Immunogenicity after vaccination of COVID-19 vaccines in patients with cancer: a prospective, single center, observational study.

BACKGROUND: Patients with cancer, particularly those undergoing chemotherapy, are at risk from the low immunogenicity of Coronavirus Disease 19 (COVID-19) vaccines. METHODS: This prospective study assessed the seroconversion rate of COVID-19 vaccines among patients with cancer and hospital staff. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific IgG (S-IgG) concentrations were evaluated before the first vaccination, and 1-3 and 4-6 months after the second vaccination. The primary endpoint was the seroconversion rate measured 1-3 months after the second vaccine. RESULTS: In total, 590 patients and 183 healthy hospital staff were analyzed. At 1-3 months after the second vaccination, the S-IgG antibody concentration exceeded the cut-off value (20 BAU/mL) in 96.1% (567/590) of the patients with cancer and 100% (183/183) of the healthy controls (p = 0.0024). At 4-6 months after the second vaccination, the S-IgG antibody concentration exceeded the cut-off value (20 BAU/ml for S-IgG) in 93.1% (461/495) of the patients with cancer and 100% (170/170) of the healthy controls (p < 0.0001). Old age, being male, and low lymphocyte count were related to low SARS-CoV-2 S-IgG levels 1-3 months after the second vaccination among patients, while body mass index, smoking history, and serum albumin level were not. Patients undergoing platinum combination therapy and alkylating agent among cytotoxic drugs, and PARP inhibitor, mTOR inhibitor, and BCR-ABL inhibitor exhibited a low S-IgG antibody concentration compared to the no treatment group. CONCLUSIONS: COVID-19 vaccine immunogenicity was reduced among patients with cancer, especially under several treatment regimens.

Totally robotic en bloc left upper lobectomy and chest wall resection after neoadjuvant chemoradiation.

This patient presented with a stage IIIB advanced lung cancer with chest wall invasion. She was treated with neoadjuvant chemoradiation therapy and had an excellent treatment response. The management of T3N2 disease is controversial, but given her treatment response and age, she was discussed by the multidisciplinary tumour board and referred for surgical evaluation. She was offered a robotic en bloc lobectomy and chest wall dissection.

Development of a Japanese Scale that Evaluates the Level of Nursing Support Provided to Patients for Decision-Making in Cancer Clinical Trials.

Clinical nurses need learning programs that are useful in nursing support for patients' decision-making (NSPDM) regarding cancer clinical trials (CCTs). The usefulness of the learning program can be evaluated if the practices of NSPDM before and after participation in the learning program can be compared. We developed a scale to measure the level of self-assessed NSPDM regarding participation in a CCT. Thirty-two items of scale were developed in Japanese based on previous literature. Based on the results of a pilot study, items with similar meanings were removed and the validity of the 26 scale items was statistically examined in terms of construct validity and reliability. The study population was clinical nurses and included clinical research nurses. We received 102 valid responses from clinical nurses. Based on the bias of the boxplot distribution and the ceiling and floor effects for the items analysis of the 26-item draft scale, 17 items remained. Exploratory factor analysis (EFA) revealed that the scale consisted of three subscales and 17 items. Regarding fit indices of the model, the goodness-of-fit index (GFI), adjusted GFI (AGFI), comparative fit index (CFI), and root mean square error of application (RMSEA) were 0.775, 0.704, 0.477, and 0.081, respectively. The Cronbach's alpha coefficient for the overall scale was 0.951, with subscales ranging from 0.820 to 0.942. The validity and reliability of this scale were acceptable. This scale may be helpful to evaluate the usefulness of learning programs, i.e., the practice level of NSPDM.

Difference in SARS-CoV-2 Antibody Status Between Patients With Cancer and Health Care Workers During the COVID-19 Pandemic in Japan.

