Patients with pulmonary hypertension (PH) have an impaired functional capacity and poor health-related quality of life (HRQoL). The one-minute sit-to-stand test (1-min STST) can be used for the ...assessment of functional capacity.
Our aim was to evaluate the 1-min STST performance and its association with patient-reported HRQoL in patients with PH.
We prospectively assessed functional capacity in 98 PH patients (mean age 66 ± 15 years, 55% female) using the 1-min STST. Patients had to stand up and sit down from a chair as many times as possible within one minute. Patients' HRQoL was evaluated with the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire, which consists of the three subcategories symptoms, activities and quality of life (QoL).
We observed a significant correlation of the 1-min STST performance with all HRQoL subcategories assessed with the CAMPHOR questionnaire: A lower number of 1-min STST repetitions correlated with more symptoms (rs = -.398, p < .001), worse functioning (rs = -.551, p < .001) and a decreased QoL (rs = -.407, p < .001). Furthermore, in the multivariable linear regression analysis, adjusted for age, sex, body mass index (BMI) and mean pulmonary artery pressure (mPAP), lower 1-min STST performance was an independent predictor for worse symptoms (est. β = -0.112, p = .003), activities (est. β = -0.198, p < .001) and QoL (est. β = -0.130, p < .001) assessed with the CAMPHOR questionnaire.
Our results indicate that regardless of age, sex, BMI and mPAP the 1-min STST performance is associated with all CAMPHOR HRQoL subcategories in patients with PH. Therefore, the 1-min STST performance might be a new option to assess functional capacity correlated to HRQoL in patients with PH.
Background
Duration of invasive mechanical ventilation (IMV) prior to extracorporeal membrane oxygenation (ECMO) affects outcome in acute respiratory distress syndrome (ARDS). In coronavirus disease ...2019 (COVID-19) related ARDS, the role of pre-ECMO IMV duration is unclear. This single-centre, retrospective study included critically ill adults treated with ECMO due to severe COVID-19-related ARDS between 01/2020 and 05/2021. The primary objective was to determine whether duration of IMV prior to ECMO cannulation influenced ICU mortality.
Results
During the study period, 101 patients (mean age 56 SD ± 10 years; 70 69% men; median RESP score 2 IQR 1–4) were treated with ECMO for COVID-19. Sixty patients (59%) survived to ICU discharge. Median ICU length of stay was 31 IQR 20.7–51 days, median ECMO duration was 16.4 IQR 8.7–27.7 days, and median time from intubation to ECMO start was 7.7 IQR 3.6–12.5 days. Fifty-three (52%) patients had a pre-ECMO IMV duration of > 7 days. Pre-ECMO IMV duration had no effect on survival (
p
= 0.95). No significant difference in survival was found when patients with a pre-ECMO IMV duration of < 7 days (< 10 days) were compared to ≥ 7 days (≥ 10 days) (
p
= 0.59 and
p
= 1.0).
Conclusions
The role of prolonged pre-ECMO IMV duration as a contraindication for ECMO in patients with COVID-19-related ARDS should be scrutinised. Evaluation for ECMO should be assessed on an individual and patient-centred basis.
The one-minute sit-to-stand-test (1-min STST) is a quick, space saving test to evaluate functional capacity. Exercise testing plays an important role in the long-term follow-up of pulmonary ...hypertension (PH) patients and is currently evaluated using the six-minute-walk-test (6MWT). The aim of the study was to assess the convergent validity of the 1-min STST in patients with PH and its association with markers of PH severity.
We evaluated 106 PH patients with the 1-min-STST and 6MWT and measured cardiorespiratory parameters (heart rate, blood pressure, oxygen saturation) before and after test conduction. N-terminal pro brain-type natriuretic peptide (NT-proBNP), WHO functional class (WHO-FC) and mean pulmonary artery pressure (mPAP) were defined as markers of PH severity.
Strong correlation was found between performances of 1-min STST and 6MWT (r = .711, p < .001), indicating convergent validity. Both tests were inversely associated with NT-proBNP (STST: r = -.405, p < .001; 6MWT: r = -.358, p < .001), WHO-FC (STST: r = -.591, p < .001; 6MWT: r = -.643, p < .001) and mPAP (STST: r = -.280, p < .001; 6MWT: r = -.250, p < .001). Significant changes in cardiorespiratory parameters were observed in both tests (all p < 0.001). Further the post-exercise cardiorespiratory parameters correlated strongly between the 1-min STST and 6MWT (all r ≥ .651, all p < .001).
The 1-min STST demonstrated good convergent validity with the 6MWT and was associated with markers of PH severity. Furthermore, both exercise tests caused similar cardiorespiratory responses.
