bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiomatoid Fibrous Histiocytoma with EWSR1 Rearrangement in an Unusual Location
Authors: Sinha A K , Arze E 
Published: November 2022

Abstract

Introduction/Objective
Angiomatoid fibrous histiocytoma (AFH) is a rare mesenchymal neoplasm most often arising in the superficial extremities of children and young adults. AFH can mimic clinical, histologic, and radiologic presentation of several different tumors, therefore diagnosis can be quite challenging.

Methods/Case Report
We report the case of a 32-year-old woman with no significant medical history who presented with three days of right upper quadrant pain. Radiologic studies showed a 2.3 centimeter right lower lobe soft tissue nodule abutting the right lower lobe bronchus.

Results (if a Case Study enter NA)
Subsequent lobectomy with mediastinal lymph node dissection was performed. Histopathologic examination of the right middle and lower lobes revealed a fibrohistiocytic appearing neoplasm with bland nuclear features and brisk associated lymphoplasmacytic and histiocytic infiltrate. Given the suspicion for AFH, fluorescent in situ hybridization for EWSR1 and FUS were performed at an outside facility with detection of EWSR1 gene rearrangement supporting the diagnosis of AFH.

Conclusion
AFH is a rare soft tissue neoplasm that is often indolent but intermediate in potential given the rare possibility of metastasis. While most common in superficial extremities, increasing unusual anatomic sites are being reported. Histologically, the tumor can show a spectrum of morphologic patterns including nodules to sheets of often monomorphic bland, spindle or ovoid cells in an inflammatory background and with associated fibrous pseudocapsule. Three characteristic chromosomal translocations have been identified: EWSR1-CREB1, EWSR1-ATF1 and FUS- ATF1. Treatment is wide surgical excision or radiotherapy if unresectable. The differential diagnosis can be broad with a spectrum from reactive, benign lesions to malignant neoplasms, including a variety of sarcomas.
Pulmonary Sclerosing Pneumocytoma; A Frozen Section Diagnostic Dilemma
Authors: Zenezan D , Tabet G , Mollaee M , Akhtar I 
Published: November 2022

Abstract

Introduction/Objective
Pulmonary Sclerosing Pneumocytoma (PSP)is a benign neoplasm with features of pneumocytic differentiation and dual-cell population. It is a rare tumor of adults with female predilection. The tumor is mostly asymptomatic. However, it can rarely show pleural invasion or lymph node metastasis. Presenting as a mass lesion by imaging studies frequently mandates a frozen section, which can be extremely challenging, and misdiagnosed as lung adenocarcinoma. We report a case of PSP with focal visceral pleural invasion that was submitted for frozen section.

Methods/Case Report
We report a case of a 57- year old female found to have a 2.5 cm nodule of the right lower lobe of lung on the CT scan. The patient underwent a wedge resection and the specimen was sent for intraoperative diagnosis. Sectioning revealed a firm, tan-white lesion measuring 2.1 x 2.0 x 1.1 cm. Frozen section diagnosis was suggestive of lepidic pattern adenocarcinoma with areas of fibrosis. Respectively, permanent section of the lesion revealed sheets of bland appearing cuboidal cells lining the papillary and sclerotic areas with round, bland appearing cells within the stroma. A few cells showed mild cytologic atypia with occasional prominent nucleoli and scattered mitotic figures were noted, besides visceral pleural invasion. Foci of atypical adenomatous hyperplasia were noted in close vicinity raising the suspicion of lepidic pattern adenocarcinoma on frozen section.The immunohistochemical staining was positive for Napsin, keratin, and CK7 in the surface cells but not in the round cells and EMA immunostain highlighted the surface cells and scattered round cells. Additional immunostains showed expression of estrogen receptor in the round cell component and TTF1 in both the round and surface components. The immunoprofile further supported the diagnosis of PSP and the elastic stain highlighted the visceral pleural involvement. Combined morphology and immunoprofile supported the diagnosis of PSP.