Importance: Patients with cancer and health care workers (HCWs) are at high risk of SARS-CoV-2 infection. Assessing the antibody status of patients with cancer and HCWs can help understand the spread of COVID-19 in cancer care. Objective: To evaluate serum SARS-CoV-2 antibody status in patients with cancer and HCWs during the COVID-19 pandemic in Japan. Design, Setting, and Participants: Participants were enrolled for this prospective cross-sectional study between August 3 and October 30, 2020, from 2 comprehensive cancer centers in the epidemic area around Tokyo, Japan. Patients with cancer aged 16 years or older and employees were enrolled. Participants with suspected COVID-19 infection at the time of enrollment were excluded. Exposures: Cancer of any type and cancer treatment, including chemotherapy, surgery, immune checkpoint inhibitors, radiotherapy, and targeted molecular therapy. Main Outcomes and Measures: Seroprevalence and antibody levels in patients with cancer and HCWs. Seropositivity was defined as positivity to nucleocapsid IgG (N-IgG) and/or spike IgG (S-IgG). Serum levels of SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured by chemiluminescent enzyme immunoassay. Results: A total of 500 patients with cancer (median age, 62.5 years [range, 21-88 years]; 265 men [55.4%]) and 1190 HCWs (median age, 40 years [range, 20-70 years]; 382 men [25.4%]) were enrolled. In patients with cancer, 489 (97.8%) had solid tumors, and 355 (71.0%) had received anticancer treatment within 1 month. Among HCWs, 385 (32.3%) were nurses or assistant nurses, 266 (22.4%) were administrative officers, 197 (16.6%) were researchers, 179 (15.0%) were physicians, 113 (9.5%) were technicians, and 50 (4.2%) were pharmacists. The seroprevalence was 1.0% (95% CI, 0.33%-2.32%) in patients and 0.67% (95% CI, 0.29%-1.32%) in HCWs (P = .48). However, the N-IgG and S-IgG antibody levels were significantly lower in patients than in HCWs (N-IgG: ß, -0.38; 95% CI, -0.55 to -0.21; P < .001; and S-IgG: ß, -0.39; 95% CI, -0.54 to -0.23; P < .001). Additionally, among patients, N-IgG levels were significantly lower in those who received chemotherapy than in those who did not (median N-IgG levels, 0.1 [interquartile range (IQR), 0-0.3] vs 0.1 [IQR, 0-0.4], P = .04). In contrast, N-IgG and S-IgG levels were significantly higher in patients who received immune checkpoint inhibitors than in those who did not (median N-IgG levels: 0.2 [IQR, 0.1-0.5] vs 0.1 [IQR, 0-0.3], P = .02; S-IgG levels: 0.15 [IQR, 0-0.3] vs 0.1[IQR, 0-0.2], P = .02). Conclusions and Relevance: In this cross-sectional study of Japanese patients with cancer and HCWs, the seroprevalence of SARS-CoV-2 antibodies did not differ between the 2 groups; however, findings suggest that comorbid cancer and treatment with systemic therapy, including chemotherapy and immune checkpoint inhibitors, may influence the immune response to SARS-CoV-2.

The impact of marginal lung function on outcomes in the era of minimally invasive thoracic surgery.

BACKGROUND: The effect of marginal lung function on outcomes after lung resection has traditionally been studied in the context of open thoracic surgery. Its impact on postoperative outcomes in the era of minimally invasive lung resection is unclear. METHODS: In this retrospective cohort study, we included adult patients who underwent minimally invasive lung resection at our institution between January 2017 and May 2020 for known malignancy or lung nodule. Marginal lung function was defined as pre-operative forced expiratory volume in 1 second (FEV1) and/or diffusion lung capacity of carbon monoxide <60% of predicted. Our outcomes included a composite outcome of pulmonary morbidity and/or 30- and 90-day mortality, and hospital length of stay. We used multivariable logistic and Poisson regression models to identify associations with outcomes, and Kaplan-Meier and Cox models to estimate survival. RESULTS: Of 300 patients, 88 (29%) had marginal lung function. Patients in the marginal group were more likely to be female (69% vs. 56%; P=0.028), and more likely to have: hypertension (HTN) (83% vs. 71%; P=0.028), chronic obstructive pulmonary disease (COPD) (38% vs. 12%; P<0.001), interstitial lung disease (ILD) (9% vs. 3%; P<0.019), and ischemic heart disease (28% vs. 18%; P=0.033). Patients were similar in terms of age (68±8 vs. 68±10 years; P=0.932), and other comorbidities. Anatomic lung resection comprised 56.8% of the marginal group vs. 74% in the non-marginal group (P=0.003). The most common complication was prolonged air leak (18.2% vs. 11.8%; P=0.479). Marginal lung function had a trend toward increased composite respiratory complications (22.7% vs. 15.1%; P=0.112) and 90-day mortality (5.7% vs. 4.2%; P=0.591), although they did not reach statistical significance. There was a statistically significant 1-day average increase in length of stay in the marginal lung function cohort (4.6 vs. 3.4 days; P<0.015) with a stronger association with diffusion lung capacity of carbon monoxide than FEV1. Survival was similar (marginal function HR =1.0; P=0.994). CONCLUSIONS: In the era of minimally invasive thoracic surgery, lung resection in patients with marginal lung function may be considered in select patients. These findings aid in the selection consideration and counseling of this patient population.

