Emergency Department and Inpatient Utilization Reductions and Cost Savings Associated With Trauma Center Mental Health Intervention: Results From a 5-year Longitudinal Randomized Clinical Trial Analysis.

OBJECTIVE: To identify and refer patients at high risk for the psychological sequelae of traumatic injury, the American College of Surgeons Committee on Trauma now requires that trauma centers have in-place protocols. No investigations have documented reductions in utilization and associated potential cost savings associated with trauma center mental health interventions. BACKGROUND: The investigation was a randomized clinical trial analysis that incorporated novel 5-year emergency department (ED)/inpatient health service utilization follow-up data. METHODS: Patients were randomized to a mental health intervention, targeting the psychological sequelae of traumatic injury (n = 85) versus enhanced usual care control (n = 86) conditions. The intervention included case management that coordinated trauma center-to-community care linkages, psychotropic medication consultation, and psychotherapy elements. Mixed model regression was used to assess intervention and control group utilization differences over time. An economic analysis was also conducted. RESULTS: Over the course of the 5-year intervention, patients demonstrated significant reductions in ED/inpatient utilization when compared with control patients [ F (19,3210) = 2.23, P = 0.009]. Intervention utilization reductions were greatest at 3 to 6 months (intervention 15.5% vs control 26.7%, relative risk = 0.58, 95% CI: 0.34, 1.00) and 12 to 15 months (intervention 16.5% vs control 30.6%, relative risk = 0.54, 95% CI: 0.32, 0.91) postinjury time points. The economic analysis suggested potential intervention cost savings. CONCLUSIONS: Mental health intervention is associated with significant reductions in ED and inpatient utilization, as well as potential cost savings. These findings could be productively integrated into future American College of Surgeons Committee on Trauma policy discussions.

Contemporary transcatheter aortic valve implantation related thrombocytopenia.

BACKGROUND: Transcatheter aortic valve implantation related thrombocytopenia (TAVI-rTP) is an inevitable phenomenon. However, no study has been performed on TAVI-rTP in the current setting of extended clinical indications combined with technology improvements. METHODS: Patients with severe symptomatic aortic stenosis who underwent transfemoral TAVI, from January 2016 to December 2019 were enrolled. RESULTS: Two-hundred and one consecutive patients (mean age 81.1 ± 7.1 years, 96 men) enrolled. Platelet count was recorded before and after aortic valve implantation. Dropped platelet count (DPC) occurred in all but 11 patients who were included. Two groups were created: DPC <30 and DPC ≥30%. DPC was compared with in-hospital major adverse cardiovascular events. The mean DPC was 26 ± 14%. We found that 67 patients (33.3%) had DPC of more or equal to 30%. In the univariable analysis, the time of the procedure (94.4 ± 32.7 vs 79.4 ± 21.9, p = .002), the amount of the contrast used (125.4 ± 55.4 vs 108.4 ± 44.1, p = .02) and the residual AV gradient (13.3 ± 7.2 vs 14.7, p = .05) were related to a DCP ≥30%. A DPC ≥30% was associated with increased risk of life-threatening/major bleeding (11.9% vs 1.5%, p = .001), major vascular complications (16.4% vs 5.2% p = .009) and death (3.0% vs 0%, p = .044) at 30 days. After multivariable analysis, the factors associated with a higher DPC were time and contrast. CONCLUSION: Contemporary TAVI-rTP in this cohort of patients continues to be a common phenomenon but severe thrombocytopenia is less frequent. Patients developing a DPC ≥30% are associated with poor outcomes at 30 days.

Natural Anti-Endothelial Cell Antibodies in Patients Undergoing Coronary Angiography.

