The Georgetown University's Cancer Legal Assistance and Well-being Project launched in 2020 as a medical-legal partnership that works with health care providers at a Washington, D.C. safety-net ...hospital to treat the health-harming legal needs of historically and intentionally marginalized patients with cancer.
Introduction The ThinPrep Imaging System (Imager, Cytyc Corporation, Hologic, Inc.) for cervical cytology is commonly employed in laboratories. It uses a proprietary stain that allows measurement of ...cellular DNA content. We evaluated the initial effect of implementing the Imager stain on atypical squamous cells of undetermined significance (ASCUS) and squamous intraepithelial lesion (SIL) diagnoses, and high-risk human papillomavirus (hrHPV) rates. Materials and methods This study included 264 Imager-stained ASCUS cases from the first 5 months of Imager use. All cases were analyzed for hrHPV using Hybrid Capture II assay (Digene Corporation, Qiagen). ASCUS/SIL ratios and hrHPV-positive rates were calculated for the laboratory overall and for 3 cytopathologists. ASCUS/SIL ratios were also calculated for 5 cytotechnologists. These metrics were compared with those from the equivalent 5-month period 1 year prior. Slide review of all Imager-stained ASCUS cases was performed to assess for potential factors involved in ASCUS misinterpretation. Results The proportion of ASCUS diagnoses increased after Imager stain introduction, from 1.79% to 3.14% ( P < 0.001). The proportion of SIL diagnoses also increased, from 0.69% to 1.1% ( P < 0.001). However, the hrHPV-positive rate declined from 61.3% to 53.6% ( P = 0.104). Review of Imager-stained ASCUS cases showed marked nuclear hyperchromasia, particularly in benign squamous metaplastic cells. Conclusions Imager stain implementation, required for the ThinPrep Imaging System, led to significant increase in ASCUS rates while the hrHPV-positive rate declined. Cytopathologists will need to recalibrate thresholds for an ASCUS diagnosis when interpreting Imager-stained slides. In particular, nuclear hyperchromasia in squamous metaplastic cells should not be overdiagnosed as ASCUS.
Injuries related to participation in golf are becoming more common given the increasing popularity of the sport itself. Golf is considered to be an activity associated with a moderate risk for sports ...injuries. Golf injuries are usually attributable to overuse or traumatic mechanisms and primarily occur at the elbow, wrist, shoulder, and lumbar spine. None of these injuries are unique to golf, but each of these injuries represent the most common injuries associated with golfing. This article reviews a wide range of injuries that are encountered in golfers and describes the magnetic resonance imaging findings of each of these injuries.
In order to manage the COVID-19 systemic inflammatory response, it is important to identify clinicopathological characteristics across multiple cohorts. The aim of the present study was to compare ...the 4C mortality score, other measures of the systemic inflammatory response and clinicopathological characteristics in two consecutive cohorts of patients on admission with COVID-19. Electronic patient records for 2 consecutive cohorts of patients admitted to two urban teaching hospitals with COVID-19 during two 7-week periods of the COVID-19 pandemic in Glasgow, U.K. (cohort 1: 17/3/2020-1/5/2020) and (cohort 2: 18/5/2020-6/7/2020) were examined for routine clinical, laboratory and clinical outcome data. Compared with cohort 1, cohort 2 were older (p<0.001), more likely to be female (p<0.05) and have less independent living circumstances (p<0.001). More patients in cohort 2 were PCR positive, CXR negative (both p<0.001) and had low serum albumin concentrations (p70 (p<0.05), male gender (p<0.05), COPD (p<0.05), cognitive impairment (p<0.05), frailty (p150mg/L (p<0.05), albumin <30 g/L (p<0.01), elevated perioperative Glasgow Prognostic Score (p<0.05), elevated neutrophil-lymphocyte ratio (p<0.001), low haematocrit (p<0.01), elevated PT (p<0.05), sodium <133 mmol/L (p<0.01) elevated urea (p<0.001), creatinine (p<0.001), glucose (p<0.05) and lactate (p<0.001) and the 4C score (p3) (OR 11.3, 95% C.I. 2.3-96.7, p<0.05), low albumin (<30g/L) (OR 2.5, 95% C.I. 1.0-6.2, p<0.05), high NLR (greater than or equal to3) (OR 2.2, 95% C.I. 1.5-4.5, p<0.05) and the 4C score (OR 2.4, 95% C.I. 1.0-5.6, p<0.05) remained independently associated with 30-day mortality. In addition to the 4C mortality score, frailty score and a low albumin were strongly independently associated with 30-day mortality in two consecutive cohorts of patients admitted to hospital with COVID-19.
