bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering factors predicting BRAF mutation in cutaneous melanoma
Authors: Dudin O , Mintser O , Sulaieva O 
Published: October 2024

Abstract

Introduction/Objective
BRAF mutations are considered to be the most common genetic alteration in cutaneous melanoma (CM). Patient management relies on assessing molecular biomarkers enabling the personalization of patients’ treatment. The goal of this study was to develop the tools for predicting BRAF mutation using routine clinical and histological features.

Methods/Case Report
A total of 2041 CM cases were enrolled in the study to identify factors associated with BRAF mutation. Variables included sex, age, primary location, stage, histological type, ulceration, mitosis, Clark level, Breslow thickness, lymphocytes, lymphovascular invasion (LVI), perineural invasion (PNI), regression, microsatellite, association with nevus.

Results (if a Case Study enter NA)
The Ukrainian population demonstrated a high rate of BRAF mutation in CM, associated with the younger age and location at non-sun-expose skin. This study also revealed gender-specific differences in CM anatomic distribution and BRAF mutation subtype prevalence.
By using the genetic selection method, the minimal set of variables related to BRAF mutations was defined and included age, primary tumor location, histological type, ulceration, LVI, and association with nevus. To encounter non- linear links, the non-linear neural network modeling was applied. For this aim multilayer perceptron (MLP) with one hidden layer was used. The hidden layer architecture included 4 neurons with a logistic activating function. The AUROCMLP6 of the model was 0.79 (0.74 – 0.84). When applying the optimal threshold, the following characteristics of the model were reached: sensitivity - 89.4% (84.5 – 93.1%); specificity - 50.7% (42.2% – 59.1%); positive predictive value (PPV) - 73.1% (69.6% – 76.3%) and NPV - 76.0% (67.6% – 82.8%) respectively. The developed MLP model allows the prediction of BRAF status in CM, facilitating decisions concerning further patient management.

Conclusion
The developed MLP model, relying on 6 variables analysis allows the prediction of BRAF status in melanoma, facilitating decisions concerning further patient management.
Validation of Neutrophil gelatinase-associated lipocalin (NGAL) for Diabetes-associated Acute Kidney Injury
Authors: Bufkin K B , Karim Z , Silva J 
Published: October 2024

Abstract

Introduction/Objective
This study aimed to evaluate the analytical and clinical performance of the BioPorto NGAL Test on the Beckman Coulter AU480 to correlate plasma neutrophil gelatinase-associated lipocalin levels (pNGAL) with clinical progression and severity of diabetes-associated acute kidney injury (AKI) with hospitalized patients at an East Central Georgia Medical Center

Methods/Case Report
Analytical validation of the BioPorto NGAL Test was carried out on the AU480 and was based on imprecision, limit of blank, limit of detection, functional sensitivity, carryover, and specificity. Clinical validation studies included 45 patients hospitalized between January and November 2023 with and without diabetes at risk for developing AKI. All patients’ pNGAL levels were measured at admission until 96 hours post admission. Receiver operating characteristics and likelihood ratio methods were used to determine optimal sensitivity, specificity, cutoff value, and the discriminatory power of pNGAL.

Results (if a Case Study enter NA)
The intra-assay and inter-assay imprecision percent relative standard deviation was between 0.8 (2.7%) and 3.7 (4.2%). The limit of blank and limit of detection of Bioporto NGAL was 2.2 ng/mL and 15.4 ng/mL, respectively. An analytical coefficient of variation of 20% corresponded to a pNGAL value of 9.9 ng/mL. The optimal cutoff value for pNGAL to predict AKI for patients with DM was 293 ng/mL, with a sensitivity of 80% and specificity of 87%; AUC: 0.85, p &lt; 0.001. In a multivariate logistic regression model, pNGAL levels at 48 hours post admission were a risk factor for diabetes-associated AKI (OR 1.012, 95% CI:1.000 – 1.023; p = 0.051).

