A Rare Case of Right Atrial Thrombus in a Patient With Recurrent Classical Hodgkin Lymphoma.

Patients with cancer are at risk for thrombotic complications due to a hypercoagulable state. However, the benefit of prophylactic anticoagulation is unclear in many subsets of these patients. For the first episode of acute thromboembolic disease (VTE) in patients with active cancer, anticoagulant therapy is administered for at least three to six months. Herein, we present a 31-year-old female with active, recurrent stage IIIa classical Hodgkin lymphoma (CHL) (nodular sclerosis), previously treated for proximal upper extremity deep vein thrombosis (DVT), presenting for evaluation of shortness of breath and eventually diagnosed with bilateral pulmonary embolism (PE) secondary to a right atrial thrombus. The patient was successfully treated with surgical resection of the thrombus. With this case report, we hope to encourage physicians to use prophylactic indefinite anticoagulation in patients with active cancer and previous DVT, including patients with upper extremity DVT.

Association between the controlling nutritional status score and outcomes in ischemic stroke patients with active cancer.

BACKGROUND: The effect of nutritional status on survival in ischemic stroke patients with active cancer remains unclear. METHODS: This study retrospectively evaluated ischemic stroke patients with active cancer admitted to a university hospital in Japan between 2006 and 2016. Patients were followed for 2 years after stroke. The controlling nutritional status (CONUT) score was used to classify undernutrition degree into 4 groups: normal, light, moderate, and severe. Survival rates were compared using the Kaplan-Meier method. Hazard ratio (HR) and 95 % confidence intervals (CIs) for mortality were calculated using Cox regression models. RESULTS: A total of 158 patients (31 % women; median age: 71 years) were analyzed. Of these, 47 % had distant metastasis. The median (interquartile range) National Institute of Health Stroke Scale and CONUT scores were 4 (1-10) and 5 (3-7), respectively. Kaplan-Meier curve indicated that patients with poorer nutritional status had worse outcomes (overall log-rank test, p < 0.001). The univariable Cox regression analysis showed that the HR (95 % CI) for the light, moderate, and severe groups were 1.14 (0.45-2.86), 3.01 (1.27-7.12), and 2.94 (1.10-7.84), respectively. This statistical significance did not persist after adjustment for potential confounders (HR [95 % CI] for the light, moderate, and severe groups were 0.95 [0.36-2.49], 1.56 [0.57-4.28], and 1.34 [0.37-4.92], respectively). Past stroke, distant metastasis, and plasma D-dimer levels on admission were independent predictors of prognosis. CONCLUSIONS: This single-center, retrospective study suggests that nutritional status serves as a prognostic indicator for ischemic stroke patients with active cancer. However, the effect is not statistically independent.

Von Willebrand Factor Antigen Levels Predict Poor Outcomes in Patients With Stroke and Cancer: Findings From the Multicenter, Prospective, Observational SCAN Study.

BACKGROUND: Patients with acute ischemic stroke and active cancer have more severe neurological symptoms, elevated risks of stroke recurrence, and death compared with the general population. We examined whether von Willebrand factor (vWF) antigen levels at stroke onset were associated with the poor outcomes of patients with stroke and cancer. METHODS AND RESULTS: Using data from 90 patients with acute ischemic stroke and active cancer who were registered in the SCAN (Ischemic Stroke in Patients With Cancer and Neoplasia) study, a prospective multicenter, observational study in Japan, we divided patients into 2 groups according to their median vWF antigen levels (high, n=46; or low, n=44). The high-vWF group had a significantly higher initial National Institutes of Health Stroke Scale score (median, 7 [interquartile range, 3-11.25] versus 3 [interquartile range, 1-8.5]; P<0.05) and a significantly higher incidence of cryptogenic stroke (32 [70%] versus 16 [36%]; P<0.01) and venous thromboembolism (7 [15%] versus 0 [0%]; P<0.01), as well as multiple lesions (28 [62%] versus 12 [27%]; P<0.001), than the low-vWF group. We observed no significant difference in the rate of stroke recurrence within 1 year between the groups. However, increased vWF levels were an independent predictor of death within 1 year of stroke onset, after adjusting for potential confounders (odds ratio, 6.77 [95% CI, 1.49-30.78]; P<0.05). CONCLUSIONS: Elevated vWF antigen levels were associated with adverse outcomes in patients with cancer-associated stroke and may represent a useful biomarker to guide future therapeutic interventions.

