Non-optimal Outcome Research Articles

56. Predictive models identify patient and surgical variables that synergistically produce an optimal outcome following adult spine deformity (ASD) surgery

<h3>BACKGROUND CONTEXT</h3> Identifying the components needed for an optimal adult spinal deformity (ASD) surgical outcome could help inform surgeons and improve ASD treatment. However, defining the components that create an optimal outcome for ASD surgery is challenging because outcome metrics depend on multiple perspectives. A patient may receive a technically successful complication-free surgery but may report dissatisfaction with the treatment outcome. Conversely, a patient may incur multiple postoperative complications with high societal cost but report satisfaction with the surgical outcome. <h3>PURPOSE</h3> (1) Define an "optimal" ASD surgical outcome by integrating outcome metrics from multiple perspectives, and (2) identify the patient-specific and surgical components of ASD treatment that surgeons can employ to improve ASD surgery by creating a model that predicts a multi-perspective "optimal" surgical outcome. <h3>STUDY DESIGN/SETTING</h3> Prospective, multicenter analysis. <h3>PATIENT SAMPLE</h3> ASD patients enrolled into a prospective multicenter study. <h3>OUTCOME MEASURES</h3> Scoliosis Research Society-22r questionnaire (SRS-22r), Oswestry Disability Index (ODI), postoperative complications. <h3>METHODS</h3> Surgically treated ASD patients prospectively enrolled into a multicenter study from 2009-2018 were assessed at minimum 2-year follow-up for optimal outcome defined as (1) no major postoperative complication or complication requiring surgery, (2) patient reached MCID for ODI and SRS-22r subscore, and (3) patient satisfied and indicates would have the surgery again. Demographic, radiographic, PROM and surgical variables were assessed for associations with optimal outcome. Multivariate regression models were built based on level of upper instrumented vertebra (UIV) to identify variables that created a best fit predictive model for optimal outcome by R2 maximization and AIC/BIC minimization. <h3>RESULTS</h3> Of 1291 patients, 788 (mean 3.5 years follow-up), were eligible for study and evaluated. Optimal outcome patients (OP; n=196) had less preoperative opioid use (47.5% vs 56.8%) and fewer histories of prior spine surgery (65.4% vs 77.3%) than nonoptimal outcome (NO; n=592), respectively (p 0.05). Creation of the best fit predictive model for optimal outcome demonstrated synergy between several modifiable variables including preoperative BMI and opioid and tobacco use, final SVA and scoliosis, and use of supplemental rods and PJF prophylaxis. Refining the model for specific surgeries based upon UIV demonstrated increased synergistic impact of the modifiable variables and predictive accuracy (thoracolumbar UIV R2=0.41; upper thoracic UIV R2=0.77). <h3>CONCLUSIONS</h3> No single surgical or radiographic variable is independently predictive of an a priori defined multiperspective optimal outcome following ASD surgery. However, predictive modeling identified preoperative BMI, opioid and tobacco use, final SVA and scoliosis, and use of supplemental rods and PJF prophylaxis as variables surgeons can optimize and/or employ that act synergistically to predict an optimal ASD surgical outcome. Future research will focus on development of predictive models that highlight the synergistic effects of patient specific and interventional variables to improve surgical outcomes. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Assessment of Neonatal Intensive Care Unit Practices and Preterm Newborn Gut Microbiota and 2-Year Neurodevelopmental Outcomes

