Humoral and cellular responses to mRNA-based COVID-19 booster vaccinations in patients with solid neoplasms under active treatment.

BACKGROUND: Patients with cancer are at high risk for severe coronavirus disease 2019 (COVID-19) infection. Knowledge regarding the efficacy of the messenger RNA (mRNA) vaccines in actively treated cancer patients is limited as they had been excluded from the pivotal studies of these vaccines. We evaluated humoral and cellular immune responses in cancer patients after double vaccination and a booster dose and identified disease- and treatment-related factors associated with a reduced immune response. We also documented the number and outcome of breakthrough infections. PATIENTS AND METHODS: Patients with metastatic solid malignancies undergoing active treatment were included if they had received two doses of the severe acute respiratory syndrome coronavirus 2 mRNA vaccines BNT162b2 or mRNA-1273 and a booster dose. Other causes of immunosuppression and previous COVID-19 infections (positive anti-nucleocapsid titers) were exclusion criteria. Anti-spike antibodies, neutralizing antibodies (nAbs) and T-cell responses were assessed about 6 months after the two-dose vaccination and 4 weeks after the booster. RESULTS: Fifty-one patients had pre-booster and 46 post-booster measurements. Anti-spike titers after two vaccine doses were highly variable and significantly lower in older patients, during treatment with chemotherapy compared to targeted and endocrine treatments and in patients with low CD4+ or CD19+ cell counts. The booster dose led to a significant increase in anti-spike antibodies and nAbs, achieving almost uniformly high titers, irrespective of baseline and treatment factors. The cellular immune response was also significantly increased by the booster, however generally more stable and not influenced by baseline factors and treatment type. Seventeen patients (33%) experienced breakthrough infections, but none required hospital care or died from COVID-19. CONCLUSIONS: An mRNA vaccine booster dose is able to increase humoral and cellular immune responses and to overcome the immunosuppressive influence of baseline and treatment factors in cancer patients. Breakthrough infections were uniformly mild in this vaccinated high-risk population.

Titanium wear from magnetically controlled growing rods (MCGRs) for the treatment of spinal deformities in children.

Magnetically controlled growing rods (MCGRs) are an effective treatment method for early-onset scoliosis (EOS). In recent years, increasing titanium wear was observed in tissue adjacent to implants and in blood samples of these patients. This study aims to investigate the potential correlation between amount of metal loss and titanium levels in blood during MCGR treatment as well as influencing factors for metal wear. In total, 44 MCGRs (n = 23 patients) were retrieved after an average of 2.6 years of implantation and analyzed using a tactile measurement instrument and subsequent metal loss calculation. Titanium plasma levels (n = 23) were obtained using inductively coupled plasma-mass spectrometry (ICP-MS). The correlation of both parameters as well as influencing factors were analyzed. Titanium abrasion on MCGRs was observed in the majority of implants. There was no correlation of metal implant wear or titanium plasma values to the duration of MCGR implantation time, number of external lengthening procedures, patient's ambulatory status, gender, weight or height. Material loss on the MCGRs showed a positive correlation to titanium blood plasma values. The present study is one of the first studies to analyze retrieved MCGRs using high-precision metrological techniques and compare these results with ICP-MS analyses determining blood titanium values.

Effects of a novel mobile health intervention compared to a multi-component behaviour changing program on body mass index, physical capacities and stress parameters in adolescents with obesity: a randomized controlled trial.

BACKGROUND: Less than 2% of overweight children and adolescents in Switzerland can participate in multi-component behaviour changing interventions (BCI), due to costs and lack of time. Stress often hinders positive health outcomes in youth with obesity. Digital health interventions, with fewer on-site visits, promise health care access in remote regions; however, evidence for their effectiveness is scarce. METHODS: This randomized controlled not blinded trial (1:1) was conducted in a childhood obesity center in Switzerland. Forty-one youth aged 10-18 years with body mass index (BMI) > P.90 with risk factors or co-morbidities or BMI > P.97 were recruited. During 5.5 months, the PathMate2 group (PM) received daily conversational agent counselling via mobile app, combined with standardized counselling (4 on-site visits). Controls (CON) participated in a BCI (7 on-site visits). We compared the outcomes of both groups after 5.5 (T1) and 12 (T2) months. Primary outcome was reduction in BMI-SDS (BMI standard deviation score: BMI adjusted for age and sex). Secondary outcomes were changes in body fat and muscle mass (bioelectrical impedance analysis), waist-to-height ratio, physical capacities (modified Dordel-Koch-Test), blood pressure and pulse. Additionally, we hypothesized that less stressed children would lose more weight. Thus, children performed biofeedback relaxation exercises while stress parameters (plasma cortisol, stress questionnaires) were evaluated. RESULTS: At intervention start median BMI-SDS of all patients (18 PM, 13 CON) was 2.61 (obesity > + 2SD). BMI-SDS decreased significantly in CON at T1, but not at T2, and did not decrease in PM during the study. Muscle mass, strength and agility improved significantly in both groups at T2; only PM reduced significantly their body fat at T1 and T2. Average daily PM app usage rate was 71.5%. Cortisol serum levels decreased significantly after biofeedback but with no association between stress parameters and BMI-SDS. No side effects were observed. CONCLUSIONS: Equally to BCI, PathMate2 intervention resulted in significant and lasting improvements of physical capacities and body composition, but not in sustained BMI-SDS decrease. This youth-appealing mobile health intervention provides an interesting approach for youth with obesity who have limited access to health care. Biofeedback reduces acute stress and could be an innovative adjunct to usual care.

