bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Evaluation of RT-LAMP and RT-PCR for Detection of HIV-1 in the Sudan
Authors: Yassin M E
Published: October 2020

Introduction/Objective

Rapid, simple, cost effective, nucleic acid based test for detecting HIV-1 in areas with limited resources is badly needed. Loop-mediated isothermal amplification (LAMP) is a technique that allows the amplification of nucleic acids DNA and RNA with high specificity, sensitivity and rapidity under isothermal conditions. This study was conducted to evaluate RT-LAMP method for HIV-1 detection in comparison with RT-PCR.

Methods

In the present study, ninety EDTA blood samples were studied; seventy samples were collected from HIV-1 infected patients and 20 samples from HIV-1 negative participants. All samples subjected to RT-LAMP and RT-PCR assay targeting HIV-1 p24 gene. Additionally nine positive samples were subjected to viral load measurement using COBAS® TaqMan® HIV-1 Test, version 2.0 (v2.0), and five samples were subjected to direct DNA sequencing of p24 gene phylogenetic analysis.

Results

Of the 70 HIV-1 positive samples, 68 (97.1%) and 61 (87.1%) positive samples were detected using RT-LAMP and RT-PCR respectively. Whereas, all the 20 HIV-1 negative samples were confirmed negative by RT- LAMP, 2 (10%) were positive by RT-PCR. Furthermore, the limit of detection (LOD) for both RT-LAMP and RT-PCR assays was determined to be 130 and 325 copies/ml respectively. The viral loads for the nine samples ranged between 1.92E+4 C/ml – 1.04C6/ml. The sequencing of five samples showed similarity of the Sudanese isolates with the neighboring countries Uganda, Saudi Arabia and also Senegal and even more closely sub-grouped with the Tanzanian counterpart.

Conclusion

RT-LAMP was successfully performed under minimal laboratory conditions demonstrating it as a very useful for use in fields setting and limited resources region.
Prevalence of TEM and SHV Genes in Diarrheaogenic Escherichia Coli Resistant to Beta Lactam Antibiotics in Egyptian Infants
Authors: Soliman Y M , Elsafty A
Published: October 2020

Introduction/Objective

Diarrhea is considered as the fifth leading cause of mortality in children worldwide. It kills 1 of 9 children according to CDC and causes morbidity in 1.7 billion pediatric cases every year. The most pathogenic strain of diarrheaogenic Escherichia coli (DEC) in Egypt is entero-hemorrhagic Escherichia coli (9.38%), while the most prevalent is entero-toxigenic Escherichia coli (15.63%). The aim of this study is to measure the percentage of TEM and SHV genes in diarrheagenic Escherichia coli (DEC) that are resistant to beta lactam antibiotics among infants. Indicating the essence of different antibiotics prescription for treatment in such cases.

Methods

Inclusion criteria included age between 2 months and 12 months. Stool samples from 196 cases of acute diarrhea were collected from inpatient and outpatient pediatric clinic in pediatric department at Zagazig University hospitals in Egypt. In 56 samples, diarrheaogenic Escherichia coli strains were confirmed by multiplex PCR after being biochemically identified. Culture and susceptibility tests were conducted. Resistant DEC strains were tested for the presence of TEM and SHV genes using universal primers for conventional PCR.

Results

By using culture and susceptibility test, 91.1% (51 cases) of isolated DEC strains were found to be resistant to amoxicillin-clavulanic acid. 78.6% (44 cases) resistant to ampicillin-sulbactam. 28.6% (16 cases) resistant to cefotaxime. 28.6% (16 cases) resistant to ceftazidime. 28.6% (16 cases) resistant to cefuroxime. 26.8% (15 cases) resistant to cefoxitin. 26.8% (15 cases) resistant to ceftriaxone. 14.3% (8 cases) resistant to cefepime. 10.7% (6 cases) resistant to aztreonam. 3.5% (2 cases) resistant to imipenem. By using conventional PCR, TEM gene was positive in 28.6% (16 cases) and SHV gene in 7.1% of (4 cases).

Conclusion

TEM gene was detected in 28.6% (16 out of 56 true positive DEC cases) and SHV gene in 7.1% (4 out of 56 true positive DEC cases). Around 28.6% of diarrheaogenic Escherichia coli or about 8% of infantile diarrhea (16 out of 196 total cases) were found to be resistant to different beta lactam antibiotics due to presence of TEM and SHV genes. This reflects the usefulness of other type antibiotics for treatment in such percentage.
Quality Improvement Project Demonstrate that Prolonged Pre-Analytical Time Does Not Lead to False Negative Blood Cultures
Authors: Abada E , Khan M Y , Yerrapotu N , Pardeshi V , Zaiem F , Nguyen H , Raval K , Mitchel R , Fairfax M
Published: October 2020

Introduction/Objective

Bacterial infection is a significant cause of morbidity and mortality. Prompt identification of microorganisms and their susceptibilities to antimicrobial therapies is critical in the management of patients with bloodstream infections. Blood cultures are collected in paired aerobic and anaerobic bottles. However, transport delays might allow some organisms to grow extensively prior to incubation in the blood culture instruments, leading to false-negative culture results. The Detroit Medical Center utilizes the BD Bactec™ instruments for blood culture incubation and the Verigene DNA-based molecular assay for the identification of bacteria and major resistance genes. It has a core microbiology lab that serves 6 hospitals, however, 2 of the hospitals are remotely located.

The aim of this project was to determine if transportation delays led to significant false-negative culture results. If significant false negativity occurred, additional Bactec™ instruments would need to be purchased.

