Leveraging genomic sequencing data to evaluate disease surveillance strategies.

In the face of scarce public health resources, it is critical to understand which disease surveillance strategies are effective, yet such validation has historically been difficult. From May 1 to December 31, 2021, a cohort study was carried out in Santa Clara County, California, in which 10,131 high-quality genomic sequences from COVID-19 polymerase chain reaction tests were merged with disease surveillance data. We measured the informational value, the fraction of sequenced links surfaced that are biologically plausible according to genomic sequence data, of different disease surveillance strategies. Contact tracing appeared more effective than spatiotemporal methods at uncovering nonresidential spread settings, school reporting appeared more fruitful than workplace reporting, and passively retrieved links through survey information presented some promise. Given the rapidly dwindling cost of sequencing, the informational value metric may enable near real-time, readily available evaluation of strategies by public health authorities to fight viral diseases beyond COVID-19.

Monkeypox (Mpox) Vaccine Hesitancy Among Mpox Cases: A Qualitative Study.

Human mpox has been an increasing concern in the United States and California since late 2022. While the Jynneos vaccine offers a degree of cross-protection against the disease, vaccine hesitancy is common among those recommended for vaccination. The purpose of this study was to assess vaccine knowledge, facilitators, and barriers to vaccine uptake among individuals previously diagnosed with mpox, or mpox cases, in Santa Clara County, California. In-depth interviews were conducted by public health department staff among mpox cases diagnosed in Santa Clara County between July and September 2022. Responses were analyzed using a grounded theory data analysis approach. Among the 47 participants, 36 (77%) had heard of mpox before diagnosis, and of these, 20 (56%) did not think they were at risk of developing mpox, and 28 (78%) were aware that a vaccine was available. Those who did not receive the vaccine stated vaccine access and availability were the main barriers. Among the six participants not interested in the vaccine, the main hesitancies were lack of perceived risk, stigma of being branded by scarring and labeled gay, and vaccine safety. Overall, the following themes were attributed to reasons for vaccine hesitancy: (a) lack of awareness of the disease and vaccine, including perceived risks; (b) lack of vaccine availability and accessibility; and (c) stigma associated with receiving the vaccine, including being publicly labeled as "gay" and the scarring on forearm potentially seen as branding. We recommend tailoring outreach and educational campaigns to address reasons for mpox vaccine hesitancy.

Integrating social services with disease investigation: A randomized trial of COVID-19 high-touch contact tracing.

COVID-19 exposed and exacerbated health disparities, and a core challenge has been how to adapt pandemic response and public health in light of these disproportionate health burdens. Responding to this challenge, the County of Santa Clara Public Health Department designed a model of "high-touch" contact tracing that integrated social services with disease investigation, providing continued support and resource linkage for clients from structurally vulnerable communities. We report results from a cluster randomized trial of 5,430 cases from February to May 2021 to assess the ability of high-touch contact tracing to aid with isolation and quarantine. Using individual-level data on resource referral and uptake outcomes, we find that the intervention, randomized assignment to the high-touch program, increased the referral rate to social services by 8.4% (95% confidence interval, 0.8%-15.9%) and the uptake rate by 4.9% (-0.2%-10.0%), with the most pronounced increases in referrals and uptake of food assistance. These findings demonstrate that social services can be effectively combined with contact tracing to better promote health equity, demonstrating a novel path for the future of public health.

ExPeCT: a randomised trial examining the impact of exercise on quality of life in men with metastatic prostate cancer.

