The Short-Term Efficacy of a Three-Week Pulmonary Rehabilitation Program among Patients with Obstructive Lung Diseases.

Introduction: The recommended duration for pulmonary rehabilitation stands at a minimum of six weeks; however, this stipulation may pose constraints in various countries due to financial limitations imposed by insurance companies and/or national health funds, as is the case in Poland. Consequently, our study endeavors to analyze the short-term outcomes stemming from a condensed three-week PR regimen administered to patients diagnosed with chronic obstructive pulmonary disease (COPD), asthma, and the concomitance of these conditions (COPD-A)-this is an approach that is standard in the rehabilitation protocols endorsed by our national health fund. Methods: Patients diagnosed with COPD, asthma, and COPD-A, referred to the PR program, underwent retrospective analysis to evaluate the short-term efficacy of a three-week PR program. Patients underwent comprehensive assessment by respiratory physicians and rehabilitation consultants, leading to individualized PR programs. Clinical evaluations occurred at program onset and completion. Results: 125 patients participated: 37 COPD, 61 asthma, and 27 COPD-A. Significant improvements were observed in the COPD Assessment Test (CAT), the consensus-based GINA symptom control tool (GINA-SCT), the Modified Medical Research Council (mMRC) scale, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and the 6-min walk test (6 MWT) distance, as well as in the St. George's Respiratory Questionnaire (SGRQ) scores. All groups experienced reduced dyspnea severity and improved exercise tolerance. FEV1 and FVC improved in asthma and COPD-A, but not significantly in COPD. Multivariable logistic regression identified predictive factors for PR response. Conclusions: The study supports the short-term efficacy of the three-week PR program in improving clinical outcomes, exercise tolerance, and quality of life in COPD and asthma patients. Tailoring interventions based on predictors of PR response can optimize outcomes. Further research, particularly of the COPD-A group, is needed for individualized approaches. Larger sample sizes are necessary to confirm our findings.

Literature review of spinal hematoma case reports: causes and outcomes in pediatric, obstetric, neuraxial and pain medicine cases.

BACKGROUND: The risk of spinal epidural hematoma (SEH) has been described in the literature but the impact in various patient populations has not been assessed in the same study. We identified the risk factors for SEH and calculated the OR for recovery in the pediatric, adult and obstetric (OB) patients based on the degree of neurological deficit before surgery. METHODS: Adult non-OB cases were categorized whether they were on anticoagulants or not; SEH was related to neuraxial or pain procedure; or whether there was adherence to the American Society of Regional Anesthesia (ASRA) guidelines. Eligible cases were identified through PubMed and Embase searches in the English literature from 1954 to July 2022. RESULTS: A total of 940 cases were evaluated. In the pediatric cases, SEH was typically spontaneous, related to coagulopathy or athletic trauma. OB cases were spontaneous or related to neuraxial injections. Among adults on anticoagulant(s), SEH was mostly spontaneous with no related etiology or related to neuraxial procedure. SEH occurred despite adherence to the ASRA guidelines. Among non-OB adults not on anticoagulants, SEH was due to trauma, neuraxial injections, surgery or other causes. Neurological recovery was related to the degree of neurological deficit before surgery. CONCLUSIONS: Our data show a preponderance of spontaneous SEH in all patient populations. SEH developed even though the ASRA guidelines were followed, especially in patients on multiple anticoagulants. Patients with less impairment prior to surgery had a higher likelihood of complete recovery, regardless of the interval between surgery and onset of symptoms.

Ultrasound-Guided Occipital Nerve Blocks as Part of Multi-Modal Perioperative Analgesia in Pediatric Posterior Craniotomies: A Case Series.

Various regional anesthetics have been used for postoperative analgesia for pediatric craniotomy. In this case series, we report retrospectively collected data on postoperative pain and analgesic use in 44 patients who received ultrasound-guided occipital nerve blocks in addition to intravenous analgesic agents for posterior craniotomy procedures. In the immediate post-anesthesia care unit, pain was rated as zero or well controlled in 77% of patients, with only 43% requiring intravenous or demand patient-controlled analgesia opioids. There were no block-related complications. Occipital nerve blocks may constitute a safe and effective component of multimodal analgesia in this population.

Towards a realistic prediction of catalyst durability from liquid half-cell tests.