Results (if a Case Study enter NA)
NA

Conclusion
PSP is a rare benign neoplasm. It is important to recognize this challenging entity during intraoperative diagnosis as it can be easily mistaken for lung adenocarcinoma, especially in the presence of pleural invasion. The best treatment is still surgery for this neoplasm.
Rare Presentation of Crescentic Glomerulonephritis in a 4-Week-Old Infant
Authors: Abu-Salah A , Phillips C , Inman A 
Published: November 2022

Abstract

Introduction/Objective
Rapidly progressive glomerulonephritis is characterized by sudden decline in renal function and glomerular crescents. Crescentic glomerulonephritis develops along three pathways: glomerular basement membrane antibody in situ deposition , circulating immune complex glomerular deposition, or pauci-immune (typically ANCA-associated). For the latter, histopathologic diagnosis is more frequently obtained in adults than in children. Therefore, tissue examination opportunities in infants and neonates is exceptionally rare.

Methods/Case Report
Here we report the autopsy findings from a 4-week-old infant who was part of dichorionic, diamniotic twin pregnancy and born prematurely at 34 weeks to a 30-year-old G6P4 mother. The infant initially presented with labored breathing and poor oral intake, but subsequently developed Enterobactor meningoencephalitis and sepsis, leading to extensive strokes andstatus epilepticus. An infectious source was not identified clinically, and evaluation for an underlying immunodeficiency was indeterminant. The mother had no known autoimmune diseases or antenatal infections. At autopsy, kidney histology showed focal fibrinoid necrosis and/or cellular and fibrocellular crescents (~5%), especially mid to deep cortex. Intracapillary hypercellularity was minimal to absent. Mesangial matrix was not expanded. The interstitium contained patchy inflammatory infiltrates (mononuclear &gt; polymorphonuclear). Direct immunofluorescence (IF) on pronase-treated paraffin sections did not show glomerular deposition of IgG, IgA, or IgM. Electron microscopy (EM) did not show electron dense deposits despite autolysis.

Results (if a Case Study enter NA)
NA.

Conclusion
The absence of immune complex deposition by IF and dense deposits by EM favors the rare diagnosis of pauci-immune glomerulonephritis in this case of neonatal crescentic glomerulonephritis associated with Enterobactor meningoencephalitis and sepsis, with no associated maternal autoimmune disease or antenatal infections.
A Case of ALECT2 Renal Amyloidosis Associated with IgG4 Related Kidney Disease, Membranous Nephropathy and Early Diabetic Kidney Injury
Authors: Shaheen M , Guo S , Friedman A , bharat A 
Published: November 2022

Abstract

Introduction/Objective
ALECT-2 amyloidosis is a rare type of amyloidosis that mostly involves kidneys with other organs rarely affected. It has a high prevalence among patients of Hispanic descent. Membranous nephropathy is one of the most common causes of proteinuria in adults. IgG4-related disease is a systemic disease, which commonly involves the pancreas, but occasionally affects the kidney and manifests as chronic renal insufficiency. Here we describe a very unusual case of concurrence of membranous nephropathy, IgG4 disease involving the kidney, ALECT2 amyloidosis, and early diabetic kidney injury.

Methods/Case Report
A 49-year-old Hispanic male patient with a history of diabetes and IgG4-related autoimmune pancreatitis and primary sclerosing cholangitis presented with abrupt onset of proteinuria and hypoalbuminemia. A kidney biopsy was performed and showed severe interstitial plasma cell-rich inflammatory infiltrates and interstitial fibrosis which had a storiform pattern. The glomerular basement membranes (GBM) showed focal pinpoint holes but no spikes by silver stain. Immunofluorescence microscopy (IF) showed diffuse and finely granular capillary loop staining for IgG, with Kappa and lambda light chains of equal intensity. IF for Anti-phospholipase A2 receptor (PLA2R) was negative. Immunohistochemical (IHC) stain showed IgG4 positivity in about 60% of IgG-positive plasma cells. Congo red was positive for birefringent deposits predominantly in the interstitium and arteriolar walls with focal deposits in the glomerular mesangium and capillary wall. IHC stain for Amyloid AA and DNAJB9 were negative. Electron microscopy showed scattered subepithelial immune complex-type electron dense deposits consistent with membranous nephropathy, randomly oriented fibrils in interstitium, mesangium and GBM, consistent with amyloidosis, and thickening of GBM (average 559 nm), consistent with early diabetic kidney change. The tissue was sent for mass spectrometry which showed a peptide profile consistent with ALECT-2 (Leukocyte chemotactic factor 2) type amyloidosis.

