Nebulized recombinant tissue plasminogen activator (rt-PA) for acute COVID-19-induced severe respiratory failure: an exploratory proof of concept trial (preprint)

Nebulized thrombolysis offers locally targeted therapy with potentially lower bleeding risk than systemic administration for coronavirus disease 2019 (COVID-19) respiratory failure. In a proof-of-concept safety study, adult patients with COVID-19-induced respiratory failure and a <300mmHg PaO2/FiO2 (P/F) ratio, requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care during the first two UK COVID-19 waves. Matched historical controls (MHC; n=18) were used in C1. Safety co-primary endpoints were treatment-related bleeds and fibrinogen reduction to <1.0–1.5 g/L. A dose escalation strategy for improved efficacy with the least safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA per day for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeding events (one severe and three mild) in three patients were considered treatment-related. No significant fibrinogen reductions were reported. Greater improvement in mean P/F ratio from baseline to end of study was observed in C1 compared with MHC [C1; 154 to 299 vs MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in P/F ratio was observed in NIRS patients [NIRS; 126 to 240 vs IMV; 120 to 188) and they required fewer treatment days (NIRS; 7.86 vs IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, showing a trend of improved oxygenation and faster recovery in patients with acute COVID-19-induced respiratory failure requiring respiratory support; this effect was more pronounced in the NIRS group. Further investigation is required to study the potential of this novel treatment approach.

How has the COVID-19 pandemic affected patients with primary bladder cancer?

PURPOSE: The COVID-19-induced effects of primary bladder cancer (BC) patients have not yet been clarified. The aim of this study was to investigate the effects of the pandemic on the diagnosis, treatment, and follow-up of primary BC patients. MATERIAL AND METHODS: A retrospective single-center analysis was made of all patients who underwent diagnostic and surgical procedures due to primary BC between November 2018 and July 2021. A total of 275 patients were identified and allocated to one of the groups: Pre-COVIDBC (BC diagnosed before the COVID-19 pandemic) or COVIDBC (during the pandemic). RESULTS: The BC patients diagnosed during the pandemic were mostly at higher stages (T2) (p = 0.04), the risk of non-muscle invasive BC (NMIBC) was higher (p = 0.02), and recurrence and progression scores were increased (p = 0.001) compared to patients diagnosed before the pandemic. The time to surgery from diagnosis (p = 0.001) and symptom duration (p = 0.04) were significantly prolonged during the pandemic and the rate of follow-up significantly decreased (p = 0.03). CONCLUSIONS: The study results highlight the significant increase in muscle invasive BC and the very high risk of NMIBC in patients presenting during the COVID-19 pandemic.

ANTECEDENTES: Los efectos inducidos por la COVID-19 en pacientes con cáncer de vejiga primario no están aclarados actualmente. OBJETIVO: Investigar los efectos de la pandemia en el diagnóstico, el tratamiento y el seguimiento del cáncer de vejiga primario. MÉTODO: Se realizó un análisis retrospectivo unicéntrico de todos los pacientes que se sometieron a procedimientos diagnósticos y quirúrgicos por cáncer primario de vejiga durante noviembre de 2018 y julio de 2021. Se incluyeron 275 pacientes en el estudio. Los pacientes fueron asignados a uno de dos grupos: pre-COVIDBC (antes de la pandemia) o COVIDBC (durante la pandemia). RESULTADOS: Los pacientes con cáncer de vejiga diagnosticados durante la pandemia se encontraban en su mayoría en estadios más altos (T2) (p = 0.04), el grupo de riesgo era más alto en el cáncer de vejiga no invasivo del músculo (p = 0.02), y la recurrencia y las puntuaciones de progresión aumentaron (p = 0.001) en comparación con antes del período pandémico. Además, el tiempo hasta la cirugía desde el diagnóstico (p = 0.001) y la duración de los síntomas (p = 0.04) aumentaron considerablemente durante la pandemia, y la tasa de seguimiento disminuyó significativamente (p = 0.03). CONCLUSIONES: Destaca el aumento significativo del cáncer de vejiga invasivo del músculo y del cáncer de vejiga no invasivo del músculo de muy alto riesgo durante la pandemia.