BACKGROUND: Anti-endothelial cell antibodies (AECA) are a known biomarker of endothelial dysfunction and damage in clinical practice, especially in autoimmune disease. OBJECTIVES: To determine the relation between natural AECA levels and prognosis related to coronary artery disease. METHODS: Candidates for coronary angiography were prospectively enrolled. AECA levels were determined by ELISA assay. Mortality was evaluated after more than 5 years follow-up. RESULTS: Of a total 857 patients, 445 had high AECA levels (group 1) and 412 had low levels (< 1 OD unit, group 2). Both groups did not differ in age, sex, or presence of diabetes. The median follow up was 2293 days (76 months). Patients with high AECA levels were more likely to have normal coronary arteries on angiography (21.6% vs. 16.9%, P = 0.047) and less likely to have calcified lesions (19.0% vs. 26.6%, P = 0.028) and lower prevalence of abnormal renal functions (71.1 mg/dl vs. 66.5 mg/dl, P = 0.033). Patients with higher AECA levels had lower mortality levels (20.1% vs. 27.6%, P = 0.006). A logistic regression model demonstrated independent association between lower AECA levels and the presence of coronary atherosclerosis based on angiogram. CONCLUSIONS: After a median of more than 6 years, higher natural AECA levels were associated with less coronary artery disease and lower mortality rates in patients undergoing coronary angiography.

Whole exome sequencing unravels disease-causing genes in consanguineous families in Qatar.

Whole exome sequencing (WES) has greatly facilitated the identification of causal mutations for diverse human genetic disorders. We applied WES as a molecular diagnostic tool to identify disease-causing genes in consanguineous families in Qatar. Seventeen consanguineous families with diverse disorders were recruited. Initial mutation screening of known genes related to the clinical diagnoses did not reveal the causative mutations. Using WES approach, we identified the definitive disease-causing mutations in four families: (i) a novel nonsense homozygous (c.1034C>G) in PHKG2 causing glycogen storage disease type 9C (GSD9C) in a male with initial diagnosis of GSD3; (ii) a novel homozygous 1-bp deletion (c.915del) in NSUN2 in a male proband with Noonan-like syndrome; (iii) a homozygous SNV (c.1598C>G) in exon 11 of IDUA causing Hurler syndrome in a female proband with unknown clinical diagnosis; (iv) a de novo known splicing mutation (c.1645+1G>A) in PHEX in a female proband with initial diagnosis of autosomal recessive hypophosphatemic rickets. Applying WES as a diagnostic tool led to the unambiguous identification of disease-causing mutations in phenotypically complex disorders or correction of the initial clinical diagnosis in ˜25% of our cases.

Engaging and following physical injury survivors at risk for developing posttraumatic stress disorder symptoms: A 25 site US national study.

INTRODUCTION: Early intervention for patients at risk for Posttraumatic Stress Disorder (PTSD) relies upon the ability to engage and follow trauma-exposed patients. Recent requirements by the American College of Surgeons Committee on Trauma (College) have mandated screening and referral for patients with high levels of risk for the development of PTSD or depression. Investigations that assess factors associated with engaging and following physically injured patients may be essential in assessing outcomes related to screening, intervention, and referral. METHODS: This investigation was a secondary analysis of data collected as part of a United States level I trauma center site randomized clinical trial. All 635 patients were ages ≥18 and had high PTSD symptom levels (i.e., DSM-IV PTSD Checklist score ≥35) at the time of the baseline trauma center admission. Baseline technology use, demographic, and injury characteristics were collected for patients who were followed up with over the course of the year after physical injury. Regression analyses were used to assess the associations between technology use, demographic and injury characteristics, and the attainment of follow-up outcome assessments. RESULTS: Thirty-one percent of participants were missing one or more 3-, 6- or 12-month follow-up outcome assessments. Increased risk of missing one or more outcome assessments was associated with younger age (18-30 versus ≥55 Relative Risks [RR] = 1.78, 95 % Confidence Interval [CI] = 1.09, 2.91), lack of cell phone (RR = 1.32, 95 % CI = 1.01, 1.72), no internet access (RR = 1.47, 95 % CI = 1.01, 2.16), public versus private insurance (RR = 1.47, 95 % CI = 1.12, 1.92), having no chronic medical comorbidities (≥4 versus none, RR = 0.28, 95 % CI = 0.20, 0.39), and worse pre-injury mental health function (RR = 0.99, 95 % CI = 0.98, 0.99). CONCLUSIONS: This multisite investigation suggests that younger and publicly insured and/or uninsured patients with barriers to cell phone and internet access may be particularly vulnerable to lapses in trauma center follow-up. Clinical research informing trauma center-based screening, intervention, and referral procedures could productively explore strategies for patients at risk for not engaging and adhering to follow-up care and outcome assessments.

