Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort.

PURPOSE: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively. METHODS: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID. RESULTS: The ES diagnostic yield was 42 of 74 (57%). GS diagnoses were made in 9 of 32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8 of 9 single-nucleotide variations/copy-number variations undetected in older ES, confirming a GS-unique diagnostic rate of 1 in 32 (3%). Episignatures contributed diagnostic information in 9% with GS corroboration in 1 of 32 (3%) and diagnostic clues in 2 of 32 (6%). A genetic etiology for ID was detected in 51 of 74 (69%) families. Twelve candidate disease genes were identified. Contemporary ES followed by GS cost US$4976 (95% CI: $3704; $6969) per diagnosis and first-line GS at a cost of $7062 (95% CI: $6210; $8475) per diagnosis. CONCLUSION: Performing GS only in ID trios would be cost equivalent to ES if GS were available at $2435, about a 60% reduction from current prices. This study demonstrates that first-line GS achieves higher diagnostic rate than contemporary ES but at a higher cost.

Frailty Scales for Prognosis Assessment of Older Adult Patients after Acute Myocardial Infarction.

We aimed to compare the prognostic value of two different measures, the Fried's Frailty Scale (FFS) and the Clinical Frailty Scale (CFS), following myocardial infarction (MI). We included 150 patients ≥ 70 years admitted from AMI. Frailty was evaluated on the day before discharge. The primary endpoint was number of days alive and out of hospital (DAOH) during the first 800 days. Secondary endpoints were mortality and a composite of mortality and reinfarction. Frailty was diagnosed in 58% and 34% of patients using the FFS and CFS scales, respectively. During the first 800 days 34 deaths and 137 admissions occurred. The number of DAOH decreased significantly with increasing scores of both FFS (p < 0.001) and CFS (p = 0.049). In multivariate analysis, only the highest scores (FFS = 5, CFS ≥ 6) were independently associated with fewer DAOH. At a median follow-up of 946 days, frailty assessed both by FFS and CFS was independently associated with death and MI (HR = 2.70 95%CI = 1.32-5.51 p = 0.001; HR = 2.01 95%CI = 1.1-3.66 p = 0.023, respectively), whereas all-cause mortality was only associated with FFS (HR = 1.51 95%CI = 1.08-2.10 p = 0.015). Frailty by FFS or CFS is independently associated with shorter number DAOH post-MI. Likewise, frailty assessed by either scale is associated with a higher rate of death and reinfarction, whereas FFS outperforms CFS for mortality prediction.

Frailty Tools for Assessment of Long-term Prognosis After Acute Coronary Syndrome.

OBJECTIVE: To evaluate the 5 components of the Fried frailty phenotype (self-reported unintentional weight loss, physical activity questionnaire, gait speed, grip strength, and self-reported exhaustion) for long-term outcomes in elderly survivors of acute coronary syndrome. METHODS: A total of 342 consecutive patients (from October 1, 2010, to February 1, 2012) were included. The 5 components of the Fried score and albumin concentration, as malnutrition index, were assessed before hospital discharge. Patients were followed up until April 2020 (median follow-up, 8.7 years). The end point was postdischarge all-cause mortality. RESULTS: Mean ± SD age was 77±7 years and mean ± SD Fried score was 2.0±1.1 points. A total of 216 (63%) patients died. After adjusting for clinical covariates, the Fried phenotype was associated with mortality (per points, hazard ratio [HR], 1.35; 95% CI, 1.17 to 1.57; P<.001). Among Fried components, physical activity (HR, 2.21; 95% CI, 1.34 to 3.65; P=.002) and gait speed (HR, 1.77; 95% CI, 1.29 to 2.43; P<.001) were the deficits independendtly associated with mortality. Albumin level provided further prognostic information (per increase in g/dL; HR, 0.63, 95% CI, 0.45 to 0.88; P=.007). The model adding the components of the Fried score and albumin level to the clinical model showed the highest risk reclassification (integrated discrimination improvement, 0.040; 95% CI, 0.018 to 0.075; P=.001; continuous net reclassification improvement, 0.291; 95% CI, 0.132 to 0.397; P=.001) in comparison with the model using clinical covariates alone. CONCLUSION: Frailty assessment using the Fried phenotype has prognostic value for long-term mortality in elderly survivors of acute coronary syndrome. Physical activity and gait speed are the predictive components of the Fried score. Albumin level provides incremental prognostic information.

