Revisiting the Association of ECOG Performance Status With Clinical Outcomes in Diverse Patients With Cancer.

BACKGROUND: The ECOG performance status (PS) scale was developed to support national clinical trials, but the degree to which ECOG PS predicts clinical outcomes in patient subgroups outside of clinical trials is relatively unknown. This study examined associations between ECOG PS and adverse outcomes in a diverse community oncology population. PATIENTS AND METHODS: In this retrospective cohort study, demographic and clinical characteristics, including the most recent ECOG PS between January 1, 2017, and December 31, 2019, were examined for patients receiving cancer treatment within Kaiser Permanente Northern California (KPNC). Proportional hazard models were used to evaluate the effect of ECOG PS on adverse outcomes. RESULTS: A total of 21,730 patients were identified. Overall, most patients had an ECOG PS of 0 (42.5%) or 1 (42.5%). In multivariable analysis, an ECOG PS of 3 or 4 was associated with higher risk of 30-day emergency department visits (adjusted hazard ratio [aHR], 3.85; 95% CI, 3.47-4.26), 30-day hospitalizations (aHR, 4.70; 95% CI, 4.12-5.36), and 6-month mortality (aHR, 7.34; 95% CI, 6.64-8.11) compared with an ECOG PS of 0. Additionally, we found that upper gastrointestinal and stage IV cancers were associated with a higher risk of adverse outcomes compared with breast and stage I cancers, respectively. When adjusted for ECOG PS, African American race, Asian race, and female sex were associated with a lower risk of mortality than White race and male sex. An ECOG PS of 3 or 4 was more predictive of mortality in younger patients and those with breast cancer (P<.001). CONCLUSIONS: ECOG PS and upper gastrointestinal and stage IV cancers were independently associated with increased risk of emergency department visits, hospitalizations, and mortality, whereas African American and Asian race and female sex were associated with decreased risk of mortality. An ECOG PS of 3 or 4 was more predictive of an increased risk of mortality in younger patients and patients with breast cancer. These findings can enhance the use of ECOG PS for clinical decision-making and defining eligibility for clinical trials.

Cancer Patients' Preferences and Perceptions of Advantages and Disadvantages of Telehealth Visits During the COVID-19 Pandemic.

PURPOSE: We aimed to ascertain oncology patients' perceptions of telehealth versus in-person (IP) visits for different types of clinical encounters. METHODS: We surveyed adults undergoing cancer treatment at Kaiser Permanente Northern California infusion centers between November 2021 and May 2022 using a self-administered questionnaire. Patients were asked about visit modality preferences (video, phone, and IP) for six types of clinical discussions, overall advantages and disadvantages of telehealth (video or phone) versus IP modalities, and barriers to video visit use. RESULTS: The 839 patients who completed surveys in English were 63% female; median age 63 years; 64% White; and 73% college-educated (45% ≥bachelor's degree). For the first postdiagnosis discussion visit, 83% of patients preferred IP, followed by video (27%) and phone (18%). For follow-up visits, 52% of patients preferred IP, 50% video, and 37% phone. For discussions of bad news and sensitive topics, respectively, 68% and 62% preferred IP, 44% and 48% video, and 32% and 41% phone visits. Delivery of good news was acceptable through IP (49%), video (52%), or phone (49%) visits. Perceived advantages of IP visits were greater feelings of connection with their doctor (58%), confidence in physical examinations (73%), and ease in showing things (67%) and talking (51%) to the doctor. Advantages of telehealth visits included saved time (72%) and money (38%), less infection exposure (64%), less travel concerns (45%), and ability to include more people (28%). Of 24% of patients who felt video visits would be hard, 51% cited poor internet, 41% lack of an adequate device, and 28% difficulty signing on. CONCLUSION: Our results support continued use and reimbursement for telehealth visits with patients with cancer for most types of clinical encounters, including clinical trials.

Acute kidney injury due to myoglobin cast nephropathy in the setting of coronavirus disease 2019-mediated rhabdomyolysis: a case report.