PURPOSE: All patients living with cancer, including those with metastatic cancer, are encouraged to be physically active. This paper examines the secondary endpoints of an aerobic exercise intervention for men with metastatic prostate cancer. METHODS: ExPeCT (Exercise, Prostate Cancer and Circulating Tumour Cells), was a multi-centre randomised control trial with a 6-month aerobic exercise intervention arm or a standard care control arm. Exercise adherence data was collected via heart rate monitors. Quality of life (FACT-P) and physical activity (self-administered questionnaire) assessments were completed at baseline, at 3 months and at 6 months. RESULTS: A total of 61 patients were included (69.4 ± 7.3 yr, body mass index 29.2 ± 5.8 kg/m2). The median time since diagnosis was 34 months (IQR 7-54). A total of 35 (55%) of participants had > 1 region affected by metastatic disease. No adverse events were reported by participants. There was no effect of exercise on quality of life (Cohen's d = - 0.082). Overall adherence to the supervised sessions was 83% (329 out of 396 possible sessions attended by participants). Overall adherence to the non-supervised home exercise sessions was 72% (months 1-3) and 67% (months 3-6). Modelling results for overall physical activity scores showed no significant main effect for the group (p-value = 0.25) or for time (p-value = 0.24). CONCLUSION: In a group of patients with a high burden of metastatic prostate cancer, a 6-month aerobic exercise intervention did not lead to change in quality of life. Further exercise studies examining the role of exercise for people living with metastatic prostate cancer are needed. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT02453139) on May 25th 2015.

Automated vs. manual case investigation and contact tracing for pandemic surveillance: Evidence from a stepped wedge cluster randomized trial.

Background: Case investigation and contact tracing (CICT) is an important tool for communicable disease control, both to proactively interrupt chains of transmission and to collect information for situational awareness. We run the first randomized trial of COVID-19 CICT to investigate the utility of manual (i.e., call-based) vs. automated (i.e., survey-based) CICT for pandemic surveillance. Methods: Between December 15, 2021 and February 5, 2022, a stepped wedge cluster randomized trial was run in which Santa Clara County ZIP Codes progressively transitioned from manual to automated CICT. Eleven individual-level data fields on demographics and disease dynamics were observed for non-response. The data contains 106,522 positive cases across 29 ZIP Codes. Findings: Automated CICT reduced overall collected information by 29 percentage points (SE = 0.08, p < 0.01), as well as the response rate for individual fields. However, we find no evidence of differences in information loss by race or ethnicity. Interpretations: Automated CICT can serve as a useful alternative to manual CICT, with no substantial evidence of skewing data along racial or ethnic lines, but manual CICT improves completeness of key data for monitoring epidemiologic patterns. Funding: This research was supported in part by the Stanford Office of Community Engagement and the Stanford Institute for Human-Centered Artificial Intelligence.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) outbreak investigation in a hospital emergency department-California, December 2020-January 2021.

We describe a large outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) involving an acute-care hospital emergency department during December 2020 and January 2021, in which 27 healthcare personnel worked while infectious, resulting in multiple opportunities for SARS-CoV-2 transmission to patients and other healthcare personnel. We provide recommendations for improving infection prevention and control.

A cohort profile of the Graham Roberts study cohort.

Purpose: The Graham Roberts Study was initiated in 2018 and is the first Trials Within Cohorts (TwiCs) study for bladder cancer. Its purpose is to provide an infrastructure for answering a breadth of research questions, including clinical, mechanistic, and supportive care centred questions for bladder cancer patients. Participants: All consented patients are those aged 18 or older, able to provide signed informedconsent and have a diagnosis of new or recurrent bladder cancer. All patients are required to have completed a series of baseline questionnaires. The questionnaires are then sent out every 12 months and include information on demographics and medical history as well as questionnaires to collect information on quality of life, fatigue, depression, overall health, physical activity, and dietary habits. Clinical information such as tumor stage, grade and treatment has also been extracted for each patient. Findings to date: To date, a total of 125 bladder cancer patients have been consented onto the study with 106 filling in the baseline questionnaire. The cohort is made up of 75% newly diagnosed bladder cancer patients and 66% non-muscle invasive bladder cancer cases. At present, there is 1-year follow-up information for 70 patients, 2-year follow-up for 57 patients, 3-year follow-up for 47 patients and 4-year follow-up for 19 patients. Future plans: We plan to continue recruiting further patients into the cohort study. Using the data collected within the study, we hope to carry out independent research studies with a focus on quality of life. We are also committed to utilizing the Roberts Study Cohort to set up and commence an intervention. The future studies and trials carried out using the Roberts Cohort have the potential to identify and develop interventions that could improve the prevention, diagnosis, and treatment of bladder cancer.

Invadopodia play a role in prostate cancer progression.

