Financial burden in a US cohort of patients with HCC.

BACKGROUND: High financial burden for patients has been reported for multiple types of cancer, but there are limited data in those with HCC. We aimed to describe the financial burden for patients diagnosed with HCC and identify correlates of high financial burden. METHODS: We used the IQVIA PharMetrics Plus for Academics database to identify commercially insured patients diagnosed with HCC between 2006 and 2021. Patient financial liability was defined as the difference between allowed and paid amounts from adjudicated insurance claims. We reported total and HCC-related financial liabilities (i.e., cost for HCC-related claims), with high total financial liability defined as ≥$3000 annually and high HCC-related financial liability as ≥$1000 annually. We used multivariable logistic regression modeling to identify factors associated with high total and HCC-related financial liability. RESULTS: Among 11,609 patients with HCC, the median total financial liability during the year after HCC diagnosis was $2955 (Q1-Q3: $972-$6293). Nearly half (45%) of patients experienced high total financial liability, with the greatest liability incurred in the 3-month period immediately following HCC diagnosis. Older age, increased comorbidity, and cirrhosis-related complications were associated with higher total patient liability. Patient liability also varied by type of HCC treatment, with systemic therapy and liver transplantation having the highest financial liability in multivariable analysis. However, only 66.7% of the patients experienced HCC-related liability. CONCLUSIONS: Patients with HCC experience significant financial liability underscoring a need for price transparency as well as financial counseling in this population.

Multicenter evaluation of the addition of eltrombopag to immunosuppressive therapy for adults with severe aplastic anemia.

Eltrombopag has been shown to improve response rates when added to standard therapy in adults with severe aplastic anemia in controlled trial settings. However, outcomes in real-world populations have mostly been examined in small retrospective studies. This robust, multicenter, retrospective cohort study across six academic health systems compared outcomes in patients who received immunosuppressive therapy with or without eltrombopag. The study included 82 patients who received front-line therapy from January 2014 to August 2021. Overall response rates at 6 months did not differ significantly for patients receiving eltrombopag versus immunosuppressive therapy alone (58% v. 65%, p = 0.56). However, complete response rates at 6 and 12 months were over two times higher in the eltrombopag arm (29% v. 12%, p = 0.06 and 48% v. 18%, p = 0.005). Rates of hepatotoxicity were similar across both arms. Eltrombopag addition did not impact overall survival (median not reached in either arm at 2 years, p = 0.86) or disease-free survival (median not reached v. 13.3 months at 2 years, p = 0.20). Eltrombopag may not produce as large of a benefit in real-world settings compared to controlled trial settings but may offer patients deeper responses with similar rates of toxicity to immunosuppressive therapy alone.

The Experiences of Post-Separation Survivors of Domestic Violence During the Covid-19 Pandemic: Findings From a Qualitative Study in the United Kingdom.

Post-separation for domestic violence (DV) survivors is known to be a period of heightened risk of domestic homicide. Evidence points to increased rates of DV during the Covid-19 pandemic, with specific challenges in help-seeking from DV services, yet studies that capture this qualitatively are still emerging. This UK study investigated the experiences of 21 separated DV survivors (all women) during the Covid-19 pandemic. Inductive, thematic analysis highlighted participants' psychological distress, isolation, fear of Covid-19 transmission, and detachment from support networks. The findings reflect the interconnected nature of adversities experienced by DV survivors and the exacerbation of these due to the insidious, multifaceted, and synergistic impacts of DV and the pandemic.

Efficacy and safety of direct oral anticoagulants for secondary prevention of cancer associated thrombosis: a meta-analysis of randomized controlled trials.

Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). We conducted a meta-analysis of ten randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT. All had study populations composed in entirety or in part of patients with CAT. The primary outcome (efficacy) was recurrent VTE and the secondary outcomes (safety outcomes) included major bleeding, clinically relevant non-major bleeding (CRNMB), and all bleeding (major bleeding + CRNMB). Participants treated with DOACs had lower risk of recurrent VTE, overall (RR 0.63; 95% CI 0.51-0.79; p < 0.0001), compared to LMWH (RR 0.57; 95% CI 0.40-0.83; p = 0.003), but not compared to VKA (RR 0.69; 95% CI 0.44-1.06; p = 0.09). Compared to LMWH, DOACs showed no difference in major bleeding risk (RR 1.31; 95% CI 0.78-2.18; p = 0.31), though had higher risk of CRNMB (RR 1.60; 95% CI 1.13-2.26; p = 0.008) and all bleeding (RR 1.49; 95% CI 1.10-2.01; p = 0.010). These results indicate that DOACs are more effective than LMWH for prevention of recurrent VTE with CAT though carry an increased risk for non-major bleeding compared to standard of care, LMWH.

CAR-T design: Elements and their synergistic function.

Chimeric antigen receptor (CAR) T cells use re-engineered cell surface receptors to specifically bind to and lyse oncogenic cells. Two clinically approved CAR-T-cell therapies have significant clinical efficacy in treating CD19-positive B cell cancers. With widespread interest to deploy this immunotherapy to other cancers, there has been great research activity to design new CAR structures to increase the range of targeted cancers and anti-tumor efficacy. However, several obstacles must be addressed before CAR-T-cell therapies can be more widely deployed. These include limiting the frequency of lethal cytokine storms, enhancing T-cell persistence and signaling, and improving target antigen specificity. We provide a comprehensive review of recent research on CAR design and systematically evaluate design aspects of the four major modules of CAR structure: the ligand-binding, spacer, transmembrane, and cytoplasmic domains, elucidating design strategies and principles to guide future immunotherapeutic discovery.

Characterisation and outcomes of ARDS secondary to pneumonia in patients with and without SARS-CoV-2: a single-centre experience.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is the major cause of mortality in patients with SARS-CoV-2 pneumonia. It appears that development of 'cytokine storm' in patients with SARS-CoV-2 pneumonia precipitates progression to ARDS. However, severity scores on admission do not predict severity or mortality in patients with SARS-CoV-2 pneumonia. Our objective was to determine whether patients with SARS-CoV-2 ARDS are clinically distinct, therefore requiring alternative management strategies, compared with other patients with ARDS. We report a single-centre retrospective study comparing the characteristics and outcomes of patients with ARDS with and without SARS-CoV-2. METHODS: Two intensive care unit (ICU) cohorts of patients at the Queen Elizabeth Hospital Birmingham were analysed: SARS-CoV-2 patients admitted between 11 March and 21 April 2020 and all patients with community-acquired pneumonia (CAP) from bacterial or viral infection who developed ARDS between 1 January 2017 and 1 November 2019. All data were routinely collected on the hospital's electronic patient records. RESULTS: A greater proportion of SARS-CoV-2 patients were from an Asian ethnic group (p=0.002). SARS-CoV-2 patients had lower circulating leucocytes, neutrophils and monocytes (p<0.0001), but higher CRP (p=0.016) on ICU admission. SARS-CoV-2 patients required a longer duration of mechanical ventilation (p=0.01), but had lower vasopressor requirements (p=0.016). DISCUSSION: The clinical syndromes and respiratory mechanics of SARS-CoV-2 and CAP-ARDS are broadly similar. However, SARS-CoV-2 patients initially have a lower requirement for vasopressor support, fewer circulating leukocytes and require prolonged ventilation support. Further studies are required to determine whether the dysregulated inflammation observed in SARS-CoV-2 ARDS may contribute to the increased duration of respiratory failure.

Characteristics of early acute respiratory distress syndrome in newly diagnosed acute myeloid leukemia.

