Weaning Rate Research Articles

Utility of Early Tracheostomy in Critically Ill Covid-19 Patients: A Systematic Review.

COVID 19 has proven itself to be an agent of cataclysm and caused an uproar worldwide due to consistent strain on the finite resources available to tackle the situation. With the rapidly mutating viral nature, resultant disease is becoming more severe over time, causing significant numbers of critical cases needing invasive ventilatory support. Available literature dictates that tracheostomy might reduce the stress over healthcare infrastructure. Our systematic review is aimed towards understanding the influence of tracheostomy timing, over the course of the illness, by analyzing the relevant literature, thus aiding in decision making while managing critical COVID 19 patients. With predefined inclusion and exclusion criteria, PubMed data was explored using search terms like 'timing', 'tracheotomy'/'tracheostomy' and 'COVID'/'COVID-19'/'SARS CoV2' and 26 articles were finalised for formal review. 26 studies (3527 patients) were systematically reviewed. 60.3% and 39.5% patients underwent percutaneous dilational tracheostomy and open surgical tracheostomy respectively. We report 7.62%, 21.3%, 56% and 46.53% as approximate estimates, of complication rate, mortality rate, rate of mechanical ventilation weaning and rate of decannulation following tracheostomy in COVID 19 patients, respectively taking into account underestimation of the data. Provided that appropriate preventive measures and safety guidelines are strictly followed, moderately early tracheostomy (between 10 and 14days of intubation) can prove quite efficacious in management of critical COVID 19 patients. Also, early tracheostomy was associated with early weaning and decannulation, thus reducing the enormous competition for intensive care unit beds.

On-station comparative analysis of reproductive and survival performance between Red Maasai, Dorper, and Merino sheep breeds.

The reproductive performance of ewes and the survivability of lambs to weaning have a critical economic impact on sheep farming worldwide. Further, knowledge of major mortality causes allows an opportunity for improved flock management to evade financial losses. The maximum likelihood estimates for generalised linear mixed models and chi-square test methods were used to examine 971 mating records, 839 and 763 lambs born and weaned (singles or twins) from the Naivasha Sheep and Goats station in Kenya for the years 2011 to 2020 consisting of Dorper, Red Maasai (RedM), and Merino breeds. The RedM (P<0.05) outperformed Dorper and Merino in weaning rate, whereas reproductive performance between the three breeds was not significantly different (P>0.05) in litter size and multiple lambings per ewe lambing. On the one hand, Dorper significantly (P<0.05) outperformed the other two breeds only in weaning weight per lamb born. In addition, among all the major causes of death, pneumonia appeared to be the one to which Dorper breeds were most susceptible (chi-square test, P<0.05). According to the findings of this study, neither the Dorper nor the Merino sheep breeds were reproductively superior to the RedM in an extensive semi-arid production environment. In addition, Dorper's susceptibility to the leading causes of mortality, particularly pneumonia and sheep pox, were relatively high compared to other breeds and could be a precursor to massive economic losses for Dorper sheep producers. In contrast to the indigenous RedM breed, imported sheep breeds appeared to be more susceptible to major mortality-related under an extensive production system. Therefore, regardless of weaning weight, RedM breed production appears to be a more viable investment for small-scale farmers, particularly in semi-arid regions.

難治性院外心原性心停止に対する初期心電図によるpercutaneous cardiopulmonary support導入時間の検討(Analysis of the percutaneous cardiopulmonary support implementation time for refractory out–of–hospital cardiogenic cardiac arrest by initial electrocardiogram)

要旨【目的】治療抵抗性心停止に対する経皮的心肺補助（以下，PCPS）の転帰良好な因子として，初期心電図がショック適応心リズム（以下，ショックリズム）と心停止（以下，CA）からPCPS開始までの時間（以下，CA to PCPS）が短いことが挙げられる。しかし，近年ではショック非適応心リズム（以下，非ショックリズム）でも転帰良好な症例が報告されており，院外心原性心停止における初期心電図別のCA to PCPSと1か月後の転帰良好について検討した。【対象】これは単施設，後方視的研究であり，2000年1月から2017年3月に院外心原性心停止症例に対してPCPSを導入した219例（平均58歳，男性193例）を対象とした。【結果】ショックリズム群（167例）と非ショックリズム群（52例）において，転帰良好率は31% vs 10%（p＝0.003）であり，CA to PCPSの中央値は44.0分 vs 35.0分（p＝0.014）であった。さらにCA to PCPSを5分ごとに区切り転帰良好率を検討すると，ショックリズム群では36～40分で59%であったが，41～45分では33%まで低下しており，非ショックリズム群では40分以降に転帰良好は存在しなかった。【結語】心停止から40分以内のPCPS導入がより転帰良好になると考えられたが，非ショックリズム群ではさらに短縮する必要がある。