BACKGROUND: We present this case of coronavirus disease 2019-associated acute kidney injury with rhabdomyolysis-with noteworthy renal biopsy findings demonstrating myoglobin cast nephropathy-to add to the limited literature on coronavirus disease 2019-related acute kidney injury and rhabdomyolysis. CASE PRESENTATION: A 67-year-old Caucasian man presented to our hospital with 3 weeks of malaise and decreased oral intake and several days of abnormal taste, poor appetite, decrease urine output, gastrointestinal symptoms, and myalgias, and was ultimately diagnosed with coronavirus disease 2019. His hospital course was complicated by acute kidney injury and, upon workup of his renal failure, was diagnosed with myoglobin cast nephropathy due to coronavirus disease 2019-mediated rhabdomyolysis. Ultimately, his renal function improved following hydration back to his baseline 6 weeks after his initial diagnosis of coronavirus disease 2019. CONCLUSIONS: Given our limited knowledge of manifestations of coronavirus disease 2019, it is important to have a more in-depth understanding of the spectrum of disease of coronavirus disease 2019, which can affect various organ systems, including the kidney, and the manifestations of end-organ damage associated with it. We present this case to highlight a rarely reported finding of myoglobin cast nephropathy due to coronavirus disease 2019-mediated rhabdomyolysis.

Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance.

While great strides have been made in the treatment of advanced renal cell carcinoma (RCC) with the emergence of immune checkpoint inhibitors (ICIs) and VEGFR-targeting drugs, sizable proportions of patients still do not respond to upfront therapy and long-term responses only occur in a minority of patients. There is therefore a great need for the development of better predictors of response and an increased understanding of mechanisms of resistance to these therapies. Alternative immune checkpoints outside the PD-1/PD-L1 axis, such as LAG3, have been implicated as one mechanism of resistance to ICIs. These checkpoints thus represent attractive therapeutic targets, and indeed the LAG3 inhibitor relatlimab was recently approved for the treatment of metastatic melanoma in combination with anti-PD-1 therapy. LAG3 inhibitors are being evaluated for RCC as well. In this context, a better understanding of LAG3 expression patterns in RCC and how they relate to clinicopathologic features of disease and response to immunotherapy may give insight into mechanisms of resistance to PD-1 inhibitors and aid in the identification of subgroups of patients more likely to benefit from certain drug regimens. In this study, we assessed LAG3 protein levels in leukocytes in normal kidney adjacent to RCC, primary RCC tumors, and matched metastatic tumors, including large numbers of brain metastases. We found that LAG3 protein levels are on average lower at metastatic sites compared to matched primary tumors, and that the difference was more pronounced in patients with high-risk clinical characteristics, including those with larger primary tumor size, grade 4 tumors, IMDC poor-risk disease, and initial presentation with brain metastases. We further saw that the prognostic value of LAG3 levels varies depending on the tissue site queried (i.e., primary tumor versus metastases), and that relatively higher LAG3 levels at metastatic sites may predict a better response to immunotherapy and longer overall survival after the development of metastatic disease. These findings may have important implications for the design of future studies involving LAG3 or other immunotherapies in RCC.

Future of Teleoncology: Trends and Disparities in Telehealth and Secure Message Utilization in the COVID-19 Era.

PURPOSE: The COVID-19 pandemic created an imperative to re-examine the role of telehealth in oncology. We studied trends and disparities in utilization of telehealth (video and telephone visits) and secure messaging (SM; ie, e-mail via portal/app), before and during the pandemic. METHODS: Retrospective cohort study of hematology/oncology patient visits (telephone/video/office) and SM between January 1, 2019, and September 30, 2020, at Kaiser Permanente Northern California. RESULTS: Among 334,666 visits and 1,161,239 SM, monthly average office visits decreased from 10,562 prepandemic to 1,769 during pandemic, telephone visits increased from 5,114 to 8,663, and video visits increased from 40 to 4,666. Monthly average SM increased from 50,788 to 64,315 since the pandemic began. Video visits were a significantly higher fraction of all visits (P < .01) in (1) younger patients (Generation Z 48%, Millennials 46%; Generation X 40%; Baby Boomers 34.4%; Silent Generation 24.5%); (2) patients with commercial insurance (39%) compared with Medicaid (32.7%) or Medicare (28.1%); (3) English speakers (33.7%) compared with those requiring an interpreter (24.5%); (4) patients who are Asian (35%) and non-Hispanic White (33.7%) compared with Black (30.1%) and Hispanic White (27.5%); (5) married/domestic partner patients (35%) compared with single/divorced/widowed (29.9%); (6) Charlson comorbidity index ≤ 3 (36.2%) compared with > 3 (31.3%); and (7) males (34.6%) compared with females (32.3%). Similar statistically significant SM utilization patterns were also seen. CONCLUSION: In the pandemic era, hematology/oncology telehealth and SM use rapidly increased in a manner that is feasible and sustained. Possible disparities existed in video visit and SM use by age, insurance plan, language, race, ethnicity, marital status, comorbidities, and sex.