Methods

For one month, we tracked the collection of blood cultures to incubation time at one of the remote hospitals. All blood cultures that remain negative after 164 hours of incubation are routinely discarded. However, in this case, they were subcultured to a Petri plate containing chocolate agar for 30 days. Any organisms that grew were identified by standard lab techniques.

Results

Of the 547 negative culture bottles that were subcultured for possible false-negative results, only 3 (0.5%) bottles grew bacteria. All three were isolated from different patients. The mean time from blood collection to incubation in the instrument was 4-8 hours. The isolates either met criteria for contaminated cultures, or they grew the same pathogen that had previously been identified in the paired bottle from the same culture. The organisms isolated include coagulase negative Staphylococcus species, Staphylococcus pettenkoferi, and Pseudomonas aeruginosa. No unexpected pathogenic organisms were detected.

Conclusion

Our results demonstrate that prolonged pre-analytical time does not lead to false-negative blood culture results. The patients’ diagnoses were not changed, therefore, the purchase of additional blood culture instruments was not necessary. However, transportation time from the patient floors to the main microbiology lab needs to be improved to meet the recommended 2 hours pre-analytical time.
Risk of Urban Zoonosis from Geese Colonized with Antimicrobial Resistant Bacteria
Authors: Leu-Burke G M , Mendoza G , Rue I
Published: October 2020

Introduction/Objective

Zoonotic disease occurs through direct fecal contact with increased exposure resulting in higher infection rates. Antimicrobial resistant colonization occurs in wild birds, however the spread of microbial resistance correlates with increased human activity. Anchorage actively develops urban park environments with pastoral lawns and abundant water sources creating an inviting habitat for human and geese populations. By 2018, Alaska Fish and Game reported a 10-fold increase in migrating Canadian Geese resulting in significant environmental damage, including fecal contamination. At the same time, Anchorage experienced an uptake use of their parks and costal trails for both recreation and homeless camps. To determine potential exposure, sixty-eight geese fecal samples were collected in fourteen urban park locations.

Methods

Fecal samples were incubated in thioglycolate broth at 37oC for 24 hours then cultured to chromogenic screening agar for vancomycin resistant enterococcus (VRE), methicillin resistant Staphylococcus aureus (MRSA), and extended spectrum beta-lactamase (ESBL) enterobacteriaceae. Potential MRSA, VRE or ESBL colonies were further identified using standard biochemical testing with confirmation of antimicrobial resistance by disk diffusion.

Results

Forty percent of all fecal samples collected were colonized with VRE or ESBL producing Escherichia coli with eighty-six percent of collection sites positive for one or more antimicrobial resistant bacterium. Seven percent of fecal samples were positive for both organisms. MRSA was not identified. The highest concentration of antimicrobial resistant bacteria was discovered on the Campbell Creek Trail (83%), which winds alongside Providence Hospital.

Conclusion

Transmission of infectious agents can occur due to environmental exposure, which increases in individuals who are either housing insecure or chronically homeless. Urban green spaces are often sites for unregulated camping by individuals who lack consistent residential housing. Discovery of antimicrobial resistant colonization in geese populating nearly ninety percent of Anchorage’s parks and trails creates a significant public health issue, with the homeless population targeted for poor outcome due to their immunocompromised status.

Continued evaluation is essential to predict infection risk and impact on healthcare delivery, especially in vulnerable populations.
Novel Autoantibodies Biomarkers Panel to Prognosticate the Clinical Outcomes in Advanced-stage NSCLC Patients Receiving Anti PD-1/PD-L1 Immunotherapy
Authors: Tarhoni I , Fhied C , Borgia J A , Fidler M J , Batus M , Bonomi P
Published: October 2020

Introduction/Objective

Lung cancer is the leading cause of cancer-related deaths worldwide, with a majority of cases detected at a non-resectable advanced stage. Current anti PD-1/-L1 therapy has reformed cancer treatment strategies with remarkable clinical outcomes in non-small cell lung cancer (NSCLC). However, the overall response rate is still marginal, demonstrating the need for biomarkers predictive of response. The objective of this study is to develop a serum based panel to prognosticate clinical response in advanced NSCLC patients receiving anti PD-1/-L1 therapy.

Methods

Pooled sera from two response groups (Poor response, n=20, overall survival < 12 months; Good response, n=20, overall survival > 12 months) were evaluated via the HuProt™ Human Proteome Microarray (CDI laboratories, Baltimore, MD) to identify expressed neoantigens. Recombinant proteins representative to identified neoantigens along with their corresponding antibodies, were commercially acquired to develop a robust 13-plex bead- based immunoassay to evaluate the autoantibodies in pretreatment sera from 125 advanced-stage NSCLC patients. Finally, levels of autoantibodies were correlated to clinical outcome, including progression free survival (PFS), overall survival (OS) and grade III adverse events.

Results

Low baseline levels of ZNF695, MCM4, PRMT2, FGD3, GTF2A1, GLUL, CDCA3, ZNF277, GARS, GBP2, UBL7, and ASNA1 autoantibodies were found to be associated with a longer PFS (all p-values < 0.01), whereas increased levels were associated with a poor PFS outcome (0.06, HR=0.66, 95% CI). Low levels of ZNF695, MCM4, PRMT2, FGD3, GARS, GBP2, and UBL7 autoantibodies were associated with favorable OS (all p-values < 0.01).

