Microneedling in Combination with Topical Pimecrolimus 1% versus Topical Pimecrolimus 1% for the Treatment of Refractory Stable Vitiligo: A Randomized Clinical Trial

Objective. Vitiligo is a common, autoimmune disease that results in the destruction of the melanocytes and manifests as depigmented macules on various areas of the skin. Numerous treatment options have been proposed for vitiligo. The purpose of this study was to compare the efficacy of microneedling plus topical pimecrolimus 1% versus the sole use of topical pimecrolimus 1% for the treatment of vitiligo. Methods. This clinical trial was conducted on 30 skin lesions on 15 Al-Zahra hospital patients. Each patient had two similar lesions in the limb area, and each lesion was considered a separate treatment group. The left or right side of the patient’s lesion was randomly assigned to receive microneedling plus topical pimecrolimus for three months, while the other side received only topical pimecrolimus 1%. As part of the follow-up, digital photography was taken at the baseline and biweekly for three months after treatment and six months’ follow-up. The following methods were used to evaluate the results: DLQI questionnaires, patient satisfaction questionnaires, and two independent dermatologists comparing the improvement rate for each group. Results. Topical pimecrolimus 1% treatment led to unsatisfactory results, whereas the combination of microneedling and topical pimecrolimus1% treatment produced a more favorable overall outcome ( P < 0.001 ). Conclusion. This study established that combination therapy results in more significant patient improvement. Additionally, one patient experienced mild skin irritation as a side effect of topical pimecrolimus.

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Side effects of the metacognitive training for depression compared to a cognitive remediation training in patients with depression

Scientific Reports ◽

10.1038/s41598-021-87198-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mona Dietrichkeit ◽

Marion Hagemann-Goebel ◽

Yvonne Nestoriuc ◽

Steffen Moritz ◽

Lena Jelinek

Keyword(s):

Side Effects ◽

Side Effect ◽

Statistical Power ◽

Controlled Trial ◽

Treatment Options ◽

Cognitive Remediation ◽

Negative Effects ◽

Metacognitive Training ◽

To Receive

AbstractAlthough awareness of side effects over the course of psychotherapy is growing, side effects are still not always reported. The purpose of the present study was to examine side effects in a randomized controlled trial comparing Metacognitive Training for Depression (D-MCT) and a cognitive remediation training in patients with depression. 84 patients were randomized to receive either D-MCT or cognitive remediation training (MyBrainTraining) for 8 weeks. Side effects were assessed after the completion of each intervention (post) using the Short Inventory of the Assessment of Negative Effects (SIAN) and again 6 months later (follow-up) using the Negative Effects Questionnaire (NEQ). D-MCT and MyBrainTraining did not differ significantly in the number of side effects. At post assessment, 50% of the D-MCT group and 59% of the MyBrainTraining group reported at least one side effect in the SIAN. The most frequently reported side effect was disappointment in subjective benefit of study treatment. At follow-up, 52% reported at least one side effect related to MyBrainTraining, while 34% reported at least one side effect related to the D-MCT in the NEQ. The most frequently reported side effects fell into the categories of “symptoms” and “quality”. Our NEQ version was missing one item due to a technical error. Also, allegiance effects should be considered. The sample size resulted in low statistical power. The relatively tolerable number of side effects suggests D-MCT and MyBrainTraining are safe and well-received treatment options for people with depression. Future studies should also measure negative effects to corroborate our results.

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Plasma citrulline levels as a biomarker for bowel toxicity in prostate stereotactic radiotherapy with or without pelvic nodal radiation.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.73 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 73-73

Author(s):

Ciaran Fairmichael ◽

Kelly M. Redmond ◽

Ciara Lyons ◽

Sarah R. Stevenson ◽

Sarah O. Osman ◽

...