Clinicopathological Review of Micropapillary Urothelial Carcinoma.

PURPOSE OF REVIEW: This review will discuss micropapillary urothelial carcinoma with respect to biology, histopathologic characteristics, genetic and molecular features, diagnosis, clinical management, and future directions of research. RECENT FINDINGS: Recent consensus opinion study showed only moderate interobserver reproducibility in the diagnostic criteria. The most reproducible criteria with the highest consensus were multiple nests in the same lacunar spaces. There are recent reports of high rates of intratumoral heterogeneity of ERBB2 amplification within tumor containing both micropapillary and classic urothelial components. Micropapillary urothelial carcinoma is a well-documented highly aggressive variant of urothelial carcinoma with proven worse outcomes. Accurate recognition and reporting of this pattern is critical for optimal management. Newer therapeutic strategies related to the molecular and genetic findings seen in MPUC remain to be explored further.

Attitudes and Perceptions of Multidisciplinary Cancer Care Clinicians Toward Telehealth and Secure Messages.

Importance: Telehealth use including secure messages has rapidly expanded since the COVID-19 pandemic, including for multidisciplinary aspects of cancer care. Recent reports described rapid uptake and various benefits for patients and clinicians, suggesting that telehealth may be in standard use after the pandemic. Objective: To examine attitudes and perceptions of multidisciplinary cancer care clinicians toward telehealth and secure messages. Design, Setting, and Participants: Cross-sectional specialty-specific survey (ie, some questions appear only for relevant specialties) among multidisciplinary cancer care clinicians, collected from April 29, 2020, to June 5, 2020. Participants were all 285 clinicians in the fields of medical oncology, radiation oncology, surgical oncology, survivorship, and oncology navigation from all 21 community cancer centers of Kaiser Permanente Northern California. Main Outcomes and Measures: Clinician satisfaction, perceived benefits and challenges of telehealth, perceived quality of telehealth and secure messaging, preferred visit and communication types for different clinical activities, and preferences regarding postpandemic telehealth use. Results: A total of 202 clinicians (71%) responded (104 of 128 medical oncologists, 34 of 37 radiation oncologists, 16 of 62 breast surgeons, 18 of 28 navigators, and 30 of 30 survivorship experts; 57% (116 of 202) were women; 73% [147 of 202] between ages 36-55 years). Seventy-six percent (n = 154) were satisfied with telehealth without statistically significant variations based on clinician characteristics. In-person visits were thought to promote a strong patient-clinician connection by 99% (n = 137) of respondents compared with 77% (n = 106) for video visits, 43% (n = 59) for telephone, and 14% (n = 19) for secure messages. The most commonly cited benefits of telehealth to clinicians included reduced commute (79%; n = 160), working from home (74%; n = 149), and staying on time (65%; n = 132); the most commonly cited negative factors included internet connection (84%; n = 170) or equipment problems (72%; n = 146), or physical examination needed (64%; n = 131). Most respondents (59%; n = 120) thought that video is adequate to manage the greater part of patient care in general; and most deemed various telehealth modalities suitable for any of the queried types of patient-clinician activities. For some specific activities, less than half of respondents thought that only an in-person visit is acceptable (eg, 49%; n = 66 for end-of-life discussion, 35%; n = 58 for new diagnosis). Most clinicians (82%; n = 166) preferred to maintain or increase use of telehealth after the pandemic. Conclusions and Relevance: In this survey of multidisciplinary cancer care clinicians in the COVID-19 era, telehealth was well received and often preferred by most cancer care clinicians, who deemed it appropriate to manage most aspects of cancer care. As telehealth use becomes routine in some cancer care settings, video and telephone visits and use of asynchronous secure messaging with patients in cancer care has clear potential to extend beyond the pandemic period.