The efficacy of calorimetry-based nutritional support versus recommended dietary intake-based nutritional support in the successful weaning of chronically ventilated patients: A study protocol for a double blind randomized controlled trial

Mechanically ventilated patients are weaned during acute care hospitalization when it is determined that they are ready for withdrawal. If weaning fails, patients are admitted to a rehabilitation medical center for continued supportive care and additional weaning attempts. This study's objective is to increase the success rate of weaning from prolonged mechanical ventilation (PMV), and to shorten the overall weaning period by tailoring the patient's caloric intake according to their individually measured energy needs. We designed a randomized, controlled, double-blinded trial to be conducted among PMV patients undergoing routine ventilation-weaning attempts. Patients in the intervention arm will be fed according to energy needs determined by calorimetry. Patients in the control arm will be fed according to the standard of care, namely the Recommended Dietary Allowance (RDA) guidelines. Each patient will undergo up to five weaning attempts. Study outcomes will include successful weaning rate, time to successful weaning, and 3-12 months survival rate. This trial aims to examine the safety and efficacy of a nutritional diet based on an individual's measured caloric needs in terms of weaning rates and weaning time. We hypothesize that calorimetry-based nutrition plan will prove to be superior in both success rate and time to successful weaning compared to the standard nutrition plan based on the resting energy expenditure (REE) formula during the weaning process. ClinicalTrials.gov identifier: NCT04825717.

Improving Outcomes for Bronchiolitis Patients After Implementing a High-Flow Nasal Cannula Holiday and Standardizing Discharge Criteria in a PICU.

To decrease length of high-flow nasal cannula (HFNC), PICU, and hospital length of stay (LOS). Quality improvement project. A quaternary academic PICU. Patients with bronchiolitis less than 24 months old. After initial implementation of a respiratory therapist (RT)-driven HFNC protocol (Plan-Do-Study-Act [PDSA] 1) in October 2017, additional interventions included adjusting HFNC wean rate (PDSA 2) in July 2020, a HFNC holiday (PDSA 3), and standardized discharge criteria (PDSA 4) in October 2021. Duration of HFNC was used as the primary outcome measure. PICU LOS and hospital LOS were used as secondary outcome measures. Noninvasive ventilation use, invasive mechanical ventilation use, and 7-day PICU and hospital readmission rates were used as balancing measures. A total of 1,310 patients were included in this study. Patients in PDSA 2, PDSA 3 and 4 groups were older compared with pre-intervention and PDSA 1 (median of 9 and 10 mo compared with 8 mo; p = 0.01). HFNC duration decreased from 2.5 to 1.8 days after PDSA 1, then to 1.3 days after PDSA 2. PICU LOS decreased from 2.6 to 2.1 days after PDSA 1, 1.8 days after PDSA 2, and 1.5 days after PDSA 3 and 4. Hospital LOS decreased from 5.7 to 4.5 days after PDSA 1, 3.1 days after PDSA 2, and 2.7 days after PDSA 3 and 4. The use of noninvasive ventilation and invasive mechanical ventilation decreased throughout the study from 23.2% in the pre-intervention group, to 6.9% at the end of the project. The 7-day PICU and hospital readmission rates did not increase after implementation. The percentage of patients discharged from the PICU increased from 6.2% to 21.5%. Modifications to an existing RT-driven HFNC protocol and standardization of discharge criteria led to an improvement in outcomes for patients admitted to the PICU with bronchiolitis without an increase in adverse events.

