IMPORTANCEFewer than 50% of kidney transplant recipients (KTRs) develop antibodies against the SARS-CoV-2 spike protein after 2 doses of an mRNA vaccine. Preliminary data suggest that a heterologous vaccination, combining mRNA and viral vector vaccines, may increase immunogenicity.OBJECTIVE To assess the effectiveness of a third dose of an mRNA vs a vector vaccine in KTRs who did not have antibodies against the SARS-CoV-2 spike protein after 2 doses of an mRNA vaccine. DESIGN, SETTING, AND PARTICIPANTSThis was a single center, single-blinded, 1:1 randomized clinical trial of a third dose of vaccine against SARS-CoV-2, conducted from June 15 to August 16, 2021, in 201 KTRs who had not developed SARS-CoV-2 spike protein antibodies after 2 doses of an mRNA vaccine. Data analyses were performed from August 17 to August 31, 2021.INTERVENTIONS mRNA (BNT162b2 or mRNA-1273) or vector (Ad26COVS1) as a third dose of a SARS-CoV-2 vaccine. MAIN OUTCOMES AND MEASURESThe primary study end point was seroconversion after 4 weeks (29-42 days) following the third vaccine dose. Secondary end points included neutralizing antibodies and T-cell response assessed by interferon-γ release assays (IGRA). In addition, the association of patient characteristics and vaccine response was assessed using logistic regression, and the reactogenicity of the vaccines was compared. RESULTS Among the study population of 197 kidney transplant recipients (mean [SD] age, 61.2 [12.4] years; 82 [42%] women), 39% developed SARS-CoV-2 antibodies after the third vaccine. There was no statistically significant difference between groups, with an antibody response rate of 35% and 42% for the mRNA and vector vaccines, respectively. Only 22% of seroconverted patients had neutralizing antibodies. Similarly, T-cell response assessed by IGRA was low with only 17 patients showing a positive response after the third vaccination. Receiving nontriple immunosuppression (odds ratio [OR], 3.59; 95% CI, 1.33-10.75), longer time after kidney transplant (OR, 1.44; 95% CI, 1.15-1.83, per doubling of years), and torque teno virus plasma levels (OR, 0.92; 95% CI, 0.88-0.96, per doubling of levels) were associated with vaccine response. The third dose of an mRNA vaccine was associated with a higher frequency of local pain at the injection site compared with the vector vaccine, while systemic symptoms were comparable between groups.CONCLUSIONS AND RELEVANCE This randomized clinical trial found that 39% of KTRs without an immune response against SARS-CoV-2 after 2 doses of an mRNA vaccine developed antibodies against the SARS-CoV-2 spike protein 4 weeks after a third dose of an mRNA or a vector vaccine. The heterologous vaccination strategy with a vector-based vaccine was well tolerated and safe but not significantly better than the homologous mRNA-based strategy.

Growth retardation is a frequent finding in patients after renal transplantation (Tx). Areal bone mineral density (BMD) in these patients has usually been reported to be low for age. We investigated the possible influence of height and weight retardation on the measurement of BMD in lumbar spine (BMD(L2-4)) and total body (BMDbody) using dual-energy X-ray absorptiometry in 44 (13 female) pediatric Tx patients with a median age of 13.1 (range 3.3-23.1) years. Patients were studied at 2.9 (range 1-10) years after Tx. Median body height in female and male patients was -2.10 (-3.6 to -0.3) and -2.35 (-5.3 to +1.0) standard deviation score (SDS), respectively. BMD expressed as grams per square centimeter bone area according to age was below the 5th percentile in 10 of 44 patients, but only 1 patient had low values for BMD(L2-4), and none for BMDbody, when the data were corrected for height or weight. BMDbody was closely correlated with height, weight, and body surface area (r=0.88), whereas the correlation for BMD(L2-4) was less (r=0.76). In 6 patients who achieved final height, height SDS was -2.27 (-4.3-0.4). Z-scores for BMDbody related to age, height, and weight were -1.0 (-2.6 to -2.3), 1.25 (0.1-3.4), and 0.81 (0.0-2.4), respectively. There was no age-dependent change when areal BMD values (g/cm2) were corrected for vertebral size to obtain bone volumetric density (BMDvol, g/cm3). Independent of height, cumulative methylprednisolone dose correlated negatively with BMD(L2-4) only in patients who had received a total dose of more than 6 g/m2 of the drug (r = -0.54, P= 0.045). In conclusion, BMD in pediatric patients after Tx is no longer diminished when the data are corrected for height or weight rather than age, or when the data are expressed as bone volumetric density.