COVID-19 in Patients with Active Cancer: Higher Inflammatory Activity Predicts Poor Outcome.

INTRODUCTION: Active malignancies have been identified as an independent risk factor for severity and mortality in COVID-19. However, direct comparisons between SARS-CoV-2-infected patients with active (acP) and non-active cancers (n-acP) remain scarce. PATIENTS AND METHODS: We retrospectively analyzed a cohort of cancer patients with PCR-confirmed SARS-CoV-2 infection, enrolled from March 16, 2020, to July 31, 2021. Data on demographics, cancer, and laboratory findings were collected. Descriptive and subsequent regression analyses were performed. Endpoints were "deterioration to severe COVID-19" and "infection-associated mortality." RESULTS: In total, 987 cancer patients (510 acP vs. 477 n-acP) were included in our analysis. The majority was >55 years old, more men than women were included. At detection of SARS-CoV-2, 65.5% of patients had mild/moderate symptoms, while deterioration to severe COVID-19 was slightly more common in acP (19 vs. 16%; p = 0.284). COVID-19-associated mortality was significantly higher in acP (24 vs. 17.5%, p < 0.001). In terms of laboratory tests, severe cytopenia and elevated levels of inflammatory markers were common findings in acP at baseline, particularly in those who developed a severe infection or died. Multivariate analysis revealed that ferritin (HR 14.24 [2.1-96], p = 0.006) and CRP (HR 2.85 [1.02-8.02], p = 0.046) were associated with severity and mortality. In n-acP, association was seen for ferritin only (HR 4.1 [1.51-11.17], p = 0.006). CONCLUSION: Comparing patients with active and non-active cancer, the former showed higher mortality rates. Also, inflammatory markers were significantly increased, assuming higher levels of inflammation may play a role in the adverse outcome of COVID-19 in aCP.

COVID-19 Antibody Seroconversion in Cancer Patients: Impact of Therapy Cessation-A Single-Center Study.

BACKGROUND: The effective development of COVID-19 vaccination has mitigated its harm. Using two laboratory methods, we investigated the efficacy of the BNT162b2 mRNA and BBIBP-CorV COVID-19 vaccines on seroconversion rates in cancer patients undergoing active cancer treatment. METHODS: SARS-CoV-2 vaccines were scheduled for 134 individuals. The consenting participants submitted three venous blood samples. Three samples: T0, T1, and T2. The ABBOTT-SARS-CoV-2 IgG II Quant and Elecsys® Anti-SARS-CoV-2 assays were used to evaluate the samples and convert the antibody titers to WHO (BAU)/mL units. RESULTS: Cancer patients exhibited a higher seroconversion rate at T2, regardless of vaccination type, and the mean antibody titers at T1 and T2 were higher than those at T0. BBIBP-CorV patients required a booster because BNT162b2 showed a higher seroconversion rate between T0 and T1. Statistics indicate that comparing Abbott and Roche quantitative antibody results without considering the sample collection time is inaccurate. CONCLUSIONS: COVID-19 vaccines can still induce a humoral immune response in patients undergoing cancer-targeted therapy. The strength of this study is the long-term monitoring of antibody levels after vaccination in cancer patients on active therapy using two different immunoassays. Further multicenter studies with a larger number of patients are required to validate these findings.

Transcatheter Aortic Valve Replacement in Patients With or Without Active Cancer.

