The retinal venous pressure at different levels of airway pressure measured with a new method.

PURPOSE: This study is to investigate the increase in retinal venous pressure (RVP) induced by a stepwise increase in airway pressure (AirP) using the new IOPstim method, which is designed to artificially increase the intraocular pressure (IOP) and thus to stimulate vascular pulsation. METHODS: Twenty-eight healthy subjects were examined in the left eye. The RVP was measured at baseline and at four different levels of AirP (10, 20, 30, and 40 mmHg) using the new IOPstim method: a half balloon of 8 mm diameter is inflated laterally to the cornea under observation of the central retinal vein. As soon as the vein pulsates at a certain AirP level, the IOP is measured with a commercially available tonometer, which then corresponds to the RVP. RESULTS: Spontaneous venous pulsation was observed in all study participants. The mean RVP values at baseline and at the AirP levels of 10, 20, 30, and 40 mmHg were 17.6 ± 2.8 mmHg; 20.1 ± 3.0 mmHg; 22.1 ± 3.5 mmHg; 24.3 ± 3.7 mmHg, and 26.6 ± 4.2 mmHg, respectively. The mean RVP values of each AirP level were statistically significantly different from each other in pairwise comparison. In a linear mixed model, the effect of AirP on RVP was highly significant (p < 0.001). In the model, a 10-mmHg increase in AirP resulted in a linear increase in RVP of 2.2 mmHg. CONCLUSION: An increase in AirP was accompanied by a linear increase in RVP. The influence of AirP on RVP, and thus on retinal perfusion pressure during the Valsalva maneuver, is less than was assumed based on previous studies in which contact lens dynamometry was used.

Comparative effects of variable versus conventional volume-controlled one-lung ventilation on gas exchange and respiratory system mechanics in thoracic surgery patients: A randomized controlled clinical trial.

BACKGROUND: Mechanical ventilation with variable tidal volumes (V-VCV) has the potential to improve lung function during general anesthesia. We tested the hypothesis that V-VCV compared to conventional volume-controlled ventilation (C-VCV) would improve intraoperative arterial oxygenation and respiratory system mechanics in patients undergoing thoracic surgery under one-lung ventilation (OLV). METHODS: Patients were randomized to V-VCV (n = 39) or C-VCV (n = 39). During OLV tidal volume of 5 mL/kg predicted body weight (PBW) was used. Both groups were ventilated with a positive end-expiratory pressure (PEEP) of 5 cm H2O, inspiration to expiration ratio (I:E) of 1:1 (during OLV) and 1:2 during two-lung ventilation, the respiratory rate (RR) titrated to arterial pH, inspiratory peak-pressure ≤ 40 cm H2O and an inspiratory oxygen fraction of 1.0. RESULTS: Seventy-five out of 78 Patients completed the trial and were analyzed (dropouts were excluded). The partial pressure of arterial oxygen (PaO2) 20 min after the start of OLV did not differ among groups (V-VCV: 25.8 ± 14.6 kPa vs C-VCV: 27.2 ± 15.3 kPa; mean difference [95% CI]: 1.3 [-8.2, 5.5], P = 0.700). Furthermore, intraoperative gas exchange, intraoperative adverse events, need for rescue maneuvers due to desaturation and hypercapnia, incidence of postoperative pulmonary and extra-pulmonary complications, and hospital free days at day 30 after surgery did not differ between groups. CONCLUSIONS: In thoracic surgery patients under OLV, V-VCV did not improve oxygenation or respiratory system mechanics compared to C-VCV. Ethical Committee: EK 420092019. TRIAL REGISTRATION: at the German Clinical Trials Register: DRKS00022202 (16.06.2020).

Epidemiology of 7375 children and adolescents hospitalized with COVID-19 in Germany, reported via a prospective, nationwide surveillance study in 2020-2022.