Candida Auris Blood Stream Infection- A Descriptive Study from Qatar (preprint)

Background: Candida auris is an emerging yeast pathogen that can cause invasive infections, particularly candidemia in healthcare settings.  Candida auris is characterized by resistance to multiple classes of antifungal drugs and high mortality. Objective: To describe the risk factors, clinical characteristics, antifungal susceptibility pattern and outcomes of Candida auris blood stream infection. Methods: We conducted a retrospective review of electronic medical records of C. auris fungemia cases in the facilities under Hamad Medical corporation, Qatar from 1/11/2018 to 31/7/2021. Demographic data, risk factors, antibiogram and 30-day outcome are described Results: We identified 36 patients with C. auris fungemia. Most of the patients were in intensive care unit following severe covid-19 pneumonia and had received steroid and broad-spectrum antibiotics. Most of the cases were central line related.  Over 90% of isolates were non-susceptible to fluconazole. Amphotericin B sensitivity was only 15.2 %. Isolates from all patients were sensitive to echinocandins and these were used as first line therapy. Factors associated with high mortality included initial SOFA score of 9 or above and whether source control was attained.  Conclusion: 30-day mortality rate in Candida auris candidemia is 41.6%. Amphotericin B resistance in Qatar is much higher compared to published literature. Echinocandins are the drugs of choice for treatment, retaining almost 100% susceptibility.

Experience with Intraoperative Radiation Therapy in an Urban Cancer Center (preprint)

Background/Objective: Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large, randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial and aim to report our early results thus far. Methods: We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER+ patients with grade 1-2 DCIS ≤ 2.5cm or invasive disease ≤ 3.5cm in patients of at least 45 years of age. Results: Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER+ breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7– 54.8 months). Conclusions: IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. Trial Registration: All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018-9409).

Effects of intravesical BCG maintenance therapy duration on recurrence rate in high-risk non-muscle invasive bladder cancer (NMIBC): Systematic review and network meta-analysis according to EAU COVID-19 recommendations.

PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic, the European Association of Urology (EAU) recommended that courses of intravesical bacillus Calmette-Guérin (BCG) therapy lasting more than 1 year could be safely terminated for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Thus, we conducted a systematic review and network meta-analysis according to EAU's COVID-19 recommendations. MATERIALS AND METHODS: A systematic review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We conducted a network meta-analysis of recurrence rate in patients with NMIBC receiving induction therapy (M0) and those receiving maintenance therapy lasting 1 year (M1) and more than 1 year (M2). RESULTS: Nineteen studies of 3,957 patients were included for the network meta-analysis. In a node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there were no differences between the M1 and M2 groups in recurrence rate [odds ratio (OR) 0.95 (0.73-1.2)]. However, recurrence rate in the M0 group was higher than that in the M1 [OR 1.9 (1.5-2.5)] and M2 [OR 2.0 (1.7-2.4)] groups. P-score tests using frequentist inference to rank the treatments in the network demonstrated that the therapy used in the M2 group (P-score 0.8701) was superior to that used in the M1 (P-score 0.6299) and M0 groups (P-score 0). In rank-probability tests using MCMC modeling, the M2 group showed the highest rank, followed by the M1 and M0 groups. CONCLUSION: In the network meta-analysis, there were no differences between those receiving BCG maintenance therapies in terms of recurrence rate. In the rank tests, therapy lasting more than 1-year appears to be most effective. During the COVID-19 pandemic, 1-year maintenance therapy can be used, but after the COVID-19 pandemic, therapy lasting more than 1-year could be beneficial.

Factors associated with non-invasive positive pressure ventilation failure in a COVID-19 Intermediate Care Unit (preprint)