Conclusion
These results show that pNGAL levels at 48h are an independent risk factor for diabetes-associated AKI, and the optimal cutoff for this condition is 293 ng/mL. The optimal cutoff values for AKI for early diagnosis and risk stratification, along with its association with comorbidities, are important to improve patient outcomes and diagnosis accuracy.
Keeping The Stock Alive, A Dilemma of Hemovigilance
Authors: Haque A , Agaronov M , Talabong D , NGICHABE J , Yakut E , Rana-Gupta T , Gabutan E , Kang S 
Published: October 2024

Abstract

Introduction/Objective
Being well-prepared for emergent blood transfusions is crucial in level 1 trauma centers. As advocates of hemovigilance, we follow protocols that encourage the appropriate use of group O, D- (O-) pRBCs.
Moreover, by prioritizing using red blood cells with shorter shelf lives, we can better ensure that these valuable resources are not wasted.

Methods/Case Report
The number of O short-dated RBC units transfused in a level 1 trauma hospital in December 2023 was evaluated for type-specific distribution and utilization in bleeding patients and massive transfusion protocol. This study defines short-dated units as units expiring ≤7 days during transfusion.

Results (if a Case Study enter NA)
Of the 320 pRBCs evaluated, 59 were identified as short-dated units and 46(78%) were of the O- blood type. Interestingly, most O- units used for transfusion during this month (69%, 46/66) were short- dated; in comparison, only 5% (13/254) of group O, D+ (O+) units were transfused with a shorter shelf life. O- units were administered to 10 O- patients (17%), 27 O+ patients (46%), and 9 non-O blood type patients (15%). All short- dated O+ units were given to O+ patients, with 31% (4/13) used in massive transfusion protocols (MTP). None of the short-dated O- units were used in MTP, but over half (52%, 24/46) were utilized in patients experiencing bleeding.

Conclusion
Approximately 95% of individuals of African American descent have a blood type of D+. Given that this is the primary demographic we serve, it is unsurprising that our institution sees a relatively higher usage of O+ blood units, resulting in fewer short-dated O+ units being transfused. The cause of increased usage of short-dated O- is likely multifactorial, one of which is maintaining an adequate O- in our inventory for trauma patients. Balancing our preparedness for massive hemorrhage situations and hemovigilance for this blood type can be challenging for institutions like ours.
Serologic investigation and management of an antibody screen negative para-Bombay phenotype during pregnancy
Authors: Jamal Y A , Nicholas J A , Wang T , Abdelmonem M , Pandey S , Virk M S 
Published: October 2024

Abstract

Introduction/Objective
Individuals with the Bombay and para-Bombay red blood cell (RBC) phenotypes express anti- H antibodies associated with acute hemolytic transfusion reactions. The rarity of compatible donor units creates unique logistical challenges. However, para-Bombay individuals have been shown to tolerate transfusion of non- Bombay RBCs without acute hemolysis. Therefore, accurate serologic identification and judicious management of blood products are crucial when planning to transfuse patients with anti-H. This is especially true during pregnancy, as early onset of labor and fetal distress can occur without warning.

Methods/Case Report
A 24-year-old gravida 2 para 1 (G2P1) at approximately 38 weeks gestation with the fetus in breech position was transferred to our hospital after anti-H antibodies were detected. Although our in-house antibody screen was negative on automated solid-phase red cell adherence (SPRCA) testing, manual tube testing revealed the presence of anti-H antibodies, and forward typing with Ulex europaeus lectin confirmed the absence of H-antigen.
Further, Lewis B phenotyping and saliva neutralization demonstrated the presence of H-antigen in secretions, consistent with the O-para-Bombay phenotype. Finally, differential adsorption ruled out other clinically significant allo- antibodies.
An external cephalic version (ECV) was initially planned since vaginal delivery carries lower bleeding risk than cesarean section (CS). Three frozen Bombay RBC units were obtained, with one possibly compromised before arrival. Four pre-warmed, cross-match compatible units of O-positive RBCs (non-Bombay) were also prepared.
Acknowledging the unpredictability of ECV, the challenge of timing thawed frozen units, and the possibilities of massive hemorrhage versus wasting rare donor blood, our transfusion service ultimately recommended an elective CS with only one Bombay unit deglycerolized. The patient underwent an uneventful procedure without transfusion.