By means of a nationwide, prospective, multicenter, observational cohort registry collecting data on 7375 patients with laboratory-confirmed SARS-CoV-2 admitted to children's hospitals in Germany, March 2020-November 2022, our study assessed the clinical features of children and adolescents hospitalized due to SARS-CoV-2, evaluated which of these patients might be at highest risk for severe COVID-19, and identified underlying risk factors. Outcomes tracked included: symptomatic infection, case fatality, sequelae at discharge and severe disease. Among reported cases, median age was one year, with 42% being infants. Half were admitted for reasons other than SARS-CoV-2. In 27%, preexisting comorbidities were present, most frequently obesity, neurological/neuromuscular disorders, premature birth, and respiratory, cardiovascular or gastrointestinal diseases. 3.0% of cases were admitted to ICU, but ICU admission rates varied as different SARS-CoV-2 variants gained prevalence. Main risk factors linked to ICU admission due to COVID-19 were: patient age (> 12 and 1-4 years old), obesity, neurological/neuromuscular diseases, Trisomy 21 or other genetic syndromes, and coinfections at time of hospitalization. With Omicron, the group at highest risk shifted to 1-4-year-olds. For both health care providers and the general public, understanding risk factors for severe disease is critical to informing decisions about risk-reduction measures, including vaccination and masking guidelines.

9-Month observational Dia-Vacc study of vaccine type influence on SARS-CoV-2 immunity in dialysis and kidney transplant patients.

BACKGROUND: SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients. METHODS: We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. FINDINGS: Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time. By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent. INTERPRETATION: While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population.

Evaluation of a protocol to assess a novel artificial biofilm equivalent for dentures-A prospective clinical pilot study.

OBJECTIVES: This pilot study aimed to carry out preliminary tests of the removability of an artificial biofilm equivalent (ABE) and to verify the reproducibility of the ABE testing protocol for a planned main study. BACKGROUND: There is a lack of data to develop suitable artificial biofilm substitutes, which may be helpful to perform denture hygiene education and to carry out in vitro examinations of oral hygiene products. MATERIALS AND METHODS: This single-group, prospective, longitudinal, interventional pilot study was conducted in Dresden (Germany) from February until December 2020. Participants were recruited who wore fully functional upper complete dentures. Denture biofilm was grown on acrylic specimens by wearing dentures for 12 h and 36 h using intraoral appliances. Acrylic specimens were coated with ABEs of three compositions: chitosan (ChS) 0.3 g, methylcellulose (MC) 1.7 g; ChS 0.2 g, MC 1.8 g; ChS 0.1 g, MC 1.9 g (labelled 1.7MC, 1.8MC and 1.9MC, respectively). All specimens underwent standardised mechanical brushing. The percentages of remaining biofilm (POB) were measured. RESULTS: Thirty-one participants were prescreened, and eight (26%) were included. The appliances were well tolerated, and biofilm was collected. ABE was prepared and brushed as planned. Three and six brushing strokes were needed to remove 12-h and 36-h natural denture biofilm, respectively. Correspondingly, three brushing strokes were needed to remove 1.9MC ABE and six brushing strokes to remove 1.8MC and 1.7MC ABE. A reproducibility of ABE removal was indicated. CONCLUSION: The removability of ABE and the ABE testing protocol were feasible and reproducible for conducting the future main study.

The effect of plasma cortisol on hippocampal atrophy and clinical progression in mild cognitive impairment.

Introduction: Both elevated cortisol and hippocampal volume have been linked to an increased risk for the development of Alzheimer's disease (AD). This longitudinal study assessed the effects of plasma cortisol on hippocampal atrophy and clinical progression rates in patients with mild cognitive impairment (MCI). Methods: Patients with amnestic MCI (n = 304) were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) based on availability of baseline plasma cortisol and hippocampal volume measures, assessed at baseline and during follow-ups. We investigated associations between plasma cortisol, hippocampal volume, and risk of clinical progression to AD over a study period of up to 100 months (mean follow-up time 36.8 months) using linear mixed models, Cox proportional hazards models, and Kaplan-Meier estimators. Results: Plasma cortisol predicted greater hippocampal atrophy, such that participants with higher cortisol showed faster decline in hippocampal volume over time (interaction: ß = -0.15, p = 0.004). Small hippocampal volume predicted a higher risk of clinical progression to AD (haard ratio [HR] = 2.15; confidence in terval [CI], 1.64-2.80; p < 0.001). A similar effect was not found for cortisol (HR = 1.206; CI, 0.82-1.37; p = 0.670) and there was no statistical evidence for an interaction between hippocampal volume and cortisol on clinical progression (HR = 0.81; CI, 0.57-0.17; p = 0.260). Discussion: Our findings suggest that higher cortisol predicts higher hippocampal atrophy, which in turn is a risk factor for progression to AD. Regulation of the hypothalamic-pituitary-adrenal axis through stress-reducing lifestyle interventions might be a protective factor against hippocampal degeneration at the prodromal stage of AD.

MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination.

Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear. In an observational study (NCT04799808), we investigated whether 132 seroconverted KTR (anti-spike S1 IgG or IgA positive after 2 vaccinations) show a more rapid antibody decline with MMF/MPA than those without this medication. A total of 2 months after mRNA vaccination, average anti-spike S1 IgG levels of KTR with MMF/MPA were lower than without (p = 0.001), while no differences between these two groups were observed after 6 months (p = 0.366). Similar results were obtained for anti-RBD IgG antibodies (T2 p = 0.003 and T3 p = 0.135). The probability of severe IgG decline with MMF/MPA was three times lower than without (p = 0.003, OR 0.236, 95% CI 0.091-0.609). In the multivariate analysis, neither immunosuppressants, such as calcineurin inhibitors, mTOR inhibitors (mTOR-I; mechanistic target of rapamycin), glucocorticoids, nor vaccine type, sex, or age showed a significant influence on IgG titer decline between 2 and 6 months. For the decision on additional booster vaccinations, we consider immunosurveillance to be needed as an integral part of renal transplant follow-up after SARS-CoV-2 mRNA vaccination. Not only the lack of seroconversion but also the peak and titer decline of the specific IgG and RBD IgG antibody formation after two mRNA vaccinations is significantly influenced by MMF/MPA.

Anti-SARS-CoV-2 Revaccination Success in Kidney Transplant Recipients With No Initial Humoral Response Is Linked to Primary Vaccine Type.

Background: While anti-SARS-CoV-2 vaccination success in kidney transplant recipients (KTR) after two doses and 1273-mRNA was associated with higher seroconversion rates compared to BNT162b2-mRNA in our "DIA-Vacc Study" (NCT04799808), it remains unclear whether this may also be the case in non-responding KTR after a third vaccination dose. Materials and Methods: Non-responding KTR (after two mRNA vaccinations) were investigated 4.5-6 months after study enrollment at first vaccination. One hundred sixty-six of 193 received a third vaccination between 3.5 and 5 months after the initial study enrollment and were always investigated 4 weeks later, exploring humoral immune response (ELISA) and specific cellular responses (interferon-γ release assay). Sixty-seven of 193 measurements in KTR were done immediately before the third vaccination or in KTR without further vaccination at 4.5-6 months. Results: Of 193 KTR with no initial immune response 4 weeks after the second vaccination, 106/87 were immunized twice with 1273-mRNA/BNT162b2-mRNA, respectively. Additional mRNA booster vaccination led to positive seroconversion rates of 30-50%, while 16% of the initial non-responders demonstrated a delayed seroconversion without any booster vaccination. Using logistic regression analysis, a positive IgG response after the third vaccination was 23% more likely if the primary vaccine type was 1273-mRNA compared to BNT162b2-mRNA (OR = 4.420, 95% CI [1.208-16.173], p = 0.025). Primary vaccine type, a weak anti-SpikeS1 IgG response 4 weeks after second vaccination (3.2-35.2 BAU/ml, p < 0.001) and a lack of MMF/MPA as part of the immunosuppressive treatment (trend, p = 0.06) but no other variables studied correlated with seroconversion success. Conclusion: This observational study adds important evidence toward using 1273-mRNA as the primary mRNA vaccine type for immunosuppressed KTR.

