The combination of kidney function variables with cell cycle arrest biomarkers identifies distinct subphenotypes of sepsis-associated acute kidney injury: a post-hoc analysis (the PHENAKI study).

BACKGROUND: The severity and course of sepsis-associated acute kidney injury (SA-AKI) are correlated with the mortality rate. Early detection of SA-AKI subphenotypes might facilitate the rapid provision of individualized care. PATIENTS AND METHODS: In this post-hoc analysis of a multicenter prospective study, we combined conventional kidney function variables with serial measurements of urine (tissue inhibitor of metalloproteinase-2 [TIMP-2])* (insulin-like growth factor-binding protein [IGFBP7]) at 0, 6, 12, and 24 h) and then using an unsupervised hierarchical clustering of principal components (HCPC) approach to identify different phenotypes of SA-AKI. We then compared the subphenotypes with regard to a composite outcome of in-hospital death or the initiation of renal replacement therapy (RRT). RESULTS: We included 184 patients presenting SA-AKI within 6 h of the initiation of catecholamines. Three distinct subphenotypes were identified: subphenotype A (99 patients) was characterized by a normal urine output (UO), a low SCr and a low [TIMP-2]*[IGFBP7] level; subphenotype B (74 patients) was characterized by existing chronic kidney disease (CKD), a higher SCr, a low UO, and an intermediate [TIMP-2]*[IGFBP7] level; and subphenotype C was characterized by very low UO, a very high [TIMP-2]*[IGFBP7] level, and an intermediate SCr level. With subphenotype A as the reference, the adjusted hazard ratio (aHR) [95%CI] for the composite outcome was 3.77 [1.92-7.42] (p < 0.001) for subphenotype B and 4.80 [1.67-13.82] (p = 0.004) for subphenotype C. CONCLUSIONS: Combining conventional kidney function variables with urine measurements of [TIMP-2]*[IGFBP7] might help to identify distinct SA-AKI subphenotypes with different short-term courses and survival rates.

Determinants of postoperative complications in high-risk noncardiac surgery patients optimized with hemodynamic treatment strategies: A post-hoc analysis of a randomized multicenter clinical trial.

STUDY OBJECTIVE: This post-hoc analysis of a randomized controlled trial was undertaken to establish the determinants of postoperative complications and acute kidney injury in high-risk noncardiac surgery patients supported with hemodynamic treatment strategies. DESIGN: We conducted a post-hoc analysis of patients enrolled in the OPtimization Hemodynamic Individualized by the respiratory QUotiEnt (OPHIQUE) trial. SETTING: Operating rooms in four university medical centers and one non-university hospital from December 26, 2018, to September 9, 2021. PATIENTS: We enrolled 350 patients with a high risk of postoperative complications undergoing high-risk noncardiac surgery lasting 2 h or longer under general anesthesia. INTERVENTIONS: All patients were treated according to hemodynamic treatment strategies which included cardiac output optimization by titration of fluid challenge and targeted systolic blood pressure to remain within ±10% of the reference value. MEASUREMENTS: We assessed the association between pre-operative and intra-operative exposure of interest with a composite primary outcome of major complications or death within seven days following surgery using a multivariable logistic regression model. We also assessed the association between these exposures of interest and acute kidney injury. MAIN RESULTS: The data of 341 patients were analyzed. In multivariate analysis, the factors independently associated with the primary outcome were age (OR = 1.04 (1.01-1.06), P = 0.002), preoperative hemoglobin concentration (OR = 0.85 (0.75-0.96), P = 0.012), non-vascular surgery (OR = 0.30 (0.17-0.53), P < 0.0001), and intraoperative surgical complications (OR = 2.08 (1.02-4.24), P = 0.046). The factors independently associated with postoperative acute kidney injury were age (OR = 1.04 (1.01-1.08), P = 0.008), preoperative creatinine concentration (OR = 1.01 (1.00-1.01), P = 0.049), non-vascular surgery (OR = 0.36 (0.20-0.66), P = 0.001), and intraoperative surgical complications (OR = 3.36 (1.50-7.55), P = 0.031). CONCLUSIONS: Surgical complications, a lower preoperative hemoglobin concentration, age, and vascular surgery were associated with postoperative complications in a high-risk noncardiac surgery population supported with hemodynamic treatment strategies.

