Breath-by-breath comparison of a novel percutaneous phrenic nerve stimulation approach with mechanical ventilation in juvenile pigs: a pilot study.

About one in three critically ill patients requires mechanical ventilation (MV). Prolonged MV, however, results in diaphragmatic weakness, which itself is associated with delayed weaning and increased mortality. Inducing active diaphragmatic contraction via electrical phrenic nerve stimulation (PNS) not only provides the potential to reduce diaphragmatic muscular atrophy but also generates physiological-like ventilation and therefore offers a promising alternative to MV. Reasons why PNS is not yet used in critical care medicine are high procedural invasiveness, insufficient evidence, and lack of side-by-side comparison to MV. This study aims to establish a minimal-invasive percutaneous, bilateral electrode placement approach for sole PNS breathing and thereby enable, for the first time, a breath-by-breath comparison to MV. Six juvenile German Landrace pigs received general anesthesia and orotracheal intubation. Following the novel ultrasound-guided, landmark-based, 4-step approach, two echogenic needles per phrenic nerve were successfully placed. Stimulation effectiveness was evaluated measuring tidal volume, diaphragmatic thickening and tomographic electrical impedance in a breath-by-breath comparison to MV. Following sufficient bilateral phrenic nerve stimulation in all pigs, PNS breaths showed a 2.2-fold increase in diaphragmatic thickening. It induced tidal volumes in the lung-protective range by negative pressure inspiration and improved dorso-caudal regional ventilation in contrast to MV. Our study demonstrated the feasibility of a novel ultrasound-guided, percutaneous phrenic nerve stimulation approach, which generated sufficient tidal volumes and showed more resemblance to physiological breathing than MV in a breath-by-breath comparison.

A physiological model of phrenic nerve excitation by electrical stimulation.

Mechanical ventilation is essential in intensive care treatment but leads to diaphragmatic atrophy, which in turn contributes to prolonged weaning and increased mortality. One approach to prevent diaphragmatic atrophy while achieving pulmonary ventilation is electrical stimulation of the phrenic nerve. To automize phrenic nerve stimulation resulting in lung protective tidal volumes with lowest possible currents, mathematical models are required. Nerve stimulation models are often complex, so many parameters have to be identified prior to implementation. This paper presents a novel, simplified approach to model phrenic nerve excitation to obtain an individualized patient model using a few data points. The latter is based on the idea that nerve fibers are excited when the electric field exceeds a threshold. The effect of the geometry parameter on the model output was analyzed, and the model was validated with measurement data from a pig trial (RMSE in between 0.44 × 10-2and 1.64 × 10-2for parameterized models). The modeled phrenic nerve excitation behaved similarly to the measured tidal volumes, and thus could be used to develop automated phrenic nerve stimulation systems for lung protective ventilation.

Post-Mortem Extracorporeal Membrane Oxygenation Perfusion Rat Model: A Feasibility Study.

The development of biomedical soft- or hardware frequently includes testing in animals. However, large efforts have been made to reduce the number of animal experiments, according to the 3Rs principle. Simultaneously, a significant number of surplus animals are euthanized without scientific necessity. The primary aim of this study was to establish a post-mortem rat perfusion model using extracorporeal membrane oxygenation (ECMO) in surplus rat cadavers and generate first post vivo results concerning the oxygenation performance of a recently developed ECMO membrane oxygenator. Four rats were euthanized and connected post-mortem to a venous-arterial ECMO circulation for up to eight hours. Angiographic perfusion proofs, blood gas analyses and blood oxygenation calculations were performed. The mean preparation time for the ECMO system was 791 ± 29 s and sufficient organ perfusion could be maintained for 463 ± 26 min, proofed via angiographic imaging and a mean femoral arterial pressure of 43 ± 17 mmHg. A stable partial oxygen pressure, a 73% rise in arterial oxygen concentration and an exponentially increasing oxygen extraction ratio up to 4.75 times were shown. Considering the 3Rs, the established post-mortal ECMO perfusion rat model using surplus animals represents a promising alternative to models using live animals. Given the preserved organ perfusion, its use could be conceivable for various biomedical device testing.

Healthy ageing: Herpes zoster infection and the role of zoster vaccination.