In very preterm newborns, gut microbiota is highly variable with major dysbiosis. Its association with short-term health is widely studied, but the association with long-term outcomes remains unknown. To investigate in preterm newborns the associations among practice strategies in neonatal intensive care units (NICUs), gut microbiota, and outcomes at 2 years. EPIFLORE is a prospective observational cohort study that includes a stool sample collection during the fourth week after birth. Preterm newborns of less than 32 weeks of gestational age (GA) born in 2011 were included from 24 NICUs as part of the French nationwide population-based cohort, EPIPAGE 2. Data were collected from May 2011 to December 2011 and analyzed from September 2016 to December 2018. Eight NICU strategies concerning sedation, ventilation, skin-to-skin practice, antibiotherapy, ductus arteriosus, and breastfeeding were assessed. A NICU was considered favorable to a practice if the percentage of that practice in the NICU was more than the expected percentage. Gut microbiota was analyzed by 16S ribosomal RNA gene sequencing and characterized by a clustering-based method. The 2-year outcome was defined by death or neurodevelopmental delay using a Global Ages and Stages questionnaire score. Of 577 newborns included in the study, the mean (SD) GA was 28.3 (2.0) weeks, and 303 (52.5%) were male. Collected gut microbiota was grouped into 5 discrete clusters. A sixth cluster included nonamplifiable samples owing to low bacterial load. Cluster 4 (driven by Enterococcus [n = 63]), cluster 5 (driven by Staphylococcus [n = 52]), and cluster 6 (n = 93) were significantly associated with lower mean (SD) GA (26.7 [1.8] weeks and 26.8 [1.9] weeks, respectively) and cluster 3 (driven by Escherichia/Shigella [n = 61]) with higher mean (SD) GA (29.4 [1.6] weeks; P = .001). Cluster 3 was considered the reference. After adjustment for confounders, no assisted ventilation at day 1 was associated with a decreased risk of belonging to cluster 5 or cluster 6 (adjusted odds ratio [AOR], 0.21 [95% CI, 0.06-0.78] and 0.19 [95% CI, 0.06-0.62], respectively) when sedation (AOR, 10.55 [95% CI, 2.28-48.87] and 4.62 [1.32-16.18], respectively) and low volume of enteral nutrition (AOR, 10.48 [95% CI, 2.48-44.29] and 7.28 [95% CI, 2.03-26.18], respectively) was associated with an increased risk. Skin-to-skin practice was associated with a decreased risk of being in cluster 5 (AOR, 0.14 [95% CI, 0.04-0.48]). Moreover, clusters 4, 5, 6 were significantly associated with 2-year nonoptimal outcome (AOR, 6.17 [95% CI, 1.46-26.0]; AOR, 4.53 [95% CI, 1.02-20.1]; and AOR, 5.42 [95% CI, 1.36-21.6], respectively). Gut microbiota of very preterm newborns at week 4 is associated with NICU practices and 2-year outcomes. Microbiota could be a noninvasive biomarker of immaturity.

Mutation accumulation in cancer genes relates to nonoptimal outcome in chronic myeloid leukemia

AbstractChronic myeloid leukemia (CML) is a myeloproliferative neoplasm accounting for ∼15% of all leukemia. Progress of the disease from an indolent chronic phase to the more aggressive accelerated phase or blast phase (BP) occurs in a minority of cases and is associated with an accumulation of somatic mutations. We performed genetic profiling of 85 samples and transcriptome profiling of 12 samples from 59 CML patients. We identified recurrent somatic mutations in ABL1 (37%), ASXL1 (26%), RUNX1 (16%), and BCOR (16%) in the BP and observed that mutation signatures in the BP resembled those of acute myeloid leukemia (AML). We found that mutation load differed between the indolent and aggressive phases and that nonoptimal responders had more nonsilent mutations than did optimal responders at the time of diagnosis, as well as in follow-up. Using RNA sequencing, we identified other than BCR-ABL1 cancer-associated hybrid genes in 6 of the 7 BP samples. Uncovered expression alterations were in turn associated with mechanisms and pathways that could be targeted in CML management and by which somatic alterations may emerge in CML. Last, we showed the value of genetic data in CML management in a personalized medicine setting.