Stepped collaborative care versus American College of Surgeons Committee on Trauma required screening and referral for posttraumatic stress disorder: Clinical trial protocol.

BACKGROUND: Each year in the US, approximately 1.5-2.5 million individuals are so severely injured that they require inpatient hospital admissions. The American College of Surgeons Committee on Trauma (College) now requires that trauma centers have in place protocols to identify and refer hospitalized patients at risk injury psychological sequelae. Literature review revealed no investigations that have identified optimal screening, intervention, and referral procedures in the wake of the College requirement. METHODS: The single-site pragmatic trial investigation will individually randomize 424 patients (212 intervention and 212 control) to a brief stepped care intervention versus College required mental health screening and referral control conditions. Blinded follow-up interviews at 1-, 3-, 6-, and 12-months post-injury will assess the symptoms of PTSD and related comorbidity for all patients. The emergency department information exchange (EDIE) will be used to capture population-level automated emergency department and inpatient utilization data for the intent-to-treat sample. The investigation aims to test the primary hypotheses that intervention patients will demonstrate significant reductions in PTSD symptoms and emergency department/inpatient utilization when compared to control patients. The study incorporates a Rapid Assessment Procedure-Informed Clinical Ethnography (RAPICE) implementation process assessment. CONCLUSIONS: The overarching goal of the investigation is to advance the sustainable delivery of high-quality trauma center mental health screening, intervention, and referral procedures for diverse injury survivors. An end-of-study policy summit will harness pragmatic trial data to inform the capacity for US trauma centers to implement high-quality acute care mental health screening, intervention and referral services for diverse injured patient populations. TRIAL REGISTRATION: Clinicaltrials.govNCT05632770.

Can stepped collaborative care interventions improve post-traumatic stress disorder symptoms for racial and ethnic minority injury survivors?

Objectives: No large-scale randomized clinical trial investigations have evaluated the potential differential effectiveness of early interventions for post-traumatic stress disorder (PTSD) among injured patients from racial and ethnic minority backgrounds. The current investigation assessed whether a stepped collaborative care intervention trial conducted at 25 level I trauma centers differentially improved PTSD symptoms for racial and ethnic minority injury survivors. Methods: The investigation was a secondary analysis of a stepped wedge cluster randomized clinical trial. Patients endorsing high levels of distress on the PTSD Checklist (PCL-C) were randomized to enhanced usual care control or intervention conditions. Three hundred and fifty patients of the 635 randomized (55%) were from non-white and/or Hispanic backgrounds. The intervention included care management, cognitive behavioral therapy elements and, psychopharmacology addressing PTSD symptoms. The primary study outcome was PTSD symptoms assessed with the PCL-C at 3, 6, and 12 months postinjury. Mixed model regression analyses compared treatment effects for intervention and control group patients from non-white/Hispanic versus white/non-Hispanic backgrounds. Results: The investigation attained between 75% and 80% 3-month to 12-month follow-up. The intervention, on average, required 122 min (SD=132 min). Mixed model regression analyses revealed significant changes in PCL-C scores for non-white/Hispanic intervention patients at 6 months (adjusted difference -3.72 (95% CI -7.33 to -0.10) Effect Size =0.25, p<0.05) after the injury event. No significant differences were observed for white/non-Hispanic patients at the 6-month time point (adjusted difference -1.29 (95% CI -4.89 to 2.31) ES=0.10, p=ns). Conclusion: In this secondary analysis, a brief stepped collaborative care intervention was associated with greater 6-month reductions in PTSD symptoms for non-white/Hispanic patients when compared with white/non-Hispanic patients. If replicated, these findings could serve to inform future American College of Surgeon Committee on Trauma requirements for screening, intervention, and referral for PTSD and comorbidities. Level of evidence: Level II, secondary analysis of randomized clinical trial data reporting a significant difference. Trial registration number: NCT02655354.

