Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection.

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.

Assessment of Valvular Disorders in Survivors of Hodgkin's Lymphoma Treated by Mediastinal Radiotherapy ± Chemotherapy.

As the number of Hodgkin's lymphoma (HL) survivors grows, understanding long-term complications becomes more important. Mediastinal radiotherapy (MRT) seems to cause valvular disease, and the prevalence might increase during follow-up. In this cross-sectional study 82 HL survivors participated (52% men, mean age 47.8 years, 50 treated with MRT). Valvular disease was diagnosed by transthoracic echocardiography and compared between HL survivors treated with and without MRT. Univariate and multivariate logistic regression analysis was used to identify predictors for valvular disease. During a median follow-up of 13.4 years (range 2 to 39 years), ≥ mild valvular disease was present in 61.2% of HL survivors with MRT (n = 30), compared with 31.0% of HL survivors without MRT (n = 9; odds ratio [OR] 3.51, 95% CI 1.32 to 9.30, p = 0.01). In multivariate analysis, only current age remained predictive for ≥ mild valvular disease (OR 1.08 per year, 95% CI 1.01 to 1.14, p = 0.023). Aortic regurgitation (AR) was most prevalent and irradiated patients had significantly more ≥ mild AR (38.2% vs 6.8%, p = 0.007). Within the MRT subgroup, time after radiation of >15 years was associated with AR (OR 4.70, 95% CI 1.05 to 21.03, p = 0.043), after adjusting for current age and hypertension. Severe valvular disease was present in 24.5% of HL survivors with MRT compared with 3.4% without MRT (p = 0.016). Valvular surgery was performed in 9 HL survivors (18.0%) with MRT and in none without MRT. In conclusion, the prevalence of valvular disease in HL survivors treated with MRT is high and increases with time after irradiation. Long-time screening for valvular disease by transthoracic echocardiography might be worthwhile.

Arterial stiffness is increased in Hodgkin lymphoma survivors treated with radiotherapy.

Radiotherapy has been associated with an increased risk for cardiovascular disease (CVD) in Hodgkin lymphoma survivors (HLS). Identifying subjects most likely to develop these complications is challenging. Arterial stiffness has been frequently used as an early marker of CVD, but has never previously been investigated in patients treated with radiotherapy. The carotid-femoral pulse wave velocity (PWV) and the distensibility coefficient (DC) of the common carotid artery were used as markers of arterial stiffness. Eighty-two HLS and 40 age- and gender-matched control subjects were studied. The aorta and the carotid arteries were situated within the radiation field in 50 and 39 patients. Mean PWV was not significantly different in HLS treated with radiotherapy on the mediastinum when compared to HLS treated without mediastinal radiotherapy and to controls. If HLS were 40 years or older at radiotherapy their PWV was significantly higher (8.54 m/s) than patients irradiated at a younger age (7.14 m/s, p = 0.004) and controls (6.91 m/s, p < 0.001), after adjusting for current age and other CVD risk factors. Mean DC was lower, indicative of stiffer arteries, in HLS treated with radiotherapy on the common carotid artery (2.79) than in HLS without radiotherapy (3.35, p = 0.029) and versus controls (3.60, p = 0.001). DC was lowest in HLS treated at 35 years of age or later (2.05), compared to HLS irradiated at a younger age (2.98, p = 0.046). In HLS, radiotherapy is associated with increased arterial stiffness. The effect of radiotherapy seems most evident when radiotherapy is administered at ages above 35-40 years.

Progressive muscle atrophy and weakness after treatment by mantle field radiotherapy in Hodgkin lymphoma survivors.

