Recovery Endpoints Research Articles

Effects of aerobic training on cardiopulmonary fitness in patients with long COVID-19: a randomized controlled trial

BackgroundLong COVID-19 is characterized by systemic deterioration of the entire body, leading to significant physical and mental disorders. Exercise training has the potential to improve persistent symptoms and cardiopulmonary functions.MethodThis was a single-center, randomized, controlled trial. Twenty-four patients aged 18 to 75 years who had a history of SARS-CoV-2 infection and long COVID symptoms. Patients were randomly allocated in a 1:1 ratio to receive either a 4-week exercise training program or an attention control group. The training group participated in 12 supervised aerobic sessions on a cycling ergometer over 4 weeks. The outcomes were to assess the impact of a 4-week aerobic exercise on the persistent symptoms and cardiopulmonary fitness, the surrogate endpoints of COVID-19 recovery and cardiopulmonary health.ResultsAfter the 4-week intervention, significant reductions were observed in the total number of symptoms in the training group. Specifically, 67.8% of patients in the training group exhibited reduced or completely resolved symptoms, in comparison to 16.7% in the control group (P = 0.013). After adjusting for gender, significant improvements in the training group were observed for exercise time (Pgroup*time = 0.028), maximum load (Pgroup*time = 0.01), and peak VO2 (Pgroup*time = 0.001), as well as O2 pulse (Pgroup*time = 0.042) and maximum heart rate (Pgroup*time = 0.007). The score of Short Form-12, depression, anxiety, perceived stress, and insomnia did not show significant changes between groups (Pgroup*time > 0.05).ConclusionA supervised aerobic training program has the potential to alleviate persistent symptoms and improve exercise tolerance in patients with long COVID-19. Further research is necessary to confirm these effects in a large population. This intervention could be easily implemented in non-hospital settings, potentially benefiting a broader range of individuals.Trial registration numberClinicalTrials.gov NCT05961462. Registered on July 25, 2023.

Anthropogenic activities have accelerated the restoration of carbon sequestration services in the upper Yellow River

Carbon sequestration services stemming from ecosystems facilitate the absorption of CO2 and mitigation of greenhouse effects. Thus, investigating the spatiotemporal changes of carbon sequestration services and their response patterns to human activities is essential in relation to achieving the strategic carbon peak and carbon neutrality (“double carbon”) goal in a region. In this study, the spatiotemporal carbon sequestration patterns in the upper reaches of the Yellow River from 1985 to 2020 were assessed based on measured sample points and spatial modeling combined with multi-source remote sensing data. Specifically, the impacts of human activities on the carbon sequestration services in the area were quantitatively analyzed. The results showed that, for the past 35 years, carbon sequestration in the upper reaches of the Yellow River ranged from 80.09 Tg to 98.48 Tg, with lower levels in the northeast and southwest, and higher ones in the northwest and southeast. From 1985 to 1998, carbon sequestration in the upper reaches of the Yellow River was mainly affected by the natural climate and showed a fluctuating upward trend. From 1998 to 2001, carbon sequestration declined sharply due to the influence of human activities and the natural climate, whereas it showed a significant increasing trend from 2001 to 2020, affected by the combined effects of ecological engineering and climate change. In 1998–2001, the degree of human influence was −5.92% to approximately −11.68%, and from 2001 to 2020, it was approximately 2.32% to 6.78%. This study shows that while human social development can negatively affect the carbon sequestration services of ecosystems, ecological engineering can accelerate its recovery, recovery trends and recovery endpoints are constrained by natural factors.

Transcatheter Axial Pump Use in Pediatric Patients on Veno-Arterial Extracorporeal Membrane Oxygenation: An ACTION Collaborative Experience.

We report the largest pediatric multicenter experience with Impella pump use and peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. Utilizing the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) collaborative database, we conducted a retrospective, multicenter study of all patients with cardiogenic shock requiring VA-ECMO support with subsequent Impella implant between October 2014 and December 2021. The primary outcome was defined as death while on Impella support. Secondary outcomes were recovery, transplantation, and transition to durable ventricular assist device (VAD) at the time of Impella explantation. Adverse events were defined according to the ACTION registry criteria. Twenty subjects were supported with Impella; Impella 2.5 (n = 3), CP (n = 12), 5.0/5.5 (n = 5). The median Interquartile range (IQR) age, weight, and body surface area at implantation were 15.6 years (IQR = 13.9-17.2), 65.7 kg (IQR = 53.1-80.7), and 1.74 m2 (IQR = 1.58-1.98). Primary cardiac diagnoses were dilated cardiomyopathy/myocarditis in nine (45%), congenital heart disease in four (20%), graft failure/rejection in four (20%), and three (15%) others. Most common adverse events included hemolysis (50%) and bleeding (20%). There were two deaths (10%) in the cohort. Nine patients (45%) were explanted for recovery, eight (40%) were transitioned to a durable VAD, and one (5%) underwent heart transplantation. Impella percutaneous pump support should be considered in the older pediatric population supported with peripheral VA-ECMO, as a means of left heart decompression, and a strategy to come off ECMO to achieve endpoints of myocardial recovery, transition to a durable VAD, or transplantation.