Advancing Concerns of Spanish-Speaking Physical Injury Survivors: Equitable Trauma Care System Service Delivery.

Objective: Few investigations have focused specifically on engaging Spanish-speaking patients in early post-injury comparative effectiveness trials. The goal of this study was to identify and categorize hospitalized Spanish-speaking injury survivors' posttraumatic concerns. Method: A secondary analysis of baseline data collected as part of a larger randomized comparative effectiveness trial was conducted. Participants were 22 male and female Spanish, non-English, speaking survivors of intentional and unintentional injuries, ages ≥ 18. At baseline, while hospitalized, each patient was asked to describe the nature and severity of their post-injury concerns. Patient concern narratives were audio-recorded and later transcribed. Raters coded patients' transcribed concerns into content domains. The associations between patient self-reported concern severity and posttraumatic stress disorder symptoms assessed with the PTSD Checklist and depressive symptoms assessed with the PHQ-9 were also ascertained. Results: The concerns of Spanish-speaking patients were reliably categorized into previously described content domains (i.e., work and finance, physical health, social, psychological, medical, and legal domains). The composite Kappa statistic across domains was 0.83 (95% Confidence Interval = 0.74, 0.92). Spanish-speaking patients also expressed novel concerns, including immigration, discriminatory experiences, and Coronavirus pandemic, related concerns. The number of severe patient concerns was highly correlated with PHQ-9 depressive symptom levels (r = 0.52, p < .05). Conclusions: The concerns of Spanish-speaking trauma survivors can be readily elicited and reliably interpreted. Future research could integrate concern narrative elicitation and amelioration into stepped care intervention procedures in order to engage diverse Spanish-speaking injury survivors and advance equitable trauma care system service delivery.

Integrating pragmatic and implementation science randomized clinical trial approaches: a PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) analysis.

BACKGROUND: Over the past two decades, pragmatic and implementation science clinical trial research methods have advanced substantially. Pragmatic and implementation studies have natural areas of overlap, particularly relating to the goal of using clinical trial data to leverage health care system policy changes. Few investigations have addressed pragmatic and implementation science randomized trial methods development while also considering policy impact. METHODS: The investigation used the PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) and PRECIS-2-Provider Strategies (PRECIS-2-PS) tools to evaluate the design of two multisite randomized clinical trials that targeted patient-level effectiveness outcomes, provider-level practice changes and health care system policy. Seven raters received PRECIS-2 training and applied the tools in the coding of the two trials. Descriptive statistics were produced for both trials, and PRECIS-2 wheel diagrams were constructed. Interrater agreement was assessed with the Intraclass Correlation (ICC) and Kappa statistics. The Rapid Assessment Procedure Informed Clinical Ethnography (RAPICE) qualitative approach was applied to understanding integrative themes derived from the PRECIS-2 ratings and an end-of-study policy summit. RESULTS: The ICCs for the composite ratings across the patient and provider-focused PRECIS-2 domains ranged from 0.77 to 0.87, and the Kappa values ranged from 0.25 to 0.37, reflecting overall fair-to-good interrater agreement for both trials. All four PRECIS-2 wheels were rated more pragmatic than explanatory, with composite mean and median scores ≥ 4. Across trials, the primary intent-to-treat analysis domain was consistently rated most pragmatic (mean = 5.0, SD = 0), while the follow-up/data collection domain was rated most explanatory (mean range = 3.14-3.43, SD range = 0.49-0.69). RAPICE field notes identified themes related to potential PRECIS-2 training improvements, as well as policy themes related to using trial data to inform US trauma care system practice change; the policy themes were not captured by the PRECIS-2 ratings. CONCLUSIONS: The investigation documents that the PRECIS-2 and PRECIS-2-PS can be simultaneously used to feasibly and reliably characterize clinical trials with patient and provider-level targets. The integration of pragmatic and implementation science clinical trial research methods can be furthered by using common metrics such as the PRECIS-2 and PRECIS-2-PS. Future study could focus on clinical trial policy research methods development. TRIAL REGISTRATION: DO-SBIS ClinicalTrials.gov NCT00607620. registered on January 29, 2008. TSOS ClinicalTrials.gov NCT02655354, registered on July 27, 2015.