Background Data on clinical outcomes after transcatheter aortic valve replacement (TAVR) in specific cancer types or the presence of metastatic disease remain sparse. This study aimed to investigate the impact of active cancer on short-term mortality, complications, and readmission rates after TAVR across different cancer types. Methods and Results The authors assessed the Nationwide Readmissions Database for TAVR cases from 2012 to 2019. Patients were stratified by specific cancer types. Primary outcome was in-hospital mortality. Secondary outcomes included bleeding requiring blood transfusion and readmissions at 30, 90, and 180 days after TAVR. Overall, 122 573 patients undergoing TAVR were included in the analysis, of whom 8013 (6.5%) had active cancer. After adjusting for potential confounders, the presence of active cancer was not associated with increased in-hospital mortality (adjusted odds ratio [aOR], 1.06 [95% CI, 0.89-1.27]; P=0.523). However, active cancer was associated with an increased risk of readmission at 30, 90, and 180 days after TAVR and increased risk of bleeding requiring transfusion at 30 days. Active colon and any type of metastatic cancer were individually associated with readmissions at 30, 90, and 180 days after TAVR. At 30 days after TAVR, colon (aOR, 2.51 [95% CI, 1.68-3.76]; P<0.001), prostate (aOR, 1.40 [95% CI, 1.05-1.86]; P=0.021), and any type of metastatic cancer (aOR, 1.65 [95% CI, 1.23-2.22]; P=0.001) were individually associated with an increased risk of bleeding requiring transfusion. Conclusions Patients with active cancer had similar in-hospital mortality after TAVR but higher risk of readmission and bleeding requiring transfusion, the latter depending on certain types of cancer.

Heterogeneous distributions in clinical events preceding anticoagulant treatment nonpersistence in patients with venous thromboembolism stratified by active cancer: A nationwide cohort study.

BACKGROUND: Nonpersistence in anticoagulation therapy is common and associated with undesirable clinical outcomes in patients with venous thromboembolism (VTE). METHODS: We investigated preceding clinical events of treatment nonpersistence (e.g., switching, discontinuing, or restarting) in VTE patients with and without active cancer using Korean claims database. RESULTS: Clinically significant events including thromboembolic events, hepatic function change and surgery preceded treatment nonpersistence, but heterogeneous distributions of clinical events were observed in the presence of active cancer. Patients with active cancer had a low rate of clinical events preceding treatment nonpersistence, and new active cancer diagnosis in the nonactive cancer group was most common before the switch to parenteral anticoagulants from warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). CONCLUSION: These findings suggest that clinically significant events can precede treatment nonpersistence and largely paralleled current guidelines for patients with VTE, whereas heterogeneous distributions of clinical events were observed in the presence of active cancer.

Active cancer as the main predictor of mortality for COVID-19 in oncology patients in a specialized center.

Introduction: The role of the type, stage and status of cancer in the outcome of COVID-19 remains unclear. Moreover, the characteristic pathological changes of severe COVID-19 reveled by laboratory and radiological findings are similar to those due to the development of cancer itself and antineoplastic therapies. Objective: To identify potential predictors of mortality of COVID-19 in cancer patients. Materials and methods: A retrospective and cross-sectional study was carried out in patients with clinical suspicion of COVID-19 who were confirmed for COVID-19 diagnosis by RT-PCR testing at the National Institute of Neoplastic Diseases between April and December 2020. Demographic, clinical, laboratory and radiological data were analyzed. Statistical analyses included area under the curve and univariate and multivariate logistic regression analyses. Results: A total of 226 patients had clinical suspicion of COVID-19, the diagnosis was confirmed in 177 (78.3%), and 70/177 (39.5%) died. Age, active cancer, leukocyte count ≥12.8 × 109/L, urea ≥7.4 mmol/L, ferritin ≥1,640, lactate ≥2.0 mmol/L, and lung involvement ≥35% were found to be independent predictors of COVID-19 mortality. Conclusion: Active cancer represents the main prognosis factor of death, while the role of cancer stage and type is unclear. Chest CT is a useful tool in the prognosis of death from COVID-19 in cancer patients. It is a challenge to establish the prognostic utility of laboratory markers as their altered values it could have either oncological or pandemic origins.

Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study.

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82-5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.