Keyword(s):

Clinical Trial ◽

Small Bowel ◽

Stereotactic Radiotherapy ◽

Summary Score ◽

Pelvic Radiotherapy ◽

Exact Test ◽

Plasma Citrulline ◽

Patient Reported ◽

To Receive

73 Background: Plasma levels of citrulline, an amino acid, are derived mainly from small bowel enterocytes. Decreased levels occur in a range of bowel conditions and citrulline has been proposed as a biomarker of bowel toxicity in pelvic radiotherapy. In a prospective study, we identify no correlation between plasma citrulline and toxicity in men receiving prostate stereotactic radiotherapy randomized to receive either pelvic nodal irradiation or not. Furthermore, citrulline levels were not significantly different between these two groups. Methods: As part of an approved clinical trial, men with intermediate to high risk prostate cancer were randomised 1:1 to prostate only or prostate + pelvic nodal radiotherapy, delivered with a rectal spacer gel in situ. The prostate and proximal seminal vesicles received 40 Gy in 5 fractions. Those randomised to the pelvic nodal arm also received 25 Gy in 5 fractions to pelvic nodes. Citrulline was measured at 10 points during treatment – consent, before fraction 1, 1 and 24 hours following fraction 1, prior to each fraction 2 – 5 and at 6 weeks’ and 3 months’ follow up. Bowel toxicity was measured by EPIC patient reported scores. Results: 16 men with follow up of at least 3 months (median 9, maximum 18 months) were analysed. Reported toxicity was significantly higher in the prostate and pelvis arm: 5 of 9 men showed a decrease in EPIC bowel domain summary score of 10 points or more compared to 0 of 7 in the prostate-only arm (p = 0.0337, two tailed Fisher’s exact test). No significant correlation between toxicity and citrulline levels was seen, nor did citrulline vary significantly between arms or fall as treatment progressed. Data analysis for a further 8 men already recruited to the study is ongoing. Conclusions: Toxicity was more commonly reported by men randomised to receive pelvic radiotherapy, suggesting that the small bowel irradiated in pelvic fields plays a role in bowel toxicity experienced during stereotactic radiotherapy. Citrulline levels showed no significant correlation with toxicity or radiation dose to small bowel. We propose that citrulline is not a useful biomarker of small bowel toxicity in this setting. Clinical trial information: NCT03253978.

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Possession type affects resolution of possessive pronouns in English VP ellipsis

Proceedings of the Linguistic Society of America ◽

10.3765/plsa.v3i1.4346 ◽

2018 ◽

Vol 3 (1) ◽

pp. 52

Author(s):

Jesse Storbeck ◽

Elsi Kaiser

Keyword(s):

The Other ◽

English Speakers ◽

Discourse Representation ◽

Possessive Pronoun ◽

Vp Ellipsis ◽

To Receive ◽

L1 English ◽

Semantic Properties ◽

Selection Of

The sentence “Bill washed his car, and John did, too” has two possible interpretations if the overt his refers to Bill: (i) a coreferential interpretation, in which John washed Bill’s car, or (ii) a bound variable interpretation, in which John washed his own car. What guides comprehenders’ selection of one over the other? Previous research has identified factors such as processing economy (e.g. Reuland, 2001) and lexical semantic properties of the verb and possessed noun (e.g. Foley et al., 2003; Ong & Brasoveanu, 2014). We extend research on the contribution of possession type to resolution of this type of ambiguous VP ellipsis. We hypothesize that the range of possession types found in natural language varies in the extent to which the possessum is processed as an independent discourse referent or as dependent on the discourse representation of its possessor. Moreover, we expect that such differences modulate the possessum’s availability for coreference and, therefore, affect ambiguity resolution. We conducted an experiment testing how different possession relations modulate adult L1 English speakers’ interpretational preference. Inanimate nouns favored bound variable interpretations more than animates did, supporting our hypothesis that the overt possession’s animacy and its resultant discourse status are important factors in the resolution of the elided possessive pronoun. Follow-up experiments confirmed these results and ruled out nouns’ real-world plausibility of possession as a determinant of interpretational preference. Our results suggest that animate possessions are more likely than inanimates to receive independent status in the discourse and consequently to be available for coreference when the ellipsis is interpreted.

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Activity and duration of chemotherapy (CT) in different biologic subtype (BS) in metastatic breast cancer (MBC) patients (P).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1036 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1036-1036

Author(s):

Claudia Bighin ◽

Lucia Del Mastro ◽

Beatrice Dozin ◽

Sara Giraudi ◽

Alessia Levaggi ◽

...

