bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 Detection by Extraction-free qRT-PCR for Massive and Rapid COVID-19 Diagnosis During a Pandemic
Authors: Martirosyan G , Avetyan D , Zakaryan R , Hayrapetyan V , Khachatryan G , Sirunyan T , Ghukasyan L , Arakelyan A
Published: November 2022

Introduction/Objective

COVID-19 pandemic severely impacted the healthcare and economy on a global scale. It is widely recognized that mass testing is an efficient way to contain the spread of SARS-CoV-2 infection as well as aid in the development of informed policies for disease management. Here we optimized two different protocols for qRT- PCR with direct samples and systematically compared them with the laboratory standard qRT-PCR detection assay.

Methods/Case Report

RNA samples from 270 subjects collected in two phases at 2020-2021. The groups consisted from positive (n = 240) and negative (n = 30) samples. We compared the performance of qRT-PCR in direct heat- inactivated (95 °C for 5 min, H), heat-inactivated and pelleted (95 °C for 5 min and centrifuged for 10 min at 12,000 g, HC) against standard laboratory protocol for SARS-CoV-2 qRT-PCR (targeting ORF1ab and N genes). Accuracy, sensitivity, and specificity for PCR assays were calculated using caret and epiR packages available in the R software environment for statistical computing. The Wilcoxon matched rank test was used to compare differences in Ct values.

Results (if a Case Study enter NA)

Our study suggests that HC samples show higher accuracy for SARS-CoV-2 detection PCR assay compared to direct H (89 % (95 % CI: 80–95 %) vs 83 % (95 % CI: 74–91 %) of the detection in RNA). The median ΔCt was lower by 1.55 and 2.29 cycles (Wilcoxon signed-rank test p = 0.0018 and < 0.0001 for ORF1ab and N genes, accordingly) in HC samples compared to H samples.

Conclusion

Our results suggest that purified RNA provides more accurate results; heat-inactivated and pelleted sample testing with qRT-PCR showed a slight drop in accuracy. However, the latter could also help to significantly increase testing capacity. Switching to the direct sample testing is justified if the number of tests is doubled at least.
Filamentous Bacteria Resembling Fungal Hyphae: A Diagnostic Pitfall
Authors: Sham S , Bendari A , Hosseini H , Otero Espinal D , Vele O , Duong S
Published: November 2022

Introduction/Objective

When exposed to antibiotics or a host immune response, Gram-negative bacilli grow with inhibited septation producing long continuous cells; a phenomenon known as filamentation.

Methods/Case Report

We present a case of a 68-year-old man with quadriplegia, which was caused by the right vertebral artery dissection and subarachnoid hemorrhage requiring an emergent posterior inferior cerebellar artery direct bypass surgery. Lung lower lobe infiltrates were noted 3 days after the surgery. A bronchial wash culture was negative for growth, and a sputum specimen grew Serratia marcescens. The patient was treated with piperacillin/tazobactam, vancomycin, cefepime, cefazolin. After the surgery, he suddenly developed severe cerebral vasospasm of the posterior circulation with cerebellar strokes requiring emergent posterior fossa decompression. He remained on ventricular drainage by external ventricular drainage. After two days, the patient's cerebrospinal fluid (CSF) was sent for evaluation, on which a high segmented neutrophil count of 35% and Gram-negative filamentous organisms with occasional swellings were noted. Multi-drug resistant Serratia marcescens was isolated from the CSF specimen four days later. Neurosurgical procedures were reported to be highly associated with S. marcescens meningitis. The filamentous organisms noted on Gram-stained direct smear most likely represented Gram-negative S. marcescens with filamentation due to administration of sub-inhibitory concentrations of antibiotics.

Results (if a Case Study enter NA)

NA.

Conclusion

Gram-negative bacilli can develop abnormal morphology including elongation, swelling, and filamentation due to stress or sub-inhibitory antibiotic exposure, and it is important for microbiologists and pathologists to be aware of this phenomenon to avoid misinterpretation that may lead to inappropriate treatment.
Molecular Solid Tumor Algorithm – Simplified Patient-Centric/Cost-Effective Approach by Pathologists
Authors: Poonam F , Loos C , Wells A , Ehsan A
Published: November 2022

Introduction/Objective

The process from the time the patient is diagnosed with cancer and receives their first treatment is complex and time-consuming. It requires adherence to national comprehensive cancer network (NCCN) guidelines; is challenged with limited tissue, how and when to order tests, and reimbursement timelines with pre- authorizations. We evaluated the role of the pathologists, who are an integral part of patient care, along with oncologists and surgeons.

