bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of COVID-19 Restrictions and Changes in Guidelines on Adult Wrist Fracture Management
Authors: Tse Cheuk Yin , Lee Lawrence Hin Hai , Akbari Amir Reza , Niazi Noman Shakeel , Pillai Anand
Published: October 2021

Background The coronavirus disease 2019 (COVID-19) pandemic had an unprecedented impact on the healthcare service of the United Kingdom. This study aims to evaluate the effect on wrist fracture care as a result of the COVID-19 pandemic, changes in British Orthopaedic Association Standards of Trauma and Orthopaedics wrist fracture management guidelines, and introduction of lockdown restrictions.

Methods This is a retrospective observational study with data collected using the Pathpoint eTrauma platform (Open Medical, United Kingdom). All adults (18 years + ) admitted with wrist fractures within the study phases to Manchester University National Health Service Foundation Trust were included. Each phase of the study period represents a change in lockdown restrictions, including lockdown 1, period of eased restrictions after lockdown 1, lockdown 2, and lockdown 3. These phases were then compared with a prepandemic period. A total of 608 referrals were included for analysis.

Results The number of referrals per week decreased from 9.94 prepandemic to as low as 8.12 during lockdown 2. Falls remained the most common mechanism of injury, followed by cycling that saw an increase by more than threefold from 2.42% prepandemic to 8.17% (p = 0.500) during lockdown 1 and 8.77% (p = 0.0164) during the easing of lockdown 1. Sports-related injuries and occupational injuries decreased throughout. Assaults and altercations, road traffic accidents, roller-skate, and skateboard-related injuries increased throughout. Surgical procedures per week decreased from 5.06 prepandemic to as low as 4.55 during lockdown 1. Procedure cancellations remained steady apart from an increase during lockdown 2. Referrals managed operatively increased from 50.9% prepandemic to 58.9% in lockdown 2, before dropping to 49.2% in lockdown 3. Mean time from presentation to surgery increased from 9.08 days prepandemic to 16.27 days in lockdown 1 but decreased to just below the prepandemic baseline thereafter.

Conclusion Overall, there was a decrease in the number of wrist fracture referrals and surgical procedures compared with before the pandemic. There was also an increased wait-time to surgery and an increased rate of cancellations. Statistical analyses fail to find significance in changes other than mechanisms of injury, which resulted from lockdown restrictions. Therefore, service provision, delivery, and efficiency not affected significantly by changes in guidelines and lockdown restrictions.
The Prognostic Performance of Rotational Thromboelastometry for Excessive Bleeding and Increased Transfusion Requirements in Hip Fracture Surgeries
Authors: Tsantes Andreas G. , Papadopoulos Dimitrios V. , Trikoupis Ioannis G. , Tsante Konstantina A. , Mavrogenis Andreas F. , Koulouvaris Panagiotis , Vaiopoulos Aristeidis G. , Piovani Daniele , Nikolopoulos Georgios K. , Kokoris Styliani I. , Bonovas Stefanos , Papagelopoulos Panayiotis J. , Tsantes Argirios E.
Published: October 2021

Background Hip fracture surgeries are associated with considerable blood loss, while the perioperative coagulopathy is associated with the bleeding risk of these patients. We aimed to evaluate the ability of rotational thromboelastometry (ROTEM) to detect patients at high risk for excessive bleeding and increased transfusion requirements.

Methods We conducted a prospective observational study of 221 patients who underwent hip fracture surgeries. ROTEM analysis was performed preoperatively and immediately postoperatively. Blood loss parameters including blood loss volume, number of transfused red blood cell (RBC) units, and drop in hemoglobin levels were recorded. ROTEM parameters were compared between patients with and without excessive bleeding, and between patients with and without increased transfusion requirements (i.e., ≥2 RBC units).

Results The postoperative FIBTEM MCF value ≤15 mm had 66.6% (95% confidence interval [CI]: 59.7–74.1%) sensitivity and 92.0% (95% CI: 80.7–97.7%) specificity to prognose excessive bleeding, and preoperative FIBTEM MCF value ≤15 mm had 80.4% (95% CI: 73.5–86.2%) sensitivity and 91.2% (95% CI: 80.7–97.0%) specificity to prognose increased transfusion requirements. Preoperative FIBTEM MCF ≤11 mm and postoperative FIBTEM MCF ≤15 mm were associated with considerably increased risks of excessive bleeding (odds ratio [OR]: 44.8, 95% CI: 16.5–121.3, p < 0.001; and OR: 23.0, 95% CI: 7.8–67.0, p < 0.001, respectively).

Conclusion ROTEM parameters demonstrated high prognostic accuracy for excessive bleeding and increased transfusion requirements. This can enable implementation of blood sparing strategies in high-risk patients, while blood banks could be better prepared to ensure adequate blood supply.
Evaluation Metrics for Health Chatbots: A Delphi Study
Authors: Denecke Kerstin , Abd-Alrazaq Alaa , Househ Mowafa , Warren Jim
Published: October 2021

Background In recent years, an increasing number of health chatbots has been published in app stores and described in research literature. Given the sensitive data they are processing and the care settings for which they are developed, evaluation is essential to avoid harm to users. However, evaluations of those systems are reported inconsistently and without using a standardized set of evaluation metrics. Missing standards in health chatbot evaluation prevent comparisons of systems, and this may hamper acceptability since their reliability is unclear.

Objectives The objective of this paper is to make an important step toward developing a health-specific chatbot evaluation framework by finding consensus on relevant metrics.