Conclusion

In this study we demonstrated that serum autoantibodies have great promise to serve as a prognostic tool for immunotherapy response. We successfully developed a high performance multiplexed serum based assay to evaluate autoantibodies in an advanced NSCLC patients receiving anti PD-1/-L1 therapy.
Liquid Biopsy In Stage Iv Non-Small Cell Lung And Prostate Cancers And Prevalence Of Ethnicity And Risk Factors: A Va Medcial Center Experience
Authors: Dalal S , Jhala D
Published: October 2020

Introduction/Objective

The advent of Liquid biopsy (LB) is a milestone in precision oncology. This minimally invasive revolutionary technique analyses circulating tumor DNA and detects signature genomic alterations. Advanced-stage prostate cancers are more common in African Americans both in general and veteran patient population, while general cohort Caucasians are more prone to advanced/metastatic NSCLC. Risk factor for these cancers is smoking; agent orange exposure and its relationship with aggressiveness/ethnicity for veterans is sparse in the literature. We performed a QA study for advanced lung/prostate cancers of veteran patients on LB.

Methods

QA documentation from Foundation One (Cambridge MA, NGS) on LB performed for the regional Veteran Affairs Medical Center (VAMC) from May 2019 to April 2020 were reviewed. The testing was performed on advanced NSCLC/prostate cancer cases with evidence of advanced tumor progression. Data for ethnicity, risk factors, post therapy PSA, Gleason score and genetic mutations noted.

Results

A total of 30 LBs were performed over this time period. Of 30 LBs, 23 were prostate and 7 were lung cancers. 2/30 had unknown ethnic background. 19/28 (67.8%) were of African American origin, 18 of which had advanced prostate cancers. 11/28 were white, of which 3/30 were advanced NSCLC. One patient declined to reveal risk factor exposure, hence 17/29 (58.6%) had smoking, 15/29 (51.7%) had a risk of herbicide, agent orange exposure; and, 10/29 (34.4%) had both risk factor exposures. 6/29 (20.6%) African American veterans had combined risk factors. 9/10 (90%) veterans which had dual exposure presented with either Gleason score of 9 or as metastasis. Post therapy PSA ranged from 0.5 to 1870 ng/ml and did not corelate with the aggressiveness of the cancer or therapy response.

Conclusion

Veteran patient population has slightly higher incidence of ethnic African Americans presenting with advanced NSCLC/prostate cancers compared to general patient cohort. Although incidence of smoking is similar, combined exposure with agent orange, increases the aggressiveness of the disease three-fold. Real-time monitoring of the therapy response and multimodal benefits by LB is of immense help in morbidly ill veterans, compared to post- therapy PSA monitoring or invasive tissue biopsy. Role of LB should also be explored for early screening/triaging the veterans.
Tumor budding (TB) in Colorectal Cancer (CRC), The Best Slide To Count On!
Authors: Aldyab M , Najjar S , Rand J V , Lee H
Published: October 2020

Introduction/Objective

TB is a strong prognosticator in CRC. The international TB consensus conference (ITBCC, 2016) proposed a “hot spot” approach for TB grading. We aimed to identify the characteristics of sections with the highest TB grade utilizing ITBCC’s method.

Methods

Resected CRC cases, excluding treated cases, were retrieved. All tumor sections were examined. Section TB grade(sTB) was noted. The highest sTB was deemed the final TB grade(fTB) of each case. The following categories were assessed: 1) maximum T stage; 2) presence of benign mucosa; 3) presence of a precursor lesion; 4) highest tumor volume; 5) presence of lymphovascular invasion(LVI). In cases where a given category was demonstrated in >1 section, the section with the highest sTB was used. High risk features (HFR) included T4, <12 lymph nodes, positive margin, high grade tumor, perineural invasion and LVI. Pearson’s correlation was performed to compare two groups using a p-value of <0.05.

Results

147 cases were examined. fTB was 1=25.2%, 2=40.8% and 3=34%. 63 tumors involved the left colon and 62 had nodal disease. Of 119 cases with known MMR status 44 were MMR deficient. sTB was uniform across the categories in 101(68.7%) and uneven in 46(32.3%) cases. 12(24.5%) of 49 stage II CRC without HRF showed uneven sTB, with 2 showing 2-tier discrepancy (sTB1, fTB3). sTB was highest for category 3 (94.1%, P<.001), followed by category 2 (91.8%, P<.001), and lowest for category 1 (82.3%, P<.001), which remained true after subgrouping by MMR status and tumor location.

Conclusion

While about 70% of cases showed uniform TB grading across categories, choosing the slide(s) with a precursor lesion or benign mucosa increases the probability of correctly grading TB. Given the management implication, it may be prudent to scan all tumor slides in stage II CRC without HRF to avoid under-grading of TB.
Microarray Findings of Intraplacental Choriocarcinoma: A Report of Four Cases
Authors: Emanuel A , Schandl C , Bruner E
Published: October 2020

Introduction/Objective

Gestational trophoblastic neoplasia (GTN) is a group of poorly understood diseases characterized by an abnormal and overtly malignant proliferation of trophoblastic tissue. Choriocarcinoma, which may also be nongestational in origin, is a particularly invasive and aggressive variant of GTN that is composed of a dimorphic trophoblast population. Many studies have attempted to define choriocarcinoma via various cytogenetic, molecular, and epigenetic means; however, the exact etiology and pathogenesis of this tumor remain unclear, in large part due to its rarity. Estimates of the incidence of choriocarcinoma range from 1 in 24,000 to 1 in 40,000 pregnancies. Intraplacental tumors are even less common with 62 reported cases and an estimated incidence of 1 in 160,000 placentas. In an effort to better understand the pathogenesis of this rare entity, four cases of choriocarcinoma (of which three are intraplacental and one is intrauterine occurring one year following an unremarkable pregnancy) diagnosed at our institution since 2010 were identified for chromosomal microarray.