Can primary hepatocellular carcinoma histomorphology predict extrahepatic metastasis?

Studies comparing the histomorphologic features and phenotypic heterogeneity between primary and its corresponding metastatic hepatocellular carcinoma (HCC) are lacking. The aim of this study was to assess and compare the histomorphologic features and heterogeneity between primary and metastatic HCC. A total of 39 cases with both primary and metastatic tissues were identified from pathology archives (2000-2019). The common sites of metastasis included lung (28.21%), abdominal cavity (25.64%), lymph nodes (20.51%), bone (17.95%), soft tissue (15.38%), and adrenal gland (10.26%). Both the primary and metastatic tumors showed heterogeneity in intratumoral histologic patterns (87.18% and 76.92%, respectively). The most common histologic pattern was solid in both primary (61.54%) and metastases (56.41%), followed by macrotrabecular in primary (17.95%) and metastases (10.26%). Among HCC-subtypes, macrotrabecular-massive HCC was the most common subtype in both primary and metastases (28.21% each). Primary tumors in noncirrhotic livers were more likely to have larger size and microvascular invasion than those in cirrhotic livers. The histomorphology (histologic pattern, subtype, and grade) between the primary and metastases was discordant in about 50% cases (48.72%, 48.72%, and 51.28%, respectively). Our findings exhibit significant intratumoral heterogeneity and histomorphologic discordance between primary and metastatic HCCs. The solid and macrotrabecular histologic patterns and the macrotrabecular-massive subtype were the most common histomorphologic features seen in primary tumors associated with metastasis. Further studies to identify and explore different pathways that promote HCC metastasis and to compare the differences between primary and metastatic tumors on a larger cohort are needed to better understand the pathogenesis of metastasis.

Detecting Pneumonia using Convolutions and Dynamic Capsule Routing for Chest X-ray Images.

An entity's existence in an image can be depicted by the activity instantiation vector from a group of neurons (called capsule). Recently, multi-layered capsules, called CapsNet, have proven to be state-of-the-art for image classification tasks. This research utilizes the prowess of this algorithm to detect pneumonia from chest X-ray (CXR) images. Here, an entity in the CXR image can help determine if the patient (whose CXR is used) is suffering from pneumonia or not. A simple model of capsules (also known as Simple CapsNet) has provided results comparable to best Deep Learning models that had been used earlier. Subsequently, a combination of convolutions and capsules is used to obtain two models that outperform all models previously proposed. These models-Integration of convolutions with capsules (ICC) and Ensemble of convolutions with capsules (ECC)-detect pneumonia with a test accuracy of 95.33% and 95.90%, respectively. The latter model is studied in detail to obtain a variant called EnCC, where n = 3, 4, 8, 16. Here, the E4CC model works optimally and gives test accuracy of 96.36%. All these models had been trained, validated, and tested on 5857 images from Mendeley.

Benign lymph node microenvironment is associated with response to immunotherapy.

Introduction: Benign lymph nodes have been considered the hubs of immune surveillance in cancer patients. The microenvironment of these lymphoid tissues can be immune suppressed, hence allowing for tumor progression. Understanding the spectrum of benign findings in bystander lymph nodes in immune checkpoint blockade therapy could prove to be key to understanding the mechanism and assessing treatment response. Methods: Benign lymph nodes and spleen were evaluated from patients treated with immunotherapy who subsequently received postmortem examination. We used quantitative immunofluorescence (QIF) to assess tumor infiltrating lymphocytes (TIL) and macrophage marker expression and characterized activation status using a novel multiplexed QIF assay including CD3, GranzymeB, and Ki67. We performed immunohistochemistry to correlate results of QIF. Results: Benign lymph nodes from non-responders to immunotherapy showed significantly higher expression of cytotoxic markers and proliferation index (Ki67) in T cells compared to responders. Higher expression of PD-L1 in macrophages was also observed. There was no significant difference in CD3+ expression, but higher levels of CD8+ T cells as well as CD20+ B cells were seen in lymph nodes of non-responders. No significant differences were seen between responder and non-responder splenic tissue. Findings were supported by traditional immunostaining methods. Conclusions: While most studies in biomarkers for immunotherapy focus on tumor microenvironment, we show that benign lymph node microenvironment may predict response to immunotherapy. In responding patients, bystander lymph nodes appear to have been mobilized, resulting in reduced cytotoxic T cells. Conversely, patients whose disease progressed on immunotherapy demonstrate higher levels of macrophages that express increased PD-L1, and activated T cells not recruited to the tumor site.