Background: The use of non-invasive positive pressure ventilation (NIPPV) in COVID-19 patients with hypoxaemia is still under debate. The aim was to evaluate the efficacy of NIPPV (CPAP, HELMET-CPAP or NIV) in COVID-19 patients treated in the dedicated COVID-19 Intermediate Care Unit of Coimbra Hospital and University Centre, Portugal, and to assess factors associated with NIPPV failure. Patients admitted from December 1st 2020 to February 28th 2021, treated with NIPPV due to COVID-19 were included. Failure was defined as orotracheal intubation (OTI) or death during hospital stay. Factors associated with NIPPV failure were included in a univariate binary logistic regression analysis; those with a significance level of p < 0.001 entered a multivariate logistic regression model.Results: A total of 163 patients were included, 64.4% were males (n = 105). The median age was 66 years (IQR 56–75). NIPPV failure was observed in 66 (40.5%) patients, 26 (39.4%) were intubated and 40 (60.6%) died during hospital stay. Highest CRP (OR 1.164; 95%CI 1.036–1.308) and morphine use (OR 24.771; 95%CI 1.809-339.241) were identified as predictors of failure after applying multivariate logistic regression. Adherence to prone positioning (OR 0.109; 95%CI 0.017-0.700) and a higher value of the lowest platelet count during hospital stay (OR 0.977; 95%CI 0.960–0.994) were associated with a favourable outcome.Conclusions: NIPPV was successful in 59.5% of patients. Highest CRP during hospital stay and morphine use were predictors of failure. Adherence to prone positioning and a higher value of the lowest platelet count during hospital stay were associated with a favourable outcome.

Study protocol: Medium throughput proteomic characterization of children with PIMS-TS, and identification of candidate diagnostic biomarkers. (preprint)

SARS-CoV-2 infection in children results in a wide range of clinical outcomes. Paediatric Multisystem Inflammatory syndrome temporally associated with COVID-19(PIMS-TS) occurs weeks after a SARS-CoV-2 infection, and results in severe illness. This protocol describes a study to fully characterize the circulating proteome of children who have PIMS-TS, the proteome of healthy children who have previously been infected with SARS-CoV-2 and the proteome of febrile children with a confirmed invasive infection. Orthogonal proteomic techniques will be utilized to provide a deep proteomic characterization

High flow nasal oxygen therapy compared with conventional oxygen therapy in hospitalised patients with respiratory illness: a systematic review and meta-analysis (preprint)

Background This systematic review aims to summarise the evidence regarding any benefits of high flow nasal oxygen (HFNO) therapy compared to conventional oxygen therapy (COT) in hospitalised patients with acute or chronic respiratory illnesses.Methods A comprehensive search was performed across three databases for studies that reported any of: escalation to invasive mechanical ventilation (IMV), mortality, length of stay, carbon dioxide levels, disability, or admission rates.Results In patients with acute respiratory illnesses, pooled RCT data revealed no significant differences between HFNO and COT in overall need for IMV (RR = 0.82, 95% CI = 0.65–1.05; p = 0.11; n = 15 RCTs) or in-hospital mortality (RR = 1.00, 95% CI 0.85–1.17; p = 1.00; n = 5). Similarly, for patients with chronic respiratory illnesses, RCT data revealed no significant difference in overall need for IMV (RR = 0.86, 95% CI = 0.33–2.23; p = 0.76; n = 4) or in-hospital mortality (RR = 0.40, 95% CI = 0.04–4.10; p = 0.44; n = 1) for HFNO compared to COT. Patients with COVID-19 receiving HFNO had a significantly reduced need for IMV (RR = 0.72, 95% CI = 0.63–0.82; p < 0.001), short-term mortality (RR = 0.62, 95% CI = 0.48–0.79; p < 0.001), and long-term mortality (RR = 0.67, 95% CI = 0.48–0.92; p = 0.01).Conclusion HFNO did not significantly reduce the need for IMV escalation or in-hospital mortality in patients with acute or chronic respiratory illnesses, except for patients with COVID-19.

Sustained reductions in life-threatening invasive bacterial diseases during the first two years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries participating in the IRIS Consortium (preprint)

Background The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Streptococcus agalactiae. Here we analyse the incidence and distribution of disease during the first two years of the pandemic. Methods Laboratories in 30 countries/territories representing five continents submitted case data from 2018-2021 to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype/group were examined. Interrupted time series analyses quantified the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models estimated effect sizes and forecasted counterfactual trends by hemisphere. Findings Overall, 116,841 cases were analysed: 76,481 (2018-2019, pre-pandemic) plus 40,360 (2020-2021, pandemic). During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio: 0.47; 95% confidence interval: 0.40-0.55), H influenzae (0.51; 0.40-0.66) and N meningitidis (0.26; 0.21-0.31), whereas no significant changes were observed for the non-respiratory-transmitted pathogen S agalactiae (1.02; 0.75-1.40). No major changes in the distribution of cases were observed when stratified by patient age or serotype/group. An estimated 36,289 (17,145-55,434) cases of invasive bacterial disease were averted during the first two years of the pandemic among IRIS participating countries/territories. Interpretation COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae and N meningitidis during the first two years of the pandemic, but cases began to increase in some countries as pandemic restrictions were lifted.