Results (if a Case Study enter NA)
NA

Conclusion
In up to a third of cases reported in the literature, a concomitant renal pathology was present. Diabetic nephropathy was the most common concurrent pathology, to be followed by IgA nephropathy and membranous nephropathy. However, the concurrence of membranous nephropathy, IgG4 disease involving the kidney, ALECT2 amyloidosis, and early diabetic kidney injury has never been described before.
Paraneoplastic Nephropathy with Peculiar Immunofluorescence Pattern: Report of a Rare Case
Authors: Al-kharouf I , Fields T , Hamza A 
Published: November 2022

Abstract

Introduction/Objective
Hematolymphoid neoplasms are commonly associated with medical renal disease; however, association of renal cell carcinoma and nephrotic/nephritic syndrome is exceedingly rare. Paraneoplastic nephropathy in setting of renal cell carcinoma can manifest as membranous nephropathy, IgA nephropathy, or minimal change disease. The purpose of this report is to describe a rare case of clear cell renal cell carcinoma with associated membranous nephropathy with concurrent glomerular IgG and IgA deposition.

Methods/Case Report
A 68-year-old male presented with a penile mass. Diagnostic work up reveled an 11cm renal mass. Urinalysis demonstrated nephrotic range proteinuria (&gt;5 g/d). Subsequently, the patient underwent nephrectomy and penectomy. Pathologic evaluation showed clear cell renal carcinoma with sarcomatoid component and metastasis to penis. Nonneoplastic kidney workup revealed membranous glomerulopathy, with 3+ granular IgG predominantly within glomerular capillaries and 2+ IgA and 1+ C3 in a similar pattern. Electron microscopy demonstrated numerous subepithelial and intramembranous immune deposits, and few small mesangial deposits. Concurrent membranous and IgA nephropathy has been reported, but the IgA in that case is typically mesangial. The peculiar pattern of IgG and IgA deposition in this case can be seen with membranous nephropathy secondary to lupus or neoplasia. Lupus was excluded based on patient’s history, serology, and absence of significant C1q staining. Therefore, the findings were consistent with membranous glomerulopathy secondary to patient’s cancer. Patient’s proteinuria improved after nephrectomy. He is alive and disease-free 10months after nephrectomy, with proteinuria in 0.1-0.6 g/d range.

Results (if a Case Study enter NA)
NA

Conclusion
This case highlights the importance of thorough evaluation of non-neoplastic kidney in nephrectomy specimens for cancer, thus guiding the type of surgical intervention. Non-orthodox presentation of immunoglobulin deposition may be the herald of neoplasia in select cases.
The Accidental Discovery of a Rare and Diagnostically Challenging Antibody, Anti Diegoa
Authors: Irfan A , Jiles C , Hamdan H 
Published: November 2022

Abstract

Introduction/Objective
Anti Diegoa antibody (DiA) is a rare antibody, associated with severe hemolytic disease of the newborn. It is seen in American Indians and Asians of Mongoloid descent. Only 2.6% of Hispanics and &lt;0.01% of Caucasians and African Americans have this antibody, making it challenging to diagnose. We present a case of a DiA discovered accidentally.

Methods/Case Report
A 31-year-old G4P3 Hispanic female at 35 weeks 5 days of gestation presented with limited prenatal care and gestation complicated by chronic deep vein thrombosis, on enoxaparin. Her gestational history was significant for Anti-E Antibody (Anti-E) with a gel titer of 1:8 during her second gestation. During her current pregnancy her Anti-E Ab gel titer was 1:32 and an Anti-c Antibody (Anti-c) was also detected. R1R1 panel was used to detect further antibodies since the patient was Anti-E and Anti-c. The initial gel panel could not rule out Duffy Antibody (FyA) and Kidd Antibody (JkB). Two R1R1 panels had already been cross matched and both were compatible. A second gel panel showed Kell antigen (KpA), FyA and JkB, all with a +2 positivity in a R1R1 cell panel (Cell X). Antigen typing labelled the patient as JkB+ and FyA-. One compatible unit was FyB- making FyA- unlikely. One of the cross matched compatible units was FyA+. An additional homozygous R1R1 cell was negative for FyA. Therefore FyA- was ruled out. The positivity on Cell X was then thought to be KpA. A solid phase panel (Cell Y) was conducted and was positive, supporting KpA as the causative factor. A decision was made to repeat our test using the initial patient sample plus a CBC tube. This demonstrated KpA negativity, negating KpA as the causative factor. However the Cell Y positivity in the solid phase panel was still questionable. DiA, a low frequency antibody is also found on this cell. This led to further testing. Another R1R1 cell showed +3 positivity for DiA. Antibody identification confirmed this as DiA with a titer of 2. The patient underwent induction of labor and delivered a healthy neonate.