Sex of co-twin in utero environment does not alter reproductive fitness of Australian Merino sheep

Context Reproductive efficiency in ewes can vary widely depending on their fertility (pregnancy rate) and fecundity (litter size) and on their ability to rear multiple litters. Litter size and sex are important factors that contribute to lamb mortality, and hence reproductive efficiency. However, little is known about their interaction when fetuses of either sex grow in utero as co-twins, nor the impact that this interaction has on subsequent performance in domestic flocks. Aims and methods We examined the effect of type of birth (single, twin) and of sex of co-twin (F, F[F], F[M], M, M[M], M[F] where the symbol within brackets indicates sex of co-twin) on birth weight, survival to weaning, weaning and hogget liveweights and scrotal circumference. In addition, reproductive performance (fertility, fecundity, lamb survival, weaning rate) of female progeny was examined as well as the performance of their lambs (birth and weaning weight). This large-scale study (&gt;13 000 lambing observations) was conducted with Australian Merino sheep from four studs, mated over nine annual cycles. Key results Sex of co-twin had no effect on birth weight and on later stages of growth. Sex of co-twin altered survival, with fewer of the M[M] class surviving to weaning compared with other co-twin classes (P &lt; 0.05). Scrotal circumference did not vary between the male classes. Although reproductive performance (fecundity, lamb survival, weaning rate) was greater in ewes twin to a male (F[M]) than in single females (F) (P &lt; 0.05), this difference could be due to greater genetic merit of twin versus single-born progeny. Conclusions Reproductive performance of females with a male co-twin exceeded that of single females; the difference could be due to greater genetic merit of twin-born ewes rather than a direct effect of in utero environment. There was no difference between females with a male co-twin and females with a co-twin of the same sex. Reproductive capacity of males was not affected by co-twin class or type of birth. Implications These results suggest that an increase in twinning rate by managerial or genetic means will not result in undesirable side effects due to sex of co-twin in utero.

Levosimendan as adjuvant therapy for cardiogenic shock patients with temporary ventricular assist device

Background: Temporary ventricular-assisted device (VAD) provides timely organ perfusion in patients with cardiogenic shock and serves as a bridge to heart transplant. Intravenous levosimendan could provide pharmacologic inotropic support. Aim: We aimed to investigate the adjuvant efficacy of levosimendan in patients with temporary VAD, especially for VAD weaning. Methods: We retrospectively reviewed the medical records of patients receiving temporary VAD for cardiogenic shock between January 2017 and May 2019 in a medical center in Taiwan. Patients were divided into the levosimendan (n = 9, administered levosimendan immediately after VAD), and control groups (n = 20, no levosimendan administered). The biochemistry of systemic perfusion was compared at 1 and 3 days after VAD. After 2 months, the cardiac function of the patients with successful VAD weaning was evaluated by echocardiography. At 6 months follow-up, survival outcome and Kaplan–Meier survival curves were presented. Results: In total, 29 patients receiving temporary VAD for cardiogenic shock were enrolled, including 9 patients treated with levosimendan infusion. In the levosimendan group, both mean arterial pressure and lactate level decreased significantly (P = 0.037 and 0.023, respectively), and the ratio of arterial oxygen partial pressure to fractional inspired oxygen improved significantly (P = 0.048). No difference in inotropes tapering, consciousness, systemic perfusion biochemistry, and cardiac enzymes. Echocardiography showed significantly improved systolic function and pulmonary artery pressure 2 months later (P = 0.043 and 0.046, respectively) in patients with successful weaning. The levosimendan group had a better weaning rate (P = 0.013) and lower mortality rate (P = 0.571) at 6-month follow-up. Conclusion: The levosimendan group showed a better weaning rate and lower mortality rate.

Shelter and shade for grazing sheep: implications for animal welfare and production and for landscape health

Shade and shelter may provide protection from cold and heat stress, a source of feed during prolonged or seasonal drought, specific essential nutrients, increased pasture and crop production and improved landscape health. Cold stress contributes to the average of 8% (single) and 24% (twin) of lambs that die within 3 days of birth in Australia and the estimated 0.7% of the Australian flock that die post-shearing during extreme or unseasonal weather. Shelter has resulted in an average reduction in mortality of 17.5% for twin-born lambs and 7% for single-born lambs according to Australian studies and decreases the susceptibility of ewes to metabolic disease and possibly dystocia. Because many of the published studies are from research areas where cold stress is expected, they are not indicative of industry-wide responses, a research priority is to determine the probability of lamb and ewe deaths from cold stress across different sheep production areas. Although shelter may improve lamb survival, ewes do not always choose to lamb in a sheltered location. For this reason, there is a requirement for research into the voluntary use of shelter in commercial-sized paddocks and the role that nutritive value of shelter plays in attracting and holding ewes to shelter, and to their lambs. Heat stress may also result in lamb deaths and influences feed conversion efficiency, appetite, reproduction, wool growth and disease susceptibility. The consequences of heat stress may go unnoticed over a yearly production cycle, although there is some evidence that shade may increase weaning rates and feed intake of grazing sheep. There are ancillary benefits from shade and shelter. Trees may improve crop production through reducing wind damage and evapotranspiration and provide timber. Shrubs provide feed during the summer–autumn feed gap or drought, are useful for the management of land degradation and provide habitat for native fauna. It is clear that shade and shelter in the correct locations provide a range of benefits to livestock and the landscape; nevertheless, adoption appears low. Research that focuses on defining the benefits on a farm or landscape scale is required to support extension programs.