Results (if a Case Study enter NA)
NA

Conclusion
Overall, this case highlights key diagnostic and management considerations for patients with Bombay and para-Bombay phenotypes. First, automated SPRCA testing may provide false negative results for anti-H antibodies. Second, backup transfusion strategies for para-Bombay patients may include non-Bombay RBCs. Finally, the procurement, preparation, and use of rare donor blood products requires multidisciplinary clinical decision-making to optimize patient outcomes, especially for high-risk labor when unexpected acute bleeding events can occur.
One size does NOT fit all – factoring weight into current stem cell transplant guidelines in multiple myeloma patients
Authors: Jebackumar Travis , Marques Marisa , Singh Nirupama , Costa Luciano 
Published: October 2024

Abstract
Autologous hematopoietic stem cell (HPSC) transplantation serves as the standard of care treatment for multiple myeloma patients. The standard ASCT procedures for multiple myeloma (MM) patients often includes induction therapy, stem cell collection via apheresis and autologous hematopoietic cell transplantation (HCT) for eligible patients. The current guideline for HPSC collection for multiple myeloma established that 3x106 cells/kg of actual body weight (ABW) by the 1997 study of stem cell transplants in breast cancer. Recent research indicates that ideal body weight (IBW) utilization is a stronger predictor of post-autotransplantation neutrophil recovery than calculations based on ABW. Reducing the cost of HPSC collection and cryopreservation is critical to mitigate the cost incurred by the transplant center and the patient. This study evaluates whether using a patient’s IBW or Adjusted Ideal Body Weight (AIBW) would be satisfactory in determining the amount of stem cells required for transfusion when compared to ABW.
After institutional review board approval, a retrospective chart review study analyzed a cohort of 224 deceased MM patients, who received HCT at the UAB Medicine Hospital within the fiscal years of 2017 to 2019. The ABW for each patient was used to calculate their IBW and AIBW using the formulas shown below. The target CD34+ cell amount for patients was calculated using each body weight parameter. The platelet count and absolute neutrophil count (ANC) defined a successful platelet and neutrophil engraftment. The engraftment date was determined as the day the platelet value exceeded 20 and ANC exceeded 0.5 for three consecutive days (without any transfusion within a seven day window) and a statistical analysis was utilized to determine whether the IBW and AIBW parameters were adequate to achieve successful engraftment and HCT.
This study finds that the cohort of multiple myeloma patients are significantly more overweight than the prior study that established the current guidelines for autologous hematopoietic cell transplantation. The results for CD34+/kg cell targets for ideal and adjusted ideal body weight suggests that there are minimal differences in platelet and neutrophil engraftment and number of platelet transfusions when compared to CD34+/kg targets using actual body weight. Some methods to reduce excessive stem cell collection include decreasing target cell dosage from previous standards of 6.0 x 106 cells/kg or calculating total cell dosage with IBW or AIBW instead of ABW. Future studies should evaluate the efficacy of cell dosage decrease to lowered targets and total cell calculations using IBW or AIBW instead of ABW.
Equation 1. ABW to IBW Conversion (H = height over 5 ft. in inches)
IBW(males) = 50 kg + (2.3 kg x H)
IBW(females) = 45.5 kg + (2.3 kg x H)
Equation 2. ABW to AIBW Conversion
AIBW = IBW + 0.5(ABW-IBW)
Critical appraisal of the utility of 13 discriminant formulas for distinguishing beta thalassemia trait from iron deficiency in patients with microcytic anemia and the introduction of a new formula in a USA population
Authors: Weli Homayemem , Hernandez Patricia , Frater John 
Published: October 2024