Cryoglobulinemia as a Possible Primer for TRALI: Report of a Case.

Waldenström macroglobulinemia (WM) is a form of lymphoplasmacytic lymphoma that can cause hyperviscosity syndrome due to unchecked monoclonal antibody production. Some patients are also found to have associated cryoglobulinemia, which can cause systemic complications including vasculitis, renal disease, and pulmonary complications. Cryoglobulins can also serve as a source of interference with various laboratory assays. Therapeutic plasma exchange (TPE) is one of the recommended treatment modalities to manage hyperviscosity. Herein, we present the case of an 84-year-old female patient with Waldenström macroglobulinemia who presented with hyperviscosity syndrome and discrepant laboratory findings, and who then developed transfusion-related acute lung injury (TRALI) during TPE. This case is one of many in the emerging possible linkages observed between cryoglobulinemia and TRALI.

Diagnosis of Infectious Diseases in the Lower Respiratory Tract: A Cytopathologist's Perspective.

CONTEXT.­: Respiratory cytology continues to play an important role in the diagnosis of lower respiratory tract infections. Prompt, accurate diagnosis of causative organisms is of paramount importance, particularly in immunosuppressed patients. In addition, a rapidly expanding arsenal of ancillary testing is now available, aiding tremendously in organism identification. OBJECTIVE.­: To provide an updated review on the cytomorphologic features of common organisms in lower respiratory tract infection. Relevant ancillary tests, differential diagnoses, and potential pitfalls of organism identification will also be discussed. DATA SOURCES.­: Data for this review were gathered from PubMed searches of infectious diseases of the lower respiratory tract, especially related to the diagnoses. CONCLUSIONS.­: The lower respiratory tract is subject to infection by a wide variety of infectious agents. Pathologists should be familiar with common organisms, including their general clinical characteristics, cytomorphologic features, differential diagnoses, and ancillary methods of detection. Above all, correlation with microbiologic and clinical information is necessary to make a confident diagnosis of infection.

Corrigendum: Microenvironment Cell Contribution to Lymphoma Immunity.

[This corrects the article DOI: 10.3389/fonc.2018.00288.].

Microenvironment Cell Contribution to Lymphoma Immunity.

Lymphoma microenvironment is a complex system composed of stromal cells, blood vessels, immune cells as well as extracellular matrix, cytokines, exosomes, and chemokines. In this review, we describe the function, localization, and interactions between various cellular components. We also summarize their contribution to lymphoma immunity in the era of immunotherapy. Publications were identified from searching Pubmed. Primary literature was carefully evaluated for replicability before incorporating into the review. We describe the roles of mesenchymal stem/stromal cells (MSCs), lymphoma-associated macrophages (LAMs), dendritic cells, cytotoxic T cells, PD-1 expressing CD4+ tumor infiltrating lymphocytes (TILs), T-cells expressing markers of exhaustion such as TIM-3 and LAG-3, regulatory T cells, and natural killer cells. While it is not in itself a cell, we also include a brief overview of the lymphoma exosome and how it contributes to anti-tumor effect as well as immune dysfunction. Understanding the cellular players that comprise the lymphoma microenvironment is critical to developing novel therapeutics that can help block the signals for immune escape and promote tumor surveillance. It may also be the key to understanding mechanisms of resistance to immune checkpoint blockade and immune-related adverse events due to certain types of immunotherapy.

A study of virulence and antimicrobial resistance pattern in diarrhoeagenic Escherichia coli isolated from diarrhoeal stool specimens from children and adults in a tertiary hospital, Puducherry, India.