Phosphorus supplementation improves the growth and reproductive performance of female Brahman cattle grazing phosphorus-deficient pastures in the Victoria River District, Northern Territory, Australia

Context There is a paucity of information on the responses to phosphorus (P) supplementation of breeder herds grazing P-deficient rangelands in northern Australia. Aims A study examined the production and economic benefits of P supplementation of Brahman females grazing P-deficient pastures in the Northern Territory (NT) of Australia. Methods Two treatment groups (initially n ~ 90) grazed two similar P-deficient paddocks for 5 years after weaning (at approximately 6 months of age). Management was the same except that the loose lick mineral supplement either contained P (+P) or did not contain P (−P). Performance attributes were measured from commencement until after the cows had the opportunity to calve during three successive annual cycles. Key results The cows in the +P treatment were overall heavier (P &lt; 0.001), taller (P &lt; 0.001) and had higher plasma inorganic P (PiP) concentrations (P &lt; 0.001) than did those in the −P treatment at every measurement date after the first wet season. Pregnancy rates in lactating cows were 25%, 39% and 63% units higher (P &lt; 0.01) in +P in 2017, 2018 and 2019 respectively and overall average weaner weight was 33 kg heavier (P &lt; 0.001) in +P. Due to higher weaning rates and heavier weaning weights, +P produced about AU$39 365 more value of weaners per 100 heifers allocated to each treatment than did −P over the first three calf crops. The cumulative mortality rate was 12% higher in the −P over the 5 years (14.8% vs 2.2%, P &lt; 0.01), and would have been even higher if at-risk −P cows had not been fed additional supplements. Return on investment calculations indicated that each AU$1 spent on P supplement returned AU$4.98 in value of extra calves weaned and AU$7.88 in extra total liveweight increase over the 5 years of the study. Conclusions The large production and financial benefits from P supplementation observed in this study are relevant to most northern Australian properties where soils are P deficient, although the magnitude of response is likely to vary depending on the level of P deficiency. Implications The large production and economic benefits from P supplementation in this study demonstrated the importance of P supplementation for breeder herds grazing P-deficient pastures.

The Use of Intraoperative Extracorporeal Membrane Oxygenation in Lung Transplantation: Initial Institutional Experience.

Lung transplantation is the final treatment option for end-stage lung disease, and extracorporeal membrane oxygenation (ECMO) is increasingly being used during lung transplantation. The present study aimed to review our initial experience with patients who underwent lung transplantation with or without ECMO since the implementation of the lung transplantation program at our center. Data were prospectively collected on all patients between December 2016 and December 2018. Patients undergoing ECMO as a bridge to lung transplantation were excluded. A total of 48 lung transplants were performed, and ECMO was used in 29 (60.4%) cases. Twenty (83%) patients were female. The median age was 48.5 (range, 14-64) years. The most common indications were idiopathic interstitial pneumonia in 9 (31%) patients, chronic obstructive pulmonary disease in 7 (24.1%) patients, and bronchiectasis in 6 (20.7%) patients. Sequential bilateral lung transplantation was performed in all patients. The 30-day mortality was 20.6% (6/29) for patients with ECMO, however, it was 10.5 (2/19) for patients without ECMO (P=0.433). The median length of stay in the intensive care unit (ICU) was 5 (range, 2-25) days. The ECMO weaning rate was 82.8% (24/29). One-year survival was 62.1% with ECMO versus 78.9% without ECMO, and the 3-year survival was 54.1% versus 65.8%, respectively (P=0.317). ECMO is indicated for more severe patients who underwent lung transplantation. The use of ECMO provides adjuvant support during surgery and the mortality rate is acceptable. Survival is also as similar as non-ECMO patients. ECMO is appropriate for critically ill patients.