Methods

DNA was extracted from formalin-fixed, paraffin-embedded blocks of four matched cases: tumor and normal placenta. Single nucleotide polymorphism (SNP) microarray analysis was performed to assess genomic copy number differences between the tumor and the placenta from which it arose (Infinium Global Diversity Array-8 v1.0 BeadChip with an I Scan System; Illumina, San Diego, CA). Analysis of a placenta not affected by tumor was also performed.

Results

Early partial data review demonstrates copy number aberrations in choriocarcinoma arising in placental tissue. Additional interpretation of the data is ongoing.

Conclusion

DNA chromosomal microarray analysis was performed to search for genomic copy number differences in between the tumor and the placenta from which it arose. Recent studies suggest gestational choriocarcinoma oncogenesis may differ from that of other malignancies, but this conclusion is based on a low number of recurrent DNA mutations. SNP microarray analysis may further refine the current understanding of the oncogenesis of gestational choriocarcinoma.
Large B-Cell Lymphoma With IRF4 Rearrangement Involving Lung
Authors: Li C , Teruya B , Bhavana D , Althof P
Published: October 2020

Introduction/Objective

Large B-cell lymphoma (LBCL) with IRF4 rearrangement is a new entity described in the 2017 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. It is characterized by monotonous proliferation of medium to large sized cells with strong expression of IRF4/MUM1 and IRF4 rearrangement. It accounts for only 0.05% of all diffuse LBCLs and affects predominantly children and young adults with a median age of 12 years. The reported sites of disease include lymph nodes of head and neck, Waldeyer ring and gastrointestinal tract. Here, we report a case of LBCL in a 74-year-old female patient that presented with a lung nodule.

Methods

H&E staining, Immunohistochemistry and Fluorescence in-situ hybridization (FISH) were used to characterize this lesion.

Results

H&E stained sections of lung nodule biopsy showed diffuse proliferation of medium- to large-sized tumor cells. Immunohistochemistry showed tumor cells are positive for CD10, BCL6 and IRF4/MUM1. FISH showed rearrangement of IRF4, but is negative for MYC, BCL2 and BCL6 translocations.

Conclusion

To the best of our knowledge, this is the first case of LBCL with IRF4 rearrangement reported involving the lung in an old patient. Cases that show coexpression of CD10, BCL6 and IRF4/MUM1 should be tested for IRF4 rearrangement despite patient’s age and the site of disease. Generally, prognosis of this disease is favorable following chemotherapy with or without radiation. However, data are lacking regarding older patients and diseases involving atypical sites due to very limited number of cases reported earlier.
Epstein - Barr Virus (EBV) Associated B-Cell Lymphoma: An Unusual Involvement Of The Heart And Kidney In An HIV Positive Patient With Concurrent Cytomegalovirus (CMV) Pneumonia And Pneumocystis Jirovecii Pneumonia (PCP)
Authors: Dehghani A , Alshal M , Alawad M , Zuretti A , Shao C
Published: October 2020

Introduction/Objective

We report a 68-year-old man with Human immunodeficiency virus (HIV) infection and significant weight loss during the past two years who presented with dyspnea. He was not receiving any treatment for HIV infection, and his viral load and CD4 count were 178000 copies/ml and 8 cells/mm3, respectively. The radiologic examination was concerning for Pneumocystis jirovecii pneumonia. The Bronchoalveolar lavage was positive for Pneumocystis jirovecii. The patient expired despite the comprehensive treatment, and the autopsy was requested.

Methods

The autopsy showed heavy lungs with diffuse consolidation and white discoloration involving all lobes. The left ventricular wall and right kidney cortex showed foci of white discoloration measuring 1 and 0.8 cm, respectively.

Results

The microscopic examination of lungs showed concurrent CMV pneumonia, and PCP confirmed by immunohistochemical staining for CMV and GMS special stain. The histologic evaluation of the heart and the right kidney and immunohistochemical staining for CD20 and CD3 in addition to in situ hybridization (ISH) for EBER revealed infiltrative malignant cells, which were positive for CD20 and EBER and negative for CD3. The EBV associated B-cell lymphoma involving the heart, and the right kidney was diagnosed

Conclusion

EBV is involved in human lymphomagenesis, particularly in HIV patients. There is a tendency for the lymphoma to involve the extranodal sites, including the CNS, gastrointestinal tract, liver, and bone marrow. However, the involvement of the heart and kidneys occurs very rarely. The autopsy findings of Lung co-infection with PCP and CMV and EBV associated lymphoma involving atypical locations is a rare and unique combination of AIDS-defining illnesses in this patient.
Exophiala Dermatitidis Isolated From Blood In Patient With Steroid Use
Authors: Yurtsever N , Dougherty P , Condon S , Orsini R , Berman M , Berry G J , Duong S
Published: October 2020

Casestudy

Exophiala dermatitidis is a dematiaceous mold that is associated with subcutaneous, central nervous system and pulmonary infections; osteomyelitis; and disseminated disease. Isolation of E. dermatitidis from patients with mild symptoms may be difficult to interpret whether is a contaminant or asymptomatic patient with serious infection. However, it is important to diagnose asymptomatic patients early in the stage because of up to 25% mortality rate.