Predictors of Inappropriately Rapid Coronary Lesion Progression in Patients Undergoing Percutaneous Coronary Interventions.

Background: Patients undergoing percutaneous coronary intervention (PCI) may experience rapid atherosclerotic plaque progression in nontreated vessels that is unlikely to result from natural de novo atherosclerosis. We hypothesize that intra-lesion bleeding plays a central role in this process. The aim of this study is to investigate the factors that may contribute to accelerated narrowing in coronary diameter. Methods: We reviewed 65 interventional procedures and their consequent staged PCIs and mapped the coronary tree into 16 segments (as divided by the American Heart Association), grading the percentage of stenosis in each segment and spotting the rapidly progressing lesions. Demographic, procedural, and laboratory data were recorded and analyzed. Results: For the lesions that progressed rapidly in the time period between angiographies, the administration of eptifibatide intra-procedurally was associated with rapid progression of coronary lesions. Moreover, an increased white blood cell count prior to the index procedure was also associated with a trend toward rapid plaque progression. Conclusions: In this hypothesis-generating study, treatment with a IIb/IIIa inhibitor in the index PCI was associated with an accelerated short-term progression of some of the nontreated lesions, suggesting that this mode of anti-aggregation therapy could facilitate plaque hemorrhage and consequent acceleration of coronary atherosclerosis in eroded plaques.

Contexte: Les patients qui subissent une intervention coronarienne percutanée (ICP) peuvent présenter une progression rapide de plaques d'athérosclérose dans des vaisseaux non traités, phénomène qui n'est probablement pas le résultat d'une athérosclérose de novo naturelle. Nous formulons l'hypothèse qu'un saignement intralésionnel jouerait un rôle central dans ce processus. Cette étude vise à explorer les facteurs qui pourraient contribuer à l'accélération de la réduction du diamètre coronarien. Méthodologie: Nous avons étudié 65 interventions et les ICP en plusieurs étapes qui s'en étaient suivies, ainsi que divisé l'arbre coronarien en 16 segments (conformément à la segmentation de l'American Heart Association), afin d'évaluer le pourcentage de sténose dans chaque segment et de repérer les lésions qui progressaient rapidement. Les données démographiques et celles relatives aux interventions et aux résultats de laboratoire ont été consignées et analysées. Résultats: En ce qui concerne les lésions qui avaient progressé rapidement durant l'intervalle entre les angiographies, l'administration d'éptifibatide lors de l'intervention semblait être un facteur contributif. De plus, un nombre accru de leucocytes avant l'intervention initiale a également été associé à une évolution rapide des plaques. Conclusions: Dans le cadre de cette étude servant à émettre une hypothèse, le traitement par un inhibiteur de la glycoprotéine IIb-IIIa lors de l'ICP initiale a été associé à une accélération de la progression à court terme de certaines lésions non traitées, ce qui laisse croire que ce mode de traitement antiagrégant pourrait favoriser les hémorragies intraplaques et l'accélération de l'athérosclérose coronarienne dans les plaques érodées.

Validation of the FENCE Risk Groups for Prediction of Febrile Neutropenia With First-Cycle Chemotherapy.