Populations are ageing worldwide, with considerable time lived in ill-health, putting upwards pressure on healthcare budgets. Healthy ageing is defined as maintaining functional ability, including the ability to: meet basic needs; learn, grow and make decisions; be mobile; build and maintain relationships; and contribute to society. The risk and impact of infectious diseases increase with age due to immunosenescence. Vaccination can help to prevent disease in older adults, promoting healthy ageing and active lives. Herpes zoster (HZ) occurs when the varicella zoster virus is reactivated due to declining immunity. HZ is common, with a lifetime risk of one-third, and increases in incidence with age. HZ is associated with severe and intense pain, substantially affecting the functional status of patients as well as their overall health-related quality of life. HZ and its complications may result in prolonged morbidity, including persistent pain (post-herpetic neuralgia, PHN), hearing impairment, vision loss and increased risk of stroke and myocardial infarction. HZ and PHN are difficult to treat, substantiating the benefits of prevention. Vaccines to prevent HZ include a recombinant zoster vaccine (RZV). RZV has shown efficacy against the HZ burden of disease and HZ burden of interference on activities of daily living of over 90% in immunocompetent adults aged ≥50 years. Vaccine efficacy against HZ was maintained at over 70% at 10 years post-vaccination. Adult vaccination, including against HZ, has the potential to reduce burden of disease, thus helping to maintain functioning and quality of life to support healthy ageing in older adults.

Early versus late tracheostomy in critically ill COVID-19 patients.

BACKGROUND: The role of early tracheostomy as an intervention for critically ill COVID-19 patients is unclear. Previous reports have described prolonged intensive care stays and difficulty weaning from mechanical ventilation in critically ill COVID-19 patients, particularly in those developing acute respiratory distress syndrome. Pre-pandemic evidence on the benefits of early tracheostomy is conflicting but suggests shorter hospital stays and lower mortality rates compared to late tracheostomy. OBJECTIVES: To assess the benefits and harms of early tracheostomy compared to late tracheostomy in critically ill COVID-19 patients. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, which comprises CENTRAL, PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv, as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 14 June 2022. SELECTION CRITERIA: We followed standard Cochrane methodology. We included randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) evaluating early tracheostomy compared to late tracheostomy during SARS-CoV-2 infection in critically ill adults irrespective of gender, ethnicity, or setting. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs and the ROBINS-I tool for NRSIs. We used the GRADE approach to assess the certainty of evidence for outcomes of our prioritized categories: mortality, clinical status, and intensive care unit (ICU) length of stay. As the timing of tracheostomy was very heterogeneous among the included studies, we applied GRADE only to studies that defined early tracheostomy as 10 days or less, which was chosen according to clinical relevance. MAIN RESULTS: We included one RCT with 150 participants diagnosed with SARS-CoV-2 infection and 24 NRSIs with 6372 participants diagnosed with SARS-CoV-2 infection. All participants were admitted to the ICU, orally intubated and mechanically ventilated. The RCT was a multicenter, parallel, single-blinded study conducted in Sweden. Of the 24 NRSIs, which were mostly conducted in high- and middle-income countries, eight had a prospective design and 16 a retrospective design. We did not find any ongoing studies. RCT-based evidence We judged risk of bias for the RCT to be of low or some concerns regarding randomization and measurement of the outcome. Early tracheostomy may result in little to no difference in overall mortality (RR 0.82, 95% CI 0.52 to 1.29; RD 67 fewer per 1000, 95% CI 178 fewer to 108 more; 1 study, 150 participants; low-certainty evidence). As an indicator of improvement of clinical status, early tracheostomy may result in little to no difference in duration to liberation from invasive mechanical ventilation (MD 1.50 days fewer, 95%, CI 5.74 days fewer to 2.74 days more; 1 study, 150 participants; low-certainty evidence). As an indicator of worsening clinical status, early tracheostomy may result in little to no difference in the incidence of adverse events of any grade (RR 0.94, 95% CI 0.79 to 1.13; RD 47 fewer per 1000, 95% CI 164 fewer to 102 more; 1 study, 150 participants; low-certainty evidence); little to no difference in the incidence of ventilator-associated pneumonia (RR 1.08, 95% CI 0.23 to 5.20; RD 3 more per 1000, 95% CI 30 fewer to 162 more; 1 study, 150 participants; low-certainty evidence). None of the studies reported need for renal replacement therapy. Early tracheostomy may result in little benefit to no difference in ICU length of stay (MD 0.5 days fewer, 95% CI 5.34 days fewer to 4.34 days more; 1 study, 150 participants; low-certainty evidence). NRSI-based evidence We considered risk of bias for NRSIs to be critical because of possible confounding, study participant enrollment into the studies, intervention classification and potentially systematic errors in the measurement of outcomes. We are uncertain whether early tracheostomy (≤ 10 days) increases or decreases overall mortality (RR 1.47, 95% CI 0.43 to 5.00; RD 143 more per 1000, 95% CI 174 less to 1218 more; I2 = 79%; 2 studies, 719 participants) or duration to liberation from mechanical ventilation (MD 1.98 days fewer, 95% CI 0.16 days fewer to 4.12 more; 1 study, 50 participants), because we graded the certainty of evidence as very low. Three NRSIs reported ICU length of stay for 519 patients with early tracheostomy (≤ 10 days) as a median value, which we could not include in the meta-analyses. We are uncertain whether early tracheostomy (≤ 10 days) increases or decreases the ICU length of stay, because we graded the certainty of evidence as very low. AUTHORS' CONCLUSIONS: We found low-certainty evidence that early tracheostomy may result in little to no difference in overall mortality in critically ill COVID-19 patients requiring prolonged mechanical ventilation compared with late tracheostomy. In terms of clinical improvement, early tracheostomy may result in little to no difference in duration to liberation from mechanical ventilation compared with late tracheostomy. We are not certain about the impact of early tracheostomy on clinical worsening in terms of the incidence of adverse events, need for renal replacement therapy, ventilator-associated pneumonia, or the length of stay in the ICU. Future RCTs should provide additional data on the benefits and harms of early tracheostomy for defined main outcomes of COVID-19 research, as well as of comparable diseases, especially for different population subgroups to reduce clinical heterogeneity, and report a longer observation period. Then it would be possible to draw conclusions regarding which patient groups might benefit from early intervention. Furthermore, validated scoring systems for more accurate predictions of the need for prolonged mechanical ventilation should be developed and used in new RCTs to ensure safer indication and patient safety. High-quality (prospectively registered) NRSIs should be conducted in the future to provide valuable answers to clinical questions. This could enable us to draw more reliable conclusions about the potential benefits and harms of early tracheostomy in critically ill COVID-19 patients.

Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trial.

Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18-64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63-3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68-14.32) also satisfied the non-inferiority criterion (95% CI lower limit > -5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Extracorporeal Artificial Lungs: Co-Creating Future Technology - A Qualitative Analysis.

Background: Terminal lung diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) in progression cause a large reduction in quality of life and may lead to bilateral lung transplantation (bLTx). An artificial portable lung could provide a bridge to lung transplantation, allowing patients to remain at home and mobile for longer. To advance the development of such an artificial lung, patient feedback is essential. The aim of this study is to analyze patient acceptance about an extracorporeal artificial lung and to implement these findings into the development. Methods: In collaboration with a medical device developer, we presented a portable dummy oxygenator to patients with advanced lung disease, as potential end users. Data collection in Germany and France was based on two different methods: an online questionnaire and face-to-face interviews (F2F). Results: A total of 604 participants answered the online questionnaire and 17 participants were included in the F2F interviews. The majority of participants (COPD n=140, PH n=17) were able to walk more than 1 km with a mean suffering pressure of 2.87 and 3, respectively. Six of the 17 F2F participants who could walk <1 km were interested in an assistive device. The statistical value of Fisher's exact test for suffering pressure and desire for a portable oxygenator was 0.45. Conclusion: In patients with advanced lung disease, there is no statistically significant association between subjectively increased suffering pressure and desire for a portable oxygenator, so market introduction may be difficult. Potential end users should be implemented early in device development. Data collection via an online questionnaire combined with personal interviews has proven to be a successful approach here.

A Potential Association between Ribonuclease 1 Dynamics in the Blood and the Outcome in COVID-19 Patients.