Results

77-year-old male with history of chronic obstructive pulmonary disease presented to his pulmonologist with cough. He was started on azithromycin and steroids. His cough worsened and he was transitioned to levofloxacin with continuation of steroid treatment. In addition, he developed fatigue, weakness, poor appetite, chills and nights sweat along with some urinary complaints. His chest X-ray showed infiltrates and he was diagnosed with left lower lung pneumonia and urinary tract infection and was treated with doxycycline and ciprofloxacin. Blood cultures were drawn. Additional past medical history was not significant.

Blood culture became positive on day 4 of incubation. Gram stain showed yeast-like cells, but the blood culture multiplex PCR was negative. Serum cryptococcus antigen was negative. Three days later, a dark shiny olive-colored colony with dark obverse side was isolated. It grew at 42 C. Microscopic examination revealed hyaline and pigmented hyphae with brown conidia. It was identified as Exophiala dermatitidis and confirmed by the state public health laboratory. Blood cultures drawn after hospital admission remained negative. Patient’s symptoms improved with antibiotic treatment. Therefore the clinicians believed that the E. dermatitidis was a probable contaminant and patient was discharged with follow-up. During the follow-up process he developed respiratory infection with Coronavirus (HKU1, NL63, 229E, OC43). Follow-up continues.

Conclusion

Blood cultures are not sensitive for mold infection especially for an uncommon contaminant like E. dermatitidis, it may be difficult to decide whether a positive culture is a real result or not. Fungal antigen tests such as beta-D-glucan test may be helpful in distinguishing between invasive infection and contaminant. Additionally, we believe that in our case, steroid use could have caused a temporary immunosuppression and led to Exophiala dermatitidis infection.
Discontinuous Involvement of Spermatic Cord Soft Tissue in Testicular Germ Cell Tumors: A Multi-Institution Experience
Authors: Ali A , So J , Khani F , Kvetoslava M , Miyamoto H , Osunkoya A , Rodriguez Pena M , Magi-Galluzzi C , Raspollini M R , Scarfo F , Zynger D L
Published: October 2020

Introduction/Objective

In the 8th Edition AJCC Cancer Staging Manual, discontinuous involvement of spermatic cord soft tissue (DISC) by testicular germ cell tumors (GCT) is regarded as metastatic deposit (pM1), placing the patient in clinical prognostic stage group (CPSG) III. We conducted a multi-institution study to corroborate or refute the current recommendations. Methods: Thirty-eight cases of GCT with spermatic cord involvement were collected from 13 institutions in Europe, Phillipines and America. Clinical and pathologic data was obtained.

Results

Tumors included 28 (73%) non-seminomatous and 10 (26%) seminomatous GCTs. Mean testicular tumor size was 6.6 cm (range 1.3-18). After review by an uropathologist, cases were classified as cord LVI [T2] (n=3), continuous cord involvement (CCI) [T3] (n=13), and DISC (n=22). Mean cord tumor size for DISC was 0.9 cm (range 0.1-4.5).

CPSG was available for 33 and follow-up (FU) for22 patients with a mean length of FU of 38 months (range 2-144). Seven (39%) DISC patients were CPSG II (regional LN metastases), and 11 (61%) CPSG III (distant metastases). On FU, 5 (45%) DISC patients had no evidence of disease (NED); 6 (55%) were alive with disease (AWD). Three (25%)

CCI patients were CPSG I (local disease), 6 (50%) CPSG II, and 3 (25%) CPSG III. On FU, 6 (60%) CCI patients were NED, 4 (40%) AWD. Cord LVI patients were one in each CPSG. One cord LVI patient was NED, the others were lost at FU. All DISC (100%) patients with available CPSG had advanced disease (CPSG II or III), compared to 75% of CCI, and 67% of cord LVI patients.

Conclusion

Although it did not reach statistical significance (p=0.054; Fisher’s exact test), DISC patients were more likely to have CPSG II and III compared to CCI patients. Our findings suggest a worse behavior in patients with DISC, supporting a higher pathologic stage than CCI.
Reproducibility of Histologic Assessment in Porto-sinusoidal Vascular Disease Liver Biopsies
Authors: Kmeid M , Lee H , Lagana S M , Lin J , Affolter K , Choi W , Liu X , Choi K E , Westerhoff M , Yang Z , Fiel M
Published: October 2020

Introduction/Objective

Variable histologic findings that may be seen in porto-sinusoidal vascular disease (PSVD) liver biopsies are subject to high interobserver variability, requiring correlation with clinical history of portal hypertension (traditionally interpreted as non-cirrhotic portal hypertension NCPH). We investigated which histologic features are reproducible in PSVD biopsies.

Methods

Archived liver biopsies (n=38) from patients with NCPH (n=14) and without NCPH (n=21) were reviewed. Static H&E images of lobules (L, x100, NCPH=27, non-NCPH=23) and portal tracts (P, x200, NCPH=23, non- NCPH=27) were distributed among 9 gastrointestinal pathologists blinded to clinical history. Each pathologist answered multiple choice questions based on the presence (Q2) or absence (Q1) of portal hypertension clinically. The choice selected by 6 pathologists or more was considered consensus answer for the image. The interpretation of the image was considered reproducible when consensus was reached on both Q1 and Q2.

Results

The interpretations of 27 (54%; 17L, 10P) images from NCPH and 21 (42%; 10L, 11P) from non-NCPH were reproducible. In NCPH, the interpretations of normal (n=10, 4L, 6P), sinusoidal dilatation (n=7), and increased parenchymal draining vessels (n=3) were reproducible, while there was no consensus on the diagnoses of nodular regeneration and increased number of portal vessels. In non-NCPH, the interpretations of normal (n=8, 2L, 6P), sinusoidal dilatation (n=6), and paraportal shunting vessel(s) (n=4) were reproducible, whereas no consensus was reached on the diagnoses of nodular regeneration, incomplete fibrous septa, and increased number of portal vessels.