BACKGROUND: Emergence of atypical enteropathogenic Escherichia coli (EPEC) and hybrid E. coli (harboring genes of more than one DEC pathotypes) strains have complicated the issue of growing antibiotic resistance in diarrhoeagenic Escherichia coli (DEC). This ongoing evolution occurs in nature predominantly via horizontal gene transfers involving the mobile genetic elements like integrons notably class 1 integron. This study was undertaken to determine the virulence pattern and antibiotic resistance among the circulating DEC strains in a tertiary care center in south of India. METHODS: Diarrhoeal stool specimens were obtained from 120 children (< 5 years) and 100 adults (> 18 years), subjected to culture and isolation of diarrhoeal pathogens. Conventional PCR was performed to detect 10 virulence and 27 antimicrobial resistance (AMR) genes among the E. coli isolated. RESULTS: DEC infection was observed in 45 (37.5%) children and 18 (18%) adults, among which [18 (40%), 10 (10%)] atypical EPEC was most commonly detected followed by [6 (13.3%), 4 (4%)] ETEC, [5 (11.1%) 2 (2%)] EAEC, [(3 (6.6%), 0 (0%)] EIEC, [3 (6.6%), 0 (0%] typical EPEC, and [4 (8.8%), 1 (1%)] STEC, and no NTEC and CDEC was detected. DEC co-infection in 3 (6.6%) children, and 1(1%) adult and sole hybrid DEC infection in 3 (6.6%) children was detected. The distribution of sulphonamide resistance genes (sulI, sulII, and sulIII were 83.3 and 21%, 60.41 and 42.1%, and 12.5 and 26.3%, respectively) and class 1 integron (int1) genes (41.6 and 26.31%) was higher in DEC strains isolated from children and adults, respectively. Other AMR genes detected were qnrS, qnrB, aac(6')Ib-cr, dhfr1, aadB, aac(3)-IV, tetA, tetB, tetD, catI, blaCTX, blaSHV, and blaTEM. None harbored qnrA, qnrC, qepA, tetE, tetC, tetY, ermA, mcr1, int2, and int3 genes. CONCLUSIONS: Atypical EPEC was a primary etiological agent of diarrhea in children and adults among the DEC pathotypes. Detection of high numbers of AMR genes and class 1 integron genes indicate the importance of mobile genetic elements in spreading of multidrug resistance genes among these strains.

Microbiomes of the dust particles collected from the International Space Station and Spacecraft Assembly Facilities.

BACKGROUND: The International Space Station (ISS) is a unique built environment due to the effects of microgravity, space radiation, elevated carbon dioxide levels, and especially continuous human habitation. Understanding the composition of the ISS microbial community will facilitate further development of safety and maintenance practices. The primary goal of this study was to characterize the viable microbiome of the ISS-built environment. A second objective was to determine if the built environments of Earth-based cleanrooms associated with space exploration are an appropriate model of the ISS environment. RESULTS: Samples collected from the ISS and two cleanrooms at the Jet Propulsion Laboratory (JPL, Pasadena, CA) were analyzed by traditional cultivation, adenosine triphosphate (ATP), and propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR) assays to estimate viable microbial populations. The 16S rRNA gene Illumina iTag sequencing was used to elucidate microbial diversity and explore differences between ISS and cleanroom microbiomes. Statistical analyses showed that members of the phyla Actinobacteria, Firmicutes, and Proteobacteria were dominant in the samples examined but varied in abundance. Actinobacteria were predominant in the ISS samples whereas Proteobacteria, least abundant in the ISS, dominated in the cleanroom samples. The viable bacterial populations seen by PMA treatment were greatly decreased. However, the treatment did not appear to have an effect on the bacterial composition (diversity) associated with each sampling site. CONCLUSIONS: The results of this study provide strong evidence that specific human skin-associated microorganisms make a substantial contribution to the ISS microbiome, which is not the case in Earth-based cleanrooms. For example, Corynebacterium and Propionibacterium (Actinobacteria) but not Staphylococcus (Firmicutes) species are dominant on the ISS in terms of viable and total bacterial community composition. The results obtained will facilitate future studies to determine how stable the ISS environment is over time. The present results also demonstrate the value of measuring viable cell diversity and population size at any sampling site. This information can be used to identify sites that can be targeted for more stringent cleaning. Finally, the results will allow comparisons with other built sites and facilitate future improvements on the ISS that will ensure astronaut health.