A new statistical model for binge drinking pattern classification in college-student populations.

Background: Binge drinking (BD) among students is a frequent alcohol consumption pattern that produces adverse consequences. A widely discussed difficulty in the scientific community is defining and characterizing BD patterns. This study aimed to find homogenous drinking groups and then provide a new tool, based on a model that includes several key factors of BD, to assess the severity of BD regardless of the individual's gender. Methods: Using the learning sample (N1 = 1,271), a K-means clustering algorithm and a partial proportional odds model (PPOM) were used to isolate drinking and behavioral key factors, create homogenous groups of drinkers, and estimate the probability of belonging to these groups. Robustness of our findings were evaluated with Two validations samples (N2 = 2,310, N3 = 120) of French university students (aged 18-25 years) were anonymously investigated via demographic and alcohol consumption questionnaires (AUDIT, AUQ, Alcohol Purchase Task for behavioral economic indices). Results: The K-means revealed four homogeneous groups, based on drinking profiles: low-risk, hazardous, binge, and high-intensity BD. The PPOM generated the probability of each participant, self-identified as either male or female, to belong to one of these groups. Our results were confirmed in two validation samples, and we observed differences between the 4 drinking groups in terms of consumption consequences and behavioral economic demand indices. Conclusion: Our model reveals a progressive severity in the drinking pattern and its consequences and may better characterize binge drinking among university student samples. This model provides a new tool for assessing the severity of binge drinking and illustrates that frequency of drinking behavior and particularly drunkenness are central features of a binge drinking model.

Mitral annular plane systolic excursion for assessing left ventricular systolic dysfunction in patients with septic shock.

Background: Using easy-to-determine bedside measurements, we developed an echocardiographic algorithm for predicting left ventricular ejection fraction (LVEF) and longitudinal strain (LVLS) in patients with septic shock. Methods: We measured septal and lateral mitral annular plane systolic excursion (MAPSE), septal and lateral mitral S-wave velocity, and the left ventricular longitudinal wall fractional shortening in patients with septic shock. We used a conditional inference tree method to build a stratification algorithm. The left ventricular systolic dysfunction was defined as an LVEF <50%, an LVLS greater than -17%, or both. Results: We included 71 patients (males: 61%; mean [standard deviation] age: 61 [15] yr). Septal MAPSE (cut-off: 1.2 cm) was the best predictor of left ventricular systolic dysfunction. The level of agreement between the septal MAPSE and the left ventricular systolic dysfunction was 0.525 [0.299-0.751]. A septal MAPSE ≥1.2 cm predicted normal LVEF in 17/18 patients, or 94%. In contrast, a septal MAPSE <1.2 cm predicted left ventricular systolic dysfunction with impaired LVLS in 46/53 patients (87%), although 32/53 (60%) patients had a preserved LVEF. Conclusions: Septal MAPSE is easily measured at the bedside and might help clinicians to detect left ventricular systolic dysfunction early-especially when myocardial strain measurements are not feasible.

Annexin-V positive extracellular vesicles level is increased in severe COVID-19 disease.