Exploring a novel methodology for post impact assessments of chemical accidents on forest ecosystems: With damage, recovery, and resilience aspects of vegetation

Chemical accident leads to severe environmental problems, especially threatening the capacity of the ecosystem for ‘sustainability’. Therefore, a systematic response system, that includes performing a spatial and temporal assessment of the overall impacts due to chemical accidents, is urgently required. This study constructed a new methodology that can support the scientific implementation of post impact assessment through quantitatively assessing damaging impact and recovery endpoints for vegetation subjected to chemical accidents from both spatial and temporal aspects. Through applying a novel index ΔVI (Damage Assessment Factor), vegetation impact was quantitatively assessed. Afterward, with ΔVI applied as a chemical accident impact variable, MaxEnt was used for vegetation recovery assessment. With the change of potential habitat per each scenario, the recovery endpoint was quantitatively derived using the newly developed index, VRI (Vegetation Recovery Index). The results indicated a tendency of damaging impact to decline over time, with shortening of damage persistence and rapid recovery endpoints at a further distance from the accident site, by each spatial zone (R1-R5) in each distance range (0–1000 m). Further, vegetation resilience was analyzed based on the temporal difference between damaging impact and recovery tendency, using the newly developed index, VRCI (Vegetation Resilience Capacity Index). The forest that lacks diversity in functions·species compositions due to fragmentation and narrow areas showed low resilience, and it was spatially·quantitatively analyzed through the landscape fragmentation model (ArcGIS 10.3). This study is expected to be applied as a basis for implementing systematic post management and policies of vegetation in chemical accidents.

4 Extending the 5P Clinical Decision Rule Predicting Concussion Recovery Using an Evidence-Based Assessment Model

Objective:Construction of predictive algorithms of concussion symptom recovery at 4 and 12 weeks post-injury using an evidence-based assessment (EBA) model to guide clinical decision-making, extending the 2016 5P decision rule.Participants and Methods:Children and adolescents, ages 8-18 (n=1,551; mean age=12.78; 62% male), followed over 12 weeks in the prospective multicenter cohort study (Predicting Persistent Post-Concussive Problems in Pediatrics, 5P; Zemek et al., 2016). The age-specific PostConcussion Symptom Inventory (PCSI) (8-12, 17 items; 1318 years, 20 items) was completed at six timepoints from the ED and at 1, 2, 4, 8, and 12-weeks post-injury. Logistic regression analysis was applied to the set of key variables including the PCSI Total Retrospective-Adjusted PostInjury Difference (RAPID) scores, patient demographics and pre-injury history, and injury characteristics to predict participant recovery status (Recovered, Not Recovered) at the 4- and 12-week endpoints. The resulting recovery-predictive equations identified the significant sets of variables with symptom scores at four successive post-injury timepoints (ED, 1, 2, 4 weeks). Logistic Regression Threshold values were established at the 90th CI against which individual patient data was applied to determine recovery status. Participants with sub-threshold sums were deemed recovered at the target endpoint (4- or 12-weeks post-injury).Results:A total of 19 predictive equations were generated for the two age groups across the recovery timeline. Four sets of equations were developed to predict symptom recovery status at 4-weeks post-injury for the two age groups (8-12 AUC=0.679-0.884; 13-18 AUC=0.752-0.909). Prediction of symptom recovery status at 12-weeks post-injury yielded six equations for the 8-12 age group (AUC=0.723-0.825), and five equations for the 13-18 age group (AUC=0.724-0.887). Total PCSI RAPID score was identified as a significant variable in each of these 19 equations. Participant sex was identified as significant in 18 of the 19 constructed equations. Other variables that were identified as significant at varying timepoints included age, pre-injury history of learning disability and migraines, and an early post-injury sign in the ED (answering questions more slowly than usual). Examples of the equations include: Week 1 predicting symptom recovery status at 4-weeks: 8-12 yr group-(Sex*.802)+(week 1 Total RAPID Score*.142)+(Age2* .053)+(-3.851) with AUC=0.808; 13-18 yr group-(Sex*.980)+(Week 1 Total RAPID Score*.071)+(-3.261) with AUC=0.861.Conclusions:Clinicians’ management of the concussion recovery of children and adolescents can benefit from EBA guidance. The 5P dataset (Zemek et al., 2016) provides an important window into “typical” and “atypical” recovery trajectories, establishing an initial predictive decision rule for a 4-week recovery endpoint, at the ED timepoint only, reporting AUC=0.69. The current study extends the prediction modeling using successive post-injury timepoints reflecting a typical management timeline. Symptom reports from both 1- and 2-weeks post injury with patient demographics/ history predicted symptom recovery status at 4- and 12-weeks post-injury, significantly improve predictive accuracy over the ED timepoint alone. These predictive equations, when applied to the individual patient, can serve to assist the clinician’s understanding of the patients’ recovery trajectory, i.e., on track for a typical or atypical recovery, further informing the intervention strategy.