Abstract
Iron deficiency anemia (IDA) and beta thalassemia trait (ß-TT) are two frequent causes of microcytic anemia that often pose a diagnostic dilemma with implications for management. Many discriminant formulas have been proposed for distinguishing these two conditions. However, there is a need for independent verifications of these formulas to determine their applicability to other populations, particularly more diverse populations, as seen in the United States. To date, no study has been performed in the United States to evaluate the utility of these formulas in distinguishing both conditions. The study objective was to evaluate the utility and predictive values of 13 discriminant indices and formulas for distinguishing ß-TT from IDA in a US population. We investigated 13 formulas comprising only hematologic parameters available on all analyzers. The investigational population consisted of 238 patients with microcytic anemia; 165 with a hemoglobin electrophoresis diagnosis of ß-TT and 73 diagnosed with IDA by clinician review or iron studies. The study population comprised 55% black or African American, 35% White, 5% Asian, 1.2% Native American, and 2.5% unidentified. Receiver operating characteristic curves were employed to evaluate the diagnostic performances of the formulas. All investigated formulas had poor sensitivities but high specificities. The three best-performing indices or formulas from those previously proposed for distinguishing ß-TT from IDA were the RBC (sensitivity 62.2%, specificity 87.1%), Green and King (MCV2×RDW/100 hemoglobin, Hb) with a sensitivity of 65.4% and specificity of 82.6%, and Wongprachum et al. (MCV×RDW/RBC) – 10 Hb) with a sensitivity of 63.6% and specificity of 82.6%. Areas under the curve (AUCs) were 0.68 for the RBC and, 0.67 for both Green and King and Wongprachum formulas. The Youden indices were 0.49, 0.48, and 0.46, respectively. The Mentzer index had a sensitivity of 63.4%, specificity of 81.7% and Youden index of 0.45. We introduced a new formula comprising the sum of three of the most readily obtained red cell parameters (RBC + Hb + MCV). It had a Youden index of 0.95, sensitivity of 96.8, specificity of 98.0, and AUC of 0.97, significantly outperforming other formulas in our study population (p=0.00). This is the first study in the USA evaluating the utility of multiple indices for distinguishing ß-TT from iron deficiency anemia. The best performing formulas in other studies did not perform well in our population. This necessitated an introduction of a new formula that demonstrates excellent potential to address the unique diversity of the US population.
Reemergence of Hemoglobin Yukuhashi
Authors: Dar Abdul Jabbar , Malik Anum , Campbell Sean , Mulvey Joseph Justin 
Published: October 2024

Abstract
The abnormal hemoglobin, Hb Yukuhashi, identified in Japan in 1963, exhibits slower migration compared to Hb A and is associated with target cells on peripheral smear. A similar hemoglobin, Hb Dhofar, is found in an Omani tribesman and is defined as a substitution of arginine for proline at the 58th amino acid position of the beta-globin chain. Despite both Yukuhashi and Dhofar seemingly arising from the same exonic point mutation, variations in expression were clarified through beta-globin gene amplification. Hb Dhofar, unlike Yukuhashi, was linked to a splice-site mutation at codon 29, explaining its reduced expression. Despite these hemoglobins’ structural alterations, their functional properties on a molecular level, including oxygen affinity and heme-heme interaction, remained largely unaffected. While mutations at codon 58 have been observed alongside other mutations in Hb Dhofar and Hb C-Ziguinchor, this case represents the first sequencing and report of a beta-globin gene mutation solely at codon 58, as only Yukuhashi’s protein coding region had been sequenced, not the whole gene. “Hemoglobin D” was detected on newborn screening of a male child with no other significant medical history or physical abnormalities. Capillary Electrophoresis and Cation-Exchange HPLC showed abnormal hemoglobin fractions, with 20.1% in the S Zone and 25.7% in the D-window, respectively. This led to a presumptive diagnosis of Hemoglobin Dhofar trait; however, discrepancies in hematologic parameters and relative hemoglobin levels were noted. Genetic testing of the Beta Globin gene confirmed a C to G substitution at codon 58 but lacked the characteristic codon 29 mutations associated with Hemoglobin Dhofar. The patient, was discovered to possess a mutation at codon 58 on the beta globin gene, a mutation not previously reported in isolation. In contrast to previous studies on Hb Dhofar, where variant Hb levels were lower and accompanied by abnormal RBC indices indicative of beta thalassemia trait, this case exhibited higher variant Hb levels with normal RBC indices, suggestive of a typical beta globin variant. The mutation at codon 58 did not significantly alter intermolecular interactions of the globin which may mean the variant is clinically asymptomatic in nature. Continued follow-up is necessary to confirm this suspicion, although initial assessments at 3 and 6 months of age showed normal RBC parameters. This case represents the first instance of an isolated mutation at codon 58 of the beta globin gene, emphasizing the need to consider this mutation in interpreting hemoglobinopathy screening results.
Differences Between Serum and Plasma: An Indirect Approach to Derive a Combined Reference Interval for Total Protein, Albumin, and Globulin
Authors: Militello Leah , El-Khoury Joe , Durant Thomas 
Published: October 2024