Systemic thrombolysis in patients with acute stroke and active cancer: a systematic review and meta-analysis.

Cancer patients frequently have concomitant cerebrovascular diseases, which significantly worsen their prognosis. Prospective studies validating intravenous thrombolysis (IVT) safety profile in patients with acute ischemic stroke and active cancer are still lacking. Therefore, we aimed to evaluate IVT's efficacy and safety profile in acute ischemic stroke patients with comorbid active cancer. We included in a meta-analysis all relevant published studies, including patients with acute ischemic stroke with or without active cancer and receiving IVT, according to recommendations for IVT treatment for acute ischemic stroke. The primary outcomes were: any intracerebral hemorrhage, all-cause mortality, and good functional outcome reported as modified Rankin Scale (mRS) ≤ 2 at the end of the scheduled follow-up period. We included 11 studies in the meta-analysis. IVT was not associated with a significant increase in the incidence of intracerebral hemorrhage (OR 1.35; 95% CI 0.85-2.14; I2 76%), nor with a significant increase in death for any cause (OR 1.26; 95% CI 0.91-1.75; I2 71%); furthermore, IVT did not influence mRS between cancer and non-active cancer stroke patients (OR 0.72; 95% CI 0.35-1.49; I2 59%). IVT seems safe and effective in patients with ischemic stroke and concomitant cancer. Due to the low overall quality of the evidence, high-quality randomized controlled trials with adequate sample sizes are needed.

The Validity of a New Procedure-Based Definition of Cancer Status in Patients with Breast-, Lung- and Colorectal Cancer in the Danish National Patient Registry.

Background/Aim: The Danish National Patient Registry (DNPR) provides unique epidemiological insight, but often lacks granular data. We propose a procedure-based definition of cancer status in patients with breast-, lung- and colorectal cancer, which can be applied to administrative health databases. New definitions of cancer status are needed as mortality and morbidity are closely linked to cancer status, yet most studies only use duration since cancer diagnosis as a severity marker. The aim of the study was to validate a new pragmatic definition. Methods: Medical journals of 600 patients, with breast-, lung- and colorectal cancer from the Department of Oncology at Herlev-Gentofte Hospital were retrospectively reviewed. We defined active cancer as a cancer diagnosis, not followed by a potentially curative procedure within 6 months of the diagnosis. The remaining patients were characterized as having non-active cancer. This dichotomization was then compared to a cancer status assessment based on treatment received and paraclinical test such as their first post-procedural control scan. Based on this comparison, we calculated the positive predictive value (PPV) of our definitions of active and non-active cancer. Results: The calculated PPVs for active breast-, lung- and colorectal cancer were 87% (CI 95%: 0.74-0.99), 91% (CI 95%: 0.87-0.96) and 82% (CI 95%: 0.73-0.91). The PPVs for non-active breast-, lung- and colorectal cancer were 95% (CI 95%: 0.92-0.99), 91% (CI 95%: 0.82-0.99) and 73% (CI 95%: 0.66-0.81), respectively. Conclusion: We found an overall high PPV for both active and non-active cancer across all three types of cancer.

Oncologists' perceived confidence and attitudes toward managing pre-existing chronic comorbidities during patients' active cancer treatment.