Undetectable high-sensitivity troponin in combination with clinical assessment for risk stratification of patients with chest pain and normal troponin at hospital arrival.

BACKGROUND: Undetectable high-sensitivity cardiac troponin (hs-cTn) in a single determination upon admission may rule out acute coronary syndrome. We investigated undetectable hs-cTnT (

The Assessment of Scales of Frailty and Physical Performance Improves Prediction of Major Adverse Cardiac Events in Older Adults with Acute Coronary Syndrome.

BACKGROUND: The number of older adults admitted to hospital for acute coronary syndrome (ACS) has increased worldwide. The aim of this study was to determine which scale of frailty or physical performance provides incremental improvements in risk stratification of older adults after ACS. METHODS: A prospective cohort of 402 older (≥70 years) ACS patients were enrolled. Data about baseline characteristics, Global Registry of Acute Coronary Events (GRACE), and Thrombolysis in Myocardial Infarction (TIMI) risk scores were collected. Before hospital discharge, seven scales of frailty and physical performance were measured. The 1-year occurrence of adverse events (cardiac death, reinfarction, and cerebrovascular accident [MACCE] and all-cause mortality) was recorded. RESULTS: Out of the 402 patients, 43 (10.5%) had a MACCE and 35 (8.7%) died. Following adjustment for confounding factors, scales of frailty and physical performance were associated with adverse events. Among the scales, the addition of short physical performance battery (SPPB) produced the highest incremental value over the initial model generated by baseline characteristics both for MACCE (ΔC-statistic 0.043, p = .04; integrated discrimination improvement (IDI) 0.054, p = .001; net reclassification improvement (NRI) 0.752, p < .001) and all-cause mortality (ΔC-statistic 0.063, p = .02; IDI 0.061, p < .001; NRI 1.022, p < .001). The addition of SPPB scale on top of GRACE or TIMI risk scores led to a considerable improvement in the prediction of MACCE and all-cause mortality (about 15% and 20%, respectively). CONCLUSIONS: The assessment of the physical performance with SPPB scale before hospital discharge increases the ability to predict adverse events in older ACS patients and may be useful in the clinical decision-making process. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov NCT02386124.

Contemporary differences between men and women with acute coronary syndromes: CIAM multicenter registry.

AIM: Differences exist in the diagnosis and treatment of acute coronary syndrome (ACS) between men and women. However, recent advancements in the management of ACSs might have attenuated this sex gap. We evaluated the status of ACS management in a multicenter registry in 10 tertiary Spanish hospitals. METHODS: We enrolled 1056 patients in our study, including only those with type 1 myocardial infarctions or unstable angina presumably not related to a secondary cause in an 'all-comers' design. RESULTS: The women enrolled (29%) were older than men (71.0 ±â€Š12.8 vs. 64.0 ±â€Š12.3, P = 0.001), with a higher prevalence of hypertension (71.0 vs. 56.5%, P < 0.001), insulin-treated diabetes (13.7 vs. 7.9%, P = 0.003), dyslipidemia (62.2 vs. 55.3%, P = 0.038), and chronic kidney disease (16.9 vs. 9.1%, P = 0.001). Women presented more frequently with back or arm pain radiation (57.3 vs. 49.7%, P = 0.025), palpitations (5.9 vs. 2.0%, P = 0.001), or dyspnea (33.0 vs. 19.4%, P = 0.001). ACS without significant coronary stenosis was more prevalent in women (16.8 vs. 8.1%, P = 0.001). There were no differences in percutaneous revascularization rates, but drug-eluting stents were less frequently employed in women (75.4 vs. 67.8%, P = 0.024); women were less often referred to a cardiac rehabilitation program (19.9 vs. 33.9%, P = 0.001). There were no significant differences in in-hospital complications such as thrombosis or bleeding. CONCLUSION: ACS presenting with atypical symptoms and without significant coronary artery stenosis is more frequent in women. Selection of either an invasive procedure or conservative management is not influenced by sex. Cardiac rehabilitation referral on discharge is underused, especially in women.