Objectives: To evaluate extracellular vesicles levels in a cohort of SARS-CoV-2's patients hospitalized in an intensive care unit with and without COVID-19 associated thromboembolic events. Methods: In this study, we aim to assess endothelial and platelet membrane-derived extracellular vesicles levels in a cohort of SARS-CoV-2 patients with and without COVID-19-associated thromboembolic events who were hospitalized in an intensive care unit. Annexin-V positive extracellular vesicles levels were prospectively assessed by flow cytometry in one hundred twenty-three critically ill adults diagnosed with acute respiratory distress syndrome associated with a SARS-CoV-2 infection, ten adults diagnosed for moderate SARS-CoV-2 infection and 25 healthy volunteers. Results: On our critically ill patients, thirty-four patients (27.6%) had a thromboembolic event, Fifty-three (43%) died. Endothelial and platelet membrane-derived extracellular vesicles were drastically increased in SARS-CoV-2 patients hospitalized in the ICU compared to healthy volunteers. Moreover a slighty higher small/large ratio for platelets membrane-derived extracellular vesicles in patients was linked to thrombo-embolic events. Conclusion: A comparison between total annexin-V positive extracellular vesicles levels in severe and moderate SARS-CoV-2 infection and healthy controls showed a significant increase in patients with severe infection and their sizes could be considered as biomarkers of SARS-CoV-2 associated thrombo-embolic events.

Functional architecture of executive processes: Evidence from verbal fluency and lesion mapping in stroke patients.

The functional organization and related anatomy of executive functions are still largely unknown and were examined in the present study using a verbal fluency task. The objective of this study was to determine the cognitive architecture of a fluency task and related voxelwise anatomy in the GRECogVASC cohort and fMRI based meta-analytical data. First, we proposed a model of verbal fluency in which two control processes, lexico-semantic strategic search process and attention process, interact with semantic and lexico-phonological output processes. This model was assessed by testing 404 patients and 775 controls for semantic and letter fluency, naming, and processing speed (Trail Making test part A). Regression (R2 = .276 and .3, P = .0001, both) and structural equation modeling (CFI: .88, RMSEA: .2, SRMR: .1) analyses supported this model. Second, voxelwise lesion-symptom mapping and disconnectome analyses demonstrated fluency to be associated with left lesions of the pars opercularis, lenticular nucleus, insula, temporopolar region, and a large number of tracts. In addition, a single dissociation showed specific association of letter fluency with the pars triangularis of F3. Disconnectome mapping showed the additional role of disconnection of left frontal gyri and thalamus. By contrast, these analyses did not identify voxels specifically associated with lexico-phonological search processes. Third, meta-analytic fMRI data (based on 72 studies) strikingly matched all structures identified by the lesion approach. These results support our modeling of the functional architecture of verbal fluency based on two control processes (strategic search and attention) operating on semantic and lexico-phonologic output processes. Multivariate analysis supports the prominent role of the temporopolar area (BA 38) in semantic fluency and the F3 triangularis area (BA 45) in letter fluency. Finally, the lack of voxels specifically dedicated to strategic search processes could be due to a distributed organization of executive functions warranting further studies.

Venous Thrombosis Recurrence After Catheter-Related Upper Extremity Deep Venous Thrombosis in Cancer Patients: A Retrospective Analysis.

Long-term indwelling central venous catheters (CVC) are frequently used to secure vascular access to deliver injectable treatment. Catheter-related thrombosis (CRT) occurs in approximately 2-6% of cancer patients. We conducted a single-center retrospective study to assess the rate of venous thromboembolism (VTE) recurrence in cancer patients; 200 patients were included. Mean age was 56 ± 15.15 years, median follow-up duration was 16.5 [range: 10-36] months. The incidence of recurrence was estimated using Gray's method for competing risk with death as the competing event of VTE. Recurrent VTE occurred in 25.5% of patients with a median occurrence time of 6.5 [range: 5-11.25] months. In case of recurrence, 94.6% of patients were treated for cancer and 80.4% of them received anticoagulants; 4 major bleeds and 17 non-major bleeds occurred during follow-up. In multivariate analysis, previous VTE (Hazard Ratio (HR) 2.48 (95% CI 1.42-4.32) and presence of CVC (HR 5.56 (95% CI 1.96-15.75) were significant recurrence risk factors. After a first episode of CRT, 25.5% of patients experienced VTE recurrence as UEDVT in 30 cases (55.5%), PE in 17 cases (31.5%), and DVT in 7 cases (13%), mostly during anticoagulation therapy. Anticoagulation therapy does not avoid CRT in case of cancer and must be balanced with hemorrhagic risk.