Methods We used an adapted Delphi study design to verify and select potential metrics that we retrieved initially from a scoping review. We invited researchers, health professionals, and health informaticians to score each metric for inclusion in the final evaluation framework, over three survey rounds. We distinguished metrics scored relevant with high, moderate, and low consensus. The initial set of metrics comprised 26 metrics (categorized as global metrics, metrics related to response generation, response understanding and aesthetics).

Results Twenty-eight experts joined the first round and 22 (75%) persisted to the third round. Twenty-four metrics achieved high consensus and three metrics achieved moderate consensus. The core set for our framework comprises mainly global metrics (e.g., ease of use, security content accuracy), metrics related to response generation (e.g., appropriateness of responses), and related to response understanding. Metrics on aesthetics (font type and size, color) are less well agreed upon—only moderate or low consensus was achieved for those metrics.

Conclusion The results indicate that experts largely agree on metrics and that the consensus set is broad. This implies that health chatbot evaluation must be multifaceted to ensure acceptability.
Spermiation response to exogenous hormone therapy in hibernated and non-hibernated boreal toads (
Authors: Kouba Andrew J. , Langhorne Cecilia J. , Willard Scott T. , Smith Theodore , Kouba Carrie K.
Published: October 2021

Conservation programs for threatened high- elevation amphibian species rely on hibernation to trigger appropriate male reproductive behaviours and gametogenesis. Although common practice and anecdotal observations have supported the practice of hibernation, there is limited empirical evidence documenting the effects on reproduction in these species. In this study, the effect of hibernation on sperm quantity and quality was evaluated for the alpine species Anaxyrus boreas boreas. Hibernated (n = 19) and non-hibernated (n = 21) male toads were administered 10 IU g−1 body weight (BW) human chorionic gonadotropin (hCG) and spermic urine was collected over 24 h. Hibernation had no effect on the number of males undergoing spermatogenesis, but hibernated males produced sperm in higher concentrations. Sperm quality was measured in terms of total motility, forward progressive motility and quality of forward progression. Although there was no difference in the total sperm motility of samples from hibernated and non-hibernated toads, the percentage of sperm exhibiting forward progressive motility and the quality of forward progression was significantly greater from hibernated toads. These results support our hypothesis that hibernation impacts both sperm quantity and quality in male boreal toads. This study will better inform captive breeding management decisions for threatened alpine species, in imminent danger of extinction.
‘Any prediction is better than none’? A study of the perceptions of fire behaviour analysis users in Australia
Authors: Neale Timothy , Vergani Matteo , Begg Chloe , Kilinc Musa , Wouters Mike , Harris Sarah
Published: October 2021

Internationally, fire and land management agencies are increasingly using forms of predictive services to inform wildfire planning and operational response. This trend is particularly pronounced in Australia where, over the past two decades, there has been an alignment between increases in investments in fire behaviour analysis tools, the training and development of fire behaviour analysts (FBANs), and official inquiries recommending the expanded use of these tools and analysts. However, while there is a relative lack of scholarship on the utilisation of predictive services, existing research suggests that institutional investment and availability are poor indicators of use in contexts with established social dynamics of trust and authority. To better understand the utilisation of predictive services in Australia, we undertook a survey of key predictive services users (e.g. incident controllers, planning officers) in order to test several hypotheses developed from existing studies and ethnographic fieldwork. Our results provide directions for further research and indicate that, rather than simply invest in tools and systems, there is a need for fire management agencies to foster personal connection between predictive services practitioners, their tools and their users.
Longitudinal assessment of SARS-CoV-2 nucleocapsid antigenemia in patients hospitalized with COVID-19
Authors: Verkerke Hans , Harrington Kristin , McLendon Kaleb , O’Sick William , Potlapalli Sindhu , Shin Sooncheon , Allen Jerry William Lynn , Horwath Michael , Arthur Connie , Rha Jennifer
Published: October 2021

While RT-PCR tests of nasopharyngeal swabs remain the gold standard for the detection of SARS-CoV-2 infection and monitoring of COVID-19 disease progression, measurement of nucleocapsid antigenemia in serum and plasma samples is an underexplored alternative proxy for disease severity. To explore the dynamics of nucleocapsid antigenemia, we measured levels of nucleocapsid antigen using a highly sensitive Single Molecule Array (Simoa) assay in 817 serially collected serum and plasma samples from 93 PCR-confirmed COVID-19 patients for whom symptom onset date could be extracted by chart review. In a subset of these individuals (n=13), we measured seroconversion by titering for receptor binding domain (RBD) specific IgG, IgA, and IgM. A model of exponential decay was fit to data from individuals with high resolution daily sampling (N=34), from which the half-life of SARS-CoV-2 nucleocapsid in serum was determined. Mean nucleocapsid half-life in this group of patients was 1.17 days (SD=0.82). Nucleocapsid levels were significantly higher in the first 10 days following symptom onset in patients who died compared to those with a milder disease course (p=0.004). Further, mortality was associated with a trend toward longer nucleocapsid half-life (1.51 days vs. 0.79 days) (p=0.10). In patients who had both antibody and antigenemia data available, antibody response was temporally linked to antigen decay, reaching peak levels as antigen was cleared from the blood. Our data identify SARS-CoV-2 nucleocapsid antigenemia as a potential diagnostic tool for acute COVID-19 disease and an early biomarker associated with disease severity.
Assessment of Coagulation Tests in Hospitalized COVID19 Patients; Challenging Coagulopathies
Authors: Barouqa Mohammad , Szymanski James , Rahman Shafia , Lugo Jesus Gonzalez , Billett Henny , Sekhri Radhika , Reyes Morayma
Published: October 2021