Liquid half-cell measurements provide a convenient laboratory method for determining relevant parameters of electro-catalysts applied in e.g. polymer electrolyte membrane fuel cells. While these measurements may be effective in certain contexts, their applicability to real-world systems, such as single-cells in a membrane electrode assembly (MEA) configuration, is not always clear. This is particularly true when assessing the stability of these systems through accelerated stress tests (ASTs). Due to different electrode compositions and operating conditions, nanoscale degradation proceeds differently. Nevertheless, given the high demands of MEA measurements in terms of time, testing equipment complexity, and amount of catalyst material, application-relevant predictions of catalyst durability from liquid half-cell tests are highly desirable. This study combines electrochemical and nanoparticle analysis based on transmission electron microscopy to conduct a typical voltage cycling AST for rotating disc electrode (RDE) measurements, showing that the loss of the electrochemically active surface area (ECSA) of the used Pt/Vulcan catalyst is strongly enhanced at 80 °C compared to room temperature, which goes along with increased nanoparticle coarsening. Additionally, a high ionomer/carbon mass ratio (I/C = 0.7) accelerates the ECSA loss, and further investigations of its influence suggest a combination of several factors, including the high local proton concentration and the presence of adsorbing anions. At the same temperature (80 °C) and I/C ratio (0.7), the ECSA loss vs. AST cycle number of the Pt/Vulcan catalyst is essentially identical for a voltage cycling AST conducted in either an RDE half-cell or an MEA configuration, suggesting that liquid electrolyte half-cell based ASTs can provide application-relevant results. Thus, our study points out a way for predicting the stability of electro-catalysts in MEAs based on RDE experiments that require less specialized equipment and only µg-quantities of catalysts.

Three-dimensional nanoimaging of fuel cell catalyst layers.

Catalyst layers in proton exchange membrane fuel cells consist of platinum-group-metal nanocatalysts supported on carbon aggregates, forming a porous structure through which an ionomer network percolates. The local structural character of these heterogeneous assemblies is directly linked to the mass-transport resistances and subsequent cell performance losses; its three-dimensional visualization is therefore of interest. Herein we implement deep-learning-aided cryogenic transmission electron tomography for image restoration, and we quantitatively investigate the full morphology of various catalyst layers at the local-reaction-site scale. The analysis enables computation of metrics such as the ionomer morphology, coverage and homogeneity, location of platinum on the carbon supports, and platinum accessibility to the ionomer network, with the results directly compared and validated with experimental measurements. We expect that our findings and methodology for evaluating catalyst layer architectures will contribute towards linking the morphology to transport properties and overall fuel cell performance.

Surface Oxygen Depletion of Layered Transition Metal Oxides in Li-Ion Batteries Studied by Operando Ambient Pressure X-ray Photoelectron Spectroscopy.

A new operando spectro-electrochemical setup was developed to study oxygen depletion from the surface of layered transition metal oxide particles at high degrees of delithiation. An NCM111 working electrode was paired with a chemically delithiated LiFePO4 counter electrode in a fuel cell-inspired membrane electrode assembly (MEA). A propylene carbonate-soaked Li-ion conducting ionomer served as an electrolyte, providing both good electrochemical performance and direct probing of the NCM111 particles during cycling by ambient pressure X-ray photoelectron spectroscopy. The irreversible emergence of an oxygen-depleted phase in the O 1s spectra of the layered oxide particles was observed upon the first delithiation to high state-of-charge, which is in excellent agreement with oxygen release analysis via mass spectrometry analysis of such MEAs. By comparing the metal oxide-based O 1s spectral features to the Ni 2p3/2 intensity, we can calculate the transition metal-to-oxygen ratio of the metal oxide close to the particle surface, which shows good agreement with the formation of a spinel-like stoichiometry as an oxygen-depleted phase. This new setup enables a deeper understanding of interfacial changes of layered oxide-based cathode active materials for Li-ion batteries upon cycling.

Safety of antifibrinolytics in 6583 pediatric patients having craniosynostosis surgery: A decade of data reported from the multicenter Pediatric Craniofacial Collaborative Group.