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

Conclusion
Since DiA is located in the same panel as KpA, the positive result was presumed to be secondary to KpA. However repeat testing demonstrated KpA negativity and thereby unmasked DiA as the culprit.
Recent RhIG Administration Does Not Interfere with the Rosette Test
Authors: Zheng L , Tormey C , Guarente J 
Published: November 2022

Abstract

Introduction/Objective
Administration of Rh immune globulin (RhIG) is indicated mid-gestation (28 weeks) and after delivery to prevent Rh D sensitization in Rh D negative women. Women with sporadic prenatal care may not receive the first dose at 28 weeks, and may end up receiving their first dose closer to delivery. The rosette test (RT) is a rapid screen for fetomaternal hemorrhage (FMH) that uses an IgM anti-D antibody to detect fetal Rh D positive red blood cells (RBC) in maternal circulation. It is not currently known if or how recent administration of RhIG prior to performance of a RT may interfere with RBC agglutination and test results.

Methods/Case Report
To approximate mixing of fetal Rh D positive RBC with maternal Rh D negative RBC during FMH, 2% volume of Rh D positive RBC from fetal cord and adult donor samples were spiked into Rh D negative RBC. These mixtures were then incubated with a physiologic concentration of RhIG to occupy all Rh D antigen sites on the Rh D positive cells prior to performing the RT.

Results (if a Case Study enter NA)
Addition of Rh D positive RBC and RhIG to Rh D negative RBC did not affect rosette formation. Rh D negative cells had 0 rosettes/LPF. Rh D negative cells spiked with 2% Rh D positive adult donor and fetal cord RBC by volume produced an average of 9.8 rosettes/LPF (SD: 2.8) and 11.2 (SD: 3.3), respectively. Addition of a physiologic concentration of RhIG to the spiked Rh D positive adult donor and fetal cord RBC produced an average of 13.0 rosettes/LPF (SD: 2.5) and 11.2 rosettes/LPF (SD: 2.6), respectively.

Conclusion
Incubation of Rh D positive RBCs with physiologic concentration of RhIG does not affect the rosette test. Clinicians and laboratorians should be reassured that the rosette test continues to be an accurate way to quantitate FMH after recent RhIG administration.
Association between theLRP1BandAPOEloci and the development of Parkinson’s disease dementia
Authors: Real Raquel , Martinez-Carrasco Alejandro , Reynolds Regina H , Lawton Michael A , Tan Manuela M X , Shoai Maryam , Corvol Jean-Christophe , Ryten Mina , Bresner Catherine , Hubbard Leon , Brice Alexis , Lesage Suzanne , Faouzi Johann , Elbaz Alexis , Artaud Fanny , Williams Nigel , Hu Michele T M , Ben-Shlomo Yoav , Grosset Donald G , Hardy John , Morris Huw R 
Published: November 2022

AbstractParkinson’s disease is one of the most common age-related neurodegenerative disorders. Although predominantly a motor disorder, cognitive impairment and dementia are important features of Parkinson’s disease, particularly in the later stages of the disease. However, the rate of cognitive decline varies among Parkinson’s disease patients, and the genetic basis for this heterogeneity is incompletely understood.To explore the genetic factors associated with rate of progression to Parkinson’s disease dementia, we performed a genome-wide survival meta-analysis of 3923 clinically diagnosed Parkinson’s disease cases of European ancestry from four longitudinal cohorts. In total, 6.7% of individuals with Parkinson’s disease developed dementia during study follow-up, on average 4.4 ± 2.4 years from disease diagnosis.We have identified the APOE ε4 allele as a major risk factor for the conversion to Parkinson’s disease dementia [hazard ratio = 2.41 (1.94–3.00), P = 2.32 × 10−15], as well as a new locus within the ApoE and APP receptor LRP1B gene [hazard ratio = 3.23 (2.17–4.81), P = 7.07 × 10−09]. In a candidate gene analysis, GBA variants were also identified to be associated with higher risk of progression to dementia [hazard ratio = 2.02 (1.21–3.32), P = 0.007]. CSF biomarker analysis also implicated the amyloid pathway in Parkinson’s disease dementia, with significantly reduced levels of amyloid β42 (P = 0.0012) in Parkinson’s disease dementia compared to Parkinson’s disease without dementia.These results identify a new candidate gene associated with faster conversion to dementia in Parkinson's disease and suggest that amyloid-targeting therapy may have a role in preventing Parkinson’s disease dementia.
Quantile regression estimands and models: revisiting the motherhood wage penalty debate
Authors: Borgen Nicolai T , Haupt Andreas , Wiborg Øyvind Nicolay 
Published: November 2022