PURPOSE: To examine practicing oncologists' perceived confidence and attitudes toward management of pre-existing chronic conditions(PECC) during active cancer treatment(ACT). METHODS: In December 2018, oncologists in the National Cancer Institute's Community Oncology Research Program (NCORP) were invited to complete a was pilot-tested, IRB-approved online survey about their perceived confidence in managing PECC. Pearson chi-square test was used to identify oncologists' differences in perceived confidence to manage PECC and attitudes toward co-management of patients' PECC with non-oncologic care providers. Perceived confidence and attitudes were analyzed as a function of medical specialty while controlling demographic and medical practice variables. RESULTS: A total of 391 oncologists responded to the survey, 45.8% stated medical oncology as their primary specialty, 15.1% hematology oncology, 15.1% radiation oncology, 6.9% surgical oncology, and 17.1% other specialties such as gynecology oncology. Overall, 68.3% agreed (agree/strongly agree) that they were confident to manage PECC in the context of standard of care. However, only 46.6% and 19.7% remained confident when managing PECC previously managed by a primary care physician (PCP) and by a non-oncology subspecialist, respectively. Most oncologists (58.3%) agreed that patients' overall care was well coordinated, and 63.7% agreed that patients had optimal cancer and non-cancer care when PECC was co-managed with a non-oncology care provider. CONCLUSION: Most oncologists felt confident to manage all PECC during patients' ACT, but their perceived confidence decreased for PECC previously managed by PCPs or by non-oncology subspecialists. Additionally, they had positive attitudes toward co-management of PECC with non-oncologic care providers. These results indicate opportunities for greater collaboration between oncologists and non-oncology care providers to ensure comprehensive and coordinated care for cancer patients with PECC.

Aptamer-Based Strategies to Boost Immunotherapy in TNBC.

The immune system (IS) may play a crucial role in preventing tumor development and progression, leading, over the last years, to the development of effective cancer immunotherapies. Nevertheless, immune evasion, the capability of tumors to circumvent destructive host immunity, remains one of the main obstacles to overcome for maximizing treatment success. In this context, promising strategies aimed at reshaping the tumor immune microenvironment and promoting antitumor immunity are rapidly emerging. Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor outcomes, is highly immunogenic, suggesting immunotherapy is a viable strategy. As evidence of this, already, two immunotherapies have recently become the standard of care for patients with PD-L1 expressing tumors, which, however, represent a low percentage of patients, making more active immunotherapeutic approaches necessary. Aptamers are short, highly structured, single-stranded oligonucleotides that bind to their protein targets at high affinity and specificity. They are used for therapeutic purposes in the same way as monoclonal antibodies; thus, various aptamer-based strategies are being actively explored to stimulate the IS's response against cancer cells. The aim of this review is to discuss the potential of the recently reported aptamer-based approaches to boost the IS to fight TNBC.

Ictus asociado a cáncer: estudio de prevalencia y factores predictores entre pacientes con ictus isquémico / Cancer-associated stroke: a study of prevalence and predictors among ischaemic stroke patients

Introducción: La asociación entre cáncer e ictus está bien documentada y conlleva un peor pronóstico de ambas patologías. Sin embargo, la prevalencia de cáncer activo y cáncer oculto entre pacientes con ictus no está suficientemente establecida, ni tampoco los factores predictores al ictus asociado al cáncer. Su conocimiento es importante para una mejor identificación y optimización del tratamiento de estos pacientes. Pacientes y métodos: El objetivo de este estudio retrospectivo es analizar las características del ictus isquémico, en pacientes con y sin cáncer activo, en una muestra de pacientes ingresados durante dos años en una unidad de ictus. Se realiza un análisis descriptivo general y de casos y controles, para evaluar las diferencias entre ambos grupos. Resultados: En una muestra de 616 pacientes con ictus isquémico se encontró una prevalencia de cáncer del 19,2%, que era activo (previo o diagnosticado tras el ictus) en un 7,5%. El cáncer activo se asoció con el hallazgo de lesiones en varios territorios vasculares, valores más bajos de hemoglobina y hematocrito, y más altos de fibrinógeno y proteína C reactiva, tendencia a peor situación funcional y mayor mortalidad a los tres meses. Conclusiones: Se encontró una alta prevalencia de cáncer sistémico, de cualquier tipo, y también activo y oculto, entre pacientes con ictus isquémico. La presencia de lesiones isquémicas en varios territorios vasculares y algunos marcadores de laboratorio podrían ser factores que habría que considerar para atribuir el ictus al cáncer o buscar una neoplasia oculta en algunos pacientes.(AU)