Keyword(s):

Metastatic Breast ◽

Median Number ◽

The Other ◽

Luminal A ◽

Chi Square ◽

Luminal B ◽

Kaplan Meier ◽

Biologic Subtype ◽

To Receive

1036 Background: In MBC P the benefit of CT after the 1st line (L) is poorly defined. We evaluated activity of subsequent L of CT in different BS of MBC. Methods: MBC P treated in our center from 2007 to 2012 with ER, PgR and HER2 on primary tumor and at least 1 L of CT for MBC were evaluated. P were classified as Luminal A (ER and/or PgR +, HER2 -, Ki67≤14%), Luminal B (ER and/or PgR +, HER2 -, Ki67>14%), HER2+ (HER2+, any ER/PgR) and Triple-Negative ( ER-, PgR- and HER2-). Time on CT was calculated from the start of the 1st L to the end of the last L. Statistical analyses included Chi-square and Kruskal-Wallis tests, Kaplan-Meier curves and log-rank tests, and multivariate logistic regressions. Results: 207 P were identified, 52 were excluded because HER2 was unknown (19) or they did not receive any CT (33). Median follow-up was 31.4 months (m). The median number (N) of CT L was 2 (range 1-10). N of CT L and clinical benefit (CB) for every BS were reported in table. CB was inferior in TN P as compared with the other ones in 1st and in 2nd L ( p=.068 and p=.084 respectively in 1st and 2nd L). From 3rd L onward all P showed the same CB independently from BS. Time on CT related to median survival (S) for every BS was the same. At multivariate analysis the characteristics independently associated with a greater probability of receiving more than 4 CT L were age < 50 years (p=.021), HER2+ or TN disease (p=.027) and site of metastasis other than lung (p=.047). Conclusions: Our analysis showed that, despite the same time spent on CT, TN P received less benefit from 1st and 2nd L CT than other BS. On the other hand, young HER2+ P were more likely to receive multiple L of CT with a significant impact on median S (p=.044). [Table: see text]

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Telemedicine Video Follow-Up for Bariatric Surgery Patients: What Do Patients Prefer? A Prepandemic Pilot Randomized Clinical Trial

The American Surgeon ◽

10.1177/00031348211054547 ◽

2021 ◽

pp. 000313482110545

Author(s):

Alaa Sada ◽

William S. Harmsen ◽

Travis J. McKenzie ◽

Todd A. Kellogg ◽

Omar Ghanem ◽

...

Keyword(s):

Bariatric Surgery ◽

Clinical Trial ◽

Randomized Clinical Trial ◽

Physical Contact ◽

Video Group ◽

To Receive

While the safety of video follow-up in bariatric surgery is established, patients’ perception of telemedicine visits remained unknown. A randomized clinical trial evaluating patients’ perception of video postoperative follow-up (F/U) visits was conducted in the pre COVID-19 era. 24 patients were randomized in the preoperative clinic to receive either in-person or video F/U, and then surveyed about their experience and preference. The majority reported that if they had to do it over, they would prefer a video visit. Among those who received video visits, 11/12 reported that the lack of physical contact was acceptable. 82% of the video group expressed that their visit was better or as good as an in-person visit, while 9% were not sure, and 9% reported that video was worse. This finding suggests that postoperative video follow-up visits are acceptable among bariatric surgery patients and should be offered as an alternative to traditional visits.

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Outcomes of Patients with Chronic Phase CML Who Discontinued Ponatinib in the Frontline Setting

Blood ◽

10.1182/blood.v126.23.1580.1580 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1580-1580

Author(s):

Preetesh Jain ◽

Hagop M Kantarjian ◽

Elias Jabbour ◽

Zeev Estrov ◽

Gautam Borthakur ◽

...

Keyword(s):