Chronic kidney disease is a key risk factor for aortic stenosis progression.

BACKGROUND: Rapid progression of aortic stenosis (AS) has been observed in patients undergoing dialysis, but existing cross-sectional evidence is contradictory in non-dialysis-dependent chronic kidney disease (CKD). The present study sought to evaluate whether CKD is associated with the progression of AS over time in a large cohort of patients with AS. METHODS: We retrospectively studied all consecutive patients diagnosed with AS [peak aortic jet velocity (Vmax) ≥2.5 m/s] and left ventricular ejection fraction ≥50% in the echocardiography laboratories of two tertiary centers between 2000 and 2018. The estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) was calculated from serum creatinine values. Patients were divided into five CKD stages according to the baseline eGFR. Annual rates of change in the aortic valve area (AVA) were determined by a linear mixed-effects model. RESULTS: Among the 647 patients included, 261 (40%) had CKD. After a median follow-up of 2.9 (interquartile range 1.8-4.8) years, the mean overall rate of change in AVA was -0.077 (95% confidence interval -0.082; -0.073) cm2/year. There was an inverse relationship between the progression rate and kidney function. The more severe the CKD stage, the greater the AVA narrowing (P < .001). By multivariable linear regression analysis, the eGFR was also negatively associated (P < .001) with AS progression. An eGFR strata below 45 mL/min/1.73 m2 was associated with higher odds of rapid progression of AS than normal kidney function. During the clinical follow-up, event-free survival (patients free of aortic valve replacement or death) decreased as CKD progressed. Rapid progression of AS in patients with kidney dysfunction was associated with worse outcomes. CONCLUSIONS: Patients with CKD exhibit more rapid progression of AS over time and require close monitoring. The link between kidney dysfunction and rapid progression of AS is still unknown and requires further research.

Two-year prognosis of acute coronary syndrome during the first wave of the coronavirus disease 2019 pandemic.

BACKGROUND: The first wave of the coronavirus disease 2019 pandemic significantly changed behaviour in terms of access to healthcare. AIM: To assess the effects of the pandemic and initial lockdown on the incidence of acute coronary syndrome and its long-term prognosis. METHODS: Patients admitted for acute coronary syndrome from 17 March to 6 July 2020 and from 17 March to 6 July 2019 were included. The number of admissions for acute coronary syndrome, acute complication rates and 2-year rates of survival free from major adverse cardiovascular events or death from any cause were compared according to the period of hospitalization. RESULTS: In total, 289 patients were included. We observed a 30±3% drop in acute coronary syndrome admissions during the first lockdown, which did not recover in the 2months after it was lifted. At 2years, there were no significant differences in the combined endpoint of major adverse cardiovascular events or death from any cause between the different periods (P=0.34). Being hospitalized during lockdown was not predictive of adverse events during follow-up (hazard ratio 0.87, 95% confidence interval 0.45-1.66; P=0.67). CONCLUSIONS: We did not observe an increased risk of major cardiovascular events or death at 2years from initial hospitalization for patients hospitalized during the first lockdown, adopted in March 2020 in response to the coronavirus disease 2019 pandemic, potentially as a result of the lack of power of the study.

Respiratory Exchange Ratio guided management in high-risk noncardiac surgery: The OPHIQUE multicentre randomised controlled trial.

