Programmed cell death ligand 1 (PD-L1) is part of an immune checkpoint system that is essential for preventing autoimmunity and cancer. Recent approaches in immunotherapy that target immune checkpoints have shown great promise in a variety of cancers, including metastatic melanoma. The use of targeted molecular imaging would help identify patients who will best respond to anti-PD-L1 treatment while potentially providing key information to limit immune-related adverse effects. Recently, we developed an antibody-based PD-L1-targeted SPECT agent-In-diethylenetriaminepentaacetic acid (DTPA)-anti-PD-L1-to identify PD-L1-positive tumors in vivo. To best use such PD-L1-targeted imaging agents, it is important, as a first step, to understand how the signal is affected by different parameters. We evaluated the impact of protein concentration on the distribution ofIn-DTPA-anti-PD-L1 in a murine model of aggressive melanoma. In-DTPA-anti-PD-L1 (dissociation constant, 0.6 ± 0.1 nM) demonstrated increased uptake in B16F10 tumors at protein concentrations equaling or exceeding 1 mg/kg at 24 h and 3 mg/kg at 72 h. At 24 h, the PD-L1-rich spleen and lungs demonstrated decreasing uptake with increasing protein concentration. At 72 h, uptake in the thymus was significantly increased at protein concentrations of 3 mg/kg or greater. Both time points demonstrated increased tracer amounts remaining in circulation as the amount of cold antibody was increased. These studies demonstrate that In-DTPA-anti-PD-L1 is capable of identifying tumors that overexpresses PD-L1 and monitoring the impact of PD-L1-rich organs on the distribution of anti-PD-L1 antibodies.

Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and antiinflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19. KEY MESSAGES 1. HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. 2. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. 3. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision.

Background Coronavirus disease 2019 (COVID-19) has been reported to cause worse outcomes in patients with underlying cardiovascular disease, especially in patients with acute cardiac injury, which is determined by elevated levels of high-sensitivity troponin. There is a paucity of data on the impact of congestive heart failure (CHF) on outcomes in COVID-19 patients. Methods We conducted a literature search of PubMed/Medline, EMBASE, and Google Scholar databases from 11/1/2019 till 06/07/2020, and identified all relevant studies reporting cardiovascular comorbidities, cardiac biomarkers, disease severity, and survival. Pooled data from the selected studies was used for metanalysis to identify the impact of risk factors and cardiac biomarker elevation on disease severity and/or mortality. Results We collected pooled data on 5,967 COVID-19 patients from 20 individual studies. We found that both non-survivors and those with severe disease had an increased risk of acute cardiac injury and cardiac arrhythmias, our pooled relative risk (RR) was — 8.52 (95% CI 3.63–19.98) (p<0.001); and 3.61 (95% CI 2.03–6.43) (p=0.001), respectively. Mean difference in the levels of Troponin-I, CK-MB, and NT-proBNP was higher in deceased and severely infected patients. The RR of in-hospital mortality was 2.35 (95% CI 1.18–4.70) (p=0.022) and 1.52 (95% CI 1.12–2.05) (p=0.008) among patients who had pre-existing CHF and hypertension, respectively. Conclusion Cardiac involvement in COVID-19 infection appears to significantly adversely impact patient prognosis and survival. Pre-existence of CHF, and high cardiac biomarkers like NT-pro BNP and CK-MB levels in COVID-19 patients correlates with worse outcomes.

Objective Aim of the study was to examine the effects of the vitamin D (Vit-D) treatment and non-treatment on Vit-D-deficient patients without a prior history of myocardial infarction (MI). Materials and Methods This is an retrospective, observational, nested case-control study of patients (N=20,025) with low 25-hydroxyvitamin D [(25-OH)D] levels (&lt;20 ng/ml) who received care at the Veterans Health Administration from 1999-2018. Patients were divided into three groups: Group A (untreated, levels ≤20 ng/ml), Group B (treated, levels 21-29 ng/ml), and Group C (treated, levels ≥30 ng/ml). The risk of MI and all-cause-mortality were compared utilizing propensity score-weighted cox-proportional hazard models. Results Among the cohort of 20,025 patients, the risk of MI was significantly lower in Group C, compared to Group B [hazard ratio (HR) 0.65, 95% CI; 0.49-0.85, P=.002] and Group A (HR 0.73, 95% CI; 0.55-0.96), P=.02). There was no difference in the risk of MI between Group B and Group A (HR 1.14, 95% CI; 0.91-1.42, P=.24]. Compared to Group A, both Group B (HR 0.59, 95% CI; 0.54-0.63, P&lt;.001] and Group C (HR 0.61, 95% CI; 0.56-0.67, P&lt;.001] had significantly lower all-cause-mortality. There was no difference in all-cause-mortality between Group B and Group C (HR 0.99, 95% CI; 0.89-1.09, P=.78). Conclusions In patients with Vit-D-deficiency and no prior history of MI, treatment to the (25-OH)D level of &gt;20 ng/ml and &gt;30 ng/ml was associated with a significantly lower risk of all-cause-mortality. The lower risk of MI was observed only in individuals maintaining the (25-OH)D levels ≥30 ng/ml.

Introduction Ultrasound guided axillary vein access (UGAVA) is an emerging approach for cardiac implantable electronic device (CIED) implantation not widely utilized. Methods and Results This is a retrospective, age and sex‐matched cohort study of CIED implantation from January 2017 to July 2019 comparing UGAVA before incision to venous access obtained after incision without ultrasound (conventional). The study population included 561 patients (187 with attempted UGAVA, 68 ± 13 years old, 43% women, body mass index (BMI) 30 ± 8 kg/m2, 15% right‐sided, 43% implantable cardioverter‐defibrillator, 15% upgrades). UGAVA was successful in 178/187 patients (95%). In nine patients where UGAVA was abandoned, the vein was too deep for access before incision. BMI was higher in abandoned patients than successful UGAVA (38 ± 6 vs. 28 ± 6 kg/m2, p < .0001). Median time from local anesthetic to completion of UGAVA was 7 min (interquartile range [IQR]: 4–10) and median procedure time 61 min (IQR: 50–92). UGAVA changed implant laterality in two patients (avoiding an extra incision in both) and could have prevented unnecessary incision in four conventional patients. Excluding device upgrades, there was reduced fluoroscopy time in UGAVA versus conventional (4 vs. 6 min; IQR: 2–5 vs. 4–9; p < .001). Thirty‐day complications were similar in UGAVA versus conventional (n = 7 vs. 26, 4 vs. 7%; p = .13, p = .41 adjusting for upgrades), partly driven by a trend towards reduced pneumothorax (n = 0 vs. 3, 0 vs. 1%; p = .22). Conclusions UGAVA is a safe approach for CIED implantation and helps prevent an extra incision if a barrier is identified changing laterality preincision.