Introduction: The association between cancer and stroke is well documented and entails a worse prognosis for both pathologies. However, the prevalence of active and occult cancer among stroke patients is not sufficiently established, and neither are the predictors of cancer-associated stroke. Their knowledge is important for better identification and optimisation of the treatment of these patients. Patients and methods: The aim of this retrospective study is to analyse the characteristics of ischaemic stroke in patients with and without active cancer in a sample of patients admitted to a stroke unit for two years. An overall descriptive and case-control analysis is performed to assess the differences between the two groups. Results: In a sample of 616 patients with ischaemic stroke, a prevalence of cancer was found to be 19.2%, which was active (prior or diagnosed after the stroke) in 7.5% of them. Active cancer was associated with the finding of lesions in several vascular territories, lower haemoglobin and haematocrit values, and higher fibrinogen and C-reactive protein values, a tendency to worse functional status and higher mortality at three months. Conclusions: A high prevalence of systemic cancer, of any type, as well as active and occult, was found among patients with ischaemic stroke. The presence of ischaemic lesions in several vascular territories and some laboratory markers could be factors to consider in attributing the stroke to cancer or looking for an occult neoplasm in some patients.(AU)

Effectiveness and safety of rivaroxaban in patients with venous thromboembolism and active cancer: A subanalysis of the J'xactly study.

BACKGROUND: Data on the effectiveness and safety of rivaroxaban for the treatment of patients with venous thromboembolism (VTE) and active cancer are limited in the Japanese real-world setting. METHODS: In this subanalysis of the J'xactly study, which was a multicenter, prospective, observational study, we evaluated the effectiveness and safety of rivaroxaban in patients with acute VTE and active cancer (n = 193) versus those without active cancer (n = 823). RESULTS: Compared with patients without active cancer, those with active cancer demonstrated a significantly different age distribution, with fewer aged <65 and ≥75 years; a lower proportion of women; a lower mean body mass index; and a lower proportion of physical inactivity, injury, thrombophilia, and heart failure. There was no difference in the initial dose distribution of rivaroxaban between patients with and without active cancer. The incidences of recurrence or aggravation of symptomatic VTE and major bleeding were not significantly different [VTE: 1.44 % vs. 2.80 % per patient-year, hazard ratio (HR) 0.50, 95 % confidence interval (CI) 0.18-1.39, p = 0.172; major bleeding: 4.49 % vs. 2.55 % per patient-year, HR 1.80, 95 % CI 0.82-3.95, p = 0.137]. Approximately 10 % of patients with active cancer died at 6 months, with a significantly higher cumulative all-cause mortality rate than those without active cancer (23.29 % vs. 2.03 % per patient-year, HR 11.31, 95 % CI 7.30-17.53, p < 0.001). CONCLUSIONS: In patients with VTE and active cancer, rivaroxaban showed acceptable effectiveness, although clinically significant bleeding remains a concern. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry number, UMIN000025072.

Co-Delivery System of Curcumin and Colchicine Using Functionalized Mesoporous Silica Nanoparticles Promotes Anticancer and Apoptosis Effects.