Conclusion

Histologic assessment of normal L and P as well as sinusoidal dilatation appears to be reproducible independent of clinical history. The findings of increased parenchymal draining vessels in NCPH group and paraportal shunting vessels in non-NCPH group may be consistently diagnosed to a certain extent. The assessment for nodular regeneration without reticulin stain, incomplete fibrous septa, or increased number of portal vessels appears to be unreliable.
Passive Transfer Of Allo-Antibodies Following Rhig Administration Given For Rh-Mismatched Platelets Prophylaxis
Authors: Sostin N , Hendrickson J , Balbuena-Merle R , Tormey C
Published: October 2020

Introduction/Objective

Human platelets (PLTs) do not express any Rh system antigens; however, PLT concentrates can be contaminated with small amounts of red blood cells (RBCs), which may induce alloimmunization when transfused to Rh(D)-negative individuals. RhIG has been utilized to prevent Rh(D) alloantibody development following transfusion of Rh mismatched PLTs.

RhIG is manufactured using pooled plasma of healthy Rh(D)-negative donors, with the most common Rh haplotype being ce; treated subjects are exposed to Rh (D)-positive RBCs, with the most common Rh haplotype of donors being DCe. In this report, we detail our experiences with recipients of Rh mismatched apheresis PLTs who were noted to develop anti-D + anti-C post-RhIG administration.

Methods

Retrospective review was conducted of all Rh mismatched PLTs between December, 2018 and May, 2019 at our facility (Yale-New Haven Hospital, New Haven, CT). Inclusion in the study required: Rh(D)-negative donor receiving one or more Rh(D)-positive apheresis PLTs, Receiving RhIG, >1 antibody screen following RhIG administration demonstrating antibodies other than anti-D

Results

Our retrospective review identified 8 unique recipients of Rh mismatched apheresis PLTs who acquired anti- C, in addition to the expected anti-D, following administration of RhIG. The product (Rhophylac) was administered in all cases intravenously at a dose of 1500 IU (300 mcg) within 72 hours following Rh mismatched PLTs. In all patients, routine screening following RhIG simultaneously detected anti-D and anti-C 1-3 days after administration of Rh mismatched PLTs/RhIG, the antibody screen remained positive for a range of 27-167 days for both antibodies.

Conclusion

Based on this case series, which represented entirely men and older women, and coupled with emerging evidence about the extremely low likelihood of D-alloimmunization following Rh mismatched apheresis PLTs,2,3,6 we have changed our practice, limiting immunoprophylaxis for Rh mismatched platelets exclusively to women of reproductive age.

The blood bank and apheresis communities should be aware that passive transfer of non-D antibodies is possible when RhIG is dosed and could account for newly-detected non-D alloimmunization events. This phenomenon is another compelling reason to limit RhIG exposure to cases where it is only absolutely clinically necessary.7
Trends in Acute Appendicitis Among Pregnant Women, the Risk for Cardiac Arrest and Maternal-fetal Mortality
Authors: Oluwatoba A D
Published: October 2020

Introduction/Objective

Acute appendicitis is the most common extra-uterine surgical emergency requiring immediate surgical intervention during pregnancy. However, risks for mortality and near-miss conditions (e.g., cardiac arrest) remain poorly understood. This study was conducted to determine the temporary changes in rate of acute appendicitis in pregnant women over time compared to their non-pregnant peers in relation to cardiac arrest, maternal mortality and stillbirth.

Methods

My analysis covered the period from January 1, 2002 through December 31, 2014 using cross-sectional data from the Nationwide Inpatient Sample (NIS). The NIS, made available by the Healthcare Cost and Utilization Project (HCUP), currently constitutes the largest all-payer, publicly available inpatient database in the US.

Results

I identified a total of 64,799 cases of acute appendicitis during pregnancy, yielding a prevalence of 11/10,000. There was a significant increase in the prevalence of appendicitis over time. While the risk for cardiac arrest was not elevated, that of maternal mortality was five times (OR = 5.16, 95% CI = 2.57-10.38) as high among mothers diagnosed with appendicitis during pregnancy. The combined risk for fetal loss or stillbirth was twice as high among individuals diagnosed with appendicitis (OR = 2.05, 95% CI = 1.85-2.28).

Conclusion

Appendicitis during pregnancy increases the risk for cardiac arrest, and maternal mortality by about five- fold. We also found that the risk for fetal loss or stillbirth was doubled.
Novel Approach to Disseminate Educational Materials Using Technology
Authors: Kitchen K D , Moore M , Nance S , Mair D
Published: October 2020

Introduction/Objective

Our facility initiated a modification to an existing on-site Specialist in Blood Bank Technology and Transfusion Medicine (SBB) Program, in July 2018. The modification changed a local program to a hybrid on-site and distance learning program. The curriculum was established using a dynamic repository of recorded presentations (video/audio recordings and PowerPoint/audio presentations) as part of the self-paced, didactic educational portion of the program. The challenge was to provide a primary method for accessing the didactic portion of the program that would be flexible and available through a variety of venues. Our SBB Program was awarded $2,500 by the ASCP Foundation Laboratory Science Program Director Educational Grant in 2018 in support of modifying the current SBB program to a modified, hybrid on-site plus on-line program.