INCREASE IN INVASIVE GROUP A STREPTOCOCCAL INFECTIONS IN CHILDREN IN THE NETHERLANDS, A SURVEY AMONG 7 HOSPITALS IN 2022 (preprint)

Based on a survey sent to seven Dutch hospitals, we observed an substantial increase in invasive group A streptococcal infections in children in the Netherlands, comparing the pre-COVID-19 pandemic cohort of 2018-2019 to 2021-2022. The most affected age group were children between 0-5 years. Main diagnosis was pneumonia with empyema. Necrotizing fasciitis and streptococcal toxic shock syndrome were also reported in 11% and 7% respectively. A significant number was admitted to the Paediatric Intensive Care Unit. Vigilance is needed.

Rarely Described Renal Malignancies Associated With Venous Tumor Thrombus.

BACKGROUND/AIM: Collecting duct carcinoma, epithelioid angiosarcoma and neuroendocrine/carcinoid tumor are uncommon renal malignancies, and their association with tumor thrombus extending into the inferior vena cava is extremely rare. Owing to the rarity of the above-mentioned malignancies and short follow-up of the cases published in the literature, the prognosis and clinical behavior of these tumors remains unclear. Up to date, the culprit of treatment is surgical management with radical nephrectomy, lymph node dissection, thrombectomy and vascular reconstruction if necessary. PATIENTS AND METHODS: We herein describe in detail the first cases published of the above-mentioned renal malignancies associated with extensive inferior vena cava (IVC) thrombus, in which complex vascular reconstruction was performed. RESULTS: Three male patients were identified as having collecting duct carcinoma, epithelioid angiosarcoma and neuroendocrine/carcinoid tumor with IVC involvement. Tumor thrombus levels were II, I and IIIc respectively. Patient ages were 42, 60 and 47 years and tumor sizes were 9.2, 10.9 and 3.7 cm correspondingly. Patient 2 underwent cavectomy, IVC replacement using polytetrafluoroethylene (Gore-Tex®) vascular graft and IVC filter deployment inside the graft. None of the patients developed any pulmonary emboli postoperatively. At the last follow-up, IVC graft for patient 2 remained patent. CONCLUSION: Owing to the rarity of the aforementioned malignancies and short follow-up of cases published in the literature, the prognosis and clinical behavior of these tumors remains unclear. Up to date, the culprit of treatment is surgical management with radical nephrectomy, lymph node dissection, thrombectomy and vascular reconstruction if necessary. Polytetrafluoroethylene (Gore-Tex) vascular grafts are an excellent and safe option for complex vascular reconstructions in patients with evidence of IVC invasion.

Effect of neoadjuvant chemotherapy on overall survival of patients with T2-4aN0M0 bladder cancer: A systematic review and meta-analysis according to EAU COVID-19 recommendation.

PURPOSE: In the context of the COVID-19 outbreak, the European Association of Urology (EAU) guidelines Rapid Reaction Group provided recommendations to manage muscle invasive bladder cancer (MIBC) based on priority levels: neoadjuvant chemotherapy (NAC) should be avoided for patients with T2-3N0M0 MIBC. This meta-analysis aims to evaluate the efficacy of NAC compared with radical cystectomy (RC) alone in improving the overall survival (OS) of patients with T2-4aN0M0 MIBC. MATERIALS AND METHODS: A systematic review was performed according to the PRISMA guidelines. The PubMed/Medline, EMBASE, and Cochrane Library databases were searched. The primary outcome was OS of patients with T2-4aN0M0 MIBC, and the secondary outcome was OS of patients with only T2N0M0 MIBC. RESULTS: Eight studies were included in this meta-analysis. Overall, the quality of all studies was relatively high, and little publication bias was demonstrated. The OS was significantly better in the NAC with RC group than in RC alone (HR, 0.79; 95% CI, 0.68-0.92; p = 0.002). A subgroup analysis was performed on only patients with T2N0M0 MIBC, and five studies were included. There was no difference in the OS between the NAC with RC and the RC alone groups (HR, 0.83; 95% CI, 0.69-1.01 p = 0.06). CONCLUSIONS: As recommended by the EAU guidelines Rapid Reaction Group, patients with T2N0M0 MIBC should strongly consider omitting NAC until the end of the COVID-19 pandemic. Whether to omit NAC in T3-4aN0M0 MIBC needs further discussion, and studies targeting only T2-3N0M0 MIBC are expected to proceed further.