COVID-19 has caused a worldwide illness and New York has become the epicenter of COVID-19 in the United States. During the last year, The Bronx, one of the five boroughs of New York City, had the highest prevalence per capita in New York making it the epicenter of the pandemic. During the first wave of the pandemic, almost every labratory received tremendous amount of tests, and here we examined demographic and laboratory data, as well as trajectories of laboratory results, in order to determine the relation between these laboratory parameters, in particular tests of coagulation, to illness severity and mortality. Methods: This is a retrospective study of all positive COVID cases who were admitted between 2/22/2020-4/20/2020 at Montefiore Health System (MHS), a large tertiary care center in the Bronx. Together the ambulatory and hospital networks care for 2.8 million visits a year. All adults with positive COVID tests performed by MHS and who were admitted between 2/22/2020-4/20/2020 are considered. All hospitalized COVID positive cases were queried from the electronic medical record system. Physiological, demographic (age, sex, socioeconomic status and self-reported race and/or ethnicity) and laboratory data was captured. A subset of cases were chart-reviewed for accuracy and additional information. Statistical analysis was performed using R studio. Results: Discharge from hospital and mortality were the primary measured outcomes. 7096 patients tested positive for COVID, of which 2897 had an associated inpatient admission and 845 patients were seen in the ER and then discharged. A total of 767 COVID positive patients died during hospitalization. A multivariable logistic regression analysis shows increased odds ratio for mortality by age, gender(males > females), BMI, neutrophil to lymphocyte ratio, Charlson Score, and D-Dimer. The receiver operating characteristic curve (ROC) of D-Dimer combined with age showed an area under the curve (AUC) of 0.77. The optimal cut-point, calculated using Youden’s index, for the initial D-Dimer to predict mortality was found to be 2.43ug/ml. D-Dimer trajectories between survivors and non-survivors showed a clear separation for non-survivors since admission. Conclusions: In this study we comprehensively studied demographic, physiological and laboratory parameters of COVID19+ minority patients in the Bronx, NYC, USA. This study confirms laboratory and clinical observations made by Wuhan studies of COVID19 infected patients. In particular the association of initial D-Dimer and its trajectory during hospitalization with mortality.
Role of CD200 in the Detection of Nonhematologic Neoplasms by Routine Flow Cytometry Analysis
Authors: Laakman Joseph , Holman Carol
Published: October 2021

Objectives

While flow cytometry is routinely used in the diagnostic work-up of hematolymphoid malignancies, its role in identifying non-hematolymphoid neoplasms is controversial. While a diagnosis of “non-hematolymphoid process” may be suggested by flow cytometry, typically, CD45-negative entities are not further characterized by their immunophenotypic profile. Some markers, such as CD56, have been well documented in non-hematolymphoid malignancies, such as high-grade neuroendocrine carcinomas (Stacchini, et al, 2018; Bryson et al, 2002). Other cell surface markers that are routinely studied with flow cytometry panels, such as CD200, are less well-described in the literature with regards to their presence/absence in non-hematolymphoid processes. We examined all flow cytometry cases from our institution over a 5-year period to identify trends in the immunophenotypes of non-hematolymphoid malignancies that were known to be CD45-negative and CD56-positive by flow cytometry.

Methods

We examined 3634 flow cytometry cases (2015-2020) and identified non-hematolymphoid cases based upon lack of CD45 expression. After excluding multiple myeloma cases from the CD45-negative entities, we were left with 19 CD45-negative cases. Chart review of these cases confirmed them as non-hematolymphoid by concurrent surgical pathology/cytopathology studies. Of these 19 cases, 2 were excluded because CD56 was not evaluated.

Results

Of the 17 CD45-negative/CD56-positive cases, 16 showed CD200 positivity (94%). Of these CD200-positive cases, 10 were ultimately diagnosed as small cell carcinoma (59%), 1 was diagnosed as Merkel cell carcinoma (6%), 1 was diagnosed as melanoma (6%), 1 was diagnosed as poorly-differentiated carcinoma (6%), 1 was diagnosed as Ewing-like sarcoma (6%), and 2 were unclassified further (12%). The single CD200-negative case was diagnosed as poorly-differentiated acinar cell carcinoma (6%). All cases of small cell carcinoma that were evaluated by flow cytometry showed expression of CD200 and CD56.

Conclusions

Our findings suggest that in CD45-negative/CD56-positive non-hematolymphoid malignancies, particularly small cell carcinoma, CD200 is frequently positive. CD200 was also found to be positive in rare cases of other non-hematolymphoid malignancies within the differential diagnosis of small round blue cell tumors. These findings indicate that CD200 may be a useful marker in suggesting the possibility of small cell carcinoma in non-hematolymphoid specimens that are evaluated by flow cytometry.
Lambda monoclonal free light chain abnormalities detected by a serum immunofixation electrophoresis assay are underrepresented by quantitative serum free light chain results
Authors: Treger Rebecca , Hutchinson Kathleen , Bryan Andrew , Morishima Chihiro
Published: October 2021