AbstractThis paper discusses the crucial but sometimes neglected differences between unconditional quantile regression (UQR) models and quantile treatment effects (QTE) models. We argue that there is a frequent mismatch between the aim of the quantile regression analysis and the quantitative toolkit used in much of the applied literature, including the motherhood wage penalty literature. This mismatch may result in wrong conclusions being drawn from the data, and in the end, misguided theories. In this paper, we clarify the crucial conceptual distinction between influences on quantiles of the overall distributions, which we term population-level influences, and individual-level QTEs. Further, we use data simulations to illustrate that various classes of quantile regression models may, in some instances, give entirely different conclusions (to different questions). Finally, we compare quantile regression estimates using real data examples, showing that UQR and QTE models differ sometimes but not always. Still, the conceptual and empirical distinctions between quantile regression models underline the need to match the correct model to the specific research questions. We conclude the paper with a few practical guidelines for researchers.
Screening Failure in a Large Clinical Trial Centre for Inflammatory Bowel Diseases: Rates, Causes, and Outcomes
Authors: Outtier An , Gijbels Liese , Noman Maja , Verstockt Bram , Sabino João , Vermeire Séverine , Ferrante Marc 
Published: November 2022

Abstract

Background
Patients with inflammatory bowel diseases (IBD) sometimes require investigational medicinal therapy in a clinical trial. Before enrollment, patients must meet strict eligibility criteria, hampering recruitment rates. We investigated the rates, causes, and outcomes of screening failure (SF) in a tertiary IBD center.

Methods
We reviewed all IBD patients screened for sponsored multicenter phase 1-3 induction studies with available global SF rates between January 2008 and March 2021. We compared our SF rates with the global SF rates. Causes of SF were categorized into disease activity, hematology, chemistry, microbiology, protocol violation, and withdrawal of consent. Patient outcomes were categorized into rescreening for the same trial, screening for another trial, (re)introduction of commercially available therapy, surgery, or watchful waiting.

Results
During the study period, 642 local screenings were performed as part of 53 studies. We identified an overall SF rate of 17.1%, compared with 39.2% in the global study population (P &lt; .00001). Causes of SF at our center included ineligible disease activity (36.4%), microbiology (25.5%), protocol violation (16.4%), withdrawal of consent (9.1%), chemistry (6.4%) and hematology (6.4%). Thirty SFs could have been avoided by prescreening that was more thorough. After SF, 34 patients were rescreened for the same trial, 17 screened for another trial, 38 initiated approved therapy, 9 were referred for surgery, and 12 did not receive further therapy.

Conclusions
A significant proportion of IBD patients consenting to clinical trials fail their screening. Main causes of SF are ineligible disease activity and abnormal finding on microbiology. Approximately one-fourth of SFs could have been avoided by prescreening that was more thorough.
Public compliance with difficult political decisions in times of a pandemic: does citizen deliberation help?
Authors: Muradova Lala , Suiter Jane 
Published: November 2022

Abstract
Bridging deliberative democracy and crisis management scholarship, we construct theoretical expectations about the role of deliberative minipublics in fostering public compliance with difficult political decisions. Our expectations are tested with a randomized cross-national survey experiment (United States and United Kingdom, N = 2088), in which respondents read a realistic news item depicting a political decision-making process leading to the extension of COVID-19 lockdown measures that follows either a (1) citizen deliberation, (2) public consultation, (3) politician deliberation, or (4) nothing. The findings show minipublics are unlikely to foster public compliance during a health crisis. On the contrary, reading about a minipublic could decrease compliance when individuals are distrustful of minipublics. This study has implications for citizen participation, deliberation, and leadership during future pandemics.