Outcome groups and a practical tool to predict success of shock wave lithotripsy in daily clinical routine.

PURPOSE: To improve outcome prediction of extracorporeal shock wave lithotripsy (SWL) by development of a model based on easily available clinical and radiographical predictors and suitable for daily clinical use. MATERIALS AND METHODS: We evaluated predictive factors for SWL success in 517 consecutive patients suffering from urinary calculi who underwent SWL between 2010 and 2018. Analyses included descriptive statistics, receiver operating characteristic statistics and logistic regression. Predictive value was improved by combining parameters using model selection and recursive partitioning. RESULTS: Of the 517 patients, 310 (60.0%) had a successful SWL. Best individual predictor of SWL success was mean attenuation (MAV), with an area under the curve (AUC) of 0.668, and an optimal cutpoint (OC) of 987.5 HU. The best multivariable model, including MAV, stone size, skin to stone distance (SSD), presence of an indwelling stent, and four interaction effects, yielded an AUC of 0.736. Recursive partitioning would categorize patients into three outcome groups with high (76.9%), intermediate (41%) and low (10%) success probability. High probability of SWL success (76.9%) was found for patients with a stone with MAV ≤ 987 HU or with MAV > 987 HU but stone size ≤ 11 mm and SSD (45°) ≤ 88 mm. CONCLUSION: A model based on four established predictors, and provided as an Excel®-Tool, can clearly improve prediction of SWL success. In addition, patients can be classified into three defined outcome groups based on simple cutpoint combinations. Both tools improve informed decision-making in daily clinical practice and might reduce failure rates.

Clinical characteristics and outcome of patients over 60 years with Hodgkin lymphoma treated in Switzerland.

Hodgkin lymphoma (HL) in older patients appears to be a different disease compared with younger patients with historically lower survival rates. This is related to a variety of factors, including increased treatment-related toxicity, the presence of comorbidities, and biologic differences. In order to better assess the clinical characteristics, treatment strategies, and outcome of this particular population, we conducted a population-based, retrospective analysis including 269 patients with HL older than 60 years (median age 71 years, range 60-94), treated between 2000 and 2017 in 15 referral centers across Switzerland. Primary endpoints were overall survival (OS), progression-free survival (PFS), and cause-specific survival (CSS). The vast majority of patients were treated with curative intent, either with a combined modality approach (chemotherapy followed by radiation therapy) or with systemic therapy. At a median follow-up of 6.6 years (95% confidence interval [CI], 6.0-7.6), 5-year PFS was 52.2% (95% CI, 46.0-59.2), 5-year OS was 62.5% (95% CI, 56.4-69.2), and 5-year CSS was 85.1.8% (95% CI, 80.3-90.1) for the entire cohort. A significant difference in terms of CSS was observed for patients older than 71 years in comparison to patients aged 60-70 years (hazard ratio 2.6, 1.3-5.0, p = 0.005). Bleomycin-induced lung toxicity (BLT) was documented in 26 patients (17.7%) out of the 147 patients exposed to this compound and was more frequent in patients older than 71 years (15/60, 25%). Outcome of HL pts older than 71 years appeared to decrease substantially in comparison to the younger counterpart. Treatment-related toxicities appeared to be relevant, in particular, BLT. New, potentially less toxic strategies need to be investigated in prospective clinical trials in this particular frail population.

Advanced non-contrasted computed tomography post-processing by CT-Calculometry (CT-CM) outperforms established predictors for the outcome of shock wave lithotripsy.

OBJECTIVES: To evaluate the predictive value of advanced non-contrasted computed tomography (NCCT) post-processing using novel CT-calculometry (CT-CM) parameters compared to established predictors of success of shock wave lithotripsy (SWL) for urinary calculi. MATERIALS AND METHODS: NCCT post-processing was retrospectively performed in 312 patients suffering from upper tract urinary calculi who were treated by SWL. Established predictors such as skin to stone distance, body mass index, stone diameter or mean stone attenuation values were assessed. Precise stone size and shape metrics, 3-D greyscale measurements and homogeneity parameters such as skewness and kurtosis, were analysed using CT-CM. Predictive values for SWL outcome were analysed using logistic regression and receiver operating characteristics (ROC) statistics. RESULTS: Overall success rate (stone disintegration and no re-intervention needed) of SWL was 59% (184 patients). CT-CM metrics mainly outperformed established predictors. According to ROC analyses, stone volume and surface area performed better than established stone diameter, mean 3D attenuation value was a stronger predictor than established mean attenuation value, and parameters skewness and kurtosis performed better than recently emerged variation coefficient of stone density. Moreover, prediction of SWL outcome with 80% probability to be correct would be possible in a clearly higher number of patients (up to fivefold) using CT-CM-derived parameters. CONCLUSIONS: Advanced NCCT post-processing by CT-CM provides novel parameters that seem to outperform established predictors of SWL response. Implementation of these parameters into clinical routine might reduce SWL failure rates.