Protein and immunofixation (IFIX) electrophoresis are used to diagnose and monitor monoclonal gammopathies. While IFIX detects clonal production of intact immunoglobulins and free light chains (FLC), the latter can also be quantified using a serum free light chain (SFLC) assay, in which polyclonal antisera detects epitopes specific for free kappa (KFLC) or lambda light chains (LFLC). An abnormal KFLC: LFLC ratio (KLR) serves as a surrogate for clonality. While the SFLC assay is highly sensitive, normal LFLC (<2.63mg/dL) and KLR results (>0.26 & <1.65) were found in samples with distinct lambda monoclonal free light chains visualized by IFIX (X-LMFLC). To investigate this discordance, contemporaneous SFLC or KLR values were evaluated for their ability to accurately classify monoclonal FLCs identified by IFIX. We performed a retrospective analysis of serum and urine IFIX (Sebia Hydrasys) and SFLC (Freelite®, Binding Site) results from our institution between July 2010 through December 2020, using R 4.0.2 and Tidyverse packages. From among 9,594 encounters in which a single monoclonal component was initially identified by IFIX, 157 X-LMFLC and 131 X-KMFLC samples were analyzed. Elevated LFLC with normal KFLC was identified in 105/157 X-LMFLC samples (67%), while both LFLC and KFLC were elevated in 42/157 samples (27%). Concordance between X-KMFLC and KFLC was markedly higher, where 122/131 samples (93%) displayed elevated kappa FLC (>1.94mg/dL) with normal LFLC, and only 7/131 X-KMFLC samples (5%) possessed both elevated KFLC and LFLC. The use of KLR to identify pathogenic monoclonal free light chains improved lambda concordance to 85%; however, 19/157 (12%) of X-LMFLC samples still exhibited normal KLR. High concordance of 98% was again observed for X-KMFLC with abnormal KLR. When samples were segregated according to normal or impaired renal function (eGFR > or ≤60mL/min/1.73m², respectively), this disparate identification of X-LMFLC and X-KMFLC by the SFLC assay persisted, suggesting that renal dysfunction (as measured by eGFR) does not underlie this phenomenon. Lastly, we corroborated the above findings in a larger sample population by examining patients with urine Bence Jones FLC identified by IFIX who had free or intact monoclonal components in serum (N=724), grouped by lambda or kappa light chain involvement. The cause(s) of the discrepant performance by the Freelite® SFLC assay, relative to the Sebia Hydrasys IFIX assay, for identifying lambda FLC components is currently unclear. Possible contributory factors include assay reference range cutoffs, other patient disease parameters, and differences in assay-specific polyclonal antisera. Future analyses of these factors will help to further characterize SFLC assay performance and elucidate how interpretation of composite serum FLC test results can be improved to better guide patient management.
Limited diagnostic utility of SARS-CoV-2 serologic testing in symptomatic PCR negative patients
Authors: Tawiah Kwaku , Hock Karl , Farnsworth Christopher
Published: October 2021

Background

Guidelines from the CDC and the IDSA suggest the use of serologic testing to support the diagnosis of COVID-19 in individuals with high clinical suspicion that repeatedly test negative by diagnostic methods. Given that variability in specimen type, collection technique, and time from symptoms all reduce the sensitivity of molecular methods for SARS-CoV-2. The routine use of serology to diagnose and manage patients with symptoms concerning COVID-19 is tempting, despite limited studies in the literature supporting this approach. Here, we assessed the utility of serology testing for diagnosing SARs-CoV-2 in symptomatic, PCR-negative patients.

Methods

Remnant EDTA plasma specimens were obtained from 393 patients with clinical suspicion for COVID-19 and a negative SARs-COV-2 RNA test by the nasopharyngeal swab. The specimens were analyzed for SARs-CoV-2 IgG on an Abbott Architect i2000 (Abbott diagnostic). Patient information and symptoms adjudication were obtained from patient electronic health records.

Results

14 of 393 patients were positive for antibodies to SARS-CoV-2 (seropositivity rate of 3.6%), 6 of which were from patients with previous RT-PCR-confirmed COVID-19 infection. Among patients without previously diagnosed COVID-19, the seropositivity rate in symptomatic patients was 1.2% (2/171), in patients with altered mental status was 4.3% (2/46), and in asymptomatic patients with no known previous COVID-19 diagnoses was 2.6% (4/170). The seropositivity rate among symptomatic patients presenting ≥ 14 days after symptom onset was 0% (0/67), 7-13 days was 5% (1/20), and for patients < 7 days, was 2.1% (1/47). Among the 4 patients with AMS that were serologically positive, 2 were previously diagnosed by PCR.

Conclusion

There is a low diagnostic utility of SARS-COV-2 serological testing for identifying novel cases of acute SARS-CoV-2 infections in the ED after a negative PCR test.
Frequency and Clinical Significance of Negative Anion Gap Values in an Academic Medical Center Population
Authors: Laakman Joseph , Krasowski Matthew
Published: October 2021