BACKGROUND: Antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid are effective at reducing blood loss and transfusion in pediatric patients having craniofacial surgery. The Pediatric Craniofacial Collaborative Group has previously reported low rates of seizures and thromboembolic events (equal to no antifibrinolytic given) in open craniofacial surgery. AIMS: To query the Pediatric Craniofacial Collaborative Group database to provide an updated antifibrinolytic safety profile in children given that antifibrinolytics have become recommended standard of care in this surgical population. Additionally, we include the population of younger infants having minimally invasive procedures. METHODS: Patients in the Pediatric Craniofacial Collaborative Group registry between June 2012 and March 2021 having open craniofacial surgery (fronto-orbital advancement, mid and posterior vault, total cranial vault remodeling, intracranial LeFort III monobloc), endoscopic cranial suture release, and spring mediated cranioplasty were included. The primary outcome is the rate of postoperative complications possibly attributable to antifibrinolytic use (seizures, seizure-like activity, and thromboembolic events) in infants and children undergoing craniosynostosis surgery who did or did not receive antifibrinolytics. RESULTS: Forty-five institutions reporting 6583 patients were included. The overall seizure rate was 0.24% (95% CI: 0.14, 0.39%), with 0.20% in the no Antifibrinolytic group and 0.26% in the combined Antifibrinolytic group, with no statistically reported difference. Comparing seizure rates between tranexamic acid (0.22%) and epsilon-aminocaproic acid (0.44%), there was no statistically significant difference (odds ratio = 2.0; 95% CI: 0.6, 6.7; p = .257). Seizure rate was higher in patients greater than 6 months (0.30% vs. 0.18%; p = .327), patients undergoing open procedures (0.30% vs. 0.06%; p = .141), and syndromic patients (0.70% vs. 0.19%; p = .009). CONCLUSIONS: This multicenter international experience of pediatric craniofacial surgery reports no increase in seizures or thromboembolic events in those that received antifibrinolytics (tranexamic acid and epsilon-aminocaproic acid) versus those that did not. This report provides further evidence of antifibrinolytic safety. We recommend following pharmacokinetic-based dosing guidelines for administration.

On the role of pore constrictions in gas diffusion electrodes.

Water management by gas diffusion electrodes is a fundamental aspect of the performance of electrochemical cells. Herein, we introduce the characteristic constrictions size as a descriptor for microporous layers (MPL). This parameter is calculated by volumetric analysis of focused ion beam nanotomography and compared to mercury intrusion porosimetry measurements.

Patient and operative factors associated with unanticipated intensive care admission and outcomes following posterior fossa decompressions in children: A retrospective study.

INTRODUCTION: Posterior fossa decompression for Chiari I Malformation is a common pediatric neurosurgical procedure. We sought to identify the impact of anesthesia-related intraoperative complications on unanticipated admission to the intensive care unit and outcomes following posterior fossa decompression. METHODS: Medical records of all patients <18 years who underwent surgery for Chiari I malformation between 1/1/09 and 1/31/21 at the Ann & Robert H. Lurie Children's Hospital of Chicago were included. Records were reviewed for patient characteristics, anesthesia-related intraoperative complications, postoperative complications, and surgical outcomes. The primary outcome was the incidence of unanticipated admission to the intensive care unit, and the primary variable of interest was an anesthesia-related intraoperative complication. Patient, surgical characteristics, and year of surgery were also compared between patients with and without an unanticipated admission to the intensive care unit, and a multi-variable adjusted estimate of odds of unanticipated admission to the intensive care unit admission following an anesthesia-related intraoperative complication was performed. Secondary outcomes included anesthesia factors associated with an anesthesia-related intraoperative event, and postoperative complications and surgical outcomes between patients admitted to the intensive care unit and those who were not. RESULTS: Two hundred ninety-six patients with Chiari I Malformation were identified. Clinical characteristics associated with an unanticipated admission to the intensive care unit were younger age, American Society of Anesthesiologist (ASA) physical status >2 and an anesthesia-related intraoperative complication. 29 anesthesia-related intraoperative complications were observed in 25 patients (8.4%). Two of 25 patients (8%) with an anesthesia-related intraoperative complication compared with 3 of 271 (1%) patients without anesthesia-related intraoperative complication had an unanticipated admission to the intensive care unit, odds ratio 7.8 (95% CI 1.2-48.8, p = .010). When adjusted for age, sex, ASA physical status, presenting symptoms, concomitant syringomyelia, previous decompression surgery and year of surgery, the odds ratio for an unanticipated admission to the intensive care unit following an anesthesia-related intraoperative complication was 5.9 (95% CI 0.51-59.6, p = .149). There were no differences in surgical outcomes between patients with or without an unanticipated admission to the intensive care unit. CONCLUSION: Our study demonstrates that although anesthesia-related intraoperative complications during posterior fossa decompression are infrequent, they are associated with an increased risk of an unanticipated admission to the intensive care unit.

Providing Biological Plausibility for Exposure-Health Relationships for the Mycotoxins Deoxynivalenol (DON) and Fumonisin B1 (FB1) in Humans Using the AOP Framework.