Clinical Trial ◽

Median Time ◽

Research Funding ◽

Chronic Phase ◽

Cytogenetic Response ◽

The Other ◽

Molecular Response ◽

Vascular Events ◽

Grade 3

Abstract Background: Ponatinib is a novel TKI efficacious in relapsed refractory patients (pts) with CML and in those with T315I mutation. Despite the achievement of deep early responses in most pts observed in the frontline setting, the concern for arterio-thrombotic events led to the discontinuation (DC) of ponatinib frontline clinical trial. In this study, we have assessed the outcomes after DC of ponatinib of pts in a clinical trial of frontline ponatinib in CML-CP. Methods: Fifty one pts with CML-CP were treated with frontline ponatinib in a single-arm, clinical trial between May 2012 and September 2013. Initial dose of ponatinib was 45 mg orally daily in 43 pts and, after amendment, 30 mg in 8 pts. All pts DC ponatinib therapy after June 2014 and were switched to another TKI. Patients were assessed for cause of DC, treatment received after ponatinib DC, response achieved/maintained on subsequent TKI, adverse events (AE) and survival after ponatinib DC. Survival was calculated from the time of ponatinib DC to the time of last follow up. Results: All 51 patients DC ponatinib: 38 per FDA recommendation and 13 due to AE. Median duration of ponatinib therapy was 13.2 months (range-2.1-25.4). At the time of DC, 47/51 (92%) pts were in complete cytogenetic response (CCyR) and 4 (8%) in partial cytogenetic response (PCyR); 1 pt DC before 3-mo evaluation. Forty (78%) pts were in MMR and 26 (51%) in molecular response 4.5-log (MR4.5). Thirty-six (70%) pts were switched to dasatinib, 7 (14%) to imatinib, and 4 (8%) each to nilotinib and bosutinib. After switching to another TKI, with a median of 13 months (range, 0.2 to 26.3) of follow-up, 2 pts have lost their cytogenetic response (both PCyR on ponatinib), 1 pt improved from PCyR to CCyR and one maintained PCyR; all 47 (92%) pts with CCyR on ponatinib maintained this response. Molecular responses improved in some pts: 6 improved from no MMR to MMR; 1 to MR4.5 (median time on ponatinib 4 months; median time on subsequent TKI 17 months); 11 from MMR to MR4.5 (median time on ponatinib 13 months; median time on subsequent TKI 17 months). One pt (treated with imatinib 400) lost MR4.5 to no MMR after 2 months. At last follow-up 37 pts (72%) had MR4.5 and 45 (90%) MMR. Two pts died after ponatinib DC. One pt was treated with imatinib 400 and developed grade-3 edema and recurrent lung cancer; the second was switched to dasatinib and had recurrent progressive peripheral arterial disease (PAD). Four pts had events (2 deaths, 1 secondary MDS with -7 and 1 pt lost major CyR). Median post ponatinib survival (Figure-1) and median post ponatinib event free survival (not shown) was not reached (1-year OS 98% and EFS 95%). Forty five pts continued on their first post-ponatinib TKIs, 5 required 2 post-ponatinib TKI and 1 pt received 3 different TKIs after DC. The most common cause for post-ponatinib TKI switch was toxicity (n=6). Of the 36 pts switched to dasatinib, 5 discontinued: 4 due to pleural effusion and 1 with acute renal failure. 29/36 pts (81%) were in MMR before switch and all maintained MMR; 4 pts achieved MMR after switch to dasatinib. Four pts developed grade 3-4 non hematological vascular AEs (3 among pts with such events while on ponatinib and 1 new vascular event within 3 months of ponatinib DC). Of the 4 pts switched to nilotinib, 1 DC within 3 months due to grade-3 pancreatitis and also developed grade-1 pulmonary hypertension with 1 month of discontinuing ponatinib. This pt was then switched to bosutinib. The other 3 pts maintained MMR and had no vascular events. Of the 4 pts switched to bosutinib, one developed MDS, one was switched back to ponatinib off protocol (patient's choice), 1 lost cytogenetic response and one DC therapy after 1 month and maintains MR4.5 (this pt had TIA while on ponatinib, developed cerebral infarct within 1 month post ponatinib). Seven pts switched to imatinib. One developed a new PAD within 3 months of ponatinib DC (history of MI while on ponatinib). The other 6 pts maintained MMR on imatinib. Overall, 15 pts who had aggravated hypertension on ponatinib were under control after DC of ponatinib. Conclusion: Treatment with 2nd generation TKIs and imatinib was effective and safe in pts who DC ponatinib, and most pts were able to maintain/improve the responses achieved on ponatinib. Ponatinib-associated hypertension was usually reversible after DC and most vascular events with subsequent TKIs occurred in patients with prior such events while on ponatinib. Figure 1. Post ponatinib survival in patients Figure 1. Post ponatinib survival in patients Disclosures Jabbour: pfizer: Research Funding; ariad: Research Funding; teva: Consultancy; teva: Research Funding; pfizer: Consultancy; bms: Consultancy; ariad: Consultancy. Estrov:incyte: Consultancy, Research Funding. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Cortes:Pfizer: Consultancy, Research Funding; BerGenBio AS: Research Funding; Novartis: Consultancy, Research Funding; Teva: Research Funding; BMS: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

