Flavonoids and post haemorrhoidectomy recovery: a systematic review and meta-analysis.

BACKGROUND: Haemorrhoidectomy is the gold standard for definitive treatment of high-grade symptomatic haemorrhoids but is often associated with substantial pain. This systematic review aims to explore the potential of flavonoids in alleviating the postoperative symptom burden following excisional haemorrhoidectomy. METHODS: A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD42023472711). Randomized controlled trials (RCTs) published PubMed, MEDLINE, Embase, and Scopus from inception to 1st December 2023 were retrieved. The primary outcome investigated was post-operative pain. Meta-analysis was performed using Review Manager version 5.4.1. RESULTS: Ten articles with 775 patients were included. The meta-analysis identified statistically significant decreases in post-operative pain in favour of the flavonoid groups (Standardized Mean Difference -0.66 [95% confidence intervals (CI) -0.82, -0.52]; P < 0.00001), and bleeding (Odds Ratio 0.13 [95% CI 0.09, 0.19]; P < 0.00001). CONCLUSION: Flavonoids show promise as a means of reducing pain associated with excisional haemorrhoidectomy. Further research is required to investigate topical routes of administration and standardize regimes.

A randomized controlled trial to evaluate outcomes with Aggrenox in patients with SARS-CoV-2 infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an immunoinflammatory and hypercoagulable state that contributes to respiratory distress, multi-organ dysfunction, and mortality. Dipyridamole, by increasing extracellular adenosine, has been postulated to be protective for COVID-19 patients through its immunosuppressive, anti-inflammatory, anti-coagulant, vasodilatory, and anti-viral actions. Likewise, low-dose aspirin has also demonstrated protective effects for COVID-19 patients. This study evaluated the effect of these two drugs formulated together as Aggrenox in hospitalized COVID-19 patients. METHODS: In an open-label, single site randomized controlled trial (RCT), hospitalized COVID-19 patients were assigned to adjunctive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) with standard of care treatment compared to standard of care treatment alone. Primary endpoint was illness severity according to changes on the eight-point COVID ordinal scale, with levels of 1 to 8 where higher scores represent worse illness. Secondary endpoints included all-cause mortality and respiratory failure. Outcomes were measured through days 14, 28, and/or hospital discharge. RESULTS: From October 1, 2020 to April 30, 2021, a total of 98 patients, who had a median [IQR] age of 57 [47, 62] years and were 53.1% (n = 52) female, were randomized equally between study groups (n = 49 Aggrenox plus standard of care versus n = 49 standard of care alone). No clinically significant differences were found between those who received adjunctive Aggrenox and the control group in terms of illness severity (COVID ordinal scale) at days 14 and 28. The overall mortality through day 28 was 6.1% (3 patients, n = 49) in the Aggrenox group and 10.2% (5 patients, n = 49) in the control group (OR [95% CI]: 0.40 [0.04, 4.01], p = 0.44). Respiratory failure through day 28 occurred in 4 (8.3%, n = 48) patients in the Aggrenox group and 7 (14.6%, n = 48) patients in the standard of care group (OR [95% CI]: 0.21 [0.02, 2.56], p = 0.22). A larger decrease in the platelet count and blood glucose levels, and larger increase in creatinine and sodium levels within the first 7 days of hospital admission were each independent predictors of 28-day mortality (p < 0.05). CONCLUSION: In this study of hospitalized patients with COVID-19, while the outcomes of COVID illness severity, odds of mortality, and chance of respiratory failure were better in the Aggrenox group compared to standard of care alone, the data did not reach statistical significance to support the standard use of adjuvant Aggrenox in such patients.

Common mental disorders during the COVID-19 pandemic in Hong Kong: Age-related differences and implications for dementia risk.