Anion gap is a value calculated by determining the difference between major plasma cations (sodium, sometimes additionally potassium) and anions (namely bicarbonate and chloride), with “normal” levels falling somewhere between 8 and 16 mEq/L. Elevations in anion gap are classically described in a variety of different clinical disease states, including but not limited to uremia, ketoacidoses, lactic acidosis, and a number of drug toxicities. Comparatively little is understood about the etiology of low and negative (<0) anion gap measurements; however, certain patient populations and pathologic states have been associated with negative anion gap measurements, such as multiple myeloma and hypertriglyceridemia (Kraut, 2007). We reviewed laboratory chemistries for 340,354 pediatric and adult patients over a ten-year period (2009-2018). Laboratory testing included values from basic and comprehensive metabolic panels and blood gas analyses. Chart review was performed on adult patients with anion gaps measuring less than 0 mEq/L to assess for medical trends or other explanations such as analytical interference or data errors. Additionally, blood gas analyses from patients being cared for in the neonatal intensive care unit (NICU) over the same ten-year period were also reviewed. Of the adult patients, 0.046% (157 samples) had an anion gap measuring below 0 mEq/L. Samples obtained as part of a blood gas analysis made up 52% of all negative gaps. While no definitive trends were noted, 23 samples were noted to be from patients with history of malignancy (solid tumor and hematopoietic), including multiple myeloma (4 patients).[mkrasows1] In addition to malignancy, 17 patients with hypertriglyceridemia were also found to have negative anion gaps. Negative anion gaps were rare in outpatient populations. Negative anion gaps as a result of a laboratory error were also rare, constituting only 1.3% of cases (2 patients). Negative anion gaps were comparatively more common in the NICU population, with 983 patients having a negative anion gap[mkrasows2] (0.289 %). NICU patients constituted 91% of all blood gas analyses with a negative anion gap, demonstrating that negative anion gaps are much more prevalent in this patient population than they are in other pediatric and adult populations. Negative anion gaps are relatively rare occurrences in the adult outpatient population; however, they can be seen in association with certain underlying disease states such as malignancy. By comparison, negative anion gaps are much more common in critically-ill populations, most notably NICU patients.
Unusual, non-anaphylactic transfusion reactions associated with severe IgA and IgM deficiencies and anti-IgA
Authors: Noubouossie Denis , Marques Marisa B , Siniard R Chad , Lima Jose L O
Published: October 2021

A few individuals with undetectable IgA develop anti-IgA, which is theorized to promote anaphylactic or anaphylactoid reactions to blood products. Here, we describe a recurrent, unusual reaction in a patient with no IgA or IgM, and anti-IgA present. The patient is a 49-year-old male with cirrhosis secondary to hepatitis C, who presented to the emergency department in January of 2014 with abdominal distension, leg swelling and dyspnea. He was severely anemic with a hemoglobin of 4.5 g/dL. Several minutes into a transfusion, he complained of chills, dyspnea and back pain. The transfusion was discontinued after <10mL, and his symptoms resolved rapidly without further intervention. The patient’s blood pressure, heart rate and temperature before and after the reaction were 134/63 mmHg and 180/64 mmHg, 98 beats/minute (bpm) and 102 bpm, and 98.6⁰ F and 98.7⁰ F, respectively. A laboratory workup for hemolysis was negative pre- and post-transfusion and an “OK to transfuse” order was given if future blood products were indicated. The following day, another transfusion of PRBCs was stopped after <75 mL due to similar symptoms, which again resolved rapidly; no vital signs changes or signs of hemolysis were noted. Because he was receiving other fluids concurrently with the PRBCs, it was recommended to transfuse future products slowly and to premedicate with furosemide. Although he tolerated three subsequent PRBC transfusions during the same admission, he developed the same clinical picture as soon as <75mL of a platelet unit was started. At that time, unbeknownst to Transfusion Medicine, the primary care team ordered immunoglobulin levels and anti-IgA, and the results of these tests were entered into his electronic medical record (EMR) after discharge.

Approximately six years later, the patient was readmitted following a fall and was found to be thrombocytopenic. After receiving <30 mL of platelets, he developed back pain and headache and the transfusion was aborted. His wife informed the primary provider that her husband was IgA-deficient. When Transfusion Medicine was notified, a review of his EMR showed undetectable IgA (<6 mg/dL: reference: 46-236 mg/dL) and IgM (<25 mg/dL; reference 43-279 mg/dL) and mildly increased IgG (1787 mg/dL; reference 650-1643 mg/dL) from 2014. Additionally, a high-titer IgG anti-IgA (>1000 U/mL; reference <99 U/mL), had been reported. In lieu of these findings, we changed his transfusion requirements to issue only washed PRBCs and IgA-deficient platelets and plasma, but he has not required any blood products since the last reaction. While a definitive cause and effect has not been established, this case suggests that severe IgA- and IgM-deficiency with IgG anti-IgA may be associated with nonspecific symptoms even with the transfusion of small volumes (<75 mL). To our knowledge, similar reactions have not been previously reported.
Patterns and Utility of Calprotectin in Patients with Microscopic Colitis
Authors: Abukhiran Ibrahim , Krasowski Matthew , Bellizzi Andrew , Boukhar Sarag , Merrill Anna
Published: October 2021

Context

Calprotectin is a cytoplasmic-protein that is released upon neutrophilic activation. Measuring fecal-calprotectin (FC) is used for monitoring inflammatory bowel disease activity and distinguishing it from irritable bowel syndrome. However, its utility in other types of colitis has not been well-investigated.

Design

Cases of collagenous-colitis (CC) and lymphocytic-colitis (LC) between 2015 and 2020 were retrieved from our institution surgical pathology database. Endoscopy and histopathologic examination findings were reviewed to confirm the diagnosis. 15 CC and 13 LC cases were included as FC was done at the time of initial diagnosis (before therapy). 62 cases of normal endoscopy and histopathologic examination were selected as a control group. One-way analysis of the variance (ANOVA) and receiver operating curve (ROC) analysis of FC were performed.

Results

Abnormally elevated FC (> 50 ug/g) was identified in 77% and 64% of CC and LC cases, respectively. Only 1.6% of control cases had mildly elevated FC of 54 ug/g. The mean FC of CC and LC groups (246 and 214, respectively) were significantly higher than the control group (22.4); p= <0.05. LC and CC groups had no statistically significant difference in the mean FC (p = 0.8). The area under the curve was 0.93 with ROC analysis. At the suggested cut-off of 50 ug/g, the sensitivity was 78.6%, specificity was 98.4% with a likelihood ratio of 48.7.