Genetic Correlations between Days to Calving across Joinings and Lactation Status in a Tropically Adapted Composite Beef Herd

Female fertility is essential to any beef breeding program. However, little genetic gain has been made due to long generation intervals and low levels of phenotyping. Days to calving (DC) is a fertility trait that may provide genetic gain and lead to an increased weaning rate. Genetic parameters and correlations were estimated and compared for DC across multiple joinings (first, second and third+) and lactation status (lactating and non-lactating) for a tropical composite cattle population where cattle were first mated as yearlings. The genetic correlation between first joining DC and mature joining DC (third+) was moderate–high (0.55–0.83). DC was uncorrelated between multiparous lactating and non-lactating cows (rG = −0.10). Mature joining DC was more strongly correlated with second joining lactating DC (0.41–0.69) than with second joining non-lactating DC (−0.14 to −0.16). Thus, first joining DC, second joining DC and mature joining DC should be treated as different traits to maximise genetic gain. Further, for multi-parous cows, lactating and non-lactating DC should be treated as different traits. Three traits were developed to report back to the breeding programs to maximise genetic gain: the first joining days to calving, the second joining days to calving lactating and mature days to calving lactating.

607: IMPLEMENTING A HIGH-FLOW NASAL CANNULA HOLIDAY AND DISCHARGE CRITERIA FOR BRONCHIOLITIS PATIENTS

Introduction: Costs for bronchiolitis have risen over the years. Previous studies have shown that respiratory therapist (RT) driven high flow nasal cannula (HFNC) management protocols can decrease length of HFNC as well as pediatric intensive care unit (PICU) and hospital length of stay (LOS). The aim of this study was to determine if modifications to an existing RT-driven HFNC management protocol could further safely decrease length of HFNC and PICU and hospital LOS. Methods: This is a quality improvement project performed at a quaternary academic PICU. This study included patients less than 24 months of age admitted to the PICU with an admission diagnosis of bronchiolitis requiring HFNC. After initial implementation of a (RT)-driven HFNC protocol [Plan-Do-Study-Act (PDSA) 1] in October 2017, additional interventions included adjusting HFNC wean rate (PDSA 2) in July 2020, a HFNC holiday (PDSA 3), and standardized discharge criteria (PDSA 4) in October 2021. Duration of HFNC was used as the primary outcome measure and PICU LOS and hospital LOS were used as secondary outcome measures. Noninvasive ventilation use, invasive mechanical ventilation use and 7-day PICU and hospital readmission rates were used as balancing measures. Results: A total of 1,310 patients were included. Patients in PDSA 2, PDSA 3&4 groups were older compared to pre-intervention and PDSA 1 (median of 9 and 10 months compared to 8 months, p=0.01). HFNC duration decreased from 2.5 to 1.8 days after PDSA 1, then to 1.3 days after PDSA 2. PICU LOS decreased from 2.6 to 2.1 days after PDSA 1, 1.8 days after PDSA 2 and 1.5 days after PDSA 3&4. Hospital LOS decreased from 5.7 days to 4.5 days after PDSA 1, 3.1 days after PDSA 2 and 2.7 days after PDSA 3&4. The use of non-invasive ventilation and invasive mechanical ventilation decreased throughout the study from 23.2% in the pre-intervention group, to 6.9% at end of the project. The 7-day PICU and hospital readmission rates did not increase. The percentage of patients discharged from the PICU increased from 6.2% to 21.5%. Conclusions: Modifications to an existing RT-driven HFNC protocol and standardized discharge criteria led to an improvement in bronchiolitis patients’ outcomes without an increase in adverse events.