Background: The COVID-19 pandemic has imposed a profound negative impact on the mental health and wellbeing of societies and individuals worldwide. Older adults may be more vulnerable to the mental health effects of the pandemic, either directly from the infection itself or indirectly through the preventive measures. However, the existing literature on mental health in the older age groups has not been consistent so far. The aim of this study was therefore to assess the prevalence of common mental disorders (CMD; including depression and anxiety disorders) given their association with dementia risk, and to further examine age-related differences between older (≥60 years old) and younger (18-59 years old) adult's psychological status during the COVID-19 pandemic. Method: This was a secondary analysis of a cross-sectional survey-study conducted during the second wave of COVID-19 pandemic in Hong Kong. The survey was disseminated through different social media platforms to the general population and included sociodemographic questions, self-reported physical health, and previous encounter with SARS or COVID-19. CMD was the primary outcome and was assessed using the 6-item Kessler Scale. A total of 1030 adults fulfilled inclusion criteria. Results: The prevalence of CMD during the pandemic was 16.1%. Compared to younger adults, older adults were significantly less likely to have a CMD (unadjusted OR = 0.07, 95% CI = 0.02-0.30, p < 0.001), with 18.1% of younger adults having CMD compared to 1.6% in the older cohort. Age differences remained significant after controlling for sociodemographic factors, physical health, and previous encounter with SARS or COVID-19 (adjusted OR = 0.12, 95% CI = 0.02-0.57, p = 0.008). Conclusion: Common mental disorders are highly prevalent during the COVID-19 pandemic in Hong Kong, though older adults appeared to be less affected mentally. Present findings highlight the urgent need to implement measures and strategies to mitigate the mental health problems, with particular attention to the younger cohort. Given their association with higher dementia risk, early detection and treatment of depression and anxiety disorders will be of critical importance in providing some relief to the already pressurized dementia burden in the longer term.

Dementia and risk of visual impairment in Chinese older adults.

We had previously identified visual impairment increasing risk of incident dementia. While a bi-directional vision-cognition association has subsequently been proposed, no study has specifically examined the longitudinal association between dementia and incidence of clinically defined visual impairment. In this territory-wide community cohort study of 10,806 visually unimpaired older adults, we examined their visual acuity annually for 6 years and tested if dementia at baseline was independently associated with higher risk of incident visual impairment (LogMAR ≥ 0.50 in the better eye despite best correction, which is equivalent to moderate visual impairment according to the World Health Organization definition). By the end of Year 6, a total of 3151 (29.2%) participants developed visual impairment. However, we did not find baseline dementia associating with higher risk of incident visual impairment, after controlling for baseline visual acuity, cataract, glaucoma, diabetes, hypertension, hypercholesterolemia, heart diseases, stroke, Parkinson's disease, depression, hearing and physical impairments, physical, intellectual and social activities, diet, smoking, age, sex, educational level, and socioeconomic status. Among different covariables, baseline visual acuity appears to be more important than dementia in contributing to the development of visual impairment. Our present findings highlight the need for re-evaluating whether dementia is indeed a risk factor for visual impairment.

Developments in high-throughput functional epigenomics: CRISPR-single-cell assay for transposase-accessible chromatin using sequencing screens.

Tweetable abstract CRISPR-scATAC-seq screens pave the way for high-throughput functional epigenomics by linking perturbations to a broad view of epigenetic state and messages hidden within accessible sequences.

Increasing participation in habitual intellectual activities on modulating functional connectivity of default mode network among older adults at risk of dementia: study protocol of a randomized controlled trial.

BACKGROUND: Active participation in intellectual leisure activities such as calligraphy helps prevent cognitive decline and dementia, but the underlying mechanisms are not fully understood. With disrupted functional connectivity (FC) of default mode network (DMN) associated with cognitive decline, we speculate that intellectual activities might optimize cognitive function through modulating FC of DMN. This two-arm single-blind randomized controlled trial aims to identify the effects of increasing practice of calligraphy on cognitive function and FC of DMN in people with subjective cognitive decline (SCD). METHODS: One hundred twelve community-living Chinese aged 55 to 75 years old with SCD but without mild cognitive impairment or dementia and with prior practice of calligraphy as defined by 1 h of calligraphy per week will be recruited through elderly social centres in Hong Kong and randomized into either control or intervention group. The control group will continue with their usual practice of calligraphy, whereas the intervention group will double their practice of calligraphy. Measurement of cognitive outcomes and neuroimaging on resting-state FC will be performed at baseline and in 6 months. Repeated measures analysis of variance will be used to assess cognitive and FC changes, with time being the within-group factor, control/intervention as the between-group measure, and important covariates (age, sex, educational and occupational attainment, health, and other lifestyle factors) controlled for. DISCUSSION: This study will shed light on the underlying neurocognitive mechanisms of how intellectual activities promotes cognitive maintenance. Our anticipated findings will provide evidence that reversing or slowing FC disruption by actively participating in intellectual activities is still possible for the at-risk individuals. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024433 . Registered on 11 July 2019.

Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study.

BACKGROUND: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population. METHODS: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160. FINDINGS: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy. INTERPRETATION: In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy. FUNDING: National Institute of Allergy and Infectious Disease, Immune Tolerance Network.

Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS-STING Signaling in Triple-Negative Breast Cancer.