Conclusions

Fecal calprotectin can be elevated in patients with lymphocytic or collagenous colitis, however with no statistically significant difference between the two types. Therefore, it has the potential to be used as a marker for screening, diagnosis, and monitoring response to therapy in patients with microscopic colitis.
The surge in fatal diabetic ketoacidosis in the years of the COVID-19 pandemic: a forensic autopsy study
Authors: Geller R L , Aungst J , Lee C
Published: October 2021

Introduction/Objective

Although many deaths resulting from diabetic ketoacidosis (DKA) fall outside the legal jurisdiction of the medical examiner, a forensic pathologist may identify this cause of death through ancillary testing multiple times per year. We recognized a sharp increase in deaths due to DKA at a busy metropolitan medical examiner’s office in 2020 and 2021, coinciding with the COVID-19 pandemic. We hypothesize that in the majority of these cases, fatal DKA was the presenting symptom of previously undiagnosed diabetes mellitus (DM).

Methods/Case Report

We performed a retrospective autopsy review of all cases with a cause of death listed as “diabetic ketoacidosis” from January 1, 2018 through June 18, 2021. We compared the number of DKA deaths to all reported deaths from the same time period.

Results (if a Case Study enter NA)

We identified a total 34 cases of fatal DKA. In 2018, 5 cases of DKA were identified and all decedents had a known diagnosis of DM; the average age at death was 50.6 years (range: 40- 60 years) and 2 decedents were male (40%). In 2019, 5 cases of DKA were identified and 4 decedents had a known diagnosis of DM (80%); the average age at death was 51.4 years (range: 37- 61 years), and all decedents were male (100%). In 2021, 18 cases of DKA were identified and 9 decedents had a previous diagnosis of DM (50%); the average age at death was 43.5 years (range: 22- 64 years), 13 decedents were male (72%), and 1 decedent was COVID-19 positive (5.5%). In the first 6 months of 2021, 6 cases of DKA were identified and none of these decedents had a previous diagnosis of DM (0%); the average at death was 51.8 years (range: 35- 73 years), 4 decedents were male (66%), and 1 decedent was COVID-19 positive (16.6%). Reported deaths per year to our office are as follows: 2018 = 2585 deaths, 2019 = 2658 deaths, 2020 = 3091 deaths, and 2021 to date = 1482 deaths.

Conclusion

Coinciding with the COVID-19 pandemic, our office experienced a 16.2% increase in all reported deaths from 2019 to 2020, and a 260% increase in fatal DKA. In 2018 and 2019, 9 of the 10 decedents who died from DKA had a known diagnosis of DM (90%). However, in 2020 and the first half of 2021, DKA was the presenting symptom of previously undiagnosed DM in 15 of 24 cases of fatal DKA (62.5%). Further investigation must be done to examine the factors driving the recent surge in fatal DKA.
Fatal Moans and Bones in Crohn’s
Authors: Opara J C , Jackson N R
Published: October 2021

Introduction/Objective

Heterotopic mesenteric ossification (HMO) is a rare, reactive condition involving abnormal bone formation within the mesentery. While its etiology is uncertain, reports suggest two possible inciting events - either metaplasia from trauma and/or inflammation or dislodgment of bone fragments from other sites during abdominal surgery. With less than 50 reported cases, there is much unknown about this disease process. Herein, we present a rare, fatal case.

Methods/Case Report

A 43-year-old man with a history significant for Crohn’s disease status-post multiple abdominal surgeries and with resultant chronic abdominal pain was found unresponsive at home by family with an unknown downtime. He was taken to the local hospital where he was admitted to the Intensive Care Unit. Given a poor prognosis, family transitioned him to comfort care measures and he died shortly thereafter. Autopsy examination revealed a thin man with an ostomy and severe abdominal scarring. Internally, there were multiple aberrant bone fragments within the mesentery which neither perforated the bowel nor caused obstruction and which microscopically appeared to be mature and benign. Ancillary studies were significant severe dehydration. Follow-up conversation with his family revealed that due to debilitating abdominal pain, the decedent had significantly decreased his oral intake and had stopped taking medications to control his high output ostomy. Given the autopsy and investigative findings his death was certified as a natural death caused by dehydration due to complications of Crohn’s disease.

Conclusion

This is the first reported case of HMO occurring in inflammatory bowel disease. Awareness of this condition is important for clinicians as it can alter management of these patients. Early review and recognition from radiologists and pathologists can potentially improve the morbidity and mortality of this group.
A Case Report of Autopsy: Large Mass of Pulmonary Metastatic Calcification in a Patient with End-Stage Renal Disease
Authors: Mahalingam V D , Zhang P
Published: October 2021

Introduction/Objective

Metastatic calcifications are reported in patients with end-stage renal disease (ESRD) in radiology literature but there are no pathologic reports regarding this clinical scenario in autopsy.