The COVID-19 pandemic caused by the new SARS-CoV-2 coronavirus is the most recent and well-known outbreak of a coronavirus. RNase 1 is a small endogenous antimicrobial polypeptide that possesses antiviral activity against viral diseases. In this study, we investigated a potential association between ribonuclease 1 and the outcome in COVID-19 patients and the impact of increased and decreased RNase 1 levels serum during the course of the disease. Therefore, two patient populations, Cohort A (n = 35) and B (n = 80), were subclassified into two groups, in which the RNase 1 concentration increased or decreased from time point one to time point two. We show that the RNase 1 serum levels significantly increased in the increasing group of both cohorts (p = 0.0171; p < 0.0001). We detect that patients in the increasing group who died had significantly higher RNase 1 serum levels at both time points in Cohort A (p = 0.0170; p = 0.0393) and Cohort B (p = 0.0253; p = 0.0034) than patients who survived. Additionally, we measured a significant correlation of RNase 1 serum levels with serum creatinine as well as creatinine clearance in the increasing and decreasing group at both time points of Cohort A. Based on these results, there is now good evidence that RNase 1 may play a role in renal dysfunction associated with ICU COVID-19 patients and that increasing RNase 1 serum level may be a potential biomarker to predict outcome in COVID-19 patients.

Evaluation of electric phrenic nerve stimulation patterns for mechanical ventilation: a pilot study.

Diaphragm atrophy is a common side effect of mechanical ventilation and results in prolonged weaning. Electric phrenic nerve stimulation presents a possibility to avoid diaphragm atrophy by keeping the diaphragm conditioned in sedated patients. There is a need of further investigation on how to set stimulation parameters to achieve sufficient ventilation. A prototype system is presented with a systematic evaluation for stimulation pattern adjustments. The main indicator for efficient stimulation was the tidal volume. The evaluation was performed in two pig models. As a major finding, the results for biphasic pulses were more consistent than for alternating pulses. The tidal volume increased for a range of pulse frequency and pulse width until reaching a plateau at 80-120 Hz and 0.15 ms. Furthermore, the generated tidal volume and the stimulation pulse frequency were significantly correlated (0.42-0.84, [Formula: see text]). The results show which stimulation parameter combinations generate the highest tidal volume. We established a guideline on how to set stimulation parameters. The guideline is helpful for future clinical applications of phrenic nerve stimulation.

No Immunological Interference or Safety Concerns When Adjuvanted Recombinant Zoster Vaccine Is Coadministered With a Coronavirus Disease 2019 mRNA-1273 Booster Vaccine in Adults Aged 50 Years and Older: A Randomized Trial.

BACKGROUND: There is growing consensus that coronavirus disease 2019 booster vaccines may be coadministered with other age-appropriate vaccines. Adding to the limited available data supporting coadministration, especially with adjuvanted vaccines, could enhance vaccine coverage in adults. METHODS: In this phase 3, randomized, open-label study, eligible adults aged ≥50 years were randomly assigned (1:1) to receive mRNA-1273 (50 µg) booster vaccination and a first dose of recombinant zoster vaccine (RZV1) 2 weeks apart (Seq group) or concomitantly (Coad group). The second RZV dose (RZV2) was administered 2 months post-RZV1 in both groups. Primary objectives were noninferiority of anti-glycoprotein E (gE) and anti-spike protein antibody responses in the Coad group compared to the Seq group. Safety and further immunogenicity assessments were secondary objectives. RESULTS: In total, 273 participants were randomized to the Seq group and 272 to the Coad group. Protocol-specified noninferiority criteria were met. The adjusted geometric mean concentration ratio (Seq/Coad) was 1.01 (95% confidence interval [CI], .89-1.13) for anti-gE antibodies 1 month post-RZV2, and 1.09 (95% CI, .90-1.32) for anti-spike antibodies 1 month post-mRNA-1273 booster. No clinically relevant differences were observed in overall frequency, intensity, or duration of adverse events between the 2 study groups. Most solicited adverse events were mild/moderate in intensity, each with median duration ≤2.5 days. Administration site pain and myalgia were the most frequently reported in both groups. CONCLUSIONS: Coadministration of mRNA-1273 booster vaccine with RZV in adults aged ≥50 years was immunologically noninferior to sequential administration and had a safety and reactogenicity profile consistent with both vaccines administered sequentially. Clinical Trials Registration. NCT05047770.

Comparative life history patterns of female gorillas.