Studying beef production evolution to plan for ecological intensification of grazing ecosystems

CONTEXTA challenge facing the livestock sector is improving beef production while mitigating negative environmental impacts. Analyzing its past productive and environmental performance may elucidate strategies for improving efficiency of grassland-based systems and identify future research and public policy priorities. OBJECTIVESDescribe past and current dynamics and assess potential future scenarios of the Uruguayan beef production sector, considering historical beef production growth rate (kg carcass), partitioning in land use by the cattle sector (ha), cattle animal performance (kg carcass animal−1 year−1) and stocking rate (animal ha−1) since 1966. METHODSWe quantified drivers of beef production and total enteric methane (CH4) emissions and modeled the gap between their current and potential levels by applying new management practices at country scale. Potential systems included reduced age of replacement heifers at first pregnancy and greater cow weaning rates. Results AND CONCLUSIONSCattle land area expansion and increased animal performance explained most of beef production growth (33 and 52%, respectively), while stocking rate had a negligible effect. We identified that recent beef production was driven by improved pasture area (R2 = 0.42), which represented only 21% of cattle area. This disproportionate effect showed a dependency of national beef production on improved pastures. The current weaning rate (65%) and the number of replacement heifers that have first pregnancy by 36 months of age (480,000 heads) revealed a national inefficiency, falling short of the potential of grazing systems based on native pastures. When concepts and principles of ecological intensification of native pasture grazing systems are applied optimally, weaning rate can be increased from 65 to 85% and age of first pregnancy reduced from 36 to 24 months, decreasing national enteric CH4 emissions by 13%. The weaknesses identified in the national beef production sector support re-focusing research, public policy, and technologies applied by farmers to shift the paradigm of beef production to greater ecological intensification based on native pastures. In this way, it will be possible to increase beef production and mitigate environmental impacts of grazing systems. SIGNIFICANCEWe demonstrate that re-focusing beef production from improved pastures to native pastures, while enhancing their management, will mitigate the CH4 emissions of the beef sector at large scales and will underpin the annual beef production, leading to a stable annual production, reducing the dependency on improved pasture area and providing ecosystem services.

Early decrease of ventilatory ratio after prone position ventilation may predict successful weaning in patients with acute respiratory distress syndrome: A retrospective cohort study.

Previous studies usually identified patients who benefit the most from prone positioning by oxygenation improvement. However, inconsistent results have been reported. Physiologically, pulmonary dead space fraction may be more appropriate in evaluating the prone response. As an easily calculated bedside index, ventilatory ratio (VR) correlates well with pulmonary dead space fraction. Hence, we investigated whether the change in VR after prone positioning is associated with weaning outcomes at day 28 and to identify patients who will benefit the most from prone positioning. This retrospective cohort study was performed in a group of mechanically ventilated, non-COVID ARDS patients who received prone positioning in the ICU at Zhongda hospital, Southeast University. The primary outcome was the rate of successful weaning patients at day 28. Arterial blood gas results and corresponding ventilatory parameters on five different time points around the first prone positioning were collected, retrospectively. VR responders were identified by Youden's index. Competing-risk regression models were used to identify the association between the VR change and liberation from mechanical ventilation at day 28. One hundred and three ARDS patients receiving prone positioning were included, of whom 53 (51%) successfully weaned from the ventilator at day 28. VR responders were defined as patients showing a decrease in VR of greater than or equal to 0.037 from the baseline to within 4 h after prone. VR responders have significant longer ventilator-free days, higher successful weaning rates and lower mortality compared with non-responders at day 28. And a significant between-group difference exists in the respiratory mechanics improvement after prone (P < 0.05). A linear relationship was also found between VR change and compliance of the respiratory system (Crs) change after prone (r = 0.32, P = 0.025). In the multivariable competing-risk analysis, VR change (sHR 0.57; 95% CI, 0.35-0.92) was independently associated with liberation from mechanical ventilation at day 28. Ventilatory ratio decreased more significantly within 4 h after prone positioning in patients with successful weaning at day 28. VR change was independently associated with liberation from mechanical ventilation at day 28.

Distinct Transcriptomic and Proteomic Profile Specifies Patients Who Have Heart Failure With Potential of Myocardial Recovery on Mechanical Unloading and Circulatory Support.

Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed "responders"). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown. To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders. These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions. This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets.