BACKGROUND: Invadopodia, actin-rich structures that release metallo-proteases at the interface with extra-cellular matrix, in a punctate manner are thought to be important drivers of tumour invasion. Invadopodia formation has been observed in-vitro and in-vivo in numerous metastatic cell lines derived from multiple tumour types. However, prostate cancer cell lines have not been routinely reported to generate invadopodia and the few instances have always required external stimulation. METHODS: In this study, the invasive potential of primary prostate adenocarcinoma cell lines, which have never been fully characterised before, was investigated both in-vitro invadopodia assays and in-vivo zebrafish dissemination assay. Subsequently, circulating tumour cells from prostate cancer patients were isolated and tested in the invadopodia assay. RESULTS: Retention of E-cadherin and N-cadherin expression indicated a transitional state of EMT progression, consistent with the idea of partial EMT that has been frequently observed in aggressive prostate cancer. All cell lines tested were capable of spontaneous invadopodia formation and possess a significant degradative ability in-vitro under basal conditions. These cell lines were invasive in-vivo and produced visible metastasis in the zebrafish dissemination assay. Importantly we have proceeded to demonstrate that circulating tumour cells isolated from prostate cancer patients exhibit invadopodia-like structures and degrade matrix with visible puncta. This work supports a role for invadopodia activity as one of the mechanisms of dissemination employed by prostate cancer cells. CONCLUSION: The combination of studies presented here provide clear evidence that invadopodia activity can play a role in prostate cancer progression.

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476).

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC + AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50-0.71; P = 0.31 × 10-9 ) favoured SOC + AAP, with 5-years survival improved from 41% SOC-alone to 60% SOC + AAP. This was similar in low-risk (HR = 0.55; 95% CI: 0.41-0.76) and high-risk (HR = 0.54; 95% CI: 0.43-0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.

Safe provision of systemic anti-cancer treatment for urological cancer patients during COVID-19: a tertiary centre experience in the first wave of COVID-19.

BACKGROUND: Safe provision of systemic anti-cancer treatment (SACT) during the COVID-19 pandemic remains an ongoing concern amongst clinicians. METHODS: Retrospective analysis on uro-oncology patients who continued or started SACT between 1st March and 31st May 2020 during the pandemic (with 2019 as a comparator). RESULTS: 441 patients received SACT in 2020 (292 prostate, 101 renal, 38 urothelial, 10 testicular) compared to 518 patients in 2019 (340 prostate, 121 renal, 42 urothelial, 15 testicular). In 2020, there were 75.00% fewer patients with stage 3 cancers receiving SACT (p < 0.0001) and 94.44% fewer patients receiving radical treatment (p = 0.00194). The number of patients started on a new line of SACT was similar between both years (118 in 2019 vs 102 in 2020; p = 0.898) but with 53.45% fewer patients started on chemotherapy in 2020 (p < 0.001). Overall, 5 patients tested positive for COVID-19 (one asymptomatic, one mild, two moderate, one severe resulting in death). Compared to 2019, 30-day mortality was similar (1.69% in 2019 vs 0.98% in 2020; p = 0.649) whereas 6-month mortality was lower (9.32% in 2019 vs 1.96% in 2020; p = 0.0209) in 2020. CONCLUSION: This study suggests that delivery of SACT to uro-oncology patients during COVID-19 pandemic may be safe in high-incidence areas with appropriate risk-reduction strategies.

Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST).

PURPOSE: Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST) assessed whether magnetic resonance images (MRIs) or a reduced scan schedule could be used without an unacceptable increase in advanced relapses. METHODS: A phase III, noninferiority, factorial trial. Eligible participants had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Random assignment was to seven CTs (6, 12, 18, 24, 36, 48, and 60 months); seven MRIs (same schedule); three CTs (6, 18, and 36 months); or three MRIs. The primary outcome was 6-year incidence of Royal Marsden Hospital stage ≥ IIC relapse (> 5 cm), aiming to exclude increases ≥ 5.7% (from 5.7% to 11.4%) with MRI (v CT) or three scans (v 7); target N = 660, all contributing to both comparisons. Secondary outcomes include relapse ≥ 3 cm, disease-free survival, and overall survival. Intention-to-treat and per-protocol analyses were performed. RESULTS: Six hundred sixty-nine patients enrolled (35 UK centers, 2008-2014); mean tumor size was 2.9 cm, and 358 (54%) were low risk (< 4 cm, no rete testis invasion). With a median follow-up of 72 months, 82 (12%) relapsed. Stage ≥ IIC relapse was rare (10 events). Although statistically noninferior, more events occurred with three scans (nine, 2.8%) versus seven scans (one, 0.3%): 2.5% absolute increase, 90% CI (1.0 to 4.1). Only 4/9 could have potentially been detected earlier with seven scans. Noninferiority of MRI versus CT was also shown; fewer events occurred with MRI (two [0.6%] v eight [2.6%]), 1.9% decrease (-3.5 to -0.3). Per-protocol analyses confirmed noninferiority. Five-year survival was 99%, with no tumor-related deaths. CONCLUSION: Surveillance is a safe management approach-advanced relapse is rare, salvage treatment successful, and outcomes excellent, regardless of imaging frequency or modality. MRI can be recommended to reduce irradiation; and no adverse impact on long-term outcomes was seen with a reduced schedule.

The presenting dental status of solid tumours with bone metastases requiring bone-targeting agents - part 1: an overview.

Introduction Dental pre-assessment before bone-targeting agents (BTA) in oncology patients is a well-recognised practice; yet, guidance on this has typically been unable to differentiate between the intricacies of varying oncology groups. This study assesses the presenting dental status of oncology patients with bone metastases (BM) due to commence BTA, to determine whether differences exist with varying tumour groups.Materials and methods Data were retrospectively collected from a dedicated pre-BTA dental assessment clinic. Statistical analysis and observational data were used to compare patient and tumour demographics as well as to their peers via the Adult Dental Health Survey.Results A total of 492 patients with a solid tumour diagnosis and BM requiring BTA were included in this retrospective study. Demographics such as sex, age, smoking status and tumour site were all significant for the number of teeth present (p = 0.000). Furthermore, survival data post-BTA identified prostate, breast and thyroid groups surviving over 12 months following dental assessment (p <0.000). In contrast, the remaining groups such as lung, colorectal and gastrointestinal had poorer outcomes (p <0.000).Conclusion Pre-BTA dental assessment should consider and incorporate additional patient and tumour demographics to allow for a tailored and personalised dental treatment plan. Application of this principle would look to optimise oral function while considering tumour prognosis to avoid over- or under-prescribing pre-BTA dental treatment.

Genomic Epidemiology and Transmission Dynamics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Congregate Healthcare Facilities in Santa Clara County, California.

BACKGROUND: Outbreaks of SARS-CoV-2 in long-term care facilities (LTCFs) cause significant morbidity and mortality. Mapping viral transmission within and between facilities by combining genomic sequencing with epidemiologic investigations enables targeting infection-control interventions. METHODS: We conducted weekly surveillance of residents and staff in LTCFs in Santa Clara County, California, with ≥1 confirmed COVID-19 case between March and July 2020. Positive samples were referred for whole-genome sequencing. Epidemiological investigations and phylogenetic analyses of the largest outbreaks (>30 cases) were carried out in 6 LTCFs (Facilities A through F). RESULTS: Among the 61 LTCFs in the county, 41 had ≥1 confirmed case during the study period, triggering weekly SARS-CoV-2 testing. The 6 largest outbreaks accounted for 60% of cases and 90% of deaths in LTCFs, although the bed capacity of these facilities represents only 11% of the LTCF beds in the county. Phylogenetic analysis of 196 whole-genome sequences recovered from those facilities showed that each outbreak was monophyletic, with staff and residents sharing a common viral lineage. Outbreak investigations revealed that infected staff members often worked at multiple facilities, and in 1 instance, a staff member infected while working in 1 facility was the likely index case in another. CONCLUSIONS: We detected a pattern of rapid and sustained transmission after a single introduction of SARS-CoV-2 in 6 large LTCF outbreaks, with staff playing a key role in transmission within and between facilities. Infection control, testing, and occupational policies to reduce exposure and transmission risk for staff are essential components to keeping facility residents safe.

Qualitative Analysis of Interviews and Focus Groups Exploring Factors Contributing to Adherence to GnRH Agonists in Men with Prostate Cancer.

OBJECTIVES: Side effects from the prolonged use of gonadotropin-releasing hormone (GnRH) agonists may lead to nonadherence to the treatment in men with advanced prostate cancer (PCa). We investigated the reasons contributing to nonadherence to GnRH agonists through interviews with men with PCa and focus groups with their health care professionals. DATA SOURCES: The three stages of the study were validation of themes, interviews with men on GnRH agonists, and focus groups with oncology specialists and clinical nurse specialists. An experienced oncologist validated factors contributing to nonadherence identified from the literature. A total of 10 men with PCa were recruited from a large teaching hospital and were interviewed on a one-to-one basis using a topic guide. In stage three, two separate focus groups were held with oncology specialists and clinical nurse specialists treating men with PCa. The interviews and focus groups were audio recorded and transcribed verbatim. Initial codes identified from stage three were grouped into themes and thematically analyzed. CONCLUSION: Themes identified from the interviews and focus groups influencing adherence to treatment were side effects of treatment, patient belief system, benefits outweigh harm, quality of life over quantity of life, social support, and patient-clinician relationship. Although side effects such as hot flushes and loss of libido were sometimes overwhelming for many, these men felt that treatment benefits outweighed harm. IMPLICATIONS FOR NURSING PRACTICE: Reasons leading to nonadherence can be multifactorial and unique to each patient. Employing different strategies by health care professionals may lead to the eventual acceptance of treatment, while also acknowledging their reasons for nonadherence.

Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study.

Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution.

Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial.

PURPOSE: Docetaxel and abiraterone acetate plus prednisone or prednisolone (AAP) both improve survival when commenced alongside standard of care (SOC) androgen deprivation therapy in locally advanced or metastatic hormone-sensitive prostate cancer. Thus, patient-reported quality of life (QOL) data may guide treatment choices. METHODS: A group of patients within the STAMPEDE trial were contemporaneously enrolled with the possibility of being randomly allocated to receive either docetaxel + SOC or AAP + SOC. A mixed-model assessed QOL in those who had completed at least one QLQ-C30 + PR25 questionnaire. The primary outcome measure was difference in global-QOL (QLQ-C30 Q29&30) between patients allocated to docetaxel + SOC or AAP + SOC over the 2 years after random assignment, with a predefined criterion for clinically meaningful difference of > 4.0 points. Secondary outcome measures included longitudinal comparison of functional domains, pain, and fatigue, plus global-QOL at defined timepoints. RESULTS: Five hundred fifteen patients (173 docetaxel + SOC and 342 AAP + SOC) were included. Baseline characteristics, proportion of missing data, and mean baseline global-QOL scores (docetaxel + SOC 77.8 and AAP + SOC 78.0) were similar. Over the 2 years following random assignment, the mean modeled global-QOL score was +3.9 points (95% CI, +0.5 to +7.2; P = .022) higher in patients allocated to AAP + SOC. Global-QOL was higher for patients allocated to AAP + SOC over the first year (+5.7 points, 95% CI, +3.0 to +8.5; P < .001), particularly at 12 (+7.0 points, 95% CI, +3.0 to +11.0; P = .001) and 24 weeks (+8.3 points, 95% CI, +4.0 to +12.6; P < .001). CONCLUSION: Patient-reported QOL was superior for patients allocated to receive AAP + SOC, compared with docetaxel + SOC over a 2-year period, narrowly missing the predefined value for clinical significance. Patients receiving AAP + SOC reported clinically meaningful higher global-QOL scores throughout the first year following random assignment.

A language-matching model to improve equity and efficiency of COVID-19 contact tracing.

Contact tracing is a pillar of COVID-19 response, but language access and equity have posed major obstacles. COVID-19 has disproportionately affected minority communities with many non-English-speaking members. Language discordance can increase processing times and hamper the trust building necessary for effective contact tracing. We demonstrate how matching predicted patient language with contact tracer language can enhance contact tracing. First, we show how to use machine learning to combine information from sparse laboratory reports with richer census data to predict the language of an incoming case. Second, we embed this method in the highly demanding environment of actual contact tracing with high volumes of cases in Santa Clara County, CA. Third, we evaluate this language-matching intervention in a randomized controlled trial. We show that this low-touch intervention results in 1) significant time savings, shortening the time from opening of cases to completion of the initial interview by nearly 14 h and increasing same-day completion by 12%, and 2) improved engagement, reducing the refusal to interview by 4%. These findings have important implications for reducing social disparities in COVID-19; improving equity in healthcare access; and, more broadly, leveling language differences in public services.

Circulating Tumour Cell Numbers Correlate with Platelet Count and Circulating Lymphocyte Subsets in Men with Advanced Prostate Cancer: Data from the ExPeCT Clinical Trial (CTRIAL-IE 15-21).

Interactions between circulating tumour cells (CTCs) and platelets are thought to inhibit natural killer(NK)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or <25, were randomized to participate or not in a six-month exercise programme. Blood samples at randomization, and at three and six months, were subjected to ScreenCell filtration, circulating platelet counts were obtained, and flow cytometry was performed on a subset of samples (n = 29). CTC count positively correlated with absolute total lymphocyte count (r2 = 0.1709, p = 0.0258) and NK-cell count (r2 = 0.49, p < 0.0001). There was also a positive correlation between platelet count and CTC count (r2 = 0.094, p = 0.0001). Correlation was also demonstrated within the overweight/obese group (n = 123, p < 0.0001), the non-exercise group (n = 79, p = 0.001) and blood draw samples lacking platelet cloaking (n = 128, p < 0.0001). By flow cytometry, blood samples from the exercise group (n = 15) had a higher proportion of CD3+ T-lymphocytes (p = 0.0003) and lower proportions of B-lymphocytes (p = 0.0264) and NK-cells (p = 0.015) than the non-exercise group (n = 14). These findings suggest that CTCs engage in complex interactions with the coagulation cascade and innate immune system during intravascular transit, and they present an attractive target for directed therapy at a vulnerable stage in metastasis.

Selection of metastasis competent subclones in the tumour interior.

The genetic evolutionary features of solid tumour growth are becoming increasingly well described, but the spatial and physical nature of subclonal growth remains unclear. Here, we utilize 102 macroscopic whole-tumour images from clear cell renal cell carcinoma patients, with matched genetic and phenotypic data from 756 biopsies. Utilizing a digital image processing pipeline, a renal pathologist marked the boundaries between tumour and normal tissue and extracted positions of boundary line and biopsy regions to X and Y coordinates. We then integrated coordinates with genomic data to map exact spatial subclone locations, revealing how genetically distinct subclones grow and evolve spatially. We observed a phenotype of advanced and more aggressive subclonal growth in the tumour centre, characterized by an elevated burden of somatic copy number alterations and higher necrosis, proliferation rate and Fuhrman grade. Moreover, we found that metastasizing subclones preferentially originate from the tumour centre. Collectively, these observations suggest a model of accelerated evolution in the tumour interior, with harsh hypoxic environmental conditions leading to a greater opportunity for driver somatic copy number alterations to arise and expand due to selective advantage. Tumour subclone growth is predominantly spatially contiguous in nature. We found only two cases of subclone dispersal, one of which was associated with metastasis. The largest subclones spatially were dominated by driver somatic copy number alterations, suggesting that a large selective advantage can be conferred to subclones upon acquisition of these alterations. In conclusion, spatial dynamics is strongly associated with genomic alterations and plays an important role in tumour evolution.

Introduction, Transmission Dynamics, and Fate of Early Severe Acute Respiratory Syndrome Coronavirus 2 Lineages in Santa Clara County, California.

We combined viral genome sequencing with contact tracing to investigate introduction and evolution of severe acute respiratory syndrome coronavirus 2 lineages in Santa Clara County, California, from 27 January to 21 March 2020. From 558 persons with coronavirus disease 2019, 101 genomes from 143 available clinical samples comprised 17 lineages, including SCC1 (n = 41), WA1 (n = 9; including the first 2 reported deaths in the United States, with postmortem diagnosis), D614G (n = 4), ancestral Wuhan Hu-1 (n = 21), and 13 others (n = 26). Public health intervention may have curtailed the persistence of lineages that appeared transiently during February and March. By August, only D614G lineages introduced after 21 March were circulating in Santa Clara County.