OBJECTIVES: Several theories have been proposed to explain the impact of ecological conditions on differences in life history variables within and between species. Here we compare female life history parameters of one western lowland gorilla population (Gorilla gorilla gorilla) and two mountain gorilla populations (Gorilla beringei beringei). MATERIALS AND METHODS: We compared the age of natal dispersal, age of first birth, interbirth interval, and birth rates using long-term demographic datasets from Mbeli Bai (western gorillas), Bwindi Impenetrable National Park and the Virunga Massif (mountain gorillas). RESULTS: The Mbeli western gorillas had the latest age at first birth, longest interbirth interval, and slowest surviving birth rate compared to the Virunga mountain gorillas. Bwindi mountain gorillas were intermediate in their life history patterns. DISCUSSION: These patterns are consistent with differences in feeding ecology across sites. However, it is not possible to determine the evolutionary mechanisms responsible for these differences, whether a consequence of genetic adaptation to fluctuating food supplies ("ecological risk aversion hypothesis") or phenotypic plasticity in response to the abundance of food ("energy balance hypothesis"). Our results do not seem consistent with the extrinsic mortality risks at each site, but current conditions for mountain gorillas are unlikely to match their evolutionary history. Not all traits fell along the expected fast-slow continuum, which illustrates that they can vary independently from each other ("modularity model"). Thus, the life history traits of each gorilla population may reflect a complex interplay of multiple ecological influences that are operating through both genetic adaptations and phenotypic plasticity.

Systematic Evaluation of Different Fresh Cow Monitoring Procedures.

Establishing fresh cow monitoring procedures is considered beneficial for cow health, welfare, and productivity. However, they are time consuming and require the cows to be locked up, which restricts their natural behavior. In this study, different fresh cow monitoring procedures were evaluated. Two experiments were conducted to determine: (1) the duration of various examinations and treatments; (2) the time cows remain locked up in headlocks; and (3) the proportion of examination and treatment times relative to the total headlock time. In advance, standard operating procedures were established. Three veterinarians conducted the examinations and treatments based on changes in milk yield, clinical symptoms, and alarms by an accelerometer system. The headlock time was evaluated for three workflow strategies, which differed in the order of examinations and treatments. To determine the duration, cameras were installed, and the video footage was analyzed. The examinations lasted between 1 and 227 s, and the cows were locked up in headlocks between 0.01 and 1.76 h. The lock-up times differed significantly among the three strategies, as well as the proportion. This study provides information that can be used as a basis for the development of time-efficient strategies, and to minimize the impact on cows' time budgets.

Digestive, Anorectal, and Urogenital Functions in Patients with Type 2 Diabetes Mellitus, Impaired Glucose Tolerance and Normal Glucose Tolerance: Association with Autonomic Neuropathy.

AIMS: Gastrointestinal disorders, including constipation and fecal incontinence, are common in type 2 diabetes mellitus (T2DM) and may derive from diabetic autonomic neuropathy, severe intestinal bacterial overgrowth, or a dysfunctional anorectal sphincter. The present study aims to characterize the correlation between these conditions. METHODS: Patients with T2DM, prediabetes, and normal glucose tolerance (NGT) were included. The anorectal function was assessed with high-resolution anorectal manometry. Patients were screened for autonomic neuropathy by measuring olfactory, sweat, and erectile dysfunction as well as heart rate variability. Constipation and fecal (in-)continence were evaluated using validated questionnaires. Breath tests were used to assess severe intestinal bacterial overgrowth. RESULTS: We included 59 participants (32 (54.2%) with T2DM, 9 (15.3%) with prediabetes, and 18 (30.5%) NGT). The presence of autonomic neuropathy, severe bacterial overgrowth, and symptoms of constipation and incontinence were comparable. HbA1c was correlated with an increased anorectal resting sphincter pressure (r=0.31, P=0.019) and constipation symptoms (r=0.30, P=0.031). In patients with a long-standing diagnosis of T2DM, significantly higher values for maximum anorectal resting pressure (Δ=+27.81±7.84 mmHg, P=0.0015) and baseline pressure (Δ=20.50±9.74 mmHg, P=0.046) were found compared with NGT, but not with prediabetes. CONCLUSIONS: Long-standing T2DM increases anorectal sphincter activity, and constipation symptoms are associated with higher HbA1c levels. The lack of an association of symptoms with autonomic neuropathy suggests glucotoxicity as the primary mechanism.

Standardized pharmacological management of delirium after on-pump cardiac surgery reduces ICU stay and ventilation in a retrospective pre-post study.