Risk of strong antibody decline in dialysis and transplant patients after SARS-CoV-2mRNA vaccination: Six months data from the observational Dia-Vacc study.

Background: Vulnerable dialysis and kidney transplant patients show impaired seroconversion rates compared to medical personnel eight weeks after SARS-CoV-2mRNA vaccination. Methods: We evaluated six months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 1205 participants including medical personnel (125 MP), dialysis patients (970 DP) and kidney transplant recipients (110 KTR) with seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. Findings: Six months after vaccination, seroconversion remained positive in 98% of MP, but 91%/87% of DP/KTR (p = 0·005), respectively. Receptor binding domain-IgG (RBD-IgG) antibodies were positive in 98% of MP, but only 68%/57% of DP/KTR (p < 0·001), respectively. Compared to MP, DP and KTR were at risk for a strong IgG or RBD-IgG decline (p < 0·001). Within the DP but not KTR group male gender, peritoneal dialysis, short time on dialysis, BNT162b2mRNA vaccine, immunosuppressive drug use and diabetes mellitus were independent risk factors for a strong decline of IgG or RBD antibodies. The percentage of cellular immunity decline was similar in all groups. Interpretation: Both vulnerable DP and KTR groups are at risk for a strong decline for IgG and RBD antibodies. In KTR, antibody titres peak at a markedly lower level and accelerated antibody decline is mixed with a delayed/increasing IgG, RBD-IgG, or cellular immune response in a 16% fraction of patients. In both populations, immune monitoring should be used for early timing of additional booster vaccinations. Funding: This study was funded by the Else Kröner Fresenius Stiftung, Bad Homburg v. d. H., grant number Fördervertrag EKFS 2021_EKSE.27.

Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine.

BACKGROUND: Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality. METHODS: We conducted a prospective study exploring the eight week time course of specific cellular (interferon-γ release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273. RESULTS: SARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%). T-cellular immunity largely mimicked humoral results. Major risk factors of seroconversion failure were immunosuppressive drug number and type (belatacept, MMF-MPA, calcineurin-inhibitors) as well as vaccine type (BNT162b2 mRNA). Seroconversion rates induced by mRNA-1273 compared to BNT162b2 vaccine were 97% to 88% (p < 0.001) in dialysis and 49% to 26% in transplant patients, respectively. Specific IgG directed against the new binding domain of the spike protein (RDB) were significantly higher in dialysis patients vaccinated by mRNA-1273 (95%) compared to BNT162b2 (85%, p < 0.001). Vaccination appeared safe and highly effective demonstrating an almost complete lack of symptomatic COVID-19 disease after boost vaccination as well as ceased disease incidences during third pandemic wave in dialysis patients. CONCLUSION: Dialysis patients exhibit a remarkably high seroconversion rate of 95% after boost vaccination, while humoral response is impaired in the majority of transplant recipients. Immunosuppressive drug number and type as well as vaccine type (BNT162b2) are major determinants of seroconversion failure in both dialysis and transplant patients suggesting immune monitoring and adaption of vaccination protocols.

The Effect of Ambient Environmental Conditions on COVID-19 Mortality: A Systematic Review.

Weather conditions may have an impact on SARS-CoV-2 virus transmission, as has been shown for seasonal influenza. Virus transmission most likely favors low temperature and low humidity conditions. This systematic review aimed to collect evidence on the impact of temperature and humidity on COVID-19 mortality. This review was registered with PROSPERO (registration no. CRD42020196055). We searched the Pubmed, Embase, and Cochrane COVID-19 databases for observational epidemiological studies. Two independent reviewers screened the title/abstracts and full texts of the studies. Two reviewers also performed data extraction and quality assessment. From 5051 identified studies, 11 were included in the review. Although the results were inconsistent, most studies imply that a decrease in temperature and humidity contributes to an increase in mortality. To establish the association with greater certainty, future studies should consider accurate exposure measurements and important covariates, such as government lockdowns and population density, sufficient lag times, and non-linear associations.