BACKGROUND: The FEbrile Neutropenia after ChEmotherapy (FENCE) score was developed to estimate the risk of febrile neutropenia (FN) at first cycle of chemotherapy but has not been externally validated. We aimed to validate the FENCE score based on its risk groups in patients treated at a comprehensive cancer center. METHODS: We conducted a retrospective study of treatment-naïve adult patients with solid tumors and diffuse large B-cell lymphoma who received first-cycle chemotherapy between January and November 2019. Patients were followed until the second cycle of chemotherapy to identify any FN events (neutrophil count <0.5 × 109/L with fever ≥38.2°C). The FENCE score was determined and patients classified as low, intermediate, high, and very high risk. The discriminatory ability of classifying patients into FENCE risk groups was calculated as the area under the receiver operating characteristics curve and incidence rate ratios within each FENCE risk group. RESULTS: FN was documented during the first cycle of chemotherapy in 45 of the 918 patients included (5%). The area under the receiver operating characteristics curve was 0.66 (95% confidence interval [CI] = 0.58 to 0.73). Compared with the low-risk group (n = 285), the incidence rate ratio of developing FN was 1.58 (95% CI = 0.54 to 5.21), 3.16 (95% CI = 1.09 to 10.25), and 3.93 (95% CI = 1.46 to 12.27) in the intermediate (n = 293), high (n = 162), and very high (n = 178) risk groups, respectively. CONCLUSIONS: In this study, classifying patients into FENCE risk groups demonstrated moderate discriminatory ability for predicting FN. Further validation in multicenter studies is necessary to determine its generalizability.

Trends in Transfemoral Aortic Valve Implantation Related Thrombocytopenia.

BACKGROUND: TAVI related thrombocytopenia (TAVI-rTP) is still very common. The aim of this study was to compare the incidence, characteristics and impact of reduced platelet counts (RPC) after TAVI between an earlier and contemporary period. METHODS: the patients enrolled were those experiencing severe symptomatic aortic stenosis who underwent TAVI between January 2010 and December 2019. The exclusion criteria were no available blood tests and periprocedural death. RESULTS: 334 patients (mean age 81.9 ± 6.7 years) were enrolled. For the earlier period, the mean RPC was 33 ± 15%, and in the contemporary period (2016-2019) it was 26 ± 14%. In the early group, we found that 62% of the patients had decreased platelet counts of more or equal to 30% in comparison to 33% in the contemporary period. The time of the procedure and the amount of the contrast that had been used in the later period were associated with significant RPCs (p value = 0.002 and 0.028, respectively). An RPC of 30% or more was associated with the increased risks of life-threatening bleeding, vascular complications and death within 30 days. CONCLUSION: contemporary TAVI-rTP continued to be a common phenomenon in our cohort. However, severe thrombocytopenia was significantly less frequent. An RPC of 30% or more is associated with a poor 30-day outcome.

Mid-Term Clinical Outcomes Following Drug-Coated Balloons in Coronary Artery Disease.

OBJECTIVE: The aim of this study was to evaluate the mid-term efficacy of drug-coated balloons (DCB) in percutaneous coronary intervention (PCI) in two different pathophysiologic scenarios. BACKGROUND: There are different underlying pathological processes in coronary artery disease. Mid-term safety and efficacy of DCB approach is still limited. METHODS: Medical records of all consecutive patients undergoing DCB were evaluated. The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) after 24 months. RESULTS: Between January 2011 and December 2017, 442 patients were included, representing 4.4% of all PCIs in our institution. A total of 460 DCB lesions were treated, of which 328 (71.3%) were de novo and 132 (28.7%) were combined bare metal or drug-eluting stents with in-stent restenosis (ISR). The patients' mean age was 66.2 ± 11.7 years with a diabetes prevalence of 45.3%. The TLR rate was lower in the de novo group (5.3%) compared to the ISR group (9.4%) (p = 0.04). No differences were observed in major adverse cardiovascular events (MACE) between the de novo group (38.9%) and ISR group (42.5%) (p = 0.47). No significant differences were detected in the TLR occurrence in the subgroup analysis. CONCLUSION: Our extended experience demonstrates that the mid-term DCB approach in these two pathophysiologic settings represent a reasonable option, with low TLR rate.

Differential systemic inflammatory responses after TAVI: The role of self versus balloon expandable devices.