BACKGROUND: There is a need to develop non-invasive markers to identify the occurrence of anaerobic metabolism in high-risk surgery. Our objective was to demonstrate that a goal-directed therapy algorithm incorporating the respiratory exchange ratio (ratio between CO2 production and O2 consumption) can reduce postoperative complications. METHODS: We conducted a randomized, multicenter, controlled clinical trial in four university medical centers and one non-university hospital from December 26, 2018, to September 9, 2021. 350 patients with a high risk of postoperative complications undergoing high-risk noncardiac surgery lasting 2 h or longer under general anesthesia were enrolled. The control group was treated according to current hemodynamic guidelines. The interventional group was treated according to an algorithm based on the measurement of the respiratory exchange ratio. The primary outcome was a composite of major complications or death within seven days of surgery. The secondary outcomes were the length of hospital stay, 30-day mortality, and the total intraoperative volume of fluids administered. RESULTS: The primary outcome occurred for 78 patients (45.6%) in the interventional group and 83 patients (48.8%) in the control group (relative risk: 0.93, 95% confidence interval [CI]: 0.75-1.17; p = 0.55). There were no clinically relevant differences between the two groups for secondary outcomes. CONCLUSIONS: In high-risk surgery, a goal-directed therapy algorithm integrating the measurement of the respiratory-exchange ratio did not reduce a composite outcome of major postoperative complications or death within seven days after surgery compared to routine care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03852147.

Positive margins and plexitis increase the risk of recurrence after ileocecal resection: A systematic review and meta-analysis.

INTRODUCTION: There is debate over the impact of residual microscopic disease after ileocecal resection in Crohn's disease (CD) to predict recurrence. We conducted a meta-analysis to evaluate the impact of positive histological margins and plexitis after ileocecal resection on the risk of postoperative recurrence. METHODS: Using a systematic search, we identified. 30 studies evaluating the impact of inflammatory margins on CD recurrence. The primary outcome was the postoperative clinical recurrence and secondary outcomes were surgical, and endoscopic recurrence. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs. RESULTS: Thirty studies were analyzed, seven focused on myenteric plexitis, six on submucosal plexitis and twenty-three on positive margins. Inflammatory margins were associated with a higher rate of clinical and surgical recurrences: respectively 14 studies - OR 2.38; 95% CI, 1.54 - 3.68- I2 = 68.2%, Q test-p = 0.0003 and 8 studies - OR, 1.52; 95% CI, 1.07-2.16 - I2 =0%; Q test-p = 0.43. The presence of myenteric plexitis was associated with a higher rate of clinical recurrence (4 studies- OR, 1.60; 95%CI, 1.12-2.29; I2= 0%, Q-test-p = 0.61), and of endoscopic recurrence (4 studies - OR, 4.25; 95%CI; 2.06-8.76; I2= 0%, Q test-p = 0.97). Submucosal plexitis was not associated with an increased risk of endoscopic recurrence (4 studies - OR, 0.94; 95%CI; 0.58-1.52; I2= 0%, Q test-p = 0.79). CONCLUSION: Inflammatory margins and/or plexitis were associated with postoperative recurrence after ileocecal resection for CD. These elements should be taken into account in future algorithm for prevention of postoperative recurrence.

Comparison of the Risk of Crohn's Disease Postoperative Recurrence Between Modified Rutgeerts Score i2a and i2b Categories: An Individual Patient Data Meta-analysis.