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Involvement of bone-specific alkaline phosphatase and procollagen I carboxy-terminal propeptide as predictors of early fracture risk in Chinese Children with juvenile osteoporosis: An interventional clinical trial

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v13i2.35620 ◽

2018 ◽

Vol 13 (2) ◽

pp. 164

Author(s):

Yu Wang ◽

Jingxin Zhao ◽

Lingwei Kong ◽

Yu Jin

Keyword(s):

Clinical Trial ◽

Vitamin D ◽

Alkaline Phosphatase ◽

Bone Fracture ◽

Specific Alkaline Phosphatase ◽

Bone Specific Alkaline Phosphatase ◽

Low Levels ◽

Carboxy Terminal ◽

To Receive

<p class="Abstract">This clinical trial was designed to understand whether the children with juvenile osteoporosis receiving tablet containing vitamin D and calcium had lower incidence of bone fracture compared to the children receiving a diet rich in calcium, vitamin D, and protein. We assessed whether plasma levels of bone-specific alkaline phosphatase (BSAP) and procollagen I carboxy-terminal propeptide levels (PIPC) could be used as predictors of early bone fracture in children. A total of 120 children of either gender with a juvenile osteoporosis were enrolled and randomized (1:1 ratio) to receive tablet containing vitamin D and calcium (n=60) or diet rich in calcium, vitamin D, and protein (n=60), and undergone follow-up for up to 3 years. Blood sample was collected and BSAP and PIPC levels were measured. The results suggested that therapeutic intervention (vitamin D and calcium) does not predict bone fracture in children. However, correlations analysis revealed that the decreased level of BSAP and PIPC were associated with higher incidence of fracture. The results suggest that the low levels of BSAP and PIPC cause increase susceptibility of fracture among children with juvenile osteoporosis.</p>

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Safety of Radiosurgery Applied to Conditions with Abnormal Tumor Suppressor Genes

Neurosurgery ◽

10.1227/01.neu.0000255426.08926.95 ◽

2007 ◽

Vol 60 (5) ◽

pp. 860-864 ◽

Cited By ~ 26

Author(s):

Jeremy Rowe ◽

Alison Grainger ◽

Lee Walton ◽

Matthias Radatz ◽

Andras Kemeny

Keyword(s):

Cohort Study ◽

Tumor Suppressor Genes ◽

Retrospective Cohort ◽

Treatment Options ◽

The Other ◽

Von Hippel Lindau ◽

Increased Risk ◽

Risk Of Malignancy ◽

Von Hippel Lindau Disease

Abstract OBJECTIVE To assess the risk of radiosurgery inducing malignancy in neurofibromatosis-2 (NF2) and von Hippel-Lindau disease. METHODS A retrospective cohort study of 118 NF2 and 19 von Hippel-Lindau disease patients, totalling 906 and 62 patient-years of follow-up data, respectively. RESULTS Two cases of intracranial malignancy were identified, both of which occurred in NF2 patients. One of these was thought to have arisen before the radiosurgery; the other was a glioblastoma diagnosed 3 years after radiosurgery. CONCLUSION Because gliomas may occur in as many as 4% of NF2 patients, this may not represent an increased risk. We continue to offer radiosurgery treatment to selected NF2 and von Hippel-Lindau disease patients and consider that the late risk of malignancy arising after irradiation must be put in the context of the condition being treated, the treatment options available to these individuals, and their life expectancy.

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Randomised clinical trial comparing oral versus depot formulations of zuclopenthixol in patients with schizophrenia and previous violence

European Psychiatry ◽

10.1016/j.eurpsy.2005.07.006 ◽

2006 ◽

Vol 21 (1) ◽

pp. 34-40 ◽

Cited By ~ 55

Author(s):

C. Arango ◽

I. Bombín ◽

T. González-Salvador ◽

I. García-Cabeza ◽

J. Bobes

Keyword(s):

Clinical Trial ◽

Treatment Adherence ◽

Randomised Clinical Trial ◽

Positive Symptoms ◽

Violent Behaviour ◽

Depot Formulation ◽

Violent Acts ◽

Receive Treatment ◽

To Receive

AbstractObjectiveThe aim of this longitudinal study was to determine whether the depot formulation of an antipsychotic reduces violence in outpatients with schizophrenia as compared to oral administration of the same antipsychotic.MethodsForty-six previously violent patients with schizophrenia were randomised to receive treatment with oral or depot zuclopenthixol for 1 year. Clinicians interviewed patients at baseline and every month thereafter to assess treatment adherence. An interviewer blinded to treatment assignments interviewed an informant about any violent behaviour during the previous month.ResultsViolence during the follow-up year was inversely proportional to treatment adherence, better compliance, and greater reduction of positive symptoms. Lower frequency of violent acts was observed in the depot group. The level of insight at baseline was not significantly associated with violence recidivism. Regardless of route of administration, treatment non-adherence was the best predictor of violence.ConclusionsSome patients with schizophrenia and prior violent behaviour may benefit from the depot formulation of antipsychotic medication.