Cardiac surgery patients not only undergo a highly invasive procedure but are at risk for a diversity of postoperative complications. Up to 53% of these patients suffer from postoperative delirium (POD). This severe and common adverse event increases mortality and prolonged mechanical ventilation and extends the intensive care unit stay. The objective of this study was to test the hypothesis that standardized pharmacological management of delirium (SPMD) may reduce the length of stay in the intensive care unit (ICU), duration of postoperative mechanical ventilation, and the incidence of postoperative complications such as pneumonia or bloodstream infections in on-pump cardiac surgery ICU patients. In this retrospective, single-center observational cohort study, 247 patients were examined between May 2018 to June 2020, who underwent on-pump cardiac surgery, suffered from POD, and received pharmacological POD treatment. 125 were treated before and 122 after SPMD implementation in the ICU. The primary endpoint was a composite outcome, including the length of ICU stay, postoperative mechanical ventilation time, and ICU survival rate. The secondary endpoints were complications including postoperative pneumonia and bloodstream infections. Although the ICU survival rate was not significantly different between both groups, the length of ICU stay (control group: 23 ± 27 days; SPMD group: 16 ± 16 days; p = 0.024) and the duration of mechanical ventilation were significantly reduced in the SPMD-cohort (control group: 230 ± 395 h; SPMD group: 128 ± 268 h; p = 0.022). Concordantly, the pneumonic risk was reduced after SPMD introduction (control group: 44.0%; SPMD group: 27.9%; p = 0.012) as well as the incidence for bloodstream infections (control group: 19.2%; SPMD group: 6.6%; p = 0.004). Standardized pharmacological management of postoperative delirium in on-pump cardiac surgery ICU patients reduced the length of ICU stay and duration of mechanical ventilation significantly, leading to a decrease in pneumonic complications and bloodstream infections.

Mortality rates of severe COVID-19-related respiratory failure with and without extracorporeal membrane oxygenation in the Middle Ruhr Region of Germany.

The use of extracorporeal membrane oxygenation (ECMO) is discussed to improve patients' outcome in severe COVID-19 with respiratory failure, but data on ECMO remains controversial. The aim of the study was to determine the characteristics of patients under invasive mechanical ventilation (IMV) with or without veno-venous ECMO support and to evaluate outcome parameters. Ventilated patients with COVID-19 with and without additional ECMO support were analyzed in a retrospective multicenter study regarding clinical characteristics, respiratory and laboratory parameters in day-to-day follow-up. Recruitment of patients was conducted during the first three COVID-19 waves at four German university hospitals of the Ruhr University Bochum, located in the Middle Ruhr Region. From March 1, 2020 to August 31, 2021, the charts of 149 patients who were ventilated for COVID-19 infection, were included (63.8% male, median age 67 years). Fifty patients (33.6%) received additional ECMO support. On average, ECMO therapy was initiated 15.6 ± 9.4 days after symptom onset, 10.6 ± 7.1 days after hospital admission, and 4.8 ± 6.4 days after the start of IMV. Male sex and higher SOFA and RESP scores were observed significantly more often in the high-volume ECMO center. Pre-medication with antidepressants was more often detected in survivors (22.0% vs. 6.5%; p = 0.006). ECMO patients were 14 years younger and presented a lower rate of concomitant cardiovascular diseases (18.0% vs. 47.5%; p = 0.0004). Additionally, cytokine-adsorption (46.0% vs. 13.1%; p < 0.0001) and renal replacement therapy (76.0% vs. 43.4%; p = 0.0001) were carried out more frequently; in ECMO patients thrombocytes were transfused 12-fold more often related to more than fourfold higher bleeding complications. Undulating C-reactive protein (CRP) and massive increase in bilirubin levels (at terminal stage) could be observed in deceased ECMO patients. In-hospital mortality was high (Overall: 72.5%, ECMO: 80.0%, ns). Regardless of ECMO therapy half of the study population deceased within 30 days after hospital admission. Despite being younger and with less comorbidities ECMO therapy did not improve survival in severely ill COVID-19 patients. Undulating CRP levels, a massive increase of bilirubin level and a high use of cytokine-adsorption were associated with worse outcomes. In conclusion, ECMO support might be helpful in selected severe cases of COVID-19.

Association between Rumination Times Detected by an Ear Tag-Based Accelerometer System and Rumen Physiology in Dairy Cows.