PURPOSE: To describe the damage to the muscles and propose a pathophysiologic mechanism for muscle atrophy and weakness after mantle field radiotherapy in Hodgkin lymphoma (HL) survivors. METHODS AND MATERIALS: We examined 12 patients treated by mantle field radiotherapy between 1969 and 1998. Besides evaluation of their symptoms, the following tests were performed: dynamometry; ultrasound of the sternocleidomastoid, biceps, and antebrachial flexor muscles; and needle electromyography of the neck, deltoid, and ultrasonographically affected arm muscles. RESULTS: Ten patients (83%) experienced neck complaints, mostly pain and muscle weakness. On clinical examination, neck flexors were more often affected than neck extensors. On ultrasound, the sternocleidomastoid was severely atrophic in 8 patients, but abnormal echo intensity was seen in only 3 patients. Electromyography of the neck muscles showed mostly myogenic changes, whereas the deltoid, biceps, and antebrachial flexor muscles seemed to have mostly neurogenic damage. CONCLUSIONS: Many patients previously treated by mantle field radiotherapy develop severe atrophy and weakness of the neck muscles. Neck muscles within the radiation field show mostly myogenic damage, and muscles outside the mantle field show mostly neurogenic damage. The discrepancy between echo intensity and atrophy suggests that muscle damage is most likely caused by an extrinsic factor such as progressive microvascular fibrosis. This is also presumed to cause damage to nerves within the radiated field, resulting in neurogenic damage of the deltoid and arm muscles.

Screening Hodgkin lymphoma survivors for radiotherapy induced cardiovascular disease.

Long term prognosis of Hodgkin lymphoma (HL) survivors is affected by late toxicity of radiotherapy and chemotherapy. Cardiovascular complications of radiotherapy have been shown to have a great impact on the long term survival. The aim of this review is to summarize the available data on different screening modalities for cardiovascular disease and to suggest a screening program. Patients older than 45 years at HL diagnosis should be screened for coronary artery disease (CAD) starting 5 years after mediastinal radiotherapy; they are at increased risk of pre-existent atherosclerosis which can be accelerated by radiotherapy. Screening for CAD should start 10 years after radiotherapy in younger patients. The best screening modality for CAD is subject of discussion, based on the latest studies we suggest screening by Coronary artery calcium score measurements or CT-angiography. Valvular disorders should be looked for by echocardiography starting 10 years after radiotherapy. Electrocardiograms should be performed at each cardiovascular screening moment in order to detect arrhythmia's or conduction abnormalities. We suggest repeating these screening tests every 5 years or at onset of cardiovascular complaints; patients should be extensively instructed about signs and symptoms of cardiovascular disease. Furthermore traditional risk factors for cardiovascular disease should be carefully monitored and treated. We suggest determining a cardiovascular risk profile at diagnosis of HL in patients older than 45 years. In case of a high risk, treating HL without RT should be considered.

Comparison of two instruments measuring carotid-femoral pulse wave velocity: Vicorder versus SphygmoCor.

BACKGROUND: The carotid-femoral pulse wave velocity (PWVcf) is used as an indicator of arterial stiffness. It is often measured using applanation tonometry, for instance with the SphygmoCor. In young children, this method is difficult to perform. Therefore, techniques are needed that are less dependent on patient compliance. The Vicorder device uses the oscillometric technique to measure the PWVcf and is thought to be less time consuming and less dependent on operator skills. OBJECTIVE: To compare the PWVcf measured by an extensively used device (SphygmoCor) and the Vicorder in adults initially. METHODS: Thirty-eight healthy volunteers (20 men, mean age 48 +/- 13.1 years) participated in this cross-sectional study. The PWVcf was assessed twice using the SphygmoCor and the Vicorder by a single investigator during one visit. Intra-rater reproducibility of each instrument and comparison between the two instruments were assessed by the Bland-Altman method. RESULTS: The mean difference (95% confidence interval) between repeated measurements was 0.09 (-0.20 to 0.38) m/s and 0.24 (-0.55 to 1.03) m/s, for the SphygmoCor and Vicorder, respectively. The Limits of Agreement (LoA) were -1.53 to 1.71 m/s and -4.24 to 4.72 m/s, for the SphygmoCor and Vicorder, respectively. The mean PWVcf measured by the Vicorder was 0.58 (-0.20 to 1.35) m/s higher than the PWVcf measured by the SphygmoCor. The LoA between the two instruments were -3.50 to 4.66 m/s. CONCLUSION: The LoA of both instruments exceed a value of 1.5 m/s. The LoA of the Vicorder PWVcf measurements are considered too wide for using this technique reliably in adults or in children.