by service line, number of MTP rounds issued, and number of units transfused versus returned.

Results (if a Case Study enter NA)
MTP data was reviewed for 195 patients. MTP activation by service line included emergency department 58.5%, medical ICU (MICU) 14.4%, and surgical ICU (SICU) 11.8%. In many MTP activations, only one round of components was released. Overall, an average of 1.5 rounds were issued. Data of units transfused and returned by component type showed more RBC (43.1%) units were transfused than plasma (39.4%) suggesting MTP transfusion did not follow 1:1:1 ratio. Out of all issued blood units 58% were returned. The high fraction of returned blood components suggests MTP activation may not always truly indicate massive hemorrhage. This finding, and the notable frequency of MTP activation for MICU and SICU patients suggests that individual component order on an emergency-release basis may have been the appropriate option.

Conclusion
In general, the data suggests implementation of a quality improvement initiative focused on increasing awareness of criteria for MTP activation, and training of staff surrounding MTP is essential. We recently implemented an electronic emergency transfusion order set that allows providers to order individual components for non-massively bleeding patients.
A 6-month Review of O pRBC Utilization in Non-O Blood Type Patients in a Level 1 Trauma Center
Authors: Rana-Gupta T , Talabong D , Yakut E , NGICHABE J , Gabutan E , Kang S , Haque A , Agaronov M 
Published: October 2024

Abstract

Introduction/Objective
Using O pRBCs for non-O patients for acute events is not unusual in a level 1 trauma hospital. However, we occasionally utilize this blood type to meet the needs of our patients that are not acutely bleeding. In this study, we evaluated the utilization of O units in non-O patients to improve our transfusion practices.

Methods/Case Report
We reviewed the indications of the O pRBCs transfused to non-O patients from October 2023 to March 2024. We evaluated the number of units used in acute events such as massive transfusion protocol (MTP), acute blood loss, sickle cell disease (SCD) patients in crises, bleeding associated with surgery and in patients with symptomatic anemia.

Results (if a Case Study enter NA)
There were 258 O pRBCs transfused to non-O blood type from October 2023 to March 2024. 135(52%) of these units were used for bleeding patients, of which 91%(124/135) were used for acute events. Most of the units utilized for acute hemorrhage had activated MTP (92%, 89/124) due to trauma (88%, 78/89). Only 12%(31/258) were used by SCD patients, with a little over half of these units being used acutely and the rest used prophylactically. About 69% of the 16 units used in surgery were due to bleeding. Lastly, 76 units (29%) were used for symptomatic anemia patients with 45% of these units transfused for anemia of prematurity.

Conclusion
In a level 1 trauma hospital, advocating for conserving O units is crucial to ensure enough units are available for trauma. As anticipated, acute bleeding was found to be the leading cause for patients with non-O blood types to receive O pRBCs. Notably, the prevalence of using O units for acute and prophylactic transfusion is relatively the same for SCD patients and phenotypically matching the Rh and Kell systems likely plays a role.
A rare case of Anti-Jk3 Alloimmunization
Authors: Abdelmonem M , Ngo N , Cabungan M , Cai W , Yunce M , Virk M S , Lee J , Yoshizuka S , Osterlund A 
Published: October 2024

Abstract

Introduction/Objective
The Kidd blood group system was discovered in 1951 and consists of two antithetical antigens, Jka and Jkb, in addition to a third high-incidence antigen, Jk3. Jk null, also known as Jk(a-b-), is an extremely rare blood group in which all Kidd antigens are absent. Jk is a urea transporter found in the renal medulla, and Jk-deficient individuals are unable to concentrate urine to its maximum concentration. If these individuals are exposed to the Jk antigen via transfusion or pregnancy, they are able to produce antibodies against the Jk3 antigen with a high incidence. Jk3 is expressed in over 99.9% of the blood donor pool, which has severe clinical implications and complicates transfusion.

Methods/Case Report
CASE PRESENTATION:
A 68-year-old male was admitted to the Stanford Medical Center with chronic right midshaft tibia osteomyelitis and a sinus drainage tract for a right tibial diaphysectomy. His test for antibodies was positive. Plasma from the patient is reactive with all tested cells except auto control, AHG in PEG, and solid phase. Phenotyping yielded negative results for Jka and Jkb, suggesting that the antibody is Jk3. Anti-Jk3 was eliminated by adsorption and rendered nonreactive.

Results (if a Case Study enter NA)
NA

Conclusion
Anti-Jk3 should be suspected in a previously pregnant or transfused patient during antibody screening and identification if it demonstrates the pattern of an antibody reacting to all cells in the panel, i.e., reacting to a high- frequency antigen with negative autocontrol. Awareness on the part of blood bank personnel regarding the variability of the blood group phenotype and the capricious nature of Kidd antibodies may aid in the improved management of these patients. It is recommended that patients with rare antibodies carry an antibody ID card indicating the rare antibody they have to prevent further exposure. A patient may be advised to undergo an autologous transfusion.
Fortunately, the patient’s procedures were uncomplicated, so a blood transfusion was unnecessary. Awareness on the part of blood bank staff regarding the variability of the blood group phenotype and the unpredictability of Anti-Jk3 may aid in improving patient care. To prevent further exposure, it is recommended that patients with rare antibodies carry an Antibody ID card indicating the rare antibody they possess.Jk3 antigen blood donors are underrepresented in the general donor pool. It is recommended to develop a systematic recruitment for Jk3 antigen donors.
Buffy coat removal to mitigate reporting false normal G6PD phenotype results in patients undergoing rasburicase therapy for tumor lysis syndrome
Authors: Mathewson Nicole , Hunsaker Joshua , Young Brittany , Doyle Kelly 
Published: October 2024