Methods/Case Report

254 cases from various types of solid tumors (paraffin-embedded blocks) were collected from several pathology departments. Tests (two panels NGS-DNA/RNA expression, FISH, PD-L1, and IHC) were ordered as early as on the day of diagnosis to as late as 18 months following the diagnosis. Cancer cases reviewed were Colo-Rectal (72), Lung (48), Breast (24), Gastric (10), CNS (8), Melanoma (4), Head/Neck (20), GU (16), Sarcomas (8), Thyroid (6), Hepatic (8), Female Genital Tract (7) and Unknown Primary (23).

Results (if a Case Study enter NA)

We evaluated pathology reports, identified blocks, reviewed H&E slides, utilized NCCN guidelines in collaboration with oncologists. Tests were ordered using established billing criteria. Following tests were performed: PD-L1 (190 - 75%), FISH (50 - 20%), and NGS – two simple panel approach (215 - 85%). Using the aforesaid methods, our NGS results were successful in >95%. We were able to identify actionable and prognostic mutations in >80% of tumors.

Conclusion

Our algorithm has been designed considering NCCN guidelines and are updated frequently with new therapeutic targets and actionable mutations. The emphasis is to conserve diagnostic tissue and ensure timely ordering of tests as medically necessary. This can be adopted by pathologists in conjunction with clinical information, pathology reports, and be used as a part of diagnostic workups to reduce delays in treatment, avoid tissue loss, utilize current billing (inpatient/outpatient) practices, pre-authorization and eventually improving patient care as well as reduce overall healthcare costs.
Clinico-Demographic Characteristics of Patients with SARS-CoV-2 Antibodies: A Single Tertiary Center Retrospective Study in Bohol, Philippines
Authors: Salillas A L , Clapis A B , Almocera E G , San Juan A T
Published: November 2022

Introduction/Objective

Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 continues to be a global threat until the present. Most of the infected patients are asymptomatic which can be a challenge in controlling the spread of disease. Antibody detection by chemiluminescence immunoassay (CLIA) is a good complementary test to Real-Time Reverse Transcription – Polymerase Chain Reaction (rRT-PCR) as an indirect marker for disease.

Methods/Case Report

This retrospective study assessed the clinico-demographic characteristics of 184 SARS-CoV-2 IgM and IgG antibody-reactive patients at Gov. Celestino Gallares Memorial Hospital from July 1, 2020 – May 31, 2021.

Results (if a Case Study enter NA)

A total of 184 cases were included in the study out of 4,138 patients tested for anti-SARS-CoV-2 IgM and IgG antibodies by CLIA. Within this population, 97 were outpatients and 87 were inpatients. Majority of patients needing hospitalization were aged ≥60-year-old males (33.33%) and that the probability of being admitted decreases with younger age. Most of the outpatients who were reactive to antibodies against SARS-CoV-2 were frontline workers compared to non-frontline workers and non-workers (27.84% versus 1.03% and 19.59%). Most common comorbidities were hypertension (24.46%), cardiovascular disease (15.76%), diabetes mellitus (11.41%), and chronic kidney disease (11.41%). All five mortalities were diagnosed hypertensive who later developed critical disease.

Conclusion

The continued use of antibody detection by CLIA as a complementary test with rRT-PCR is still recommended not only for better detection of COVID-19 especially in asymptomatic patients but also to observe changes in antibody titer especially in the advent of COVID-19 vaccines.
Leadership Insights From a Pathology Peer-to-Peer Learning Collaborative in Immuno-oncology
Authors: Kim J , Kelly M , Beumer K
Published: November 2022

Introduction/Objective

As the use of immuno-oncology (IO) expands into more cancers, there is a growing need for pathologists and laboratory professionals to demonstrate leadership and guide biomarker testing processes and procedures at their own institutions. To educate and empower its members, the American Society for Clinical Pathology worked in collaboration with Q Synthesis to develop a peer-to-peer learning collaborative. This project was supported by an educational grant from Bristol Myers Squibb.

Methods/Case Report

18 pathologists and laboratory professionals participated in a 10-month program: IO ChangeMakers. Learners completed online modules covering scientific updates on IO biomarker testing. Through small-group, case-based discussions, learners reviewed operational challenges and opportunities to refine biomarker testing. They applied this knowledge to lead IO improvement projects at their own institutions.