Methods

The grant provided the necessary seed money to purchase iPads, seen as the method for delivery of the educational materials. The Apple iPad® (Apple, Inc., One Apple Park Way, Cupertino, CA 95014) was purchased to enable student access to on-line lecture materials through the company’s secure web portal. The SBB Program Director prepared the iPad for the students to ensure the on-line links were usable. The Directors demonstrated the use of the iPad to the students for accessing educational content during the orientation week.

Results

NA-Educational Practice Abstract

Conclusion

The acquisition of iPads offered the flexibility needed by the students to access learner materials throughout their day where Wi-Fi is available (at work, home, café, etc.) without being dependent upon work or home computers. Further, use of the iPads has opened the opportunity to access assignments, download required texts where electronically available, and access the company learner management system for completing quizzes related to the student assignments.
Evaluating The Effectiveness Of Donor Recruitment Strategies Towards Improving Availability Of Blood Product In Nigerian Tertiary Health Institution
Authors: Bolarinwa A , Olatinwo A T
Published: October 2020

Introduction/Objective

Over the years, many strategies has been put in place to improve blood donations and overcome socio-cultural myths and fear that has held groups of people from voluntary blood donation in Nigeria and other subsahara africa countries. Among these are adequate education, approaches through religious group leaders, non-monetary incentives like giving them special awards during world blood donor day. The aim of this study is to evaluate the effectiveness and adequacy of our blood donor recruitment and retention strategies in improving availability of blood product in our institution

Methods

For this cross sectional retrospective study, Data including blood donation and break down of pattern of donations, request for blood products, monthly units of blood issued gotten from our 5 year Transfusion services records were searched, same entered into Microsoft Excel and the were analysed

Results

Our voluntary non-renumerated blood donation steadily increased from 4.55 in 2015 to 33.3% in 2019, this represent a five fold increase in our voluntary donor recruitment within the period under review. However overall blood donation rate remained steady at approximately 12000 units per annum over this period of time. There is an increase in request rate, on the average the rate of blood request was 1214 units per month in 2015, but in 2018 this has increased to an average of 1738 units per month and by 2019 average rate of request was 2300 units per month. Out of this huge request only 67.9% of them was met, implying a huge deficit in our blood availability despite increasing pool of voluntary blood donor.

Conclusion

Findings in this study revealed a steady increase in the pool of voluntary blood donor which did not reflect in our overall blood availability. This might be due to concurrent decrease in our family replacement donor. This finding also suggests that even though our current strategy used in donor recruitment and retention might seems effective, they are still not adequat, as there is no commensurate rise in blood donation to match the progressive increase in blood demand. In the face of this inadequacy it might be expedient to also audit the blood ordering pattern in our centre in order to reduce wastage while we continue to work towards increasing the voluntary blood donor base.
Transcription factor Sp1 is upregulated by PKCι to drive the expression of YAP1 during pancreatic carcinogenesis
Authors: Yang Jinhe , Wang Junli , Zhang Hongmei , Li Changlong , Chen Changyan , Zhu Tongbo
Published: October 2020

Recently, we identified that the atypical protein kinase C isoform ι (PKCι) enhances the expression of Yes-associated protein 1 (YAP1) to promote the tumorigenesis of pancreatic adenocarcinoma harboring mutant KRAS (mu-KRAS). To advance our understanding about underlying mechanisms, we analyze the transcription of YAP1 in pancreatic cancer cells and reveal that transcription factor specificity protein 1 (Sp1) is upregulated by PKCι and subsequently binds to multiple sites in YAP1 promoter to drive the transactivation of YAP1 in pancreatic cancer cells carrying mu-KRAS. The bioinformatics analysis further substantiates that the expression of PKCι, Sp1 and YAP1 is correlated and associated with the stages and prognosis of pancreatic tumors. Moreover, our apoptotic detection data demonstrate that combination of PKCι and Sp1 inhibitors at subtoxic doses displays synergistic effects on inducing apoptosis and reversing the immunosuppression of pancreatic cancer cells, establishing the combination of PKCι and Sp1 inhibitors as a promising novel therapeutic approach, or an adjuvant strategy to potentiate the antitumor effects of other immunotherapeutic agents in pancreatic cancer treatment.
Sustained Activation of PV+ Interneurons in Core Auditory Cortex Enables Robust Divisive Gain Control for Complex and Naturalistic Stimuli
Authors: Gothner Tina , Gonçalves Pedro J , Sahani Maneesh , Linden Jennifer F , Hildebrandt K Jannis
Published: October 2020

Sensory cortices must flexibly adapt their operations to internal states and external requirements. Sustained modulation of activity levels in different inhibitory interneuron populations may provide network-level mechanisms for adjustment of sensory cortical processing on behaviorally relevant timescales. However, understanding of the computational roles of inhibitory interneuron modulation has mostly been restricted to effects at short timescales, through the use of phasic optogenetic activation and transient stimuli. Here, we investigated how modulation of inhibitory interneurons affects cortical computation on longer timescales, by using sustained, network-wide optogenetic activation of parvalbumin-positive interneurons (the largest class of cortical inhibitory interneurons) to study modulation of auditory cortical responses to prolonged and naturalistic as well as transient stimuli. We found highly conserved spectral and temporal tuning in auditory cortical neurons, despite a profound reduction in overall network activity. This reduction was predominantly divisive, and consistent across simple, complex, and naturalistic stimuli. A recurrent network model with power-law input–output functions replicated our results. We conclude that modulation of parvalbumin-positive interneurons on timescales typical of sustained neuromodulation may provide a means for robust divisive gain control conserving stimulus representations.
Parasite Circulating Cell-free DNA in the Blood of Alveolar Echinococcosis Patients as a Diagnostic and Treatment-Status Indicator
Authors: Fan Haining , Gai Wei , Zhang Lingqiang , Ma Yanyan , Wang Haijiu , Chen Xiaoping , Dong Jiahong , Zhang Yan , Bao Haihua , Zhou Ying , Ren Li , Cairang Yangdan , Hou Lizhao , Ren Bin , Wang Zhan , Wang Zhixin , Song Cuidan
Published: October 2020

Background

Alveolar echinococcosis (AE) is a serious parasitic disease caused by the larvae of Echinococcus multilocularis. It is the less common but substantially more deadly of the 2 major echinococcosis diseases that can occur globally but are concentrated in central Asia.