Purpose: Many natural agents have a high anticancer potential, and their combination may be advantageous for improved anticancer effects. Such agents, however, often are not water soluble and do not efficiently target cancer cells, and the kinetics of their action is poorly controlled. One way to overcome these barriers is to combine natural agents with nanoparticles. Our aim in the current study was to fabricate an anticancer nanoformulation for co-delivery of two natural agents, curcumin (CR) and colchicine (CL), with a core-shell structure. Using cancer cell lines, we compared the anticancer efficacy between the combination and a nanoformulation with CL alone. Methods: For the single-drug nanoformulation, we used phosphonate groups to functionalize mesoporous silica nanoparticles (MSNs) and loaded the MSNs with CL. Additional loading of this nanoformulation with CR achieved the co-delivery format. To create the structure with a core shell, we selected a chitosan−cellulose mixture conjugated with targeting ligands of folic acid for the coating. For evaluating anticancer and apoptosis effects, we assessed changes in important genes and proteins in apoptosis (p53, caspase-3, Bax, Bcl-2) in several cell lines (MCF-7, breast adenocarcinoma; HCT-116, colon carcinoma; HOS, human osteosarcoma; and A-549, non−small cell lung cancer). Results: Nanoformulations were successfully synthesized and contained 10.9 wt.% for the CL single-delivery version and 18.1 wt.% for the CL+CR co-delivery nanoformulation. Anticancer effects depended on treatment, cell line, and concentration. Co-delivery nanoformulations exerted anticancer effects that were significantly superior to those of single delivery or free CL or CR. Anticancer effects by cell line were in the order of HCT-116 > A549 > HOS > MCF-7. The lowest IC50 value was obtained for the nanoformulation consisting of CL and CR coated with a polymeric shell conjugated with FA (equivalent to 4.1 ± 0.05 µg/mL). With dual delivery compared with the free agents, we detected strongly increased p53, caspase-3, and Bax expression, but inhibition of Bcl-2, suggesting promotion of apoptosis. Conclusions: Our findings, although preliminary, indicate that the proposed dual delivery nanoformulation consisting of nanocore: MSNs loaded with CL and CR and coated with a shell of chitosan−cellulose conjugated folic acid exerted strong anticancer and apoptotic effects with potent antitumor activity against HCT-116 colon cells. The effect bested CL alone. Evaluating and confirming the efficacy of co-delivery nanoformulations will require in vivo studies.

Outcomes after endovascular thrombectomy for acute ischemic stroke patients with active cancer: A systematic review and meta-analysis.

Background: Active cancer (AC) is a known risk factor for stroke and a common comorbidity among patients being considered for treatment with endovascular thrombectomy (EVT). This systematic review and meta-analysis aimed to evaluate the current evidence for the feasibility, efficacy, and safety of EVT for patients with AC. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) and observational studies which met the inclusion criteria for EVT in patients with AC. Studies were excluded due to the mismatch of data format, article type, and group design. The risk of bias was assessed through different scales according to the study design. I 2 statistics were used to evaluate the heterogeneity. Funnel plots were used to evaluate publication bias. Results: A total of six studies and 3,657 patients were included. Compared to without active cancer (WC) patients, patients with AC had a significantly higher proportion of in-hospital mortality (OR 3.24; 95% CI, 1.03-10.15). The estimated rate of favorable outcome of six studies was lower in patients with AC than in patients with WC (OR 0.47; 95% CI, 0.35-0.65). For 90-day mortality of four studies, the AC group had a higher proportion when compared with the WC group (OR 3.87; 95% CI, 2.64-5.68). There was no difference between rate of six studies of successful recanalization (OR 1.24; 95% CI, 0.90-1.72) and four studies of symptomatic ICH (OR 1.09; 95% CI, 0.61-1.97) comparing AC and WC. Conclusion: Patients with AC are less likely to have a favorable outcome and have a higher risk of mortality after EVT. Further studies are warranted for this unique patient population.

Incidence and Predictors of Recurrence and Mortality Following First Venous Thromboembolism Among the Saudi Population: Single-Center Cohort Study.

Background: Little is written about recurrence and mortality rates after a first episode of venous thromboembolism (VTE) among Saudi population. Aim: Determine incidence rates and assess predictors of recurrence and mortality following the first VTE event. Patients and Methods: A total of 1124 patients aged ≥18 years with symptomatic VTE confirmed by imaging tests were evaluated. The incidence of VTE recurrence and mortality were assessed. The association between patient characteristics, and VTE recurrence and mortality was explored by estimating the hazard ratio (HR) and 95% confidence interval (CI). The difference between cancer-related, provoked and unprovoked VTE in terms of recurrence and mortality was explored using Kaplan-Meier curves. Results: The annual incidence rate of the first VTE was 1.7 per 1000 patients. Of 1124 patients with first VTE, 214 (19%) developed recurrent VTE, and 192 (17%) died with overall incidence rates of 15.8 per 100 person-years (95% CI, 13.8-18.0) and 10.0 per 100 person-years (95% CI, 8.7-11.5). Intensive care unit (ICU) admission (HR, 2.15; 95% CI, 1.67-3.10), presence of active cancer (HR, 2.97; 95% CI, 1.87-3.95), immobilization (HR, 2.52; 95% CI, 1.79-3.67), infection (HR, 2.32; 95% CI, 1.94-3.45), and pulmonary embolism ± deep venous thrombosis (HR, 2.22; 95% CI, 1.56-3.16) were found to be independent predictors of recurrent VTE. Recurrence carries a high hazard of mortality (HR, 5.21; 95% CI, 3.61-7.51). The estimated median time to VTE recurrence was lower in cancer-related VTE (18.7 months) compared with provoked (29.0 months) and unprovoked VTE (28.4 months). The estimated survival median time was lower in cancer-related VTE (21.8 months) compared with provoked (30.5 months) and unprovoked VTE (29.8 months). Conclusion: Immobilization and presence of active cancer, infection, and PE ± DVT were significant predictors of recurrent VTE. Patients who developed recurrent VTE had a 5.2-fold higher hazard of mortality compared with patients with no VTE recurrence.