OBJECTIVE: Transcatheter aortic valve implantation (TAVI) provokes early injury response, represented in part by dynamic changes in the inflammatory markers. The association of self-expanding valves (SEVs) and balloon-expandable valves (BEVs) with the consequent inflammatory response remains uncertain. MATERIALS AND METHODS: Patients with severe symptomatic aortic stenosis who underwent transfemoral TAVI: SEVs or BEVs, from January 2010 to December 2019 were enrolled. Whole white blood cells (WBC) and subpopulation dynamics as well the neutrophil to lymphocyte ratio (NLR) were evaluated. RESULTS: Three-hundred seventy consecutive patients (mean age 81.75 ± 6.8 years, 199 women's) were enrolled. In the entire population, significant kinetic changes in the WBC response (p <0.0001) between admission and first 24 hours post procedure, with a significant increase in total WBC (7.46 ± 2.26 to 10.08 ± 3.55) and absolute neutrophil count (4.97 ± 2.06 to 8.19 ± 3.43), NL ratio (3.72 ± 2.8 to 9.76 ± 7.29), and a meaningful decrease in absolute lymphocytes count (1.67 ± 1.1 to 1.1 ± 0.76). When compared between the types of valves, SEVs were associated with a more pronounced inflammatory response than BEVs, with total WBC (10.44 ± 3.86 vs. 9.45 ± 3.19) neutrophils (8.56 ± 3.75 vs. 7.55 ± 3.06) with p 0.016 and 0.012 respectively. CONCLUSION: This is the first description of a differential inflammatory response between the two leading delivery systems. SEV appears to trigger a more robust inflammatory response as compared to BEV. Clinical studies are warranted to assess the long term effect of our findings.

Comparative Analysis of the Kinetic Behavior of Systemic Inflammatory Markers in Patients with Depressed versus Preserved Left Ventricular Function Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Prior studies have proven the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with reduced left ventricular (LV) function. This study's aim was to investigate periprocedural inflammatory responses after TAVI. METHODS: Patients with severe symptomatic aortic stenosis and reduced LV function who underwent transfemoral TAVI were enrolled. A paired-matched analysis (1:2 ratio) was performed using patients with preserved LV function. Whole white blood cells (WBC) and subpopulation dynamics as well as the neutrophil to lymphocyte ratio (NLR) were evaluated at different times. RESULTS: A total of 156 patients were enrolled, including 52 patients with LVEF < 40% 35.00 [30.00, 39.25] and 104 with LVEF > 50% 55.00 [53.75, 60.0], p < 0.001. Baseline NLR in the reduced LV function group was significantly higher compared to the preserved LV function group, 2.85 [2.07, 4.78] vs. 3.90 [2.67, 5.26], p < 0.04. After a six-month follow-up, the inflammatory profile was found to be similar in the two groups, NLR 2.94 [2.01, 388] vs. 3.30 [2.06, 5.35], p = 0.288. No significant mortality differences between the two groups were observed in the long-term outcome. CONCLUSIONS: TAVI for severe symptomatic aortic stenosis, with reduced LV function, was associated with an improvement in the inflammatory profile that may account for some of the observable benefits of the procedure in this subset of patients.

Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Features.

Sotos syndrome, characterized by intellectual disability and characteristic facial features, is caused by haploinsufficiency in the NSD1 gene. We conducted an etiological study on two siblings with Sotos features without mutations in NSD1 and detected a homozygous frameshift mutation in the APC2 gene by whole-exome sequencing, which resulted in the loss of function of cytoskeletal regulation in neurons. Apc2-deficient (Apc2-/-) mice exhibited impaired learning and memory abilities along with an abnormal head shape. Endogenous Apc2 expression was downregulated by the knockdown of Nsd1, indicating that APC2 is a downstream effector of NSD1 in neurons. Nsd1 knockdown in embryonic mouse brains impaired the migration and laminar positioning of cortical neurons, as observed in Apc2-/- mice, and this defect was rescued by the forced expression of Apc2. Thus, APC2 is a crucial target of NSD1, which provides an explanation for the intellectual disability associated with Sotos syndrome.