Methods

We analyzed parasite circulating cell-free DNA (cfDNA) in 149 plasma samples using a DNA sequencing–based method (105 AE, 16 cystic echinococcosis, 4 liver cancer, 4 gallstones, and 20 healthy volunteers). After identifying the Echinococcus-specific cfDNA (Em-cfDNA) sequences in the samples, we determined whether Em-cfDNA could be used for AE diagnosis and as a potential indicator of the effectiveness of surgical treatment. We also examined potential associations between Em-cfDNA levels and clinical features of AE patients.

Results

Our work demonstrates that varying reads of Em-cfDNA were detectable in the plasma of 100% of preoperative AE patients and that all of the non-AE patients and healthy volunteers were negative. Em-cfDNA has good sensitivity and specificity for the diagnosis of AE. We also found that Em-cfDNA levels apparently have reference value for evaluating the therapeutic efficacy of surgery interventions for AE lesions. Finally, our analysis revealed that Em-cfDNA levels can reflect meaningful information about lesion size in preoperative AE patients.

Conclusions

We demonstrate that sequencing-based monitoring of Em-cfDNA can be used in the clinic as a powerful diagnostic indicator for AE. We also note that there is a strong potential for use of this liquid-biopsy method to monitor ongoing disease status in postintervention AE patients.
Knee Muscle Force Estimating Model Using Machine Learning Approach
Authors: Sohane Anurag , Agarwal Ravinder
Published: October 2020

Various simulation type tools and conventional algorithms are being used to determine knee muscle forces of human during dynamic movement. These all may be good for clinical uses, but have some drawbacks, such as higher computational times, muscle redundancy and less cost-effective solution. Recently, there has been an interest to develop supervised learning-based prediction model for the computationally demanding process. The present research work is used to develop a cost-effective and efficient machine learning (ML) based models to predict knee muscle force for clinical interventions for the given input parameter like height, mass and angle. A dataset of 500 human musculoskeletal, have been trained and tested using four different ML models to predict knee muscle force. This dataset has obtained from anybody modeling software using AnyPyTools, where human musculoskeletal has been utilized to perform squatting movement during inverse dynamic analysis. The result based on the datasets predicts that the random forest ML model outperforms than the other selected models: neural network, generalized linear model, decision tree in terms of mean square error (MSE), coefficient of determination (R2), and Correlation (r). The MSE of predicted vs actual muscle forces obtained from the random forest model for Biceps Femoris, Rectus Femoris, Vastus Medialis, Vastus Lateralis are 19.92, 9.06, 5.97, 5.46, Correlation are 0.94, 0.92, 0.92, 0.94 and R2 are 0.88, 0.84, 0.84 and 0.89 for the test dataset, respectively.
Institutions and literacy rates: the legacy of Napoleonic reforms in Italy
Authors: POSTIGLIOLA M , ROTA M
Published: October 2020

The provincial gap in human capital at the time of Italy’s unification is a plausible explanation for the North–South divide of the following decades. We show that the roots of the literacy gap that existed in 1861 can be traced back to Napoleonic educational reforms enacted between 1801 and 1814. We use exogenous variation in provincial distance to Paris to quantify effects, linking the duration of Napoleonic control to human capital. If the south had experienced the same Napoleonic impact as the north, southern literacy rates would have been up to 70 percent higher than they were in 1861.
Using Mixture Modeling to Construct Subgroups of Cognitive Aging in the Wisconsin Longitudinal Study
Authors: Moorman Sara M , Greenfield Emily A , Carr Kyle
Published: October 2020

Objectives

Longitudinal surveys of older adults increasingly incorporate assessments of cognitive performance. However, very few studies have used mixture modeling techniques to describe cognitive aging, identifying subgroups of people who display similar patterns of performance across discrete cognitive functions. We employ this approach to advance empirical evidence concerning interindividual variability and intraindividual change in patterns of cognitive aging.

Method

We drew upon data from 3,713 participants in the Wisconsin Longitudinal Study (WLS). We used latent class analysis to generate subgroups of cognitive aging based on assessments of verbal fluency and episodic memory at ages 65 and 72. We also employed latent transition analysis to identify how individual participants moved between subgroups over the 7-year period.

Results

There were 4 subgroups at each point in time. Approximately 3 quarters of the sample demonstrated continuity in the qualitative type of profile between ages 65 and 72, with 17.9% of the sample in a profile with sustained overall low performance at both ages 65 and 72. An additional 18.7% of participants made subgroup transitions indicating marked decline in episodic memory.

Discussion

Results demonstrate the utility of using mixture modeling to identify qualitatively and quantitatively distinct subgroups of cognitive aging among older adults. We discuss the implications of these results for the continued use of population health data to advance research on cognitive aging.