Mortality and parenteral nutrition weaning in patients with chronic intestinal failure on home parenteral nutrition: A 30-year retrospective cohort study

BackgroundHome parenteral nutrition (HPN) is the standard treatment for patients with chronic intestinal failure (CIF). Mortality and weaning rates of these patients differ widely among cohorts; however, these outcomes were often considered independent—rather than competing—events, leading to an upward bias of the retrieved estimates. ObjectivesThe aim of this retrospective cohort study was to evaluate, evaluating through a competing risk analysis, the rates and predictors of mortality and weaning in CIF patients from an Italian referral center. MethodsAll adult patients with CIF receiving > 3 mo HPN from 1985 until 2016 were enrolled. Clinical information was collected from the database of the Intestinal Failure Unit of Torino, Italy. Patients were stratified according to the presence or not of short bowel syndrome (SBS). ResultsThe cumulative incidences of death and weaning were 27.3% and 32.3% and 39.0% and 33.7% at 5 and 10 y from HPN initiation, respectively. At multivariable competing risk analyses, mortality was predicted by age (sub-distribution hazard ratio [SHR] = 1.65 per 10-y increase; 95% CI, 1.35–2.01), type 3 SBS (SHR = 0.38; 0.15–0.94), small bowel length ≥ 100 cm (SHR = 0.42; 0.22–0.83), and reconstructive surgery (SHR = 0.11; 0.02–0.64) in SBS patients, and by age (SHR = 1.38 per 10-y increase; 1.16–1.64) and presence of stoma (SHR = 0.30; 0.12–0.78) in non-SBS patients. In the same model, weaning was predicted by type 3 SBS (SHR = 6.86; 3.10–15.16), small bowel length ≥ 100 cm (SHR = 3.54; 1.99–6.30), and reconstructive surgery (SHR = 2.86; 1.44–5.71) in SBS patients, and by age (SHR = 0.79 per 10-y increase; 0.66–0.94) and presence of stoma (SHR = 2.64; 1.38–5.07) in non-SBS patients. ConclusionsSurgical procedures strongly affected mortality and weaning risk in CIF patients.

Extracorporeal Membrane Oxygenation in Children With COVID-19: A Systematic Review and Meta-Analysis.

The indication, complications, and outcomes of extracorporeal membrane oxygenation (ECMO) in children with COVID-19-related illnesses remain unelucidated. Our study aimed to investigate the characteristics and outcomes of ECMO in children with COVID-19-related illnesses. We searched PubMed and EMBASE databases in March 2022. We retrieved all studies involving children (age ≤ 18 yr) with COVID-19-related illnesses who received ECMO. Two authors independently extracted data and assessed the risk of bias. Mortality, successful weaning rate, and complications while on ECMO were synthesized by a one-group meta-analysis using a random-effect model. Meta-regression was performed to explore the risk factors for mortality. We included 18 observational studies, four case series, and 22 case reports involving 110 children with COVID-19-related illnesses receiving ECMO. The median age was 8 years (range, 10 d to 18 yr), and the median body mass index was 21.4 kg/m 2 (range, 12.3-56.0 kg/m 2 ). The most common comorbidities were obesity (11% [7/63]) and congenital heart disease (11% [7/63]), whereas 48% (30/63) were previously healthy. The most common indications for ECMO were multisystem inflammatory syndrome in children (52% [47/90]) and severe acute respiratory distress syndrome (40% [36/90]). Seventy-one percent (56/79) received venoarterial-ECMO. The median ECMO runtime was 6 days (range, 3-51 d) for venoarterial ECMO and 11 days (range, 3-71 d) for venovenous ECMO. The mortality was 26.6% (95% CI, 15.9-40.9), and the successful weaning rate was 77.0% (95% CI, 55.4-90.1). Complications were seen in 37.0% (95% CI, 23.1-53.5) while on ECMO, including stroke, acute kidney injury, pulmonary edema, and thromboembolism. Corticosteroids and IV immunoglobulin therapies were associated with lower mortality. The mortality of children on ECMO for COVID-19 was relatively low. This invasive treatment can be considered as a treatment option for critically ill children with COVID-19.

Pharmacokinetic Modeling of Optimized Midazolam and Pentobarbital Dosing Used in Treatment Protocols of Refractory Status Epilepticus.

To model bolus dosing, infusion rate, and weaning rate on theoretical serum concentration of midazolam and pentobarbital used in the treatment of refractory status epilepticus (RSE). One- and two-compartment in silico pharmacokinetic models of midazolam and pentobarbital. Not applicable. Not applicable. We compared the model variables used in midazolam and pentobarbital protocols for standard RSE. Standard RSE treatment protocols result in steady-state serum concentrations that are 6.2-9.0-fold higher for the one-compartment model and 2.3-4.7-fold higher for the two-compartment model. In the model, not including bolus doses delays the achievement of serum steady-state concentration by 0.5 and 2.7 hours for midazolam and pentobarbital, respectively. Abrupt discontinuation of these medications reduces modeled medication exposure by 1.1 and 6.4 hours, respectively. Our in silico pharmacokinetic modeling of standard midazolam and pentobarbital dosing protocols for RSE suggests potential variables to optimize in future clinical studies.