The efficacy of nalmefene on anesthetic recovery of patients: a study protocol for a multicenter randomized controlled trial

IntroductionSo far, the recovery quality after general anesthesia is still unsatisfied. Nalmefene is a drug to treat opioid overdose and reverse opioid actions. We aim to investigate the efficacy of nalmefene on optimizing the recovery quality of patients after general anesthesia.MethodsIt is a prospective, placebo-controlled, two-arm parallel groups, multicentre, double-blind, randomized (PPPMDR) clinical trial. The participants (n = 520) will be randomly assigned into two groups. Each patient will receive either: a single dose of nalmefene 0.25 µg/kg in the intervention group, or the same volume of 0.9% NaCl solution in the control group at the end of the surgery. The primary outcome will be the time interval between the end of anaesthesia and recovery endpoints achieved (Aldrete recovery score ≥ 9) in post-anesthesia care unit (PACU). The other variables are the time interval from the end of operation to extubation; Richmond Agitation Sedation Scale (RASS) score at extubation; the time at Montreal Cognitive Assessment Scale (MoCA) orientation score ≥ 5; visual analog scale (VAS) score and adverse effects including postoperative nausea and vomiting (PONV), and pruritus in PACU and 24 h postoperatively.AnalysisThis trial aims to study whether small dose of nalmefene can shorten the time from the end of surgery to Aldrete score ≥ 9 and improve opioid-induced side effects.This trial focuses on providing the reliable clinical evidence for satisfactory quality of recovery.Ethics and disseminationThis clinical trial has been approved and supported by the ethics committee of the Renji Hospital, Shanghai Jiaotong University, School of Medicine (KY2020-150); Shanghai Tongren Hospital (2021–030-01);The First Affiliated Hospital of Guangxi Medical University (2021–032); and The First Affiliated Hospital of Zhengzhou University(2021-KY-0495–003). Analysis of the study results will be submitted to a peer-reviewed journal for publication.Trial registrationClinicalTrials.gov, NCT04713358, Registered on September 23, 2021.

Randomized Controlled Trial of Robot-Assisted Gait Training versus Therapist-Assisted Treadmill Gait Training as Add-on Therapy in Early Subacute Stroke Patients: The GAITFAST Study Protocol.

The GAITFAST study (gait recovery in patients after acute ischemic stroke) aims to compare the effects of treadmill-based robot-assisted gait training (RTGT) and therapist-assisted treadmill gait training (TTGT) added to conventional physical therapy in first-ever ischemic stroke patients. GAITFAST (Clinicaltrials.gov identifier: NCT04824482) was designed as a single-blind single-center prospective randomized clinical trial with two parallel groups and a primary endpoint of gait speed recovery up to 6 months after ischemic stroke. A total of 120 eligible and enrolled participants will be randomly allocated (1:1) in TTGT or RTGT. All enrolled patients will undergo a 2-week intensive inpatient rehabilitation including TTGT or RTGT followed by four clinical assessments (at the beginning of inpatient rehabilitation 8-15 days after stroke onset, after 2 weeks, and 3 and 6 months after the first assessment). Every clinical assessment will include the assessment of gait speed and walking dependency, fMRI activation measures, neurological and sensorimotor impairments, and gait biomechanics. In a random selection (1:2) of the 120 enrolled patients, multimodal magnetic resonance imaging (MRI) data will be acquired and analyzed. This study will provide insight into the mechanisms behind poststroke gait behavioral changes resulting from intensive rehabilitation including assisted gait training (RTGT or TTGT) in early subacute IS patients.