Results (if a Case Study enter NA)

The learners identified the following leadership insights around IO biomarker testing: Reflex testing: Develop or refine reflex biomarker testing processes to ensure that tissue is sent for PD-L1 testing at the time of cancer diagnosis. Establish testing criteria with oncologists and implement steps to reduce delays in testing. Interobserver concordance: Evaluate interobserver concordance among pathologists scoring PD-L1, especially in upper GI cancers where the combined positive score (CPS) is used. Scoring upper GI cancers is challenging because of the spatial distribution of PD-L1 within a tumor. Tissue handling: Identify ways to improve tissue processing and handling to preserve small amounts of tissue for biomarker testing. If quantity is not sufficient, prioritize PD-L1 testing and contact the oncologist to order a liquid biopsy. Confusion around different PD-L1 antibody clones: Pathologists and clinicians are often confused about the use of different PD-L1 antibody clones (eg, 22C3, SP142, etc.) and scoring criteria (eg, TPS ≥ 1%, CPS ≥ 10, TC ≥ 25%, etc.). Develop education and reference guides to ensure the right PD-L1 test is ordered based on the type of tumor and intended treatment. Test ordering to reporting: In many cancer centers, biopsy samples are being sent out for PD-L1 testing. Refine electronic test ordering, tracking status, and reporting results.

Conclusion

Pathologists have numerous opportunities to lead improvement efforts in IO biomarker testing. As the use of IO expands into more cancers, there will be a growing need for pathologists to demonstrate leadership in this area.
An Exceedingly Rare Case of Nodular Fasciitis of Tongue in an Infant
Authors: Ansari S , Blessing M
Published: November 2022

Introduction/Objective

Nodular fasciitis is a rapidly growing but benign self-limited myofibroblastic/fibroblastic tumor of unknown etiology. It was first described in the literature by Konwaler in 1955 and can occur in any location. Nodular fasciitis of the tongue is a rare entity in infancy with only one case reported so far. Accurate diagnosis of this entity is crucial to avoid a possible misdiagnosis of malignancy leading to radical resections.

Methods/Case Report

A 6-month old, previously heathy full term male presented to pediatric otolaryngology clinic with a rapidly growing painless mass on the right tongue. The mass was associated with feeding difficulty. There was no history of trauma to the area, no personal and family history of cancer was noted. Computed tomography scan demonstrated a 1.5 x 1.4 x 1.5 cm mass confined to the right anterior undersurface of tongue. Biopsy of the mass showed ulcerated mucosa with an underlying spindle cell lesion composed of reactive-appearing myofibroblasts arranged in a variably fascicular to "tissue-culture" pattern, intermixed with inflammatory cells and scattered extravasated erythrocytes. These morphologic features in conjunction with immunohistochemistry and demonstration of fusion of SRSF3 [serine and arginine rich splicing factor 3] and USP6 [ubiquitin specific peptidase 6] by Targeted next-generation RNA sequencing confirmed the diagnosis of nodular fasciitis. On follow up, spontaneous regression of the mass occurred in 3 months.

Results (if a Case Study enter NA)

NA.

Conclusion

Nodular fasciitis of tongue in infancy is an exceedingly rare entity and this case demonstrates the importance of including this unique entity in the differential diagnosis of a rapidly-growing tongue lesion. Because it can simulate malignancy both clinically and histologically, awareness and familiarity with this benign proliferative lesion is crucial in effective management.
Angiomatoid Fibrous Histiocytoma with EWSR1 Rearrangement in an Unusual Location
Authors: Sinha A K , Arze E
Published: November 2022

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

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

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 > 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

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

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 (>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

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 <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

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

Parkinson’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

This 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

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 < .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

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.
Do you prefer Obamacare or the affordable care act? Simulating an informed public to improve survey measurement
Authors: Li Gabriel Miao , Pasek Josh
Published: November 2022

Researchers have long known that the terms used in questions posed to respondents shape the answers they give. Processes underlying these differences have generally been attributed to respondents’ interpretations of the questions (i.e., what do the terms lead them to focus on) and examined as a framing effect. Yet evidence that people often answer questions they do not fully understand means it is also possible that some of this difference may stem from respondents’ ability to parse what the questions are asking about (i.e., do they comprehend the question). In three online survey experiments, we manipulate wordings for policy attitude questions about the DREAM Act, Trump’s trade disputes, and the Affordable Care Act to assess how both question comprehension and interpretation depend on the wordings selected. We find that reported attitudes vary as a joint function of both processes. By comparing response patterns and simulating individuals’ “informed responses” across wordings, we can disentangle differences due to incomplete understandings (and misunderstandings) from those attributable to partisan interpretations. Evidence that individuals with greater topical knowledge better recognize the similarity of different wordings confirms that some of the wording effect is associated not just with framing, but also with comprehension.
Knowledge, context, and public trust in scientists and scientific research in the United States, 2006–2018
Authors: Yen Steven T , Zampelli Ernest M
Published: November 2022