Abstract 13900: Combined Use of Venoarterial Extracorporeal Menbrane Oxygenation and Impella Improves the Outcome in Patients With Cardiogenic Shock

Introduction: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides benefit to patients in refractory cardiac arrest and cardiogenic shock. However, VA-ECMO elevates LV afterload and causes pulmonary edema and LV distension. Additional IABP support has been recommended in Japan to reduce LV afterload. Alternatively, transcatheter left ventricular assist device, Impella has been recently introduced. However, it remains to be evaluated if there is clinical benefit of concomitant use of VA-ECMO and Impella (ECPELLA). Methods: Aim of this single-site cohort study is to assess the effects of ECPELLA as compared with ECMO with IABP in patients who were managed with VA-ECMO due to refractory cardiogenic shock including cardiac arrest. Results: We retrospectively reviewed 253 consecutive patients, who received VA-ECMO from January 2012 to May 2022 in our institute. Among them, 67 patients who were managed with VA-ECMO alone were excluded. Patients were divided into two groups, ECEPLLA (n=68) and ECMO with IABP (n=118). We applied propensity score analysis with 1:1 score matching using dependent variables of age, the rate of sex, acute coronary syndrome, out-of-hospital and in-hospital cardiac arrest, and extracorporeal cardio-pulmonary resuscitation. We assessed 30-day survival rate, hemodynamic data, and safety profiles including acute kidney injury, blood transfusion and embolic cerebral infarction. Results: Following propensity score matching, 60 ECPELLA and 60 ECMO with IABP patients were included for analysis. The 30-day survival was significantly higher with ECPELLA group compared with ECMO with IABP group (ECPELLA: 48% vs. ECMO with IABP: 28%, p= 0.01, log-rank test). There were no statistical differences in ECMO weaning rate and safety profiles between treatment groups. Conclusions: ECPELLA may be associated with improved 30-day survival in patients with refractory cardiac shock including cardiac arrest.

Abstract 9551: Extracorporeal Membrane Oxygenation for Covid-19 in Children: A Systematic Review and Meta-Analysis

Introduction: In the wake of the COVID-19 pandemic, extracorporeal membrane oxygenation (ECMO) has been widely used to treat severe acute respiratory distress syndrome (ARDS) in adults. However, the indications, complications, and outcomes of ECMO in children with COVID-19 remain unelucidated. We conducted a systematic review and meta-analysis to investigate the characteristics and outcomes of ECMO use in children with COVID-19. Methods: PubMed and EMBASE databases were searched in March 2022 without language restrictions, and studies involving children (aged≤18) with COVID-19 who received ECMO were included. Two investigators extracted data and assessed the risk of bias independently. Mortality, successful weaning rate, and complications related to ECMO were synthesized by a one-group meta-analysis using a random-effect model. Results: We included 18 observational studies, 4 case series, and 22 case reports encompassing 110 children with COVID-19 requiring ECMO. The median age was 8 years (range: 10 days to 18 years), and the median body mass index was 21.4 kg/m 2 (range: 12.3-56.0). The most common comorbidities were obesity (11% [7/63]) and congenital heart diseases (11% [7/63]), while 48% (30/63) were previously healthy. The major indications were multisystem inflammatory syndrome in children (52% [47/90]) and ARDS (40% [36/90]). Seventy-one percent (56/79) received venoarterial-ECMO. The median ECMO runtime was 7 days (range: 3-71). The mortality rate was 26.6% (95% confidence interval [CI] 15.9-40.9), and the successful weaning rate was 77.0% (95% CI 55.4-90.1). ECMO-related complications, including stroke, acute kidney injury, pulmonary edema, and thromboembolism, were seen in 37.0% (95% CI 23.1-53.5). Conclusions: This meta-analysis demonstrated relatively favorable outcomes of ECMO for COVID-19 in children. Our findings will contribute to establishing the evidence of ECMO and serve as a guide to managing children with severe COVID-19.