CD4+ T cell-induced inflammatory killing controls immune evasive tumours (preprint)

Current clinically applied cancer immunotherapies largely focus on the ability of CD8+ cytolytic T-cells to directly recognise and kill tumour cells1–3. These strategies are limited by the emergence of MHC-I-deficient or IFN-unresponsive tumour cells and the development of an immunosuppressive tumour microenvironment4–6. CD4+ effector T-cells can contribute to tumour immune defence independent of CD8+ T-cells. However, the potential and the mechanisms of CD4+ T-cell-mediated anti-tumour immunity are incompletely understood7–12. Here, we show how an indirect CD4+ T-cell-mediated mode of action, that is fundamentally different from CD8+ T-cells, enables the eradication of tumours that would otherwise escape direct T-cell targeting. CD4+ effector T-cells preferentially cluster at tumour invasive margins where they engage in antigen-specific interactions with MHC-II+CD11c+ cells, while CD8+ T-cells briskly infiltrate tumour tissues. CD4+ T-cells and innate immune stimulation reprogram the tumour-associated inflammatory monocyte network towards IFN-activated antigen-presenting and tumouricidal effector phenotypes. This results in an amplification loop driving the release of T-cell-derived IFNγ and myeloid cell-derived nitric oxide which cooperatively induce apoptotic death of MHC-deficient and IFN-unresponsive tumour cells that escape cytolytic CD8+ T-cell therapy. Exploiting the ability of CD4+ T-cells to orchestrate indirect inflammatory killing of tumour cells complements the direct cytolytic activity of T-cells to advance cancer immunotherapies.

Outcomes by time to definitive chemoradiation treatment for patients with muscle-invasive bladder cancer.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has raised concerns about delaying treatment for localized cancer and its impact on long-term outcomes. OBJECTIVE: We aimed to investigate the impact of time to chemoradiation (CRT) on recurrence and survival outcomes for patients with muscle-invasive bladder cancer (MIBC). METHODS: In the national Veterans Affairs' database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 to 2018 and treated with definitive CRT. Time to treatment was defined as the number of days between date of diagnosis and start date of CRT. The cohort was stratified into < 90 (early) or ≥ 90 days (delayed) groups. Endpoints of locoregional failure (LRF), distant failure (DF), overall survival (OS), and bladder cancer-specific survival (BCS) were evaluated in multivariable Cox and Fine-Gray models. RESULTS: 305 patients with MIBC underwent CRT - 190 (62.3%) received early CRT, 115 (37.7%) received delayed CRT. Multivariable analysis (including success of transurethral resection of bladder tumor and type of chemotherapy) revealed no difference in recurrence between groups - LRF HR 1.12 (95%CI 0.76-1.67, P = 0.56) and DF HR 1.03 (95%CI 0.70-1.53, P = 0.88). Similarly, there were no differences in survival outcomes. The lack of association was maintained at both earlier and later time cutoffs (60-120 days). CONCLUSIONS: Our findings suggest that a short-term delay in definitive therapy may not affect long-term outcomes for patients with MIBC undergoing CRT. This study does not endorse delays in therapy, but rather provides information to aid patients and clinicians navigate the unique challenges of MIBC care in both pandemic and non-pandemic times.

Interlobular Septal Thickening in a Young Man With Dyspnea.