In Preterm Infants, Length Growth below Expected Growth during Hospital Stay Predicts Poor Neurodevelopment at 2 Years

Background: In preterm infants, neonatal weight growth is associated with neurodevelopmental outcome but is a poor indicator of growth quality. Objective: The aim of this work was to measure the relationship between neonatal length growth and the 2-year neurological outcome in preterm infants. Methods: A total of 2,403 infants enrolled in the LIFT cohort with gestational age less than 34 weeks were studied. Neonatal observed length growth (OLG) was calculated as the change in length Z-score between birth and discharge. Expected length growth (ELG) was estimated based on gestational age, birth weight Z-score, birth length Z-score, gender, and observed neonatal weight growth. The difference between OLG and ELG (∆_OLG-ELG) was calculated as OLG – ELG, and infants were ranked into 3 classes depending on their ∆_OLG-ELG (≤–0.5, –0.49 to 0.49, ≥0.50 Z-score). We explored the relationship between ∆_OLG-ELG and 2-year neurodevelopmental outcome (n = 2,036), and, in a subgroup (n = 85), between ∆_OLG-ELG and body composition at discharge. Results: ELG was strongly predicted from the above-mentioned parameters (R² = 0.73, p = 0.001). OLG correlated closely with gestational age (p = 0.001) but ∆_OLG-ELG did not (p = 1.0). OLG was not associated with a 2-year nonoptimal outcome after adjustment for gestational age, but ∆_OLG-ELG ≤–0.5 was; the crude and adjusted odds ratios were 1.63 and 1.56, respectively. ∆_OLG-ELG correlated negatively with fat mass (R² = 0.29, p = 0.006) before and after adjustment for gestational age. Conclusion: ∆_OLG-ELG is a marker of neonatal growth that does not depend on gestational age, and may reflect quality of growth. A ∆_OLG-ELG ≤–0.5 Z-score is associated with a higher risk for 2-year nonoptimal neurodevelopmental outcome.

Pharmacological inhibition of carnitine palmitoyltransferase 1 restores mitochondrial oxidative phosphorylation in human trifunctional protein deficient fibroblasts

BackgroundMitochondrial Trifunctional Protein deficiency (TFPD) is a severe genetic disease characterized by altered energy metabolism and accumulation of long-chain (LC) acylcarnitines in blood and tissues. This accumulation could impair the mitochondrial oxidative phosphorylation (OxPhos), contributing to the non-optimal outcome despite conventional diet therapy with medium-chain triglycerides (MCT). MethodAcylcarnitine and OxPhos parameters were measured in TFPD-fibroblasts obtained from 8 children and cultured in medium mimicking fasting (LCFA) or conventional treatment (MCT), with or without Etomoxir (ETX) an inhibitor of carnitine palmitoyltransferase 1 (CPT1) activity, and were compared to results obtained with fibroblasts from 5 healthy-control children. The effects of various acylcarnitines were also tested on control fibroblasts. ResultsIn the LCFA-condition, TFPD-fibroblasts demonstrated a large accumulation of LC-acylcarnitines associated with decreased O2-consumption (63±3% of control, P<0.001) and ATP production (67±5%, P<0.001) without modification of coupling efficiency. A dose-dependent decrease in O2-consumption was reproduced in control fibroblasts by addition of increasing dose of LC-acylcarnitines, while it was almost preserved with MC-acylcarnitines. The MCT-condition reduced LC-acylcarnitine accumulation and partially improved O2-consumption (80±3%, P<0.01) in TFPD-fibroblasts. The addition of ETX in both LCFA- and MCT-conditions normalized acylcarnitine profiles and restored O2-consumption and ATP production at the same levels than control. ConclusionAccumulation of LC-acylcarnitines plays a major role in the pathophysiology of TFPD, reducing OxPhos capacities. These deleterious effects could be partially prevented by MCT-therapy and totally corrected by ETX. Inhibition of CPT1 may be view as a new therapeutic target for patients with a severe form of TFPD.