1. Utilizing a case-based approach, as well as data, participants will self-report the characteristics and methods used to perform monthly multi-specialty and multi- institutional rounds in order to ...meet the need of outpatient individuals receiving cancer treatment.
2. Drawing from our model, participants will explore and report ways to identify and engage local stakeholders and to replicate similar programs at their institutions to best service palliative care patients in their communities.
We will present a unique model for collaborating care for patients with advanced cancer across institutions and teams, to break through the silos of outpatient care. In addition to describing the Supportive Care Rounds through data and case examples, we will discuss ways to replicate the rounds in other medical centers.Abstract: Patients living with cancer often bear the burdens of physical, emotional, and spiritual suffering as well as financial, functional, nutritional, social, legal, and systematic challenges. The different teams that address these multiple dimensions of suffering typically operate within silos, with limited communication and collaboration. At MedStar Washington Hospital Center (Washington, DC) our outpatient palliative care (PC) team recognized these gaps in care for patients receiving treatment at the Georgetown Cancer Institute at MedStar Washington Hospital Center, a population that is highly diverse – 60% self-identify as Black/African American, 31% self-identify as White/Caucasian and 6.2% self-identify as Other. We created Supportive Care Rounds, a unique program bringing together PC, oncology social work, physical medicine and rehabilitation, physical therapy, nutritional support and pain psychology from the MedStar Washington Hospital Center, the Georgetown Cancer Institute and MedStar National Rehabilitation Hospital. We meet monthly to discuss patients referred by the participating teams, to identify patient needs, barriers to meeting those needs and specific interventions, aligning our respective institutions to deliver more comprehensive care. This collaboration is particularly important for our patients who are under-resourced and patients who have encountered roadblocks of bias and neglect in the medical system.
This session will emphasize gaps in care for outpatients with cancer and an overview of how our unique program identifies and fills those gaps. We will provide data describing the patients, diagnoses, and interventions as well as examples of complex cases in which multi-dimensional suffering was addressed. The session will also encourage participants to explore supportive care resources in their own communities and consider pathways to comprehensive supportive care program development.
Interdisciplinary Teamwork / Professionalism / Models of Palliative Care Delivery
Background It is unclear whether single nucleotide polymorphisms (SNPs) in the gene for IL-13 ( IL13 ) influence asthma severity and/or asthma morbidity. Objectives To examine the relation between ...IL13 SNPs and asthma-related phenotypes in 2 independent populations. Methods We used family-based methods to test for association between SNPs in IL13 and asthma-related phenotypes in Costa Rican children with asthma. We attempted to reproduce significant findings in white (non-Hispanic) children with asthma in the Childhood Asthma Management Program (CAMP). Results In Costa Rica and in CAMP, the A allele (Gln) of IL13 coding SNP (rs20541) was significantly associated with increased eosinophil count ( P < .011 in both studies) and increased serum total IgE ( P < .054 in both studies). The T allele of IL13 promoter SNP (rs1800925) was inversely associated with asthma exacerbations in Costa Rica ( P = .069). Although this SNP (rs1800925) was not associated with asthma exacerbations among all white children in CAMP, it was associated with increased risk of asthma exacerbations among children on inhaled corticosteroids ( P = .02). Conclusion Polymorphisms in IL13 were significantly associated with serum total IgE and eosinophil count in 2 populations. IL13 polymorphisms may also be associated with asthma exacerbations, and this effect may be dependent on medication use. Our study is the first to report a potential negative interaction between a genetic polymorphism and response to inhaled corticosteroids. Clinical implications Polymorphisms in IL13 are associated with serum total IgE and eosinophil count and may be associated with asthma exacerbations.