Purpose The goal of our study was comparison of external beam radiotherapy (EBRT) and I‑125 seeds brachytherapy in terms of biochemical control and development of late gastrointestinal and genitourinary side effects. Patients and methods 477 low-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seeds brachytherapy or EBRT with a dose of 74 or 78 Gy were reviewed for our analysis. 213 patients were treated with EBRT and 264 with seeds. Results Patients were followed up yearly with a median follow-up of 70 (3–192) months. The biochemical no evidence of disease (bNED) rates after 5 years were 95% for both EBRT and seeds, and after 10 years 87% for EBRT and 94% for seeds using the Phoenix criteria, although no significant difference was observed. Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥2 toxicity compared to seeds, but at no point in follow-up more than 15% of all patients. On the other hand, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 40% RTOG grade ≥2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time. Conclusion Both EBRT and seeds provide excellent biochemical control with bNED rates after 10 years of about 90%. In terms of side effects, patients treated with seeds show higher grades of genitourinary side effects, while patients treated with EBRT show higher grades of gastrointestinal side effects.

Extracorporeal lung support includes the risk of hemolysis due to suction pressures. Manufacturers measure the negative suction pressure across drainage cannulas for their products in vitro using water. Clinical experience suggests that hemolysis occurs in vivo already at much lower flow rates. The aim of this study was to analyze the in vivo suction pressure for veno-venous extracorporeal membrane oxygenation (VV-ECMO) cannulas. Prospective, observational study at a tertiary-care intensive care unit: 15 patients on VV-ECMO for severe ARDS were prospectively included. In vitro, the 25 Fr drainage cannula pressure drops below a critical level of around –100 mm Hg at a flow rate of 7.9 L/min, the 23 Fr drainage cannula at 6.6 L/min. In the clinical setting, critical suction pressures were reached at much lower flow rates (5.5 and 4.7 L/min; p < 0.0001, nonlinear regression). The in vitro data largely overestimate the safely achievable flow rates in daily clinical practice by 2.4 L/min (or 44%, 25 Fr) and 1.9 L/min (or 41%, 23 Fr). In vivo measurement of suction pressure of venous drainage cannulas differed significantly from in vitro derived measurements as the latter largely underestimate the resulting suction pressure.

Deflazacort (DFZ) has been proposed as an alternative drug for immunosuppression after renal transplantation (TX), with fewer side effects than conventional glucocorticoids. We investigated renal function, body growth, body fat, and bone mineral density (BMD) after switching from oral methylprednisolone (MPR) to equivalent doses of DFZ 1-9 years after TX in 20 patients aged 5-20 years, selected because of severe adverse effects from previous steroid therapy. At conversion the patients received a mean dose of 7.4 +/- 2.4 mg DFZ/m2 per day. The drug was continued for a mean of 3.7 (1.2-5.5) years. Under DFZ, the glomerular filtration rate dropped slightly (NS). A single rejection episode occurred. Growth velocity significantly improved in the 1st year on DFZ treatment and height standard deviation score (SDS) increased steadily after introduction of DFZ (from -2.64 to -1.96 after 4 years, P = 0.06). However, in 10 prepubertal children the height gain (+0.20 SDS in 2 years on DFZ) was not significant and the overall mean annual growth rate after TX was similar to that in 10 matched prepubertal TX children on continued MPR treatment. Relative obesity, estimated from mean body mass index corrected for height, was reduced from +1.11 SDS at the start of DFZ to +0.71 SDS after 2 years (P = 0.03) and to +0.39 SDS after 4 years (NS). BMD-SDS of the lumbar spine (L2-4) increased after 1 year on DFZ (P = 0.005). In conclusion, DFZ is well tolerated and safe in pediatric patients after TX. It improves relative obesity and bone mineralization. However, body growth is not significantly influenced pre puberty.