Evaluating the effect of an artificial intelligence system on the anesthesia quality control during gastrointestinal endoscopy with sedation: a randomized controlled trial

BackgroundSedative gastrointestinal endoscopy is extensively used worldwide. An appropriate degree of sedation leads to more acceptability and satisfaction. Artificial intelligence has rapidly developed in the field of digestive endoscopy in recent years and we have constructed a mature computer-aided diagnosis (CAD) system. This system can identify the remaining parts to be examined in real-time endoscopic procedures, which may help anesthetists use anesthetics properly to keep patients in an appropriate degree of sedation.AimsThis study aimed to evaluate the effects of the CAD system on anesthesia quality control during gastrointestinal endoscopy.MethodsWe recruited 154 consecutive patients at Renmin Hospital of Wuhan University, including 76 patients in the CAD group and 78 in the control group. Anesthetists in the CAD group were able to see the CAD system’s indications, while anesthetists in the control group could not. The primary outcomes included emergence time (from examination completion to spontaneous eye opening when doctors called the patients’ names), recovery time (from examination completion to achievement of the primary recovery endpoints) and patient satisfaction scores. The secondary outcomes included anesthesia induction time (from sedative administration to successful sedation), procedure time (from scope insertion to scope withdrawal), total dose of propofol, vital signs, etc. This trial was registered in the Primary Registries of the WHO Registry Network, with registration number ChiCTR2100042621.ResultsEmergence time in the CAD group was significantly shorter than that in the control group (p < 0.01). The recovery time was also significantly shorter in the CAD group (p < 0.01). Patients in the CAD group were significantly more satisfied with their sedation than those in control group (p < 0.01). Vital signs were stable during the examinations in both groups. Propofol doses during the examinations were comparable between the two groups.ConclusionThis CAD system possesses great potential for anesthesia quality control. It can improve patient satisfaction during endoscopic examinations with sedation.Trial registrationChiCTR2100042621.

Response to heart failure treatment in patients with anthracyclines and trastuzumab induced left ventricular dysfunction

Abstract Background Chemotherapy treatments with anthracyclines and Trastuzumab are widely used in different hematologic or solid malignancies but myocardial injury and left ventricular dysfunction, usually called cardiotoxicity (CTX), is a frequent adverse effect. Some studies have demonstrated that early detection and treatment of CTX is essential for the recovery of left ventricular ejection fraction (LVEF), however its behavior after starting treatment is not well established. Purpose Evaluate the behavior of LVEF after starting treatment for heart failure in patients with diagnosis of CTX. Methods Patients with diagnosis of solid or hematologic malignancies scheduled to receive therapy including anthracyclines and/or trastuzumab were prospectively included. Echocardiogram was performed before starting treatment, and then 3 and 6 months after. CTX was defined, according to guidelines, as a drop of LVEF ≥10% to a value &amp;lt;53% and in these patients treatment of left ventricular dysfunction with B blockers and Enalapril/Losartan was promptly initiated and up-titrated to the maximal tolerated dose. Myocardial injury was defined as a drop of LVEF ≥10% and a value ≥53%, with a watchful waiting strategie, considering these patients as a control group. LVEF was re-evaluated 6 months after starting treatment or after diagnosis of myocardial injury. Primary endpoint was defined as a recovery of LVEF ≥10%. Results Of a total of 141 patients of the entire cohort (mean age 56±15 years, 85,8% women and 61,7% with diagnosis of breast cancer),17 patients (12%) met criteria of CTX and 21 (14,9%) of myocardial injury. There were no differences in relation to clinical characteristics or chemotherapy schemes between groups. In patients with CTX (intervention group), 88,2% reached the primary endpoint of recovery of LVEF ≥10% while only 23,8% did it in the control group (p&amp;lt;0,001). Patients with CTX had lowest LVEF at baseline, however no significant differences were observed at 12 months of follow up. Figure 1 represents the behavior of LVEF at baseline, 3, 6 and 12 months. A paired before-after analysis was performed between LVEF at baseline and at 12 months. Patients who received treatment showed no differences in LVEF (63,3±7,2% vs 61,5±9,6%, p=0,5). In contrast, patients who did not receive treatment showed a significant drop in LVEF (72,7±4,4% vs 66,2±5,4%; p&amp;lt;0,001) (figure 2). Conclusion Treatment of left ventricular dysfunction in patients with CTX is associated with a greater recovery of LVEF. Funding Acknowledgement Type of funding sources: None.