Acute respiratory complications occur frequently during the early phase of acute myeloid leukemia (AML) but information on the most severe form, acute respiratory distress syndrome (ARDS), is lacking. We retrospectively analyzed 280 patients with newly diagnosed AML in order to describe the incidence, risk factors and early mortality associated with ARDS within 15 d. Univariate and then multivariate analysis were performed. ARDS developed in 9% of patients and was associated with 64% day-30 mortality. White blood cell count on admission was an independent risk factor for ARDS (OR = 1.007, 95% CI = 1.001-1.012, p = .012) with a moderate prediction ability (AUC 0.704, p = .001). Other variables were associated with ARDS in univariate but not in multivariate analysis: body mass index (p = .06), transfusions (p = .001) and sepsis (p < .0001). Leukemia-specific complications and documented infections were the most frequent ARDS etiologies and were sometimes associated, with no clear distinctive temporal pattern.

Chest radiographic and CT findings in hyperleukocytic acute myeloid leukemia: A retrospective cohort study of 73 patients.

Hyperleukocytic acute myeloid leukemia (AML) is associated with pulmonary complications and high early mortality rate, but given its rarity, data on chest radiographic presentation are scarce.We retrospectively reviewed the charts of 73 AML patients admitted with white blood cell count >100 × 10/L between 2003 and 2014 in order to describe the chest radiographic and computed tomography (CT) findings and to correlate them with AML subtype and respiratory symptoms.Forty-two of the 73 patients (58%) overall and 36 of the 54 patients (67%) with clinical signs of pulmonary leukostasis had abnormal radiographs on admission. The presence of radiographic abnormalities was significantly associated with dyspnea and oxygen/ventilatory support requirements (P < 0.01) and with day 28 mortality (45% vs 13%, P = 0.005) but not with monocytic subtype of AML. Sixteen patients had isolated focal basilar airspace opacities, unilateral (n = 13) or bilateral (n = 3), while 16 patients had bilateral diffuse opacities, interstitial (n = 12) or airspace and interstitial (n = 4). Two patients had isolated pleural effusion, 2 patients had unilateral midlung airspace opacities, and 6 patients had a combination of focal airspace and diffuse interstitial opacities. Overall, 2 patterns accounted for 75% of abnormal findings: bilateral diffuse opacities tended to be associated with monocytic AML, whereas basilar focal airspace opacities were more frequent in nonmonocytic AML (P < 0.05). Eighteen patients had CT scans, revealing interlobular septal thickening (n = 12), airspace (n = 11) and ground-glass (n = 9) opacities, pleural effusions (n = 12), and acute pulmonary embolism (n = 2).Hyperleukocytic AML is frequently associated with abnormal chest radiographs, involving mostly focal basilar airspace opacities (more frequent in nonmonocytic AML) or diffuse bilateral opacities. CT scan should be considered broadly due to the suboptimal resolution of radiographs for detecting signs of leukostasis.

Hypoxemia During Extreme Hyperleukocytosis: How Spurious?