To investigate the course of inflammatory and angiogenic cytokines in the aqueous humor of patients with persistent/recurrent neovascular age-related macular degeneration (nAMD) under ranibizumab ...monotherapy (IVM) or ranibizumab plus dexamethasone combination treatment.
In this 12-month prospective study, 40 eyes with nAMD were treated with either IVM or combined treatment with ranibizumab plus intravitreal dexamethasone implant (IVC). Patients in the IVM group were treated following an "as needed" treatment regimen; patients in the IVC group received ranibizumab and a dexamethasone implant at baseline and were re-treated with ranibizumab. At baseline and at each time of retreatment aqueous humor samples were taken.
Before treatment, levels of macrophage chemoattractant protein (MCP)-1, monokine induced by γ interferon (MIG), and lipocalin-2/ neutrophil gelatinase-associated lipocalin (NGAL) were elevated in nAMD patients compared to healthy controls (P = 0.024; P = 0.04; P = 0.01). In contrast, tumor necrosis factor α, IL-12p70, and secreted protein acidic and rich in cysteine (SPARC) concentrations were lower (P = 0.001; P = 0.008; P = 0.03), while vascular endothelial growth factor (VEGF) was not altered (45 ± 6/51 ± 12 pg/mL nAMD/control group; P = 0.6). During IVC, levels of VEGF, MIG, platelet-derived growth factor (PDGF)-AA, and transforming growth factor β1 (P = 0.005; P = 0.011; P = 0.008; P = 0.013) were reduced. Ranibizumab monotherapy did not influence the course of any inflammatory/angiogenic cytokine. Interleukin 6 and PDGF-AA levels correlated with central retinal thickness changes (P = 0.007; P = 0.022). Over the 12-month period visual function was maintained with no significant differences during or between both treatment groups.
Inflammatory proteins are involved in the pathogenesis of chronic macular edema due to AMD and are associated with disease activity. During combined treatment, levels of inflammatory and angiogenic cytokines decreased over a 12-month period with no superiority in functional outcome.
To investigate the effects of intravitreal 0.7 mg dexamethasone implants (Ozurdex) on arterial and venous oxygen saturation, retinal vessel diameter, and retrobulbar blood flow velocity in patients ...with macular edema (ME) due to retinal vein occlusion (RVO).
This prospective, nonrandomized clinical trial included 40 eyes of 40 patients with ME due to RVO. Measurements of arterial and venous oxygen saturation and retinal vessel diameters were performed using the Dynamic Vessel Analyzer. The main outcome measure was the retinal arteriovenous oxygen difference, calculated as the difference between arterial and venous oxygenation. Color Doppler imaging was performed for measuring peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) in ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCAs). Follow-up was monthly for 6 months following an initial dexamethasone implant injection. As statistical analysis, a mixed model was performed to investigate the effect treatment.
The arteriovenous oxygen difference showed a significant increase (P < 0.01). Arterial oxygenation and vessel diameter did not respond to the treatment (P > 0.05), while the venous oxygen saturation and diameter decreased significantly (P < 0.01) compared to baseline. The retrobulbar blood flow velocities PSV, EDV, and RI showed no change in the OA, CRA, and PCA (P > 0.05).
In patients with RVO, intravitreal dexamethasone treatment leads to an increase in arteriovenous oxygen saturation difference indicating improved retinal oxygenation. Arterial oxygenation and vessel diameter showed no response, whereas venous oxygenation and vessel diameter decreased after treatment.
The availability of firearms in homes and at aggregate levels is a risk factor for suicide and homicide. One method of reducing access to suicidal means is the restriction of firearm availability ...through more stringent legislation.
To evaluate the impact of firearm legislation reform on firearm suicides and homicides as well as on the availability of firearms in Austria.
Official statistics on suicides, firearm homicides and firearm licences issued from 1985 to 2005 were examined. To assess the effect of the new firearm law, enacted in 1997, linear regression and Poisson regressions were performed using data from before and after the law reform.
The rate of firearm suicides among some age groups, percentage of firearm suicides, as well as the rate of firearm homicides and the rate of firearm licences, significantly decreased after a more stringent firearm law had been implemented.
Our findings provide evidence that the introduction of restrictive firearmlegislation effectively reduced the rates of firearm suicide and homicide. The decline in firearm-related deaths seems to have been mediated by the legal restriction of firearm availability. Restrictive firearm legislation should be an integral part of national suicide prevention programmes in countries with high firearm suicide rates.
Nasopharyngeal carcinoma (NPC) is endemic in East Asia but rare in the western world. Programmed death ligand 1 (PD-L1) expression on NPC correlates with clinical outcomes. However, data for ...Caucasian NPC patients are missing. Thus, we performed this retrospective analysis for investigating the potential association of immune checkpoint protein expression with outcome parameters in Caucasian NPC patients.