The Hospital Recovery Scale: A clinically useful endpoint in patients hospitalized with influenza

Background: Currently, no single best primary endpoint exists for measuring the efficacy of treatments in seriously ill patients with respiratory infections, such as influenza, who require hospitalization. The Hospital Recovery Scale is an ordinal endpoint used to evaluate treatment outcomes in clinical studies of hospitalized patients infected with influenza.Methods: To determine whether Hospital Recovery Scale outcomes correspond to those for other clinical endpoints in patients hospitalized due to influenza, data from the phase 3 randomized, double-blind ZORO clinical trial (NCT01231620) were analyzed. Randomized influenza-infected patients were divided into subgroups of interest based on prespecified baseline and infection-related characteristics, as well as randomized treatment arms (intravenous zanamivir 300 mg or 600 mg, or oral oseltamivir 75 mg). Clinical endpoints relevant to this population were included to analyze differences in outcomes between the subgroups, and correspondence of these endpoints and hospital recovery endpoint was evaluated.Results: Data from 488 patients were analyzed. There were strong correlations (ρs > 0.8) between the Hospital Recovery Scale assessed on the day after completion of a 5-day antiviral therapy (Day 6) and both time to hospital discharge and time to intensive care unit discharge, and moderate to strong correlations (0.6 < ρs < 0.8) between the Hospital Recovery Scale on Day 6 and several other relevant clinical endpoints.Conclusions: The Hospital Recovery Scale is applicable as a primary endpoint in trials to evaluate new therapies for severely ill patients hospitalized due to influenza, and may have utility in other severe respiratory illnesses such as COVID-19.

Advancing freshwater ecological forecasts: Harmful algal blooms in Lake Erie

Ecological models help provide forecasts of ecosystem responses to natural and anthropogenic stresses. However, their ability to create reliable predictions requires forecasts with track records sufficiently long to build confidence, skill assessments, and treating uncertainty quantitatively. We use Lake Erie harmful algal blooms as a case study to help formalize ecological forecasting. Key challenges for models include uncertainty in the deterministic structure of the load-bloom relationship and the need to assess alternative drivers (e.g., biologically available phosphorus load, spring load, longer term cumulative load) with a larger dataset. We enhanced a Bayesian model considering new information and an expanded data set, test it through cross validation and blind forecasts, quantify and discuss its uncertainties, and apply it for assessing historical and future scenarios. Allowing a segmented relationship between bloom size and spring load indicates that loading above 0.15 Gg/month will have a substantially higher marginal impact on bloom size. The new model explains 84 % of interannual variability (9.09 Gg RMSE) when calibrated to the 19-year data set and 66 % of variability in cross validation (12.58 Gg RMSE). Blind forecasts explain 84 % of HAB variability between 2014 and 2020, which is substantially better than the actual forecast track record (R2 = 0.32) over this same period. Because of internal phosphorus recycling, represented by the long-term cumulative load, it could take over a decade for HABs to fully respond to loading reductions, depending on the pace of those reductions. Thus, the desired speed and endpoint of the lake's recovery should be considered when updating and adaptively managing load reduction targets.Results are discussed in the context of ecological forecasting best pactices: incorporate new knowledge and data in model construction; account for multiple sources of uncertainty; evaluate predictive skill through validation and hindcasting; and answer management questions related to both short-term forecasts and long-term scenarios.

The Effect of Aging on Retinal Function and Retinal Ganglion Cell Morphology Following Intraocular Pressure Elevation.

Aging and elevated intraocular pressure (IOP) are two major risk factors for glaucomatous optic neuropathy; a condition characterized by the selective, progressive injury, and subsequent loss of retinal ganglion cells (RGCs). We examined how age modified the capacity for RGCs to functionally recover following a reproducible IOP elevation (50 mmHg for 30 min). We found that RGC functional recovery (measured using electroretinography) was complete by 7 days in 3-month-old mice but was delayed in 12-month-old mice until 14 days. At the 7-day recovery endpoint when RGC function had recovered in young but not older eyes, we examined RGC structural responses to IOP-related stress by analyzing RGC dendritic morphology. ON-RGC cell volume was attenuated following IOP elevation in both young and older mice. We also found that following IOP elevation OFF-RGC dendritic morphology became less complex per cell volume in young mice, an effect that was not observed in older eyes. Our data suggest that adaptations in OFF-RGCs in young eyes were associated with better functional recovery 7 days after IOP elevation. Loss of RGC cellular adaptations may account for delayed functional recovery in older eyes.