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Cardiosphere-derived exosomal microRNAs for cardiac repair in pediatric dilated cardiomyopathy: preclinical and safety lead-in phase 1 clinical studies

European Heart Journal ◽

10.1093/ehjci/ehaa946.3608 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

K Hirai ◽

K Baba ◽

S Ohtsuki ◽

H Oh

Keyword(s):

Clinical Trial ◽

Cardiac Function ◽

Dilated Cardiomyopathy ◽

Myocardial Fibrosis ◽

Cardiac Repair ◽

Secondary Outcome ◽

Swine Model ◽

Funding Source ◽

To Receive

Abstract Introduction Stem cell therapies have been shown to improve cardiac function; however, therapeutic potential of cardiosphere-derived cells (CDCs) in dilated cardiomyopathy (DCM) and the underlying mechanisms of paracrine effectors include CDC-secreted exosomes (CDCex) mediating cardiac repair remain unknown. Purpose- We aimed to evaluate the safety and therapeutic efficacy of CDCs in swine model of DCM and translate the preclinical results into children with DCM. Methods As a preclinical study, female Yorkshire pigs (n=15) were treated by intracoronary administration of microspheres (1.0×104 particles) to develop diffuse cardiac dysfunction and animals were randomly assigned to receive placebo or 9.0×106 CDC injection pretreated by DMSO or exosome inhibitor (EI; GW4869). CDCex-derived microRNAs (miRs) profile was assessed and ventricular ejection fraction (EF) was evaluated before and 1 month after cell infusion. In safety lead-in clinical trial, 5 patients with DCM (<18 years) with reduced EF (<40%) were prospectively enrolled to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function over 12 months. Results Compared with placebo control, DMSO-treated CDC infusion resulted in improved cardiac function with decrease in myocardial fibrosis (18.2±4.1% versus; 9.5±3.6%; P<0.001) and enhanced cardiomyocyte cycling (Ki67: 27.2±3.6/106 myocytes versus 43.9±6.0/106 myocytes; P=0.002) and neovascularization (von Willebrand factor: 644.8±84.3/mm2 versus 820.7±159.7/mm2; P=0.01) at 1 month. miR expression analysis showed that CDCex were highly enriched with miR-126, miR-132, miR-146a, miR-181b, miR-210, and miR-451. Inhibition of CDCex-derived miRs production by EI pretreatment did not affect CDC viability but rendered CDC ineffective in functional improvement (ΔEF: +5.4%±2.0% versus −1.0%±2.1%; P=0.002). One-year follow-up of clinical trial was completed in 5 patients with favorable profile and preliminary efficacy outcomes. Echocardiographic measurements revealed that CDC infusion increased EF from baseline to 12 months of follow up (28.5±10.7% versus 33.0±11.1%; P=0.038) in accordance with reduced native T1 mapping (1041.6±60.4 ms versus 984.8±39.3 ms; P=0.025). CDCex-derived miRs profiles from patients demonstrated that several miRs were exclusively enriched in CDCs but human cardiac fibroblasts included miR-126, miR-132, miR-146a, miR-181b, and miR-210. Notably, miR-146a expression levels were positively correlated with the reduction in myocardial fibrosis 12 months after CDC infusion (Δnative T1: r=0.896, P=0.040). Conclusions Intracoronary delivery of CDCs is safe and improves cardiac function through CDCex-derived miRs secretion in swine model of DCM. The safety lead-in results in patients warrant further assessment of clinical benefits and highlight miR-146a as a major paracrine mediator of CDC's antifibrotic function for clinical therapeutics. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Research Project for Practical Application of Regenerative Medicine (16bk0104052h0001, 17bk0104052h0002, 18bk0104052h0003) by the Japan Agency for Medical Research and Development

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