CASE PRESENTATION: A 30-year-old man with a history of childhood asthma, a 15-pack-year smoking history, and methamphetamine abuse was intubated and started on mechanical ventilation because of acute hypoxic respiratory failure after experiencing progressive dyspnea and a nonproductive cough over the previous year. During the previous 3 months, he had multiple clinic visits, with chest radiographs showing diffuse, bilateral, reticulonodular opacities and small bilateral pleural effusions and was treated for community-acquired pneumonia. Testing for COVID pneumonia was negative, and he failed to respond to antimicrobial therapy. Physical examination on admission showed diffuse fine crackles bilaterally on lung auscultation. Admission laboratory test results were unremarkable.

How Does Invasive Breast Cancer Oncotype Dx Recurrence Score on Core Needle Biopsies Influence Neoadjuvant Treatment Decision? A Descriptive Study.

BACKGROUND: Oncotype Dx (ODx) is a genomic assay which estimates the risk of distant recurrence and predicts adjuvant chemotherapy benefit in early stage breast cancer patients. Most ODx data is derived from excisional specimens. AIM: We assess the utility of ODx on core needle biopsies (CNB) and measure its impact on neoadjuvant treatment decisions, particularly in patients with clinically complicated situations. METHODS: Consecutive ODx results on breast CNBs with invasive carcinoma from 2012-2020 at 3 tertiary care hospitals with dedicated Breast Health Centers were reviewed. Clinical indications to perform ODx on CNB were recorded through a review of patients' electronic medical records. Clinicopathologic features, surgical or oncologic modalities and follow-up data were recorded. RESULTS: Three distinct clinical indications for performing ODx on CNB in 85 ER+ invasive breast carcinomas were identified: 1) Excisions with insufficient tissue to perform ODx, 2) adjudicate neoadjuvant therapy versus primary surgical resection, and 3) select neoadjuvant chemotherapy (NAC) versus neoadjuvant endocrine therapy (NET). Primary surgery was selected in patients with low score RS (<18), and NET was preferred in patients with intermediate or high RS (>18). NET was preferred over NAC in patients with low RS (<18). CONCLUSION: This study shows that CNB ODx RS helps guide treatment decisions in a neoadjuvant setting along with other contributing factors such as the presence of pathogenic mutations, node positivity, patient age, and comorbidities. The use of ODx on CNB is furthermore valuable in the midst of the COVID-19 pandemic for early breast cancer patients to administer effective therapy in a timely manner.

Right Ventricular Dysfunction in Ventilated Patients with COVID-19 (COVID-RV) (preprint)

ABSTRACT Purpose COVID-19 is associated with cardiovascular complications, with right ventricular dysfunction (RVD) commonly reported. The combination of acute respiratory distress syndrome (ARDS), injurious invasive ventilation, micro/macro thrombi and the potential for direct myocardial injury create conditions where RVD is likely to occur. No study has prospectively explored the prevalence of RVD, and its association with mortality, in a cohort requiring mechanical ventilation. Methods Prospective, multi-centre, trans-thoracic echocardiographic, cohort study of ventilated patients with COVID-19 in Scottish intensive care units. RVD was defined as the presence of severe RV dilatation and interventricular septal flattening. To explore role of myocardial injury, high sensitivity troponin and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured in all patients. Results One hundred and twenty-one patients were recruited to COVID-RV, 118 underwent imaging and it was possible to determine the primary outcome in 112. RVD was present in seven (6.2% [95%CI; 2.5%, 12.5%]) patients. Thirty-day mortality was 85.7% in those with RVD, compared to 44.8% in those without (p=0.051). Patients with RVD were more likely to have; pulmonary thromboembolism (p<0.001), higher plateau pressure (p=0.048), lower dynamic compliance (p=0.031), higher NT-proBNP (p<0.006) and more frequent abnormal troponin (p=0.048). Abnormal NT-proBNP (OR 4.77 [1.22, 21.32], p=0.03) and abnormal Troponin (16.54 [4.98, 67.12], p<0.001) independently predicted 30-day mortality. Conclusion COVID-RV demonstrates a prevalence of RVD in ventilated patients with COVID-19 of 6.2% and is associated with a mortality of 85.7%. Association is observed between RVD and each of the aetiological domains of; ARDS, ventilation, micro/macro thrombi and myocardial injury.