Humans are chronically exposed to the mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1), as indicated by their widespread presence in foods and occasional exposure in the workplace. This exposure is confirmed by human biomonitoring (HBM) studies on (metabolites of) these mycotoxins in human matrices. We evaluated the exposure-health relationship of the mycotoxins in humans by reviewing the available literature. Since human studies did not allow the identification of unequivocal chronic health effects upon exposure to DON and FB1, the adverse outcome pathway (AOP) framework was used to structure additional mechanistic evidence from in vitro and animal studies on the identified adverse effects. In addition to a preliminary AOP for DON resulting in the adverse outcome (AO) 'reduced body weight gain', we developed a more elaborated AOP for FB1, from the molecular initiating event (MIE) 'inhibition of ceramide synthases' leading to the AO 'neural tube defects'. The mechanistic evidence from AOPs can be used to support the limited evidence from human studies, to focus FB1- and DON-related research in humans to identify related early biomarkers of effect. In order to establish additional human exposure-health relationships in the future, recommendations are given to maximize the information that can be obtained from HBM.

FUSE-ML: development and external validation of a clinical prediction model for mid-term outcomes after lumbar spinal fusion for degenerative disease.

BACKGROUND: Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. METHODS: Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. RESULTS: Models were developed and integrated into a web-app ( https://neurosurgery.shinyapps.io/fuseml/ ) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59-0.74], back pain (0.72, 95%CI: 0.64-0.79), and leg pain (0.64, 95%CI: 0.54-0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. CONCLUSIONS: Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk-benefit estimation, truly impacting clinical practice in the era of "personalized medicine" necessitates more robust tools in this patient population.

Healthcare utilization and satisfaction with treatment before and after direct discharge from the Emergency Department of simple stable musculoskeletal injuries in the Netherlands.

PURPOSE: To evaluate healthcare utilization and satisfaction with treatment before and after implementing direct discharge (DD) from the Emergency Department (ED) of patients with simple, stable musculoskeletal injuries. METHODS: Patients with simple, stable musculoskeletal injuries were included in two Dutch hospitals, both level-2 trauma centers: OLVG and Sint Antonius (SA), before (pre-DD-cohort) and after implementing DD (DD-cohort). With DD, no routine follow-up appointments are scheduled after the ED visit, supported by information leaflets, a smartphone application and a telephone helpline. Outcomes included: secondary healthcare utilization (follow-up appointments and X-ray/CT/MRI); satisfaction with treatment (scale 1-10); primary healthcare utilization (general practitioner (GP) or physiotherapist visited, yes/no). Linear regression was used to compare secondary healthcare utilization for all patients and per injury subgroup. Satisfaction and primary healthcare utilization were analyzed descriptively. RESULTS: A total of 2033 (OLVG = 1686; SA = 347) and 1616 (OLVG = 1396; SA = 220) patients were included in the pre-DD-cohort and DD-cohort, respectively. After DD, the mean number of follow-up appointments per patient reduced by 1.06 (1.13-0.99; p < 0.001) in OLVG and 1.07 (1.02-0.93; p < 0.001) in SA. Follow-up appointments reduced significantly for all injury subgroups. Mean number of follow-up X-rays per patient reduced by 0.17 in OLVG (p < 0.001) and 0.18 in SA (p < 0.001). Numbers of CT/MRI scans were low and comparable. In OLVG, mean satisfaction with treatment was 8.1 (pre-DD-cohort) versus 7.95 (DD-cohort), versus 7.75 in SA (DD-cohort only). In OLVG, 23.6% of pre-DD-cohort patients visited their GP, versus 26.1% in the DD-cohort, versus 13.3% in SA (DD-cohort only). Physiotherapist use was comparable. CONCLUSION: This study performed in a large population and additional hospital confirms earlier pilot results, i.e., that DD has the potential to effectively reduce healthcare utilization, while maintaining high levels of satisfaction. LEVEL OF EVIDENCE: II.

A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer.

Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.

Modelling the Renal Excretion of the Mycotoxin Deoxynivalenol in Humans in an Everyday Situation.

The dietary exposure to the mycotoxin deoxynivalenol (DON) can be assessed by human biomonitoring (HBM). Here, we assessed the relation between dietary DON intake and the excretion of its major metabolite DON-15-glucuronide (DON15GlcA) through time, in an everyday situation. For 49 volunteers from the EuroMix biomonitoring study, the intake of DON from each meal was calculated and the excretion of DON and its metabolites was analyzed for each urine void collected separately throughout a 24-h period. The relation between DON and DON15GlcA was analyzed with a statistical model to assess the residence time and the excreted fraction of ingested DON as DON15GlcA (fabs_excr). Fabs_excr was treated as a random effect variable to address its heterogeneity in the population. The estimated time in which 97.5% of the ingested DON was excreted as DON15GlcA was 12.1 h, the elimination half-life was 4.0 h. Based on the estimated fabs_excr, the mean reversed dosimetry factor (RDF) of DON15GlcA was 2.28. This RDF can be used to calculate the amount of total DON intake in an everyday situation, based on the excreted amount of DON15GlcA. We show that urine samples collected over 24 h are the optimal design to study DON exposure by HBM.