Methods/Case Report

We report the case of a 27-year-old African American man with nephrotoxic injury secondary to gentamicin treatment at a young age leading to ESRD requiring dialysis who then later developed congestive heart disease and arrhythmia. Prior to the patient’s last hospitalization, he had normal breath sounds with no signs of respiratory distress, rales, or wheezing. Imaging of the chest showed a patchy density in the right lung and a large parenchymal calcification. During autopsy, the patient was found to have bilateral markedly small and atrophic kidneys (left kidney weight: 27.5 g, size: 5.7 x 4.4 x 3.0 cm and right kidney weight: 30.6 g, size: 5.9 x 4.4 x 3.1 cm). Microscopically, the kidneys showed diffuse global glomerulosclerosis, atrophy of cortex, severe interstitial fibrosis, and tubular atrophy with thickened arteries as well as many foci of calcifications. A large mass measuring 3.5 x 2.4 x 1.9 cm was identified in the right middle lobe of the lung. Sections of the mass revealed large calcifications which were confirmed microscopically. In addition, concentric heart hypertrophy was identified with heart weight of 925 g and left ventricle measuring up to 2.2 cm. Calcifications (ranging from 0.2 – 0.5 mm) were also identified on the left atrial wall as well as a 1.2 x 0.8 x 0.6 cm mitral valve nodule along with additional microcalcifications within the myocardium.

Results (if a Case Study enter NA)

NA

Conclusion

In conclusion, our autopsy case supports previous radiologic reports that metastatic calcification can be dramatically present in the lung in patients with ESRD.
Echogenic Intestine: a Case of Intrauterine Fetal Demise at Term
Authors: Panah E , Zelman B , Gvozdjan K
Published: October 2021

Introduction/Objective

Parvovirus B19 is a non-enveloped, single-stranded DNA virus that preferentially infects early erythroids, and is commonly associated with second trimester hydrops fetalis. Third trimester non-hydropic intrauterine fetal demise due to parvovirus B19 infection with associated pathologic changes has rarely been described, particularly in the context of IgG seroconverted mother.

Methods/Case Report

We present a case of a 37 weeks’ gestation stillborn female fetus born to a 29 year-old mother who presented with lack of fetal movement for one day. Fetal ultrasound demonstrated diffuse intestinal echogenicity. Maternal parvovirus B19 IgG level was high (5.48, reference: <=0.90 Index). Postmortem examination revealed a non-dysmorphic fetus. Gross examination was unremarkable. Microscopic examination of small intestine revealed mucosal inflammation and multifocal calcifications. Prominent extramedullary hematopoiesis was present in the liver. Viral cytopathic effect was noted microscopically within nucleated red blood cells present intravascularly within chorionic villi, small intestine, liver, and spleen. Parvovirus B19 infection was confirmed by immunohistochemistry.

Results (if a Case Study enter NA)

NA

Conclusion

The cause of clinically puzzling intrauterine fetal demise at term with prominent intestinal echogenicity on ultrasound was determined to be parvovirus B19 infection on postmortem examination. We emphasize the possibility of this diagnostic differential in non-hydropic, third trimester fetal demise in presence of maternal IgG seroconversion and lack of signs of active infection.
Extraskeletal mesenchymal chondrosarcoma mimicking a thrombosed venous aneurysm with femoral vein involvement: A case report
Authors: Muldoon J , Warmke L
Published: October 2021

Introduction/Objective

Mesenchymal chondrosarcoma is a high-grade primitive mesenchymal tumor, which accounts for <5% of all chondrosarcomas and commonly affects young adults (peak incidence in second to third decade of life). The tumor has a widespread anatomic distribution, frequently involving the craniofacial bones as well as extraskeletal sites. The clinical presentation of an inguinal mass mimicking a thrombosed venous aneurysm is unusual and represents a potential diagnostic pitfall.

Methods/Case Report

A 42-year-old female with hypertension and obesity initially presented with a two-week history of left lower leg swelling. Venous doppler revealed presumed venous thrombosis, and she was prescribed apixaban while no history of coagulopathy, immobility, or recent surgery was noted. Two months later, she had residual swelling. Follow-up CT scan favored a large, peripherally thrombosed venous aneurysm arising from the left common femoral vein, while MRI showed a lobulated, inguinal soft tissue mass abutting the vein. Biopsy of the mass demonstrated a spindle cell mesenchymal neoplasm; subsequent resection revealed a pink-to-tan, well-circumscribed, and encapsulated mass (5.2 cm) with focal left common femoral vein invasion. Microscopically, the lesion demonstrated poorly-differentiated, oval-to-spindle cells with prominent staghorn vasculature interspersed were focal areas of well-differentiated hyaline cartilage. Immunohistochemical stains showed that the lesional cells were negative for cytokeratin cocktail, EMA, SMA, desmin, S100 protein, SOX10, STAT6, MUC4, MDM2, and ER. Next-generation sequencing (NGS) revealed a HEY1-NCOA2 gene fusion, confirming the diagnosis of extraskeletal mesenchymal chondrosarcoma.

Results (if a Case Study enter NA)

N/A

Conclusion

Extraskeletal mesenchymal chondrosarcoma can rarely present as an inguinal soft tissue mass with vascular invasion, mimicking a thrombosed venous aneurysm. Molecular confirmation of HEY1-NCOA2 gene fusion can help confirm the diagnosis in unusual clinical presentations.
Analysis of Low Estrogen Receptor (ER+) Breast Carcinomas in a Large Community Breast Cancer Center in Northern California
Authors: Bulusu G , Duncan K , Wheeler A
Published: October 2021

Introduction/Objective

Estrogen Receptor (ER) expression in breast cancers is a crucial factor for endocrine therapy in patients with tumors expressing ER in ≥1% of tumor cells. The 2019 guidelines published by ASCO/CAP states that breast cancers that have a 1% to 10% of cells staining Estrogen Receptor (ER) positive should be reported as ER Low Positive cases. This study aims to address this subset of low-positive ER tumors and compare the clinical features to other known breast cancer subtypes.