Attentional deployment impacts neural response to regret

Regret results from comparing non-optimal outcomes containing both gain and loss parts to better alternatives during decision-making. The present fMRI study aimed to explore whether levels of regret could change when gain or loss part of a non-optimal outcome was focused during a sequential risk taking task, i.e. the effect of an important emotional regulation strategy named as attentional deployment on regret. Participants were asked to open a series of boxes consecutively and decided when to stop. Each box contained a reward, except for one containing a devil to zero one’s gain in the trial. After participants stopped, both collected gains and missed chances were revealed. Besides, participants were induced to focus on collected gains (GF) or missed chances (MF), by highlighting different parts of the outcome with red squares. Behaviorally, participants rated less regret to their decisions in GF than MF context. Moreover, participants tended to be less risk-taking after GF context relative to MF. At the neural level, bilateral straitum showed increased activations in both optimal outcome and GF context. However, right MFG and IPL only showed stronger activation in GF than MF context. Additionally, pgACC and mPFC activations were found only in optimal outcome.

Predictive value of serum cytokine levels in chronic myeloid leukemia patients

Serum samples taken at diagnosis in 28 chronic myeloid leukemia patients were tested for the presence of 20 cytokines by a magnetic bead-based Bio-plex immunoassay. According to complete cytogenetic remission achieved at 12 months of treatment, patients were divided into groups with either optimal or non-optimal outcome. Patients with increased cytokine levels tended to react optimally to the therapy more frequently than those others. TGF-β3 was a notable exception; its levels were significantly higher in patients with non-optimal outcomes. Further analysis enabled us to define two combinations of cytokine cut-off levels – namely low TGF-β3 and either high IL-8 or high MCP-1–each of which corresponded to therapy outcome better than either Sokal or EUTOS scores.

Neonatal EEG and neurodevelopmental outcome in preterm infants born before 32 weeks

ObjectiveTo assess the value of neonatal EEG for predicting non-optimal neurodevelopmental outcomes in very preterm infants, using a multimodal strategy of evaluation comprising brain imaging and clinical assessment.Design and settingBetween...

Early growth and neurodevelopmental outcome in very preterm infants: impact of gender

Background and objectiveNutrition in the neonatal unit may impact the neurological outcome of very preterm infants, and male preterms are more likely to suffer neonatal morbidity and adverse neurological outcomes....

Neurodevelopmental impairment in preterm infants with late-onset infection: not only in extremely preterm infants

Late-onset infection is known to increase the risk of neurodevelopmental impairment in infants born extremely preterm. However, little data is available regarding infants born moderately preterm. The aim of this study was to determine whether late-onset infection in moderately preterm infants (<35weeks of gestation) was associated with a non-optimal neurodevelopmental outcome at 2years of age. We analyzed a regional, population-based cohort of infants (LIFT cohort) between January 2003 and December 2009, and we used a propensity score method to reduce bias. Among the 4,618 preterm infants assessed at 2years, 618 had acquired late-onset infection (13.4%), and 764 had a non-optimal outcome (16.5%). The rate of non-optimal outcomes was significantly higher in preterm infants with late-onset infection, irrespective of subgroups of gestational age and birth weight Z-score. After adjusting for the propensity score, the relationship between late-onset infection and non-optimal neurodevelopmental outcome at 2years among infants born before 35weeks of gestation remained significant (aOR = 1.3; 95% CI 1.01-1.7; p = .04). Late-onset infection is associated with poor neurological outcome at 2years of age among infants born moderately preterm before and after adjustment for the propensity score.