BACKGROUND: Spurious hypoxemia has been described in case reports during extreme hyperleukocytosis and has led to recommendations for immediate cooling and analysis of arterial blood gases (ABGs). We sought to determine, in samples processed as recommended, the magnitude of spurious hypoxemia in acute leukemia subjects with hyperleukocytosis. METHODS: A retrospective chart review was conducted of all subjects admitted between 2003 and July 2014 for acute leukemia, who presented with white blood cell (WBC) count > 50 × 10(9) cells/L and had ABGs performed. For each ABG, we collected PaO2 , SaO2 , simultaneous WBC count, and SpO2 when available. Bland and Altman analysis was used to assess the agreement between SpO2 and SaO2 . RESULTS: One-hundred forty-six samples (from 45 subjects) were included, of which 57 samples (from 18 subjects) had data available for Bland and Altman analysis. Mean (SpO2 - SaO2 ) was 2.5%, and 95% CI for limits of agreement between SpO2 and SaO2 was (-10.1,15.1)%. The mean (SpO2 - SaO2 ) was significantly higher for WBC count > 100 × 10(9)/L as compared with WBC count < 100 × 10(9)/L (3.8% vs 0.4%, P = .04), and the 95% CIs for limits of agreement were (-10.3,18)% versus (-7.9,8.6)%. SpO2 and SaO2 were poorly correlated (r(2) = 0.19), whereas the difference (SpO2 - SaO2 ) was fairly correlated with WBC count (r(2) = 0.44). Overall, 11 of 19 samples with WBC count > 150 × 10(9)/L had PaO2 < 55 mm Hg whereas SpO2 was > 94%, the proportion being 5 of 62 samples for WBC count < 150 × 10(9)/L (P < .001). Three subjects with WBC count > 150 × 10(9)/L exhibited large SpO2 to SaO2 differences (10-20%) before leukapheresis, which decreased to below 5% afterward. CONCLUSIONS: In subjects with acute leukemia and hyperleukocytosis, despite cooling and quickly analyzing the samples, we observed poor correlation and agreement between SpO2 and SaO2 , unacceptably low for WBC count > 100 × 10(9)/L. Our results suggest that current guidelines may not totally prevent the diagnosis of spurious hypoxemia.

Initial respiratory status in hyperleukocytic acute myeloid leukemia: prognostic significance and effect of leukapheresis.

This study investigated whether initial respiratory status in hyperleukocytic acute myeloid leukemia (AML), as defined by oxygen/ventilatory support, is (1) associated with early mortality and overall survival and (2) improved after leukapheresis. A retrospective chart review of 89 patients requiring leukapheresis was performed. White blood cell count (WBC) decreased from 153 (56-475) × 10(9)/L to 60 (17-259) × 10(9)/L after first leukapheresis (p < 0.01). Initial respiratory status was room air (n = 40), low (n = 31) or high flow oxygen therapy (n = 8) or mechanical ventilation (n = 10). As compared to admission, respiratory status significantly deteriorated after both first and second leukapheresis (p < 0.01) and was not different at day 5 for patients still alive (p = 0.131). Both day 28 mortality and overall survival were significantly affected by initial respiratory status (p < 0.01). Despite being effective in reducing WBC, leukapheresis did not improve respiratory status of hyperleukocytic AML patients, a factor strongly associated with survival.

Frequency of Chlamydia trachomatis-specific T cell interferon-γ and interleukin-17 responses in CD4-enriched peripheral blood mononuclear cells of sexually active adolescent females.

An evaluation of CD4 T cell responses to candidate Chlamydia trachomatis vaccine antigens was conducted in an adolescent female cohort exposed through natural infection to explore antigen immunogenicity and correlation with protection from reinfection. The frequency of peripheral blood CD4 T cell IFN-γ and IL-17 responses to three candidate vaccine antigens, polymorphic membrane protein G (PmpG), F (PmpF), and major outer membrane protein (MOMP), were determined by ELISPOT; responses to chlamydial heat shock protein 60 (HSP60) and to elementary bodies (EB) were included for comparison. Responses of Infected (n=8), Seropositive/Uninfected (n=13), and Seronegative/Uninfected (n=18) participants were compared. The median CD4 IFN-γ response to EB was significantly increased in Infected (P=0.003) and Seropositive/Uninfected (P=0.002) versus Seronegative/Uninfected female subjects. Higher rates of positive IFN-γ responders to EB, PmpF, and MOMP were detected in Seropositive/Uninfected versus Seronegative/Uninfected participants (P=0.021). IL-17 responses were generally low. A positive IFN-γ response to any of the antigens tested was associated with a trend toward a reduced risk of reinfection, although not statistically significant. Among this adolescent cohort, chlamydial-specific CD4 IFN-γ but not IL-17 responses were detected in acutely and previously infected participants and a positive CD4 IFN-γ response was associated with a non-significant reduced risk of reinfection.