Methods/Case Report

We conducted a retrospective review of a prospectively maintained breast cancer registry from 2013 to 2021 at Mills-Peninsula Medical Center, a Sutter Health Affiliate. The study reviewed patient charts with respect to the pathology report, operative report, chemotherapy regimen, and clinical outcomes. Statistical analyses were conducted using R Project for Statistical Coding, with The Student’s T-test used to compare continuous variables. Two-sided P values less than 0.05 indicate statistical significance.

Results (if a Case Study enter NA)

Our study identified 1316 cases of invasive breast carcinomas, of which 29 (2.16%) demonstrated ER Low-Positive expression. We aimed to evaluate the clinical and pathological features, such as histological grade, ER, PR, HER-2, Ki-67%, and patient age for these tumors. We found that ER Low-Positive tumors demonstrated higher mean histological grade morphology (2.5 out of 3, p<0.001) that was similar to that of Triple Negative Breast Cancers (TNBC) (3 of 3, p<0.001) than to High ER-Positive (1.6 of 3, p<0.001) cancers. Further observations, through examining proliferation rates by utilizing the Ki-67 index, indicate comparative trends between the ER Low-Positive cohort and the TNBC cohort.

Conclusion

The results suggest that the ER Low-Positive carcinomas, despite reported as ER-positive cases, present with similar clinicopathological features to those of ER-negative tumors. Through this study and future research, we would like to emphasize a stricter set of guidelines that can be adopted to reduce variability for reporting biomarkers. This standardization will allow oncologists to provide more appropriate treatment options and improve the quality of patient care.
High take-off of coronary arteries contributing to lethal myocardial ischemia: report of two cases
Authors: Conte J T , Prisneac I , Amin M
Published: October 2021

Introduction/Objective

High take-off coronary arteries (HTO) are defined by coronary ostia arising above the sinotubular junction (STJ). Although asymptomatic in most individuals, there is increasing evidence that HTO is a risk factor for sudden cardiac death. Here we present two patients where HTO contributed to death.

Methods/Case Report

Patient A was a 52 year old morbidly obese male with atypical chest pain, new inferior ST elevations and troponinemia. Multiple coronary angiographies did not reveal any stenosis, but 3 stents were placed in the RCA due to concern for vasospasm. 3 days later the patient died. Autopsy revealed cardiac tamponade and non- atherosclerotic ischemic heart disease with remote apical LV scar and diffuse patchy interstitial fibrosis in the myocardium, which could be attributed to HTO of the RCA 0.5 cm above the STJ and early intramuscular courses of both coronaries. Multiple angiographies likely caused iatrogenic coronary injury and subsequent tamponade. Patient B was a healthy 33 year old female at 34 weeks gestation, who developed anaphylaxis during IV iron infusion for severe iron deficiency anemia. She was transferred to the OR for emergent C-section. Minutes after delivery she died. Autopsy revealed HTO, with coronary ostia being 0.4 cm and 0.7 cm above the STJ, respectively and acute angle take-off of LCA. No atherosclerosis was noted. The inability to increase myocardial perfusion through the coronary arteries during a high stress situation due to pregnancy, iron deficiency anemia and anaphylaxis likely contributed to lethal myocardial ischemia.

Results (if a Case Study enter NA)

NA

Conclusion

HTO and other coronary artery anomalies (CAAs) should be considered in cases of cryptogenic acute and chronic myocardial ischemia. Hemodynamic characterization of HTO, including those < 1 cm above the STJ in presence and absence of other CAAs may help better understand their pathophysiologic significance. Antemortem diagnosis requires high clinical suspicion and appropriate surgical intervention could be life-saving.
The sensitivity of temporal artery biopsy in the detection of giant cell arteritis is independent of tissue length
Authors: Hurley H J , Deb P Q
Published: October 2021

Introduction/Objective

Giant cell arteritis (GCA) is the most common vasculitis of the elderly, and the most common primary systemic vasculitis overall, with an annual incidence of 200/million. The long term sequelae, namely vision loss and stroke, are permanent and devastating. While GCA is often treated empirically based on clinical presentation, panarteritis on temporal artery biopsy is required for diagnosis. However, these biopsies have the tendency to be falsely negative due to skip lesions, a common feature of GCA. Therefore, we set out to determine whether longer biopsy specimens were more sensitive in the detection of GCA.

Methods/Case Report

A census of temporal artery biopsies performed with the indication of clinical symptoms of GCA was taken at our institution. The patient age, sex, biopsy laterality, biopsy length, and pathological diagnosis were recorded for each cataloged sample. Statistical significance of difference in biopsy length was tested using an unpaired t-test in R 4.1.0.

Results (if a Case Study enter NA)

A total of 114 temporal artery specimens were biopsied from 94 different patients with the indication of GCA and assigned a definitive positive or negative diagnosis. Of the 94 patients, 54 were female and 40 were male. Of the total pathological specimens, 11 were positive and 103 were negative. The overall average length of biopsy specimens was 2.13 cm with a standard deviation of 0.65 cm. The average positive biopsy was 2.26 cm long, and the average negative was 2.12 cm, an insignificant difference (0.14 cm, t = 0.7, p = 0.43). In 25 patients, biopsies were taken from both the left and right temporal arteries. Of those patients, 2 were positive for GCA and the remaining 23 were negative. Interestingly, the biopsy result in every case was identical between the left and right samples; we found no instances of pathological evidence of GCA in only one of the two samples from the same patient.

Conclusion

According to data taken at our institution, there is no indication to lengthen the biopsy requirements from the existing 1.5 cm. However, we have demonstrated evidence that it may be unnecessary to biopsy both temporal arteries in a single patient. Larger studies would be required to confirm our findings.