Glycosylated phospholipid-coated upconversion nanoparticles for bioimaging of non-muscle invasive bladder cancers.

Detection of non-muscle invasive bladder cancer (NMIBC) is crucial to facilitate complete tumor resection, thus improving the survival rate as well as reducing the recurrence frequency and treatment expense. Fluorescence imaging cystoscopy is an effective method for the detection of NMIBC. However, its application is limited as the commonly applied fluorescent agents such as dyes and photosensitizers usually lack specific tumor accumulation and are vulnerable to photobleaching. Furthermore, the broad emission band of conventional fluorescent agents limits their imaging and detection efficacy. To overcome these limitations, upconversion nanoparticles (UCNPs) have been selected as the fluorescent agent, due to their resistance to photobleaching, less background auto-fluorescence, and narrow emission bands. In order to achieve active tumor targeting, the UCNPs are coated with a glycosylated phospholipid layer. The glycosylated phospholipid-coated UCNPs exhibited high selective accumulation in cancer cells over normal cells and enhanced the upconversion luminescence (UCL) (at 540 nm and 660 nm) from bladder cancer cells under 980 nm laser irradiation. Glycosylated phospholipid coating that promotes uptake of UCNPs by cancer cells, and UCL emitted from UCNPs under NIR (980 nm) laser irradiation for cancer cell imaging.

Development of Cancer Immunotherapies.

Cancer immunotherapy, or the utilization of components of the immune system to target and eliminate cancer, has become a highly active area of research in the past several decades and a common treatment strategy for several cancer types. The concept of harnessing the immune system for this purpose originated over 100 years ago when a physician by the name of William Coley successfully treated several of his cancer patients with a combination of live and attenuated bacteria, later known as "Coley's Toxins", after observing a subset of prior patients enter remission following their diagnosis with the common bacterial infection, erysipelas. However, it was not until late in the twentieth century that cancer immunotherapies were developed for widespread use, thereby transforming the treatment landscape of numerous cancer types. Pivotal studies elucidating molecular and cellular functions of immune cells, such as the discovery of IL-2 and production of monoclonal antibodies, fostered the development of novel techniques for studying the immune system and ultimately the development and approval of several cancer immunotherapies by the United States Food and Drug Association in the 1980s and 1990s, including the tuberculosis vaccine-Bacillus Calmette-Guérin, IL-2, and the CD20-targeting monoclonal antibody. Approval of the first therapeutic cancer vaccine, Sipuleucel-T, for the treatment of metastatic castration-resistant prostate cancer and the groundbreaking success and approval of immune checkpoint inhibitors and chimeric antigen receptor T cell therapy in the last decade, have driven an explosion of interest in and pursuit of novel cancer immunotherapy strategies. A broad range of modalities ranging from antibodies to adoptive T cell therapies is under investigation for the generalized treatment of a broad spectrum of cancers as well as personalized medicine. This chapter will focus on the recent advances, current strategies, and future outlook of immunotherapy development for the treatment of cancer.