BACKGROUND: The modified Rutgeerts' score [RS] differentiates i2a-lesions confined to the anastomosis-and i2b-more than five aphthous ulcers in the neoterminal ileum with normal intervening mucosa, with or without anastomotic lesions-categories. Its relevance for the therapeutic management of Crohn's disease [CD] patients after ileocolic resection is still debated. Our objective was to compare the postoperative recurrence risk in patients with an i2a or i2b score, using an individual patient data meta-analysis. METHODS: We conducted a systematic literature search until July 2020, to identify all relevant studies reporting the i2a/i2b status in the year following ileocolic resection and clinical and/or surgical postoperative CD recurrence in their follow-up. Individual patient-level data were obtained from the corresponding authors. The association between the modified RS and time-to-event was evaluated using a mixed Cox model with the centre as the random effect. RESULTS: Seven studies published between 2008 and 2019 were included, corresponding to 400 patients: 189 [47%] i2a and 211 [53%] i2b. Median [interquartile range, IQR] time from ileocolic resection to ileocolonoscopy was 6.2 [5.5, 7.9] months and median [IQR] follow-up time after ileocolonoscopy was 4.5 [2.9, 7.3] years. The risk of clinical postoperative recurrence at 1 and 3 years was 11% [6-15%], and 25% [18-32%] in the i2a group versus 9% [5-13%] and 33% [26-41%] in the i2b group [p = 0.63 and p = 0.12, respectively]. No significant difference was observed in terms of time to clinical postoperative recurrence [p = 0.16] or surgical postoperative recurrence [p = 0.87]. Results did not change after excluding patients having initiated an immunosuppressant or a biologic in the 3 months after endoscopy [remaining cohort, n = 361]. CONCLUSIONS: In this individual patient data meta-analysis, no difference was observed between i2a and i2b subcategories with regards to clinical or surgical postoperative recurrence. As we wait for prospective trials, the same treatment strategy could be applied to all patients classified as i2 on the Rutgeerts score.

Atrial fibrillation in severe aortic stenosis: Prognostic value and results of aortic valve replacement.

OBJECTIVES: Although atrial fibrillation (AF) is common, its impact on long-term mortality has not been reliably determined in patients with aortic stenosis (AS). We aimed to assess whether AF is associated with survival in patients with severe AS and to determine the impact of AF on the results of aortic valve replacement (AVR). METHODS: The study included 1838 consecutive patients with severe AS (77 ± 11 years, male 47%). Upon AS diagnosis, patients were screened for AF using a 12-lead electrocardiogram. The treatment strategy (conservative management or AVR) was selected by the heart team in accordance with current guidelines. The effect of AVR on survival was analyzed as a time-dependent covariate using the entire follow-up period. RESULTS: AF, diagnosed in 593 (32%) patients was associated with poor survival at 5 years (55 ± 2% vs 74 ± 1% for patients in sinus rhythm, P < .001), even after adjustment for established outcome predictors (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.33-1.84; P < .001). In patients with AF, AVR was associated with lower mortality (HR, 0.16; 95% CI, 0.12-0.22; P < .001) even in those with no or minimal symptoms (HR, 0.12; 95% CI, 0.08-0.20; P < .001). However, among patients who underwent AVR, those in AF had an excess mortality (HR, 1.59; 95% CI, 1.22-2.08; P < .001). CONCLUSIONS: In severe AS, AF is a strong predictor of mortality even in asymptomatic or minimally symptomatic patients. After AVR, AF remains associated with poorer survival than sinus rhythm. In patients in AF, AVR is associated with lower mortality compared with conservative treatment. Further studies are needed to confirm the benefits of AVR in asymptomatic patients in AF with severe AS.

Transperineal ultrasound in routine uterine cervix measurement.

PURPOSE: Transvaginal ultrasound (TVUS) is used in routine practice to evaluate cervical length (CL). This technique is nevertheless invasive and often viewed as uncomfortable, which is less the case with transperineal ultrasound (TPUS). This study was conducted in light of recent technological improvements in the ultrasound field to evaluate whether TPUS could be used as an alternative to TVUS in CL assessment. METHODS: This was a prospective single-blind study. Pregnant women requiring CL measurement during their emergency consultation were offered a second assessment by TPUS after an initial TVUS. TPUS was performed by a third-year OBGYN resident, unaware of the CL measurement obtained via TVUS. RESULTS: Seventy-three women were included. The mean ∂ was 0.59 mm. The interclass Pearson correlation coefficient between the two techniques was 0.8987 (95% CI [0.8429; 0.9353]). None of the tested factors were found to be associated with a difference between TPUS and TVUS CL measurements. ROC curve analysis indicated that a transperineal CL cut-off measurement of 24.9 mm was predictive of a transvaginal CL measurement below 25 mm. This threshold enabled a 95% sensitivity [75.1-99.9%] and a 100% specificity [93.3-100%] for the TPUS CL measurement technique. CONCLUSION: TPUS should be acknowledged as a reliable alternative to TVUS for CL assessment in routine every day practice.