Oxigenación con membrana extracorpórea en el paciente COVID-19: resultados del Registro Español ECMO-COVID de la Sociedad Española de Cirugía Cardiovascular y Endovascular

Background and aimCOVID-19 patients with severe heart or respiratory failure are potential candidates for extracorporeal membrane oxygenation (ECMO). Indications and management of these patients are unclear. Our aim is to describe the results of a prospective registry of COVID-19 patients treated with ECMO. MethodsAn anonymous prospective registry of COVID-19 patients treated with veno-arterial (V-A) or veno-venous (V-V) ECMO was created on march 2020. Clinical, analytical and respiratory preimplantation variables, implantation data and post-implantation course data were recorded. The primary endpoint was all cause in-hospital mortality. Secondary events were functional recovery and the combined endpoint of mortality and functional recovery in patients followed at least 3 months after discharge. ResultsThree hundred and sixty-six patients from 25 hospitals were analyzed, 347 V-V ECMO and 18 V-A ECMO patients (mean age 52.7 and 49.5 years respectively). Patients with V-V ECMO were more obese, had less frequently organ damage other than respiratory failure and needed less inotropic support; Thirty three percent of V-A ECMO and 34.9% of V-A ECMO were discharged (P=NS). Hospital mortality was non-significantly different, 56.2% versus 50.9% respectively, mainly during ECMO therapy and mostly due to multiorgan failure. Other 51 patients (14%) remained admitted. Mean follow-up was 196± 101.7 days (95%CI: 170.8-221.6). After logistic regression, body weight (OR 0.967, 95%CI: 0.95-0.99, P=0.004) and ECMO implantation in the own centre (OR 0.48, 95%CI: 0.27-0.88, P=0.018) were protective for hospital mortality. Age (OR 1.063, 95%CI: 1.005-1.12, P=0.032), arterial hypertension (3.593, 95%CI: 1.06-12.19, P=0.04) and global (2.44, 95%CI: 0.27-0.88, P=0.019), digestive (OR 4,23, 95%CI: 1.27-14.07, P=0.019) and neurological (OR 4.66, 95%CI: 1.39-15.62, P=0.013) complications during ECMO therapy were independent predictors of primary endpoint occurrence. Only the post-discharge day at follow-up was independent predictor of both secondary endpoints occurrence. ConclusionsHospital survival of severely ill COVID-19 patients treated with ECMO is near 50%. Age, arterial hypertension and ECMO complications are predictors of hospital mortality, and body weight and implantation in the own centre are protective. Functional recovery is only predicted by the follow-up time after discharge. A more homogeneous management of these patients is warranted for clinical results and future research optimization.

Early high-energy feeding in infants following cardiac surgery: a randomized controlled trial.

BackgroundEffective nutrition programs are beneficial for nutritional recovery in infants. Few studies have focused on the effect of early high-energy feeding after open heart surgery. This study sought to assess the effects of early high-energy feeding in infants after congenital heart surgery.MethodsPatients at a tertiary pediatric cardiology center who underwent open heart surgery between July 2016 and July 2018 were recruited and randomly allocated to 1 of the following 2 groups: (I) the intervention group (postoperative early high-energy feeding; n=124); and (II) the control group (no intervention; n=120).The primary endpoints of average energy delivery and growth Z-scores [i.e., weight-for-height Z-score (WHZ), weight-for-age Z-score (WAZ), and height-for-age Z-score (HAZ)] were recorded preoperatively, during the intensive care unit (ICU) stay, at discharge, and at 1 and 3 months postoperatively. The secondary endpoints of malnutrition recovery, ventilator support time, infection rate, and cardiac ICU (CICU) stay were also recorded.ResultsA total of 244 infants were included in the study. There were no significant differences in the baseline features between the 2 groups. The intervention group received higher calories on average than the control group (44.5 vs. 34.7; P<0.001). At discharge from the ICU, the WHZ (−2.29 vs. −2.76; P<0.001) and WAZ (−3.08 vs. −3.43; P=0.005) of patients in the intervention group were higher than those of patients in the control group. Ventilator support time (P=0.004), CICU stay (P=0.045), and infection rate (P=0.001) were significantly lower in the intervention group than the control group. At 3 months post-surgery, the intervention group exhibited a higher malnutrition recovery rate than the control group (19.4% vs. 6.5%; P=0.002).ConclusionsThe administration of early high-energy feeding to infants after congenital heart surgery is associated with improved growth, reduced CICU stay, decreased ventilator support time, and reduced postoperative infection rates.Trial RegistrationClinicalTrials NCT04609358.

Retrospective Analysis of Reoperation Rate After Standard Lumbar Discectomy and Microdiscectomy - Single Center Experience

Abstract Discectomy is a surgical procedure in the treatment of lumbar disc herniation (LDH) if sciatica or neurological deficits occur and still persist after a course of conservative therapy. Standard discectomy (SD) and microdiscectomy (MD) are still equal in curent clinical practice. Many retrospective and prospective studies have shown that there is no clinically significant difference in the functional outcome after two treatment modalities. The aim of our study was to determine whether there are differences in the incidence of reoperation after performing SD and MD. The research included 545 patients with average period of postoperative follow-up of approximately 5.75 years. Standard discectomy was performed in 393 patients (72.11%), and micro-discectomy in 152 (27.8%) patients. The total number of reoperated patients was 37/545, or 6.78%. In the SD group, the number of reoperated patients was 33/393 (8.39%) and in the MD group 4/152 or 2.63%. Statistically significant difference (p &lt;0.05) was recorded in favor of the MD group. Although it has been proven that both SD and MD give good endpoints of treatment and similar functional recovery, the advantage is given to microdiscectomy due to statistically significantly lower rates of recurrent herniation. This result is attributed to better visualization of neural structures and pathological substrates, as well as their mutual relationship.