Long-term outcome of brachytherapy treatment for coronary in-stent restenosis: Ten-year follow-up.

OBJECTIVES: The objective of this study was to determine the long-term major adverse cardiac events (MACE) in patients treated with intracoronary brachytherapy (ICBT) for coronary in-stent restenosis (ISR). BACKGROUND: ICBT was commonly used to treat coronary ISR prior to the availability of drug-eluting stents (DES). The long-term outcomes of ICBT for ISR remain unknown. METHODS: Six hundred and eighty consecutive patients who underwent ICBT treated for ISR between September 1998 and April 2005 were included in the study. Clinical and angiographic data were collected and the long-term MACE were measured for all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR) at 10-year follow-up. RESULTS: Patients were 63 ± 11 years old (66% male). The majority of patients were treated with a bare metal stent 670/680 (99%) prior to ICBT. Significant baseline clinical findings include high incidence of smokers 479/680 (70%), hyperlipidemia 638/680 (94%), and multivessel disease 526/680 (77%). The majority of target lesions were diffuse 407/680 (60%), and either in the left anterior descending 258/680 (38%) or right coronary artery 215/680 (32%). At 10-year follow-up, the rate of death was 25%, MI was 22.4%, and TVR was 48%. CONCLUSION: MACE at 10-year follow-up following ICBT for ISR indicates steady rate of death and MI and declining rate of TVR after 5 years.

Adeno-associated virus-mediated CASQ2 delivery rescues phenotypic alterations in a patient-specific model of recessive catecholaminergic polymorphic ventricular tachycardia.

Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin-2 (CASQ2) gene. We have previously demonstrated that viral transfer of the wild-type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induced mouse model of the disease homozygous carrier of the R33Q mutation. In the present study, we investigated the efficacy of the virally mediated gene therapy in cardiomyocytes (CMs) differentiated from induced pluripotent stem cells (iPSCs) obtained from a patient carrying the homozygous CASQ2-G112+5X mutation. To this end, we infected cells with an Adeno-Associated Viral vector serotype 9 (AAV9) encoding the human CASQ2 gene (AAV9-hCASQ2). Administration of the human WT CASQ2 gene was capable and sufficient to restore the physiological expression of calsequestrin-2 protein and to rescue functional defects of the patient-specific iPSC-derived CMs. Indeed, after viral gene transfer, we observed a remarkable decrease in the percentage of delayed afterdepolarizations (DADs) developed by the diseased CMs upon adrenergic stimulation, the calcium transient amplitude was re-established and the density and duration of calcium sparks were normalized. We therefore demonstrate the efficacy of the AAV9-mediated gene replacement therapy for CPVT2 in a human cardiac-specific model system, supporting the view that the gene-therapy tested is curative in models with different human mutations of CPVT.

Generation of Cardiomyocytes from Pluripotent Stem Cells.

The advent of pluripotent stem cells (PSCs) enabled a multitude of studies for modeling the development of diseases and testing pharmaceutical therapeutic potential in vitro. These PSCs have been differentiated to multiple cell types to demonstrate its pluripotent potential, including cardiomyocytes (CMs). However, the efficiency and efficacy of differentiation vary greatly between different cell lines and methods. Here, we describe two different methods for acquiring CMs from human pluripotent lines. One method involves the generation of embryoid bodies, which emulates the natural developmental process, while the other method chemically activates the canonical Wnt signaling pathway to induce a monolayer of cardiac differentiation.