Number of drugs used in secondary cardiovascular prevention and late survival in the population of Valencia Community, Spain.

BACKGROUND: Drug treatment for secondary prevention of cardiovascular disease is recommended by guidelines, but it is not always followed in real life. This study wanted to assess the size of this gap and its impact on mortality in subjects after a cardiovascular event (MACE). METHODS: Patients with any of MACE in the period from January 1st 2011 to December 31st 2013, and more than one year of follow-up were selected from population of the Valencian Community. Drugs for secondary prevention were antiplatelets, renin-angiotensin system blockers and statins. Assessment of treatment was performed one year after the initial event. Mortality risk was assessed using Cox by the number of drug classes (G0 no medication, G1 one, G2 two and G3 three drugs) adjusted by confounders. RESULTS: A total of 92,436 patients (62% men, mean age 72 years) of whom 60.5% presented with stroke, 30.6% with myocardial infarction and 8.9% with revascularization were included. Among them, 4.1% were G0, 20.2% G1, 32.9% G2 and 42.7% G3. A progressive decrease in mortality was observed in G1 (HR 0.83, CI 95% 0.73-0.95), G2 (HR 0.70, CI 95% 0.60-0.82) and G3 (HR 0.61, CI95% 0.51-0.74) vs. G0. In diabetic subgroup, significant reduction of risk was observed in the G2 (0.79, CI 95% 0.63-0.98) and G3 (0.72, CI9 5% 0.56-0.95), but not in G1 (0.97, CI 95% 0.80-1.17). CONCLUSION: A gap between guidelines and reality in the use of cardiovascular protecting drugs one year after the initial event still exists and it is largely related with all-cause late mortality.

Comorbidity assessment for mortality risk stratification in elderly patients with acute coronary syndrome.

BACKGROUND: The Charlson's is the most used comorbidity index. It comprises 19 comorbidities, some of which are infrequent in elderly patients with acute coronary syndrome (ACS), while some others are manifestations of cardiac disease rather than comorbidities. Our goal was to simplify comorbidity assessment in elderly non-ST-segment elevation ACS patients. METHODS: The study group consisted of 1 training (n = 920, 76 ±â€¯7 years) and 1 testing (n = 532; 84 ±â€¯4 years) cohorts. The end-point was all-cause mortality at 1-year follow-up. Comorbidities were assessed selecting those medical disorders other than cardiac disease that were independently associated with mortality by multivariable analysis. RESULTS: A total of 130 (14%) patients died in the training cohort. Six comorbidities were predictive: renal failure, anemia, diabetes, peripheral artery disease, cerebrovascular disease and chronic lung disease. The increase in the number of comorbidities yielded a gradient of risk on top of well-known clinical predictors: ≥3 comorbidities (27% mortality, HR = 1.90, 95% CI 1.20-3.03, p = .006); 2 comorbidities (16% mortality, HR = 1.29, 95% CI 0.81-2.04, p = .30); and 0-1 comorbidities (7.6% mortality, reference category). The discrimination accuracy (C-statistic = 0.80) and calibration (Hosmer-Lemeshow test, p = .20) of the predictive model using the 6 comorbidities was comparable to the predictive model using the Charlson index (C-statistic = 0.80; Hosmer-Lemeshow test, p = .70). Similar results were reproduced in the testing cohort (≥3 comorbidities: 24% mortality, HR = 2.37, 95% CI 1.25-4.49, p = .008; 2 comorbidities: 14% mortality, HR = 1.59, 95% CI 0.82-3.07, p = .20; 0-1 comorbidities: 7.5% reference category). CONCLUSION: A simplified comorbidity assessment comprising 6 comorbidities provides useful risk stratification in elderly patients with ACS.

Recommendations of the Geriatric Cardiology Section of the Spanish Society of Cardiology for the Assessment of Frailty in Elderly Patients With Heart Disease.