Development and reliability of the coding system evaluating maternal sensitivity to social interactions with 34- to 36-week postmenstrual age preterm infants.

Maternal sensitivity (MS), the ability to perceive and synchronously respond to the social signals (SSs), is affected by prematurity. The development of early supportive psychotherapy to foster MS, before discharge of the infant from the neonatal intensive care unit (NICU) is a major challenge in the prevention of subsequent developmental and mental disorders in the child. There are currently no reliable methods for evaluating MS to social interactions with very to moderate preterm infants. We investigated the reliability of a newly developed procedure for assessing MS in interactions between the mother and her 34- to 36-week postmenstrual age (PMA) preterm infant: the Preterm Infant Coding System for Maternal Sensitivity (PRICOSMAS). Method: This study encompassed three steps: testing of the capacity to videorecord SSs in very to moderate preterm infants, selection, by an expert committee, of the recordable and relevant SSs, and investigation of the internal consistency and interrater reliability. The synchronicity between infant and mother's SSs was determined on a 1 s period basis, using ELAN software. Preterm infants born after 25-weeks gestational age (GA) were included while being between 34- and 36-weeks PMA. A perinatal risk inventory score > 10 for the infant precluded from inclusion. Interrater reliabilities were assessed independently by two raters blind to the clinical situation of the mother and infant. Results: The resulting PRICOSMAS encompassed two four-item SS sections, one covering the preterm infant's SSs and the other, the mother's SSs. Reliability was assessed on a sample of 26 videorecorded observations for 13 mother-preterm infant dyads. Infants' mean age at birth was 30.4 ± 3.1-weeks GA (range: 26.4-35) and PMA at the time of the test was 34.7-weeks (±0.8). Internal consistency ranged from 0.81 to 0.89. Interrater reliability ranged from substantial to almost perfect (0.73-0.88). Conclusion: This study shows that the infants' SSs and MS can be reliably scored in preterm infants as young as 34- to 36-weeks PMA. Our findings suggest that the PRICOSMAS is sufficiently reliable for use, including in NICU, by healthcare professionals or researchers for coding early parent-infant interactions with 34- to 36-week PMA preterm infants.

Walking speed at the acute and subacute stroke stage: A descriptive meta-analysis.

Gait disorders are one of the leading patient complaints at the sub-acute stroke stage (SSS) and a main determinant of disability. Walking speed (WS) is a major vital and functional index, and the Ten-Meter Walk Test is considered the gold standard after stroke. Based on a systematic review of the literature, studies published between January 2000 and November 2021 were selected when WS was reported (ten-meter walk test for short distance and/or 6-min walking distance for long distance) within 6 months following a first ischemic and/or hemorrhagic stroke (SSS) in adults prior to receiving specific walking rehabilitation. Following PRISMA guidelines, a meta-analysis was conducted on two kinds of WS: the principal criterion focused on short-distance WS (ten-meter walking test) and the secondary criteria focused on long-distance WS (6-min test) and meta-regressions to study the association of WS with balance, cognitive disorders and autonomy. Nine studies comprising a total of 939 data on post-stroke patients were selected. The weighted average age was 61 years [95% IC [55-67] and males represented 62% ± 2.7 of patients [57-67]. Average short-distance WS was 0.36 ± 0.06 m.s-1 [95% CI (0.23-0.49)]. Average long-distance WS was 0.46 ± 0.1 m.s-1 [95% CI (0.26-0.66)]. The funnel plot revealed asymmetry of publication bias and high heterogeneity of the nine studies (I 2 index 98.7% and Q-test p < 0.0001). Meta-regressions of secondary endpoints could not be performed due to a lack of study data. At the SSS, WS would be lower than data in general population published in literature, but above all, lower than the WS required for safe daily autonomy and community ambulation after stroke. WS must be a priority objective of stroke rehabilitation to increase walking function but also for survival, autonomy, social participation and health-related quality of life.