The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study.

The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery. In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery. Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2-5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1-0.7) or in OT (HR = 0.1, 95% CI = 0.0-0.8) treated with tocilizumab. To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.

The effectiveness and feasibility of fluid resuscitation directed by microcirculation monitoring in patients with septic shock: a randomized controlled trial.

This study sought to examine fluid resuscitation in septic shock patients by monitoring their sublabial point of care microcirculation score (POEM) scores (a 3.5 cut-off value was used as the end point of recovery). It also sought to explore the effectiveness and safety of using the POEM score in the fluid resuscitation of septic shock. Patients were randomly allocated to the experimental group or the control group. In the experimental group, a POEM score >3 was used as the end point of fluid resuscitation. In the control group, the doctor just monitor, don't know the data. Patients' heart rates, mean arterial pressure (MAP), Acute Physiology and Chronic Health Disease Classification System II (APACHE II) scores, Sequential Organ Failure Assessment (SOFA) scores, and oxygenation index scores were recorded at 2, 24, 48, 72 h, and on the 7th day after admission to the study. Statistically significant differences between the 2 groups were examined. Thirty-one septic shock patients (comprising 14 patients in the experimental group and 17 patients in the control group) participated in our study. Patients' parameters upon admission to the study, including MAP, blood lactate and APACHE score, SOFA score, POEM score, cardiac output (CO), and central venous pressure (CVP), were recorded at 2 h; There was no significant difference in the APACHE II scores, SOFA scores, and oxygenation index scores at 48 h between the 2 groups; however, at 72 h, the scores of the experimental group were significantly better than those of the control group (P<0.05). Under the guidance of POEM scores, limited fluid resuscitation reduced the intake of fluid any unnecessary amounts of fluids. POEM scores also offered certain protective effects to organ function at the early stage of septic shock, and did not affect patients' circulation. Chinese Clinical Trial Registry (ChiCTR2100049510).

Performance Analysis of the National Early Warning Score and Modified Early Warning Score in the Adaptive COVID-19 Treatment Trial Cohort.

We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores. We assessed prognostic value for the end points of recovery, mechanical ventilation, and death for score at enrollment, average, and slope of score over the first 48 hours. A multisite international inpatient trial. A total of 1,062 adult nonpregnant inpatients with severe coronavirus disease 2019 pneumonia. Adaptive COVID-19 Treatment Trial 1 randomized participants to receive remdesivir or placebo. The prognostic value of predictive scores was evaluated in both groups separately to assess for differential performance in the setting of remdesivir treatment. For mortality, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.60-0.68), and improved with addition of age (c-index, 0.66-0.74). For recovery, baseline National Early Warning Score and Modified Early Warning Score demonstrated somewhat better prognostic ability (c-index, 0.65-0.69); however, National Early Warning Score+age and Modified Early Warning Score+age further improved performance (c-index, 0.68-0.71). For deterioration, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.59-0.69) and improved with addition of age (c-index, 0.63-0.70). All prognostic performance improvements due to addition of age were significant (p < 0.05). In the Adaptive COVID-19 Treatment Trial 1 cohort, National Early Warning Score and Modified Early Warning Score demonstrated moderate prognostic performance in patients with severe coronavirus disease 2019, with improvement in predictive ability for National Early Warning Score+age and Modified Early Warning Score+age. Area under receiver operating curve for National Early Warning Score and Modified Early Warning Score improved in patients receiving remdesivir versus placebo early in the pandemic for recovery and mortality. Although these scores are simple and readily obtainable in myriad settings, in our data set, they were insufficiently predictive to completely replace clinical judgment in coronavirus disease 2019 and may serve best as an adjunct to triage, disposition, and resourcing decisions.