Frailty is an age-associated clinical syndrome characterized by a decrease in physiological reserve in situations of stress, constituting a state of vulnerability that involves a higher risk of adverse events. Its prevalence in Spain is high, especially in elderly individuals with comorbidity and chronic diseases. In cardiovascular disease, frailty is associated worse clinical outcomes and higher morbidity and mortality in all scenarios, in both acute and chronic settings, and could consequently influence diagnosis and treatment. However, frailty is often not addressed or included when planning the management of elderly patients with heart disease. In this article, we review the available scientific evidence and highlight the most appropriate scales for the measurement and assessment of frailty, some of which are more useful and have better predictive capacity than others, depending on the clinical context. We also underline the importance of properly identifying and assessing frailty in order to include it in the treatment and care plan that best suits each patient.

Global Geriatric Assessment and In-Hospital Bleeding Risk in Elderly Patients with Acute Coronary Syndromes: Insights from the LONGEVO-SCA Registry.

BACKGROUND: Bleeding risk scores have shown a limited predictive ability in elderly patients with acute coronary syndromes (ACS). No study explored the role of a comprehensive geriatric assessment to predict in-hospital bleeding in this clinical setting. METHODS: The prospective multicentre LONGEVO-SCA registry included 532 unselected patients with non-ST segment elevation ACS (NSTEACS) aged 80 years or older. Comorbidity (Charlson index), frailty (FRAIL scale), disability (Barthel index and Lawton-Brody index), cognitive status (Pfeiffer test) and nutritional risk (mini nutritional assessment-short form test) were assessed during hospitalization. CRUSADE score was prospectively calculated for each patient. In-hospital major bleeding was defined by the CRUSADE classification. The association between geriatric syndromes and in-hospital major bleeding was assessed by logistic regression method and the area under the receiver operating characteristic curves (AUC). RESULTS: Mean age was 84.3 years (SD 4.1), 61.7% male. Most patients had increased troponin levels (84%). Mean CRUSADE bleeding score was 41 (SD 13). A total of 416 patients (78%) underwent an invasive strategy, and major bleeding was observed in 37 cases (7%). The ability of the CRUSADE score for predicting major bleeding was modest (AUC 0.64). From all aging-related variables, only comorbidity (Charlson index) was independently associated with major bleeding (per point, odds ratio: 1.23, p = 0.021). The addition of comorbidity to CRUSADE score slightly improved the ability for predicting major bleeding (AUC: 0.68). CONCLUSION: Comorbidity was associated with major bleeding in very elderly patients with NSTEACS. The contribution of frailty, disability or nutritional risk for predicting in-hospital major bleeding was marginal.

An Easy Assessment of Frailty at Baseline Independently Predicts Prognosis in Very Elderly Patients With Acute Coronary Syndromes.

BACKGROUND: Information about the impact of frailty in patients with acute coronary syndromes (ACS) is scarce. No study has assessed the prognostic impact of frailty as measured by the FRAIL scale in very elderly patients with ACS. METHODS: The prospective multicenter LONGEVO-SCA registry included unselected patients with ACS aged 80 years or older. A comprehensive geriatric assessment was performed during hospitalization, including frailty assessment by the FRAIL scale. The primary endpoint was mortality at 6 months. RESULTS: A total of 532 patients were included. Mean age was 84.3 years, 61.7% male. Most patients had positive troponin levels (84%) and high GRACE risk score values (mean 165). A total of 205 patients were classified as prefrail (38.5%) and 145 as frail (27.3%). Frail and prefrail patients had a higher prevalence of comorbidities, lower left ventricle ejection fraction, and higher mean GRACE score value. A total of 63 patients (11.8%) were dead at 6 months. Both prefrailty and frailty were associated with higher 6-month mortality rates (P < .001). After adjusting for potential confounders, this association remained significant (hazard ratio [HR] 2.71; 95% confidence interval [CI] 1.09-6.73 for prefrailty and HR 2.99; 95% CI 1.20-7.44 for frailty, P = .024). The other independent predictors of mortality were age, Charlson Index, and GRACE risk score. CONCLUSIONS: The FRAIL scale is a simple tool that independently predicts mortality in unselected very elderly patients with ACS. The presence of prefrailty criteria also should be taken into account when performing risk stratification of these patients.

Burden of Recurrent Hospitalizations Following an Admission for Acute Heart Failure: Preserved Versus Reduced Ejection Fraction.