Unsupervised clustering of patients with severe aortic stenosis: A myocardial continuum.

BACKGROUND: Traditional statistics, based on prediction models with a limited number of prespecified variables, are probably not adequate to provide an appropriate classification of a condition that is as heterogeneous as aortic stenosis (AS). AIMS: To investigate a new classification system for severe AS using phenomapping. METHODS: Consecutive patients from a referral centre (training cohort) who met the echocardiographic definition of an aortic valve area (AVA) ≤ 1 cm2 were included. Clinical, laboratory and imaging continuous variables were entered into an agglomerative hierarchical clustering model to separate patients into phenogroups. Individuals from an external validation cohort were then assigned to these original clusters using the K nearest neighbour (KNN) function and their 5-year survival was compared after adjustment for aortic valve replacement (AVR) as a time-dependent covariable. RESULTS: In total, 613 patients were initially recruited, with a mean±standard deviation AVA of 0.72±0.17 cm2. Twenty-six variables were entered into the model to generate a specific heatmap. Penalized model-based clustering identified four phenogroups (A, B, C and D), of which phenogroups B and D tended to include smaller, older women and larger, older men, respectively. The application of supervised algorithms to the validation cohort (n=1303) yielded the same clusters, showing incremental cardiac remodelling from phenogroup A to phenogroup D. According to this myocardial continuum, there was a stepwise increase in overall mortality (adjusted hazard ratio for phenogroup D vs A 2.18, 95% confidence interval 1.46-3.26; P<0.001). CONCLUSIONS: Artificial intelligence re-emphasizes the significance of cardiac remodelling in the prognosis of patients with severe AS and highlights AS not only as an isolated valvular condition, but also a global disease.

Combining imaging flow cytometry and machine learning for high-throughput schistocyte quantification: A SVM classifier development and external validation cohort.

BACKGROUND: Schistocyte counts are a cornerstone of the diagnosis of thrombotic microangiopathy syndrome (TMA). Their manual quantification is complex and alternative automated methods suffer from pitfalls that limit their use. We report a method combining imaging flow cytometry (IFC) and artificial intelligence for the direct label-free and operator-independent quantification of schistocytes in whole blood. METHODS: We used 135,045 IFC images from blood acquisition among 14 patients to extract 188 features with IDEAS® software and 128 features from a convolutional neural network (CNN) with Keras framework in order to train a support vector machine (SVM) blood elements' classifier used for schistocytes quantification. FINDING: Keras features showed better accuracy (94.03%, CI: 93.75-94.31%) than ideas features (91.54%, CI: 91.21-91.87%) in recognising whole-blood elements, and together they showed the best accuracy (95.64%, CI: 95.39-95.88%). We obtained an excellent correlation (0.93, CI: 0.90-0.96) between three haematologists and our method on a cohort of 102 patient samples. All patients with schistocytosis (>1% schistocytes) were detected with excellent specificity (91.3%, CI: 82.0-96.7%) and sensitivity (100%, CI: 89.4-100.0%). We confirmed these results with a similar specificity (91.1%, CI: 78.8-97.5%) and sensitivity (100%, CI: 88.1-100.0%) on a validation cohort (n=74) analysed in an independent healthcare centre. Simultaneous analysis of 16 samples in both study centres showed a very good correlation between the 2 imaging flow cytometers (Y=1.001x). INTERPRETATION: We demonstrate that IFC can represent a reliable tool for operator-independent schistocyte quantification with no pre-analytical processing which is of most importance in emergency situations such as TMA. FUNDING: None.