Monitoring rumination activity is considered a useful indicator for the early detection of diseases and metabolic disorders. Accelerometer-based sensor systems provide health alerts based on individual thresholds of rumination times in dairy cows. Detailed knowledge of the relationship between sensor-based rumination times and rumen physiology would help detect conspicuous animals and evaluate the treatment's success. This study aimed to investigate the association between sensor-based health alerts and rumen fluid characteristics in Holstein-Friesian cows at different stages of lactation. Rumen fluid was collected via a stomach tube from 63 pairs of cows with and without health alerts (ALRT vs NALRT). Pairs were matched based on the day of lactation, the number of lactations, and health criteria. Rumen fluid was collected during and after health alerts. The parameters of color, odor, consistency, pH, redox potential, sedimentation flotation time, and the number of protozoa were examined. Results showed differences between both groups in odor, rumen pH, sedimentation flotation time, and protozoan count at the first rumen fluid collection. Within the groups, greater variations in rumen fluid parameters were found for ALRT cows compared to NALRT cows. The interaction between health alert and stage of lactation did not affect the rumen fluid parameters.

Tissue Engineering of Vascular Grafts: A Case Report From Bench to Bedside and Back.

For over 25 years, our group has used regenerative medicine strategies to develop improved biomaterials for use in congenital heart surgery. Among other applications, we developed a tissue-engineered vascular graft (TEVG) by seeding tubular biodegradable polymeric scaffolds with autologous bone marrow-derived mononuclear cells. Results of our first-in-human study demonstrated feasibility as the TEVG transformed into a living vascular graft having an ability to grow, making it the first engineered graft with growth potential. Yet, outcomes of this first Food and Drug Administration-approved clinical trial evaluating safety revealed a prohibitively high incidence of early TEVG stenosis, preventing the widespread use of this promising technology. Mechanistic studies in mouse models provided important insight into the development of stenosis and enabled advanced computational models. Computational simulations suggested both a novel inflammation-driven, mechano-mediated process of in vivo TEVG development and an unexpected natural history, including spontaneous reversal of the stenosis. Based on these in vivo and in silico discoveries, we have been able to rationally design strategies for inhibiting TEVG stenosis that have been validated in preclinical large animal studies and translated to the clinic via a new Food and Drug Administration-approved clinical trial. This progress would not have been possible without the multidisciplinary approach, ranging from small to large animal models and computational simulations. This same process is expected to lead to further advances in scaffold design, and thus next generation TEVGs.

Population dynamics of western gorillas at Mbeli Bai.

Long-term studies of population dynamics can provide insights into life history theory, population ecology, socioecology, conservation biology and wildlife management. Here we examine 25 years of population dynamics of western gorillas at Mbeli Bai, a swampy forest clearing in Nouabalé-Ndoki National Park, the Republic of Congo. The Mbeli population more than doubled from 101 to 226 gorillas during the study. After adjusting for a net influx of gorillas into the study population, the increase represents an inherent growth rate of 0.7% per year, with 95% confidence limits between -0.7% and 2.6%. The influx of gorillas mainly involved immigration of individuals into existing study groups (social dispersal), but it also included the appearance of a few previously unknown groups (locational dispersal). The average group size did not change significantly during the study, which is consistent with the possibility that western gorillas face socioecological constraints on group size, even when the population is increasing. We found no significant evidence of density dependence on female reproductive success or male mating competition. The distribution of gorillas among age/sex categories also did not change significantly, which suggests that the population had a stable age structure. Our results provide evidence of population stability or growth for some western gorillas (albeit within a small area). The results highlight the value of law enforcement, long-term monitoring, and protected areas; but they do not diminish the importance of improving conservation for this critically endangered species.

Identification of the Tidal Volume Response to Pulse Amplitudes of Phrenic Nerve Stimulation Using Gaussian Process Regression.

While mechanical ventilation (MV) can lead to ventilator-induced diaphragmatic atrophy due to diaphragm inactivity, electrical phrenic nerve stimulation (PNS) can keep the diaphragm active and therefore prevent diaphragmatic weakness. To quantify the effectivity of PNS, an identification experiment during PNS is presented, and its data is used in Gaussian process regression (GPR) of the tidal volume based on the constant voltage amplitude of the stimulation pulses. The measurements were split into training data of variable size and test data for cross validation. For variable training sizes and different PNS settings, the GPR had a root mean square deviation (RMSD) between 0.39 and 0.91 mL/kg. An identification experiment as short as one and a half minutes was able to characteristically capture the relationship between tidal volume and voltage amplitude. The proposed method needs to be validated in further experiments.