INTRODUCTION AND OBJECTIVES: Heart failure with preserved ejection fraction and reduced ejection fraction share a high mortality risk. However, differences in the rehospitalization burden over time between these 2 entities remains unclear. METHODS: We prospectively included 2013 consecutive patients discharged for acute heart failure. Of these, 1082 (53.7%) had heart failure with preserved ejection fraction and 931 (46.2%) had heart failure with reduced ejection fraction. Cox and negative binomial regression methods were used to evaluate the risks of death and repeat hospitalizations, respectively. RESULTS: At a median follow-up of 2.36 years (interquartile range: 0.96-4.65), 1018 patients (50.6%) died, and 3804 readmissions were registered in 1406 patients (69.8%). Overall, there were no differences in mortality between heart failure with preserved ejection fraction and heart failure with reduced ejection fraction (16.7 vs 16.1 per 100 person-years, respectively; P=0794), or all-cause repeat hospitalization rates (62.1 vs 62.2 per 100 person-years, respectively; P=.944). After multivariable adjustment, and compared with patients with heart failure with reduced ejection fraction, patients with heart failure with preserved ejection fraction exhibited a similar risk of all-cause readmissions (incidence rate ratio=1.04; 95%CI, 0.93-1.17; P=.461). Regarding specific causes, heart failure with preserved ejection fraction showed similar risks of cardiovascular and heart failure-related rehospitalizations (incidence rate ratio=0.93; 95%CI, 0.82-1.06; P=.304; incidence rate ratio=0.96; 95% confidence interval, 0.83-1.13; P=.677, respectively), but had a higher risk of noncardiovascular readmissions (incidence rate ratio=1.24; 95%CI, 1.04-1.47; P=.012). CONCLUSIONS: Following an admission for acute heart failure, patients with heart failure with preserved ejection fraction have a similar rehospitalization burden to those with heart failure with reduced ejection fraction. However, patients with heart failure with preserved ejection fraction are more likely to be readmitted for noncardiovascular causes.

Clinical Evaluation Versus Undetectable High-Sensitivity Troponin for Assessment of Patients With Acute Chest Pain.

Decision-making in acute chest pain remains challenging despite normal (below ninety-ninth percentile) high-sensitivity troponin (hs-cTn). Some studies suggest that undetectable hs-cTn, far below the ninety-ninth percentile, might rule out acute coronary syndrome. We investigated clinical data in comparison to undetectable hs-cTnT. The study comprised 682 patients (November 2010 to September 2011) presenting at the emergency department with chest pain and normal hs-cTnT (<14 ng/l). The main end point was major adverse cardiac events (MACE: death, myocardial infarction, readmission for unstable angina, or revascularization) at a 4-year median follow-up; secondary end point was 30-day MACE. A clinical score was built by assigning points according to hazard ratios of the independent predictive variables: 1 point (male and effort-related pain) and 2 points (recurrent pain and prior ischemic heart disease). The negative predictive values of the clinical score and undetectable hs-cTnT (<5 ng/l), were tested. A total of 72 (10.6%) patients suffered long-term MACE. The C-statistics of the clinical score for long-term (0.75) and 30-day (0.88) MACE were higher than with the TIMI(Thrombolysis In Myocardial Infarction) risk (0.68, 0.77) or GRACE(Global Registry of Acute Coronary Events) (0.50, 0.47) scores. Likewise, the negative predictive values of score = 0 (97.5%, 100%) and ≤1 point (95.9%, 100%) were higher than using undetectable hs-cTnT (91.9%, 98.1%). Both clinical scores of 0 and ≤1 better classified patients at risk of MACE (p = 0.0001, log-rank test) than hs-cTnT <5 ng/l (p = 0.06). In conclusion, clinical data can guide decision-making and perform at least equally well as undetectable hs-cTnT, in patients presenting at the emergency department with chest pain and normal hs-cTnT.

Usefulness of delta troponin for diagnosis and prognosis assessment of non-ST-segment elevation acute chest pain.