Early Goal-Directed Renal Replacement Therapy in Acute Decompensated Heart Failure Patients with Cardiorenal Syndrome

Introduction: The aim of this study was to clarify the efficacy of early goal-directed renal replacement therapy (GDRRT) for treatment of cardiorenal syndrome (CRS) patients after acute decompensated heart failure (ADHF). Methods: In the retrospective, observational study, we enrolled 54 patients in the early GDRRT group and 63 patients in the late GDRRT group. Baseline characteristics, clinical data at initiation renal replacement therapy time, and the clinical outcome were collected and several parameters were compared and analyzed between 2 groups. Results: The urine volume at GDRRT initiation time in the early group was higher than that in the late GDRRT group (1,060.3 ± 332.1 vs. 300.5 ± 148.3 mL, p < 0.001). Hemodynamic parameters such as mean artery pressure were higher (70.06 ± 32.99 vs. 54.34 ± 40.88 mm Hg, p = 0.012), the heart rate was slower (80.17 ± 15.26 vs. 99.21 ± 25.45 bpm, p = 0.002), and the diameter of inferior vena cava was narrower (22.00 ± 1.91 vs. 25.77 ± 5.5 mm, p = 0.04) in early GDRRT. Primary end point was inhospital all-cause mortality and cardiovascular mortality, which was obviously lower in the early GDRRT group (respectively 24.1 vs. 60.3%, p = 0.002 and 20.3 vs. 50.8%, p = 0.005). The second end point of kidney recovery in the early GDRRT group was much better than that in the latter GDRRT group (p = 0.018). Moreover, urine volume after GDRRT of the early group was more significant than that of the late group (1,432 ± 172 vs. 702 ± 183 mL, p = 0.005). Conclusion: This study clarified the effectiveness of the early GDRRT strategy in ADHF patients suffered from CRS, which reduced inhospital mortality and improved the urine output and clinical kidney recovery outcome.

Interim analysis of STARTAR: A phase II salvage trial of androgen receptor (AR) inhibition with androgen deprivation therapy (ADT) and apalutamide with radiation therapy (RT) followed by docetaxel in men with PSA recurrent prostate cancer (PC) after radical prostatectomy (RP).

90 Background: ADT with salvage RT improves survival for men with PSA recurrence after RP. Current standard duration of ADT for high risk PSA recurrence is up to 2 years with RT; therefore shortening but intensifying systemic therapy may improve outcomes. The STREAM trial showed 6 mo of enzalutamide added to ADT/RT had a 3-year progression free survival (PFS) of 53% in high risk patients including lymph node (LN) positive. Given that docetaxel improves survival in men with mHSPC, we evaluated the combination of salvage RT, ADT/apalutamide and docetaxel in this setting. Methods: STARTAR is a multicenter phase 2 trial for salvage treatment of PSA recurrent PC following RP conducted within the US Dept. of Defense Prostate Cancer Clinical Trials Consortium (DOD PCCTC). Key inclusion criteria included PC with Gleason 7 with T3/positive margin/1-4 positive LNs or Gleason 8-10 disease and PSA relapse within 4 years of RP (min PSA 0.2 ng/mL to max PSA 4 ng/mL). Men with up to 4 positive resected LNs were eligible. Men started ADT with apalutamide, continued with RT (66-74 Gy to the prostate bed +/- pelvic LNs over 6-8 weeks), and finally completed docetaxel 75mg/m2 IV q3 weeks for 6 cycles. Men were treated with ADT and apalutamide for approximately 9 months. The primary endpoint was PSA PFS at 36 months. This interim analysis evaluated secondary endpoints of 1-year PSA recurrence, testosterone recovery, and safety of this treatment sequence. Results: From 3/2018 to 12/2019, 39 men were enrolled at Duke, Wake Forest, Cornell, and the GU Research Network. With a data cutoff in 9/2020, median follow up from enrollment was 14 months. Baseline patient characteristics included Gleason 4+3 = 7 in 54% and Gleason 8-10 in 46%, and 23% LN positive; median PSA at the time of enrollment was 0.58 ng/mL (range 0.21-3.40) and the median time from RP to enrollment was 7 mo (range 2-98). At 1 year, there have been no progression events with 38% (12/31) of men with post-treatment testosterone recovery into normal range (recovery time median 10 mos [1-17 mos]). Common adverse events (AEs) of any-grade at least possibly related to the regimen were 98% hot flashes, 88% fatigue, 77% alopecia, 57% dysgeusia, and 53% rash (28% grade 1; 15% grade 2, 10% grade 3), with neutropenia as the most common grade 3/4 AE (27/39 men, 70%) with two grade 3 febrile neutropenia. Conclusions: In this first phase 2 trial of ADT, apalutamide, radiation, and 6 cycles docetaxel in the salvage setting for high risk PSA recurrence, short term outcomes are excellent with no recurrences at 12 months of follow-up. This salvage treatment was well tolerated in the majority of men with the exception of a high rate of drug rashes and neutropenia related to the course of treatment, in line with known safety profiles of the study agents. Clinical trial information: NCT03311555.