Abstract
Glucose-6-phosphate dehydrogenase (G6PD) is the primary source of NADPH in red blood cells (RBCs). NADPH reduces reactive oxygen species (ROS) thereby protecting RBCs from oxidative stress-mediated hemolytic anemia (HA). Individuals with partial or full G6PD deficiency are therefore susceptible to acute HA provoked by medications that generate high ROS loads in vivo, e.g., rasburicase. Rasburicase is an enzyme-based therapeutic used to degrade uric acid (UA) in patients with tumor lysis syndrome (TLS); however, catalysis of UA generates H2O2, a potent ROS, which poses a risk of HA in individuals who are deficient in G6PD activity. Screening G6PD activity prior to rasburicase administration is clinically indicated in ethnic groups with high rates of G6PD deficiency, although reports of HA in rasburicase-treated patients have been reported across low prevalence ethnic groups as well. TLS occurs most commonly during the treatment of highly proliferative neoplasms, such as leukemia and lymphoma. Since WBCs contain significant G6PD activity, an elevated WBC count in these patients can cause the false assurance of low HA risk due to a falsely normal G6PD activity. We sought to establish and evaluate a novel method to mitigate WBC contamination of G6PD measurements in patients undergoing rasburicase therapy. In this study, we first developed and validated an innovative method (“piercing method”) to minimize the interference of WBCs in G6PD measurements. The piercing method demonstrated acceptable accuracy (slope: 1.008; bias: -6.22%) and precision (1.4% CV between 9.9 to 20.7 U/g Hb) and was effective at eliminating a broad range of WBC types and concentrations from whole blood samples (N = 85, tested range = 0.31 – 413.05 K/μL, 93% reduction in WBCs). We compared G6PD activity in rasburicase-treated patients (N = 39) with varying WBC counts before and after buffy coat removal using the piercing method. Average percent change in G6PD activity (post-pierce – pre-pierce) between patients with and without elevated WBCs was substantial (45% versus 12%). In comparing G6PD activity in patients before and after the initiation of rasburicase therapy, there is no evidence that in vivo-generated ROS from rasburicase affect G6PD measurement in vitro in an assay that relies on monitoring absorbance of NADPH (22.2 U/g Hb versus 22.9 U/g Hb, p=0.721). Results demonstrate how WBCs increase risk for false elevation in G6PD activity in patients being considered for rasburicase therapy. At greatest risk are patients with partial G6PD deficiency, e.g., heterozygous females, where G6PD from WBCs could mask deficiency. Literature describing testing of G6PD in specimens with elevated WBCs is lacking. This study shows that the piercing method provides accurate G6PD results in samples with elevated WBCs from patients at risk of TLS, who might develop HA after starting rasburicase therapy.
Pre-operative CBC reflex testing prior to cardiac surgery identifies treatable causes of anemia
Authors: Maucione Carly , Jackups Ron 
Published: October 2024

Abstract

Blood transfusion during or after cardiac surgery has been linked to poor patient outcomes. It is therefore desirable to optimize hemoglobin status by identifying and treating anemia pre-operatively. In order to identify reversible causes of anemia efficiently in this patient cohort, we implemented a reflex order for our institution’s cardiothoracic surgery center, to be ordered for patients undergoing assessment for cardiac surgery. When ordered, complete blood count (CBC) results with a hemoglobin (Hgb) of less than 13 g/dL reflex automatically to the following laboratory tests: iron profile, ferritin, vitamin B12, and reticulocyte count.

Methods
The purpose of our study was to investigate the impact of this reflex order over the initial 6 months of implementation. Test results and patient notes were extracted from the electronic health record and analyzed.

Results
Over six months, the order was placed 99 times (median Hgb 13.4 g/dL), with 36 (36%) triggering the reflex (Hgb &lt; 13 g/dL). Of these 36 patients, 19 were women and 17 were men, and the cohort had a median age of 69 years. The median Hgb was 11.9 g/dL, ranging from 7.1 to 12.9 g/dL, with a median mean corpuscular volume (MCV) of 89.6 fl. The median Hgb differed by sex: 11.6 g/dL for men, 12.2 g/dL for women. Of these 36 patients, 16 had signs of iron deficiency anemia (IDA) based on laboratory results (below reference interval for iron, transferrin saturation, or ferritin), and two patients were found with vitamin B12 below the reference interval. Chart review demonstrated that 13 of the 36 patients underwent follow-up after reflex laboratory tests resulted, defined as a new diagnosis, new treatment, and/or new consult addressing the patient’s anemia. Five of these patients were given a new diagnosis of IDA, all of which were started on iron therapy. Three patients were transfused packed red blood cells prior to surgery; one was started on vitamin B12 supplementation; two had consults placed to address anemia; and two were given a new diagnosis of unspecified anemia.

Conclusion
Pre-operative CBC reflex testing facilitates the efficient and timely identification of reversible causes of anemia in patients undergoing diagnostic workup prior to cardiac surgery, while avoiding unnecessary panel testing in non-anemic patients.