BACKGROUND: The additional diagnostic and prognostic information provided by delta high-sensitivity troponin T (hs-cTnT) in patients with acute chest pain and hs-cTnT elevation remains unclear. METHODS: The study group consisted of 601 patients presenting at the emergency department with non-ST-segment elevation acute chest pain and hs-cTnT elevation after two determinations (admission and within the first six hours). Maximum hs-cTnT and delta hs-cTnT (absolute or percentage change between the two measurements) were considered. Cutoff values were optimized using the quartile distribution for the endpoints. The endpoints were diagnostic (significant stenosis in the coronary angiogram) and prognostic (death or recurrent myocardial infarction at one year). RESULTS: Regarding the diagnostic endpoint, 114 patients showed a normal angiogram. Both maximum hs-cTnT ⩾80 ng/ml (OR 2.5, 95% CI 1.3-4.8, P=0.005) and delta hs-cTnT ⩾20 ng/l (OR 2.1, 95% CI 1.1-4.0, P=0.02) median value cutoffs were related to significant coronary stenosis. Furthermore, the combination of hs-cTn <80 ng/l and delta hs-cTn <20 ng/l showed the lowest probability of significant coronary stenosis (OR 0.3, 95% CI 0.1-0.4, P=0.001). During follow-up, 86 patients experienced the prognostic endpoint. After full adjustment for clinical data, maximum hs-cTnT ⩾30 ng/l, first quartile cutoff, was related to the outcome (HR 1.8, 95% CI 1.0-3.4, P=0.05), while delta hs-cTnT, either absolute or percentage change, lacked prognostic value. CONCLUSIONS: Maximum hs-cTnT captures all the prognostic information provided by hs-cTnT in non-ST-segment elevation acute chest pain. Low maximum and low delta hs-cTnT are associated with a normal coronary angiogram, which could make the final diagnosis challenging in some cases.

Optimization of anemia treatment in hemodialysis patients via reinforcement learning.

OBJECTIVE: Anemia is a frequent comorbidity in hemodialysis patients that can be successfully treated by administering erythropoiesis-stimulating agents (ESAs). ESAs dosing is currently based on clinical protocols that often do not account for the high inter- and intra-individual variability in the patient's response. As a result, the hemoglobin level of some patients oscillates around the target range, which is associated with multiple risks and side-effects. This work proposes a methodology based on reinforcement learning (RL) to optimize ESA therapy. METHODS: RL is a data-driven approach for solving sequential decision-making problems that are formulated as Markov decision processes (MDPs). Computing optimal drug administration strategies for chronic diseases is a sequential decision-making problem in which the goal is to find the best sequence of drug doses. MDPs are particularly suitable for modeling these problems due to their ability to capture the uncertainty associated with the outcome of the treatment and the stochastic nature of the underlying process. The RL algorithm employed in the proposed methodology is fitted Q iteration, which stands out for its ability to make an efficient use of data. RESULTS: The experiments reported here are based on a computational model that describes the effect of ESAs on the hemoglobin level. The performance of the proposed method is evaluated and compared with the well-known Q-learning algorithm and with a standard protocol. Simulation results show that the performance of Q-learning is substantially lower than FQI and the protocol. When comparing FQI and the protocol, FQI achieves an increment of 27.6% in the proportion of patients that are within the targeted range of hemoglobin during the period of treatment. In addition, the quantity of drug needed is reduced by 5.13%, which indicates a more efficient use of ESAs. CONCLUSION: Although prospective validation is required, promising results demonstrate the potential of RL to become an alternative to current protocols.

A minimally invasive methodology based on morphometric parameters for day 2 embryo quality assessment.

The risk of multiple pregnancy to maternal-fetal health can be minimized by reducing the number of embryos transferred. New tools for selecting embryos with the highest implantation potential should be developed. The aim of this study was to evaluate the ability of morphological and morphometric variables to predict implantation by analysing images of embryos. This was a retrospective study of 135 embryo photographs from 112 IVF-ICSI cycles carried out between January and March 2011. The embryos were photographed immediately before transfer using Cronus 3 software. Their images were analysed using the public program ImageJ. Significant effects (P < 0.05), and higher discriminant power to predict implantation were observed for the morphometric embryo variables compared with morphological ones. The features for successfully implanted embryos were as follows: four cells on day 2 of development; all blastomeres with circular shape (roundness factor greater than 0.9), an average zona pellucida thickness of 13 µm and an average of 17695.1 µm² for the embryo area. Embryo size, which is described by its area and the average roundness factor for each cell, provides two objective variables to consider when predicting implantation. This approach should be further investigated for its potential ability to improve embryo scoring.