Abstract
The objective of our study is to derive reference intervals (RI) for total protein (TP), albumin and globulin that are appropriate for both plasma and serum samples by applying statistical analyses to retrospective patient data. Both plasma and serum are acceptable matrices for these tests at our institution, with a single RI that applies to all specimens. The widespread shortage of lithium heparin (LH) tubes that occurred as a consequence of the pandemic prompted our lab to switch the primary tube type for comprehensive metabolic panels (CMPs) from LH to serum separator tubes (SST) in October 2021. The primary tube type reverted to LH in October 2023, and no adjustments were made to RIs at either time. To determine how well our RIs align with the accepted matrices, we used R Statistical Programing version 4.3.1 to apply an indirect, nonparametric statistical approach to data extracted from the laboratory information system (LIS) between July 2018 and December 2023. All orders for TP, albumin and globulin were queried to include the following components in the analysis: TP, albumin, globulin, serum TP, serum albumin and serum globulin. The records were divided into 3 epochs based on the primary tube type for CMP on the order date, with epochs 1 and 3 reflecting LH and epoch 2 reflecting SST. We attempted to identify a subset of serum and plasma samples in healthy individuals by applying exclusion criteria based on inpatient status, age, and draw station at which the specimen was collected. For each component, a resampling bootstrap method was used to calculate the RIs and corresponding 95% confidence intervals by epoch. Our results show that the RI of TP, albumin and globulin changed significantly between the epochs, reflecting the difference in primary matrix. The components serum TP, serum albumin, and serum globulin did not see a significant change in values over the epochs. A verification study looking at plasma and serum samples in 20 healthy individuals support these results. Based on these findings, our reference intervals were updated from 6.6-8.7 g/dL to 5.9-8.3 g/dL for TP, from 3.6-4.9 g/dL to 3.6-5.1 g/dL for albumin and from 2.3-3.5 g/dL to 1.5-3.9 g/dL for globulin. We show that there are statistically and potentially clinically significant differences in the reference intervals of TP, albumin and globulin in serum compared to plasma. This study demonstrates a big data analytics approach to derivation of RIs and emphasizes the importance of RI assessment and adjustment for patient population and acceptable specimen type.
Mind the Gap: Influence of Monoclonal Immunoglobulin on Anion Gap in Multiple Myeloma
Authors: Chen Lechuang , Meng Qing H 
Published: October 2024

Abstract

Background
Multiple myeloma (MM) is a plasma cell disorder in which anion gap and sodium measurement are critically influenced by the presence of abnormal protein concentrations. This study investigates the relationship between anion gap, pseudohyponatremia, and monoclonal immunoglobulin levels (IgG, IgA, IgM), particularly the common IgG. Focusing on the clinical implications of these laboratory results.

Methods
We retrospectively analyzed data from 136 patients diagnosed with MM, focusing on anion gap values, monoclonal immunoglobulin levels, and sodium levels. The patients were categorized based on their anion gap values (&lt;8) into five groups (anion gap=3, 4, 5, 6, and 7). Monoclonal immunoglobulin levels were standardized to the same units as the anion gap for direct comparison. Additionally, we investigated the pseudohyponatremia by examining sodium levels in these patients.

Results
Among the 136 MM patients, 70 patients’ anion gap were lower than 8. A negative correlation between MM monoclonal immunoglobulins and anion gap values were observed. The anion gap decreased from 7 to 3 as the IgG average levels ranged increasing from 1755 mg/dL to 2655 mg/dL (RI 610-1616 mg/dL). Similarly, the anion gap decreased from 6 to 3 as the IgM average levels ranged increasing from 1170 mg/dL to 2880 mg/dL (RI 35-242 mg/dL). Additionally, a number of low sodium levels (&lt;136 mmol/L) was observed in each group.

Conclusion
Our study highlights the negative impact of MM monoclonal immunoglobulins, particularly IgG and IgM, on the anion gap. Both laboratory and clinical personnel should be aware of these phenomena, might prevent unnecessary diagnosis, streamlining patient management and avoiding potential mismanagement.