H2 Evolution from Electrocatalysts with Redox-Active Ligands: Mechanistic Insights from Theory and Experiment vis-à-vis Co-Mabiq.

Electrocatalytic hydrogen production via transition metal complexes offers a promising approach for chemical energy storage. Optimal platforms to effectively control the proton and electron transfer steps en route to H2 evolution still need to be established, and redox-active ligands could play an important role in this context. In this study, we explore the role of the redox-active Mabiq (Mabiq = 2-4:6-8-bis(3,3,4,4-tetramethlyldihydropyrrolo)-10-15-(2,2-biquinazolino)-[15]-1,3,5,8,10,14-hexaene1,3,7,9,11,14-N6) ligand in the hydrogen evolution reaction (HER). Using spectro-electrochemical studies in conjunction with quantum chemical calculations, we identified two precatalytic intermediates formed upon the addition of two electrons and one proton to [CoII(Mabiq)(THF)](PF6) (CoMbq). We further examined the acid strength effect on the generation of the intermediates. The generation of the first intermediate, CoMbq-H1, involves proton addition to the bridging imine-nitrogen atom of the ligand and requires strong proton activity. The second intermediate, CoMbq-H2, acquires a proton at the diketiminate carbon for which a weaker proton activity is sufficient. We propose two decoupled H2 evolution pathways based on these two intermediates, which operate at different overpotentials. Our results show how the various protonation sites of the redox-active Mabiq ligand affect the energies and activities of HER intermediates.

Liposomal Bupivacaine Versus Standard Bupivacaine in the Adductor Canal for Total Knee Arthroplasty: A Randomized, Controlled Trial.

Peripheral nerve blocks are commonly used in total knee arthroplasty (TKA). Liposomal bupivacaine is an extended-release anesthetic medication that maintains efficacy upwards of 72 hours. This study compared single-shot liposomal bupivacaine (LB) with the standard single-shot bupivacaine (SB) in a preoperative adductor canal block in TKA patients. A double-blind randomized, controlled trial at a single institution was performed in patients undergoing TKA. A standard preoperative single-shot adductor canal nerve injection was performed in 31 patients using 266 mg of liposomal bupivacaine (20 mL), whereas 32 patients received a standard formulation of 0.5% bupivacaine hydrogen chloride (20 mL). The primary outcome measure was postoperative gait velocity. Secondary outcomes included knee range of motion, pain scores, patient satisfaction, knee extension strength, opioid consumption, length of stay, and adverse events. There were no differences in baseline measures between groups. Improved pain ratings with activity (P=.009) were noted on postoperative day 1 with LB (mean, 4.4; SD, 2.0) compared with SB (mean, 5.9; SD, 2.6). Fewer opioids were used with LB compared with SB on postoperative day 1 (mean, 51.2 vs 66.1; P=.020) and on postoperative day 2 (mean, 39.5 vs 54.8; P=.016). No statistically significant differences in gait velocity, knee range of motion, knee extension strength, or patient satisfaction occurred. Peripheral nerve blockade with a single-shot adductor canal injection demonstrated improved pain scores with activity and diminished postoperative narcotic use when using LB compared with SB in TKA patients. There may be early postoperative advantages with LB as a single-shot injection in adductor canal blockade for patients undergoing TKA. [Orthopedics. 2021;44(4):249-255.].

A new electron diffraction approach for structure refinement applied to Ca3Mn2O7.

The digital large-angle convergent-beam electron diffraction (D-LACBED) technique is applied to Ca3Mn2O7 for a range of temperatures. Bloch-wave simulations are used to examine the effects that changes in different parameters have on the intensity in D-LACBED patterns, and atomic coordinates, thermal atomic displacement parameters and apparent occupancy are refined to achieve a good fit between simulation and experiment. The sensitivity of the technique to subtle changes in structure is demonstrated. Refined structures are in good agreement with previous determinations of Ca3Mn2O7 and show the decay of anti-phase oxygen octahedral tilts perpendicular to the c axis of the A21am unit cell with increasing temperature, as well as the robustness of oxygen octahedral tilts about the c axis up to ∼400°C. The technique samples only the zero-order Laue zone and is therefore insensitive to atom displacements along the electron-beam direction. For this reason it is not possible to distinguish between in-phase and anti-phase oxygen octahedral tilting about the c axis using the [110] data collected in this study.

Prognostic utility of the assessment of diastolic function in patients undergoing cardiac resynchronization therapy.

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.