The effect of donor (D)–acceptor (A) alignment on the materials electronic structure was probed for the first time using novel purely organic porous crystalline materials with covalently bound two‐ ...and three‐dimensional acceptors. The first studies towards estimation of charge transfer rates as a function of acceptor stacking are in line with the experimentally observed drastic, eight‐fold conductivity enhancement. The first evaluation of redox behavior of buckyball‐ or tetracyanoquinodimethane‐integrated crystalline was conducted. In parallel with tailoring the D‐A alignment responsible for “static” changes in materials properties, an external stimulus was applied for “dynamic” control of the electronic profiles. Overall, the presented D–A strategic design, with stimuli‐controlled electronic behavior, redox activity, and modularity could be used as a blueprint for the development of electroactive and conductive multidimensional and multifunctional crystalline porous materials.
A journey into the deep confines of the forest can sometimes lead to new discoveries. Electron acceptors prepared themselves for travel into the unknown of the COF electron‐donating “forest”. Instead of getting lost in the deep, dark forest, the acceptor‐based (purely organic) covalently bound, crystalline, and porous scaffolds exhibited not only increases in conductivity, but also retention of the redox‐active nature.
Patients with severe coronavirus disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with ARDS. Respiratory failure in COVID-19 might ...represent a novel pathologic entity.
How does the lung histopathology described in COVID-19 compare with the lung histopathology described in SARS and H1N1 influenza?
We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020, using search terms for COVID-19, H1N1 influenza, and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-Individual Participant Data guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients.
In COVID-19, acute-phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared with 24% of H1N1 influenza patients.
DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza, and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared with H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.
The macronuclear genome of the ciliate Oxytricha trifallax displays an extreme and unique eukaryotic genome architecture with extensive genomic variation. During sexual genome development, the ...expressed, somatic macronuclear genome is whittled down to the genic portion of a small fraction (∼5%) of its precursor "silent" germline micronuclear genome by a process of "unscrambling" and fragmentation. The tiny macronuclear "nanochromosomes" typically encode single, protein-coding genes (a small portion, 10%, encode 2-8 genes), have minimal noncoding regions, and are differentially amplified to an average of ∼2,000 copies. We report the high-quality genome assembly of ∼16,000 complete nanochromosomes (∼50 Mb haploid genome size) that vary from 469 bp to 66 kb long (mean ∼3.2 kb) and encode ∼18,500 genes. Alternative DNA fragmentation processes ∼10% of the nanochromosomes into multiple isoforms that usually encode complete genes. Nucleotide diversity in the macronucleus is very high (SNP heterozygosity is ∼4.0%), suggesting that Oxytricha trifallax may have one of the largest known effective population sizes of eukaryotes. Comparison to other ciliates with nonscrambled genomes and long macronuclear chromosomes (on the order of 100 kb) suggests several candidate proteins that could be involved in genome rearrangement, including domesticated MULE and IS1595-like DDE transposases. The assembly of the highly fragmented Oxytricha macronuclear genome is the first completed genome with such an unusual architecture. This genome sequence provides tantalizing glimpses into novel molecular biology and evolution. For example, Oxytricha maintains tens of millions of telomeres per cell and has also evolved an intriguing expansion of telomere end-binding proteins. In conjunction with the micronuclear genome in progress, the O. trifallax macronuclear genome will provide an invaluable resource for investigating programmed genome rearrangements, complementing studies of rearrangements arising during evolution and disease.
Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to ...characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two patients with prostate cancer, including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were present in matched tissue. Moreover, we identified 10 early trunk and 56 metastatic trunk mutations in the non-CTC tumor samples and found 90% and 73% of these mutations, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic.