ABSTRACT
Breast cancer is the most common form of cancer and the second cancer-causing death in females. Although remission rates are high if detected early, survival rates drop substantially when breast cancer becomes metastatic. The most common sites of metastatic breast cancer are bone, liver and lung. Respiratory viral infections inflict illnesses on countless people. The latest pandemic caused by the respiratory virus, SARS-CoV-2, has infected more than 600 million worldwide, with documented COVID-related death upward of 1 million in the United States alone. Respiratory viral infections result in increased inflammation with immune cell influx and expansion to facilitate viral clearance. Prior studies have shown that inflammation, including through neutrophils, can contribute to dormant cancer cells reawakening and outgrowth. Moreover, inhibition of IL6 has been shown to decrease breast cancer lung metastasis in mouse models. However, how respiratory viral infections contribute to breast cancer lung metastasis remains to be unraveled. Using MMTV/PyMT and MMTV/NEU mouse models of breast cancer lung metastasis and influenza A virus as a model respiratory virus, we demonstrated that acute influenza infection and the accompanying inflammation and immune cell influx awakens and dramatically increased proliferation and expansion of dormant disseminated cancer cells (DCC) in the lungs. Acute influenza infection leads to immune influx and expansion, including neutrophils and macrophages, with increased proportion of MHCII+ macrophages in early time points, and a sustained decrease in CD206+ macrophages starting 6 days post-infection until 28 days after the initial infection. Additionally, we observed a sustained accumulation of CD4+ T cells around expanding tumor cells for as long as 28 days after the infection. Notably, neutrophil depletion or IL6 knockout reversed the flu-induced dormant cell expansion in the lung. Finally, awakened DCC exhibited downregulation of vimentin immunoreactivity, suggesting a role for phenotypic plasticity in DCC outgrowth following viral infection. In conclusion, we show that respiratory viral infections awaken and increase proliferation of dormant breast cancer cells in the lung, and that depletion of neutrophils or blocking IL6 reverses influenza-induced dormant cell awakening and proliferation.
ABSTRACT
Background: mRNA vaccines have proven useful in protecting vulnerable populations against SARS-CoV-2 infection. However, certain therapeutics, specifically those used in cancer treatment, reduce mRNA vaccine-induced humoral responses against SARS-CoV-2. The effects on T cell responses are not well characterized. Here, we evaluate SARS-CoV-2 spike-specific T cell responses over the course of one year in solid tumor patients in BC, Canada. Method(s): 18 female, solid-tumor patients from the BC Cancer Agency were enrolled in this prospective, cohort study, with 7 patients receiving cytotoxic chemotherapy and 11 patients receiving non-cytotoxic treatments. Whole blood was collected 1-month (T1) and one-year +/- 1-month (T2) post series completion (2 mRNA doses). Antigen-induced marker assays (AIM assays) were used to quantify CD4+ and CD8+ T cell responses, where whole blood was stimulated with ancestral or omicron SARS-CoV2 Spike peptide pools or unstimulated for 48 hours at 37degree C, fluorescently stained for activation markers CD25 and OX40 (CD4+ T cells) or CD69 and CD137 (CD8+ T cells), and analyzed using a 5-laser flow cytometer. Phenotyping of antigen-specific CD4+ T cells was done in parallel to assess the frequency of spike-specific Tregs, Th1, Th2, Th9, Th17, and Th17.1 cells. Result(s): All individuals had detectable levels of spike-specific CD4+ T cells at T2, while only 72.2% of individuals had detectable levels of spike-specific CD8+ T cells. Treatment type did not significantly impact the magnitude or phenotype of T cell responses, including those to Omicron. However, increased age was associated with decreased ancestral CD8+ T cell responses at T2. Further, ancestral and omicron responses were significantly different at T2, with decreased magnitude and altered phenotype of omicron-specific CD4+ T cells. Conclusion(s): Here, we report that solid tumor patients, treated with either chemotherapy or biologics, mount robust T cell immunity to SARS-CoV-2 following vaccination. Additional data is needed to determine if these responses correlate with antibody levels and clinical illness.
ABSTRACT
Since the first detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus remains a public health concern. Several public health measures have been implemented in an effort to curb the infections. However, the effectiveness of these strategies was threatened with the emergence of numerous SARS-CoV-2 variants in all parts of the globe, due to the persistent mutations as part of the viral evolution. Mutations that usually occur in its spike glycoprotein, allow SARS-CoV-2 to possess advantageous characteristics for its survivability and persistence. This has led to poor performance of diagnostic kits which have caused non-specific and insensitive detection of these variants, resulting in undetermined infection. The variants also have caused the increased severity of COVID-19, involving hospitalisation rates, ICU admissions, and deaths. Many have reported the vaccine-breakthrough infections and reduced effectiveness of vaccination, which is supposed to provide an effective degree of protection against COVID-19 infections. Due to these issues, this review summarises the impacts related to SARS-CoV-2 variants emergence towards the performance of diagnostic kits, transmissibility of the virus, severity of disease, and effectiveness of COVID-19 vaccines.
ABSTRACT
Since the first detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus remains a public health concern. Several public health measures have been implemented in an effort to curb the infections. However, the effectiveness of these strategies was threatened with the emergence of numerous SARS-CoV-2 variants in all parts of the globe, due to the persistent mutations as part of the viral evolution. Mutations that usually occur in its spike glycoprotein, allow SARS-CoV-2 to possess advantageous characteristics for its survivability and persistence. This has led to poor performance of diagnostic kits which have caused non-specific and insensitive detection of these variants, resulting in undetermined infection. The variants also have caused the increased severity of COVID-19, involving hospitalisation rates, ICU admissions, and deaths. Many have reported the vaccine-breakthrough infections and reduced effectiveness of vaccination, which is supposed to provide an effective degree of protection against COVID-19 infections. Due to these issues, this review summarises the impacts related to SARS-CoV-2 variants emergence towards the performance of diagnostic kits, transmissibility of the virus, severity of disease, and effectiveness of COVID-19 vaccines. Copyright © The Author(s) 2022.
ABSTRACT
BACKGROUND: Suboptimal transitions from emergency department (ED) to ambulatory settings contribute to poor clinical outcomes and unnecessary non-urgent ED utilization. Primary care-staffed care transition clinics (CTCs) are a potential solution to reduce ED crowding by providing ED follow-up care and facilitating the bridge to longer-term primary care. This study is a preliminary evaluation of the initiation of an ED transitions clinic on 30-day ED and hospital readmissions. METHODS: This retrospective cross-sectional study included adults discharged from the ED at UC hicago Medicine referred to the transitions clinic between November 2020 and May 2021. Appointment attendance, frequency of care type provided, and percent contacted with patient advocate were computed to assess clinic utilization. 30-day ED and hospital readmissions were compared between patients who completed their CTC appointment and patients who missed their CTC appointment using a chi-square test. RESULTS: In the first 6 months of program initiation, 116 patients were referred to the CTC from the ED and around half (47%) completed their follow-up appointment. The majority of patients were of black race (90%) and on public insurance (81%). Almost a quarter of referred patients (22%) were contacted by a patient advocate for referral to longer-term care. The most common reasons for referral were wound check (top 3: cellulitis, abscess, suture removal) and clinical problem management (top 3: SOB, chest pain, covid). Wound checks were 20% more likely to be completed compared to clinical appointments (58% show rate vs 38%). Patients who completed their CTC appointment had a lower rate of ED revisits (15% vs 20%) but the effect was not statistically significant (p>0.05). No statistically significant effects were seen for CTC appointment completion on hospital readmission. CONCLUSIONS: Transition clinics may have the potential to help reduce excess ED use for ambulatory care needs, particularly if they can help facilitate patients being connected to more permanent ambulatory care sites and clinicians. In addition to ongoing analysis of this program evaluation regarding ED and hospital utilization, additional research is needed to investigate the factors influencing follow-up completion and identifying effective interventions for increasing appointment attendance.
ABSTRACT
Background: When the first wave of COVID-19 hit globally in early 2020, concerns were raised about access to surgical interventions for cancer patients. It was considered that neoadjuvant therapy (NAT) although conventionally given to locally advanced breast cancer may need to also be provided to earlier-stage disease. In addition, due to the temporary closure of breast cancer screening programs during the pandemic, concerns were raised about patients presenting with later-stage disease at initial diagnosis. This project aims to assess the impact of COVID-19 on the volume of neoadjuvant referrals at a large cancer centre, as well as any stage migration, impact on treatment timelines and impact on outcomes for breast cancer patients compared to the pre-pandemic population. Methods: The BC Cancer Vancouver centre has a neoadjuvant breast cancer program to ensure high quality of care is maintained. This program's prospective database of breast cancer patients referred for and treated with NAT between the years 2012-2021 was queried to assess data on neoadjuvant referrals, clinical stage, receptor status, treatment timelines, and outcomes between January 1, 2019-December 31, 2020. Data from the years 2019 and 2020 were compared to evaluate the impact of COVID-19 on NAT. Summary data available from earlier years were also utilized as reference. Results: The COVID-19 pandemic resulted in a 51% increase in Sthe number of patients referred to the neoadjuvant program, with 102 patients referred for NAT in 2019, whereas 154 patients were referred in 2020. This proportional increase in referrals is higher than any other year since the database inception. Of note, during 2020 there were no COVID related closures for cancer surgeries in the province. The proportion of patients referred who received NAT remained similar between 2019 and 2020 (69.1% vs 70.8% in 2020). The trend in referrals by month varied between the two years. In 2019, the majority of patients were referred between April to July with the lowest proportion of referrals in October to December. In 2020, the opposite occurred with the lowest proportion of referrals transpiring between January-June, and the greatest proportion in October to December. The proportion of patients who presented with de-novo metastatic disease was consistent between the two years (7.8% in 2019 vs 9.7% in 2020). Despite the closure of all screening mammography programs between March-June of 2020, the clinical stage and receptor status are equivalent between 2019 and 2020. With regards to treatment timelines, there was a 3 day increase in the median time between referral date and medical oncology consultation in 2020 compared to 2019. No other treatment timeline delays were found between 2019 and 2020. With regards to outcomes, 34.9% of patients achieved pCR in 2019, but only 24.1% achieved pCR in 2020, despite similar stage and receptor subtypes. Conclusion: During the COVID-19 pandemic in 2020, a higher volume of patients were referred for NAT than had ever before been referred, despite the fact that there were no closures of operating rooms in our province for COVID-19. From a quality of care perspective there was a delay in referral to consultation for medical oncology, but no delay on referral to treatment, treatment to surgery, or surgery to radiation. However, and a significantly lower pCR rates was seen in 2020 compared to 2019. The 10% decrease in pCR rates may have resulted from increased complexity in breast cancer cases. This trend may continue, as the impact of COVID-19 on breast cancer outcomes will likely take many years to fully appreciate. Attention should be paid to encouraging women to return to regular breast screening programs to decrease the number of patients needing neoadjuvant therapy.
ABSTRACT
As businesses adapt during the recovery phase of COVID-19, there has been a major reset in the way work activities are prepared, conducted, and delivered. In this challenging environment, it may not be prudent or possible to have face-to-face workshops involving key personnel. This certainly applies to the conduct of hazard management training, where personnel would typically learn, apply, and reinforce the required learning competencies in a collegiate environment. It has become evident that facilitators have had to alter the way they organize and deliver content in a virtual environment to ensure that there is no adverse change in quality. The challenge is to maintain engagement and foster a nurturing environment to promote learning and communication among the learners as well as between the learners and facilitator(s). This paper relays the good and bad experiences from Sherpa's delivery of hazard management virtual training to operating facilities located nationally and overseas. Sherpa identified eight key steps in the plan and prepare phase of developing a training session that can be used to equip facilitators with operational agility. Sherpa then developed solutions to overcome the challenges of a virtual environment and ensure that key learning outcomes are successfully delivered. © 2022 American Institute of Chemical Engineers
ABSTRACT
We aimed to perform meta-analyses to summarize the overall effectiveness of the mRNA-1273 vaccine against COVID-19 caused by the Delta variant from real-world studies. A systematic literature search with no language restriction was performed in electronic databases to identify eligible observational studies that reported the effectiveness of the mRNA-1273 vaccine to prevent reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19 caused by Delta variant of SARS-CoV-2 (B.1.617.2). A random-effects meta-analysis model was used to estimate the pooled odds ratio (OR) at a 95% confidence interval (CI), and the vaccine effectiveness was indicated as (pooled OR - 1)/OR. Five studies were included for this systematic review and meta-analysis. The meta-analysis revealed that the administration of mRNA-1273 vaccine protected against RT-PCR confirmed COVID-19 caused by Delta variant ≥21 days post first dose, with pooled vaccine effectiveness of 66% (95% CI: 65%-67%), as well as ≥14 days after the second dose, with pooled vaccine effectiveness of 91% (95% CI: 84%-95%). In conclusion, the mRNA-1273 vaccine offers a substantial protection rate against RT-PCR confirmed COVID-19 caused by the Delta variant upon full vaccination, although with slightly reduced effectiveness relative to other strains of SARS-CoV-2.