Past studies establish that general education and scientific knowledge foster more favorable public attitudes toward scientists and scientific research. They also highlight important attitudinal impacts of group identities, in particular, political ideology, party affiliation, religion, and race. The primary purpose of this paper is to determine whether and how these identities might moderate the effects of general education and scientific knowledge on public attitudes toward scientists and scientific research. Main findings include effects of education and scientific knowledge remain significant to varying degrees but are not uniformly generalizable across different group identities; attitudes toward scientists and scientific research have remained fairly stable since 2006; and to love science and hate scientists is not confined to political conservatives.
Hiding in plain sight
Authors: Connell David
Published: November 2022

This paper identifies documented collections of red-sulphur gem casts by Christian Dehn (1696–1770) that have survived unrecognized in three British country houses: Burton Constable in Yorkshire, Burghley House in Lincolnshire, and Mountstuart on the Isle of Bute in Scotland. All three collections resulted from Grand Tours to Italy, where, in Rome, Dehn’s workshop supplied bespoke collections of casts representing engraved gemstones.
O001 Providing feedback and guidance on sleep perceptions using sleep wearables improves insomnia: Findings from the randomised Novel Insomnia Treatment Experiment (“NITE”)
Authors: Spina M , Andrillon T , Quin N , Wiley J , Rajaratnam S , Bei B
Published: November 2022

Study Objectives

Insomnia is diagnosed based on self-reported sleep complaints. There are often differences between objectively recorded and self-reported sleep (sleep-wake state discrepancy), which is well-documented but not well understood. This two-arm, parallel-group, single-blind, superiority randomised controlled trial examined whether monitoring sleep using wearable sleep-measurement devices and providing feedback with support for helpful interpretation of objective sleep data improved insomnia symptoms.

Methods

113 (age M=47.53, SD=14.37, 64.9% female) individuals with insomnia symptoms (Insomnia Severity Index >= 10; ISI) from the community were randomised (permuted block randomization) to receive 5 weeks of (a) Feedback (n=57): feedback about objectively recorded sleep (actigraphy and optional EEG headband) with guidance for data interpretation and ongoing monitoring; (b) No-Feedback (n=56): sleep hygiene. Both conditions received one individual session and two check-in calls. The ISI (primary outcome), PROMIS Sleep Disturbance (SD), Sleep-Related Impairment (SRI), Depression, and Anxiety were assessed at baseline and post-intervention.

Results

103 (91.2%) participants completed the study. Preliminary intention-to-treat multiple regression showed that after controlling for baseline symptoms, the Feedback condition (n=52) had lower ISI (p=.0069, d=0.53) and SD (p=.033, d=0.38), but differences in SRI, Depression and Anxiety were not meaningful (p-values>.37) compared to No-Feedback condition (n=51).

Conclusion

Providing feedback and guidance about objectively recorded sleep reduced insomnia severity and sleep disturbance in individuals with insomnia symptomology. With increasing access to wearable sleep-measurement devices, these findings explore how objective sleep measures, in combination with data interpretation guidance, could supplement and enhance current insomnia treatment.

Australian New Zealand Clinical Trials Registry: ACTRN12619001636145.
O002 A novel, optogenetics based therapy for obstructive sleep apnea
Authors: Knapman F , Cohen M , Kulaga T , Lisowski L , Lovell N , McMullan S , Burke P , Bilston L
Published: November 2022

INTRODUCTION

Many obstructive sleep apnea (OSA) patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel stimulation therapy that sensitises the dilator muscles to light activation (‘optogenetics') and activates the muscles with light during sleep. This study aims to determine feasibility in a rodent model of OSA and identify effective optogenetic constructs.

METHODS

Rats received intramuscular injections of a viral vector encapsulating the opsin ChR2, driven by either a muscle-specific or non-specific promotor. Three weeks post-injection, opsin expression was quantified via confocal imaging. Light-induced tongue muscle activity afforded by the superior promotor was then measured in an acute model of OSA. The superior promotor was then combined with a novel muscle-targeted viral vector and, light-induced airway dilation was measured with ultrasound imaging.

RESULTS

With the muscle-specific promotor, opsin expression in the tongue was 470%(p=0.013, RM-ANOVA) greater, and brainstem expression was abolished. In the animals who received this superior promotor, light stimulation facilitated a 56% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA(p<0.001, linear mixed model). Ultrasound imaging confirmed that light stimulation of the optogenetic construct with a muscle-specific promotor encapsulated in a muscle-targeted viral vector produced airway dilation in the same OSA model.