Interobserver reliability of the Amiel-Tison neurological assessment at term

The eligibility criteria currently used for neurodevelopmental follow-up are traditionally based on perinatal events and characteristics of the infants at birth. However, they seem unsatisfactory to target efficiently all children who will manifest long-term neurologic sequelae and eventually require rehabilitation services. The updated version of the Amiel-Tison's Neurological Assessment At Term (ATNAAT) is expected to allow a better prediction of the neurodevelopmental outcome in high-risk infants. The main objective of the present study, which was performed on 35 infants, was to analyze the interobserver reliability of the updated version of ATNAAT. The evaluator and the observer coded the items of the test simultaneously. Among the 35 items tested, 16 demonstrated an excellent reliability based on the kappa coefficient, 11 items yielded a fair to good reliability, whereas only two items produced an agreement below 0.40. The final synthesis, which was a global appreciation of the neurologic status based on the different findings, yielded a good reliability with a kappa coefficient of 0.76. Among the infants who had a nonoptimal outcome from the assessment, only 38.5% met the traditional criteria currently used for follow-up. It would be important to conduct further research on predictive validity to demonstrate the capacity of the ATNAAT to forecast the long-term neurologic outcome of infants at risk.

Study of a group of extremely preterm infants (25-27 weeks): how do they function at 1 year of age?

The functional outcome of 49 extremely preterm infants (gestational age: 25-27 weeks) was studied at the corrected age of 12 months. Apart from pediatric follow-up, a full neurologic assessment and the Bayley Motor and Mental Scales of Infant Development was done. Emphasis was placed on postural control, spontaneous motility, hand function, and elicited infantile reactions. Special attention was given to symmetric development. The infants were then categorized as having optimal or nonoptimal or asymmetric outcome. Overall, an optimal outcome was found in 19 infants (39%) and nonoptimal outcome in 30 infants (61%), 7 of whom failed on all domains of function. Postural control had a significant influence on the different domains of development such as motility (P < or = .001) and persistent infantile reactions (P < or = .001) and slightly less on hand function (P = .08) and asymmetry (P = .06). The outcome on spontaneous motility was significantly related to the results on infantile reactions (P < or = 005) and hand function (P = .05). Also, the score on the motor scale of the Bayley Developmental test was clearly related to outcome on spontaneous motility (P < or = .001) and reactions (P< or = .02). Abnormal brain ultrasonograms were related to the asymmetry of the infantile reactions (P < or = .05). Poor coordination of gross motor function will have consequences for appropriate visuomotor and sensorimotor integration, thereby hampering motor learning and later cognitive function, as is often described in preterm infants. It is suggested that the poor postural control found in many infants born preterm is the result of both myogenic and neurogenic deviations caused by the preterm birth and its nursing consequences.

P110Neurodevelopmental outcome of children with intrauterine growth retardation and pathological antenatal color Doppler: a 1‐year follow‐up

ObjectiveThe aim of the study is to determine the neuro‐developmental outcome of children with IUGR due to placental insufficiency diagnosed by Color Doppler during pregnancy.Patients and methods25 children who were diagnosed with IUGR were included. The intrauterine growth was evaluated by repeated US and Doppler examinations and the resistance indexes in umbilical and cerebral fetal blood vessels were registered. The C/U ratio lower than one was considered pathological, implying the phenomena of fetal circulation centralization and brain sparing effect. All children underwent protocol that included the evaluation of other perinatal risk factors and extensive neurological follow‐up with repeated brain US, electrophysiological tests, visual and hearing acuity testing, as well as developmental assessment.ResultsThe gestational age ranged from 30 + 6 to 41 gestational weeks. The follow‐up period ranged from 2 to 16 months. None of the children has severe disorder. Some children have signs of dystonic syndrome (6 cases) or global neuroedevelopmental delay (2 cases). The nonoptimal outcome was always connected to neonatal complications and pathological brain US finding (PV‐IVH or cortical brain atrophy). Further neurodevelopmental evaluation for assessment of higher cognitive functioning at later (even school age) age will be necessary.

On the Outcome of the 1983 Conservative Leadership Convention: How They Shot Themselves in the Other Foot

AbstractSocial choice theory demonstrates that interesting and nonobvious perversities can result when majoritarian methods are applied to the selection of a single alternative from among more than two alternatives. The “voters paradox” is a well-known example of this phenomenon. This note demonstrates that the outcome of the 1983 federal Conservative party leadership convention is another example of the interaction of a decision rule and preferences producing a nonoptimal outcome.