Fifty-five patients with NPC treated between 1993 and 2018 at the Medical University of Vienna were identified. After the exclusion of Asian patients, data on baseline demographic, tumor stage, overall survival (OS), and disease-free survival (DFS) of 30 patients were analyzed. Their tumor samples were stained and scored (low vs. high) for PD-L1, programmed death receptor 1 (PD-1), lymphocyte activating gene 3 (LAG3), and cluster of differentiation 8 (CD8) antibodies. Statistical analysis was performed with Kaplan-Meier plots and log-rank test. Estimated hazard ratios of dichotomized analysis were calculated, together with 95% confidence intervals and
-values of Wald tests.
PD-L1 expression was ≥50% in 6 (20%) patients, whereas 19 (63%) had ≥1% expression and 5 (17%) tumor samples were PD-L1-negative. While sex and age had no impact on DFS or OS, <50% PD-L1 expression on tumor cells (TC) was associated with a significantly longer OS (log rank test
= 0.037; HR 0.275; 95% CI 0.073-1.03). There was no influence on DFS (log rank test
= 0.34; HR 0.599; 95% CI 0.208-1.728). However, <10% PD-L1 expression on tumor infiltrating lymphocytes (TILs) was correlated with a worse DFS (log rank test
= 0.0057; HR 4.06; 95% CI 1.389-11.868). LAG3 expression or the number of TILs did not play any prognostic role in our population.
The PD-L1 expression rate on Caucasians was comparable to that in Asian patients. Although these results have to be interpreted with caution due to the limited number of Caucasian patients available, our data suggest that ≥50% PD-L1 expression on TC is associated with a poor outcome, while ≥10% PD-L1 expression on TILs is correlated with improved DFS. A prospective biomarker analysis of a predefined Caucasian NPC subpopulation would be desirable in future trials.
Out of hospital cardiac arrest is a life-threatening condition. To improve the chances of survival, lay-person cardio-pulmonary-resuscitation (CPR) is a crucial factor. Many bystanders fail to react ...appropriately, even if life supporting first aid (LSFA) programs and campaigns including CPR tried to increase the handling of basic cardiac life support. To achieve an enhanced learning of CPR a pupil's grade after grade teaching program was established in a school with medical students.
The learning of CPR was investigated in a prospective, case-controlled study at an international school. Pupils (12 ± 3 years old) joining our LSFA courses (n = 538, female: 243, attendance for evaluation: 476) were compared to a control group (n = 129, female: 52, attendance for evaluation: 102). Surveys and quality of CPR (QCPR%) through a computer linked "Resusci Anne" dummy were compared with Chi-squared tests, t-tests pair wisely, and by one-way ANOVA.
Knowledge and skills on the "Resusci Anne" were significantly better in trained grade 9 pupils compared to the control group (QCPR, 59 vs. 25%). The number of LSFA courses each grade 9 student had, correlated with improved practical performance (r
= 0.21, p < 0.001). The willingness to deliver CPR to strangers increased with improved practical performance. Attitudes towards performing CPR were high in all participating grades.
Repetitive teaching LSFA to grade 5-9 pupil's grade after grade by medical students has been successfully established. Pupils who finish the program will eventually be able to teach LSFA to younger students. This is furthermore a good way of sharing a "learning by teaching" role and it enables to have more pupils as trainers who can provide instruction to a larger number of pupils with the purpose of having a better-trained population in LSFA.
Hygiene management protocols in laboratory mouse husbandries worldwide most commonly employ soiled bedding-exposed sentinel mice to monitor the occurrence of infections in mouse colonies. Using this ...approach, sentinel mice repeatedly receive a mixture of used bedding, supplied by a variety of cages of a defined hygienic unit for a period of several months. Hereby, microorganisms shed in the used bedding can infect the sentinel animals and can be detected in subsequent health monitoring procedures. However, murine excrements carry more than only microorganisms. Mouse feces and urine also contain a multitude of olfactory molecules, which the animals use to code information about social status and context. However, if and how the persistent and repeated experience with these odor cues affects the behavior of sentinel mice, has not yet been explored. To address this question, we conducted a longitudinal study for neurochemical output parameters related to an organism's responsiveness to challenging conditions, and for the exploratory assessment of a panel of home cage behaviors in soiled bedding and control female C57BL/6J mice. We found that the number of mice showing abnormal repetitive behaviors, including barbering and bar mouthing, was lower in the soiled bedding group. While neutrophil/lymphocyte ratios and fecal corticosterone metabolites did not differ between groups, the within-group variance of the neutrophil/lymphocyte ratio was reduced in the soiled bedding group. These results show that the occurrence of abnormal repetitive behaviors is lower in sentinel than in control mice and suggest a beneficial effect of soiled bedding on the welfare of laboratory mice and on outcome variability.
We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with ...transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients.
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