DISCUSSION

The combined muscle-specific promotor and muscle-specific viral vector resulted in a novel and highly effective method of inducing light-sensitivity in upper airway muscles and facilitating light-induced airway dilation. This study provides proof-of-concept for a non-invasive optogenetics-based OSA therapy.
O003 Longitudinal associations of obstructive sleep apnea and sleep macroarchitecture with future cognitive function in middle-aged and older men from a community-based cohort study
Authors: Parker J , Vakulin A , Melaku Y , Wittert G , Martin S , D'Rozario A , Catcheside P , Lechat B , Teare A , Toson B , Appleton S , Adams R
Published: November 2022

Study objectives

Prospective studies examining associations of obstructive sleep apnea (OSA) and sleep macroarchitecture with future cognitive function remain limited to older participants, many with baseline cognitive impairment, which may be a confounder. This study examined OSA and sleep macroarchitecture predictors of cognitive function (visual attention, processing speed, and executive function) after 8–10 years in community-dwelling middle-aged and older men.

Methods

Of 433 Florey Adelaide Male Ageing Study participants who underwent home-based polysomnography (2010–2011), 157 completed baseline and follow-up cognitive testing. Trail-making tests A (TMT-A) and B (TMT-B) were administered at baseline (2007–2010) and follow-up (2018–2019) examinations. Linear regression analyses examined associations of OSA and sleep macroarchitecture with cognitive task performance adjusted for baseline demographic, biomedical, and behavioural factors and cognitive performance, with sleep macroarchitecture models additionally adjusted for the apnea-hypopnea index (AHI).

Results

At baseline, participants were mean (SD) aged 58.9 (8.9) years with normal cognition. OSA prevalence (AHI ≥10/h) was 52.9%, with severe OSA (AHI ≥30/h) in 9.6%. Following covariate adjustment, higher N1 sleep (%) was associated with better TMT-A performance at follow-up (B= -0.04, 95% CI [-0.06, -0.01], p=0.003), whereas higher mean oxygen saturation was associated with worse TMT-A performance at follow-up (B=0.11, 95% CI [0.02, 0.19], p=0.012).

Conclusions

In this sample of community-dwelling middle-aged and older men, N1 sleep % and mean oxygen saturation showed independent associations with visual attention and processing speed after 8–10 years. Further longitudinal studies remain warranted to determine whether finer-grained sleep microarchitecture parameters identify individuals at risk of future cognitive dysfunction.
O005 Overnight consolidation of spatial navigation memories is impaired in Mild Cognitive Impairment and is associated with loss of sleep spindles and hippocampal subfield volumes
Authors: Haroutonian C , Johnston I , Kao T , McKinnon A , Lam A , Ricciardiello A , D'Rozario A , Naismith S
Published: November 2022

Introduction

Allocentric spatial navigation (SN) is considered a measure for conversion from mild cognitive impairment (MCI) to Alzheimer’s disease. NREM sleep slow waves and spindles, and hippocampal volume (HV) are impaired in MCI, however their relationship with SN overnight memory consolidation (OMC) is unknown. This study aimed to examine: 1) SN OMC in MCI, and, 2) associations between SN OMC and NREM oscillations and HV.

Methods

Cognitively-intact (n=25), non-amnestic MCI (naMCI, n=22) and amnestic-MCI (aMCI, n=10) older adults completed neuropsychological assessment, neuroimaging, overnight routine and high-density EEG polysomnography (hdEEG subset; controls=17, MCI=8). Slow oscillations, slow wave activity, slow and fast spindle density and power were computed. OMC% was calculated by: ([post-sleep error score/pre-sleep error score]*100) from a familiar and novel (allocentric) location. Right CA1, dentate gyrus (DG) and entorhinal cortex were computed using ASHS software.

Results

MCI performed worse on familiar location-OMC% compared to controls (Cohens d= -.67, p= .016). aMCI performed worse on allocentric-OMC% compared to controls (omega2= .09, p= .032). Reduced spindles were associated with worse allocentric-OMC% in aMCI (frontal-slow spindles [rho= -.782 p= .008], parietal-fast spindles [rho= -.576, p= .082]). Using hdEEG, widespread fast spindle and allocentric-OMC% associations were indicated in MCI. Reduced right HV (DG [r= -.453, p= .023], CA1 [r= -.426, p= .068]) was related to worse allocentric-OMC% in MCI.

Discussion

In MCI, SN OMC is impaired, with worse consolidation associated with spindle and right HV loss. Future studies should examine whether SN OMC and spindles capture conversion to Alzheimer’s disease in ‘at-risk’ older adults.