Taxanes remain one of the most effective medical treatments for breast cancer. Clinical trials have coupled taxanes with immune checkpoint inhibitors in patients with triple-negative breast cancer (TNBC) with promising results. However, the mechanism linking taxanes to immune activation is unclear. To determine if paclitaxel could elicit an antitumoral immune response, we sampled tumor tissues from patients with TNBC receiving weekly paclitaxel (80 mg/m2) and found increased stromal tumor-infiltrating lymphocytes and micronucleation over baseline in three of six samples. At clinically relevant concentrations, paclitaxel can induce chromosome missegregation on multipolar spindles during mitosis. Consequently, post-mitotic cells are multinucleated and contain micronuclei, which often activate cyclic GMP-AMP synthase (cGAS) and may induce a type I IFN response reliant on the stimulator of IFN genes (STING) pathway. Other microtubule-targeting agents, eribulin and vinorelbine, recapitulate this cGAS/STING response and increased the expression of immune checkpoint molecule, PD-L1, in TNBC cell lines. To test the possibility that microtubule-targeting agents sensitize tumors that express cGAS to immune checkpoint inhibitors, we identified 10 patients with TNBC treated with PD-L1 or PD-1, seven of whom also received microtubule-targeting agents. Elevated baseline cGAS expression significantly correlated with treatment response in patients receiving microtubule-targeting agents in combination with immune checkpoint inhibitors. Our study identifies a mechanism by which microtubule-targeting agents can potentiate an immune response in TNBC. Further, baseline cGAS expression may predict patient treatment response to therapies combining microtubule-targeting agents and immune checkpoint inhibitors.

Chromosomal instability upregulates interferon in acute myeloid leukemia.

Chromosome instability (CIN) generates genetic and karyotypic diversity that is common in hematological malignancies. Low to moderate levels of CIN are well tolerated and can promote cancer proliferation. However, high levels of CIN are lethal. Thus, CIN may serve both as a prognostic factor to predict clinical outcome and as a predictive biomarker. A retrospective study was performed to evaluate CIN in acute myeloid leukemia (AML). Chromosome mis-segregation frequency was correlated with clinical outcome in bone marrow core biopsy specimens from 17 AML cases. Additionally, we induced chromosome segregation errors in AML cell lines with AZ3146, an inhibitor of the Mps1 mitotic checkpoint kinase, to quantify the phenotypic effects of high CIN. We observed a broad distribution of chromosome mis-segregation frequency in AML bone marrow core specimens. High CIN correlated with complex karyotype in AML, as expected, although there was no clear survival effect. In addition to CIN, experimentally inducing chromosome segregation errors by Mps1 inhibition in AML cell lines causes DNA damage, micronuclei formation, and upregulation of interferon stimulated genes. High levels of CIN appear to be immunostimulatory, suggesting an opportunity to combine mitotic checkpoint inhibitors with immunotherapy in treatment of AML.

Tribute to Milton D. Heifetz (1921-2015): The Man Behind the Heifetz Aneurysm Clip.

Milton Dave Heifetz (1921-2013) was a pioneer American neurosurgeon who spent the majority of his career at Cedars-Sinai Hospital in California. Heifetz greatly influenced the field of neurosurgery as an innovator, leader, and academic neurosurgeon. His redesign of the aneurysm clip addressed the long-standing issue of a fatiguing spring. Heifetz's innovation allowed the spring to maintain adequate closing force despite repetitive opening and closing. This clip was recognized as one of the most effective aneurysm clips for approximately 15 yr. While he was best known for this eponymous aneurysm clip, Heifetz also developed other various microsurgical instruments and tools for stereotactic approaches. Beyond neurosurgery, he was an influential figure and well-published author in fields such as medical ethics, philosophy, astronomy, and poetry. In 1975, he published The Right to Die: A Neurosurgeon Speaks of Death With Candor, a book which played a major role in our modern-day advanced directives. Throughout his life, Heifetz was an inspirational individual who consistently worked towards solutions to surgical and ethical problems. We present a historical vignette on his life, career, and contributions to neurosurgery.

Immune landscapes associated with different glioblastoma molecular subtypes.

Recent work has highlighted the tumor microenvironment as a central player in cancer. In particular, interactions between tumor and immune cells may help drive the development of brain tumors such as glioblastoma multiforme (GBM). Despite significant research into the molecular classification of glioblastoma, few studies have characterized in a comprehensive manner the immune infiltrate in situ and within different GBM subtypes.In this study, we use an unbiased, automated immunohistochemistry-based approach to determine the immune phenotype of the four GBM subtypes (classical, mesenchymal, neural and proneural) in a cohort of 98 patients. Tissue Micro Arrays (TMA) were stained for CD20 (B lymphocytes), CD5, CD3, CD4, CD8 (T lymphocytes), CD68 (microglia), and CD163 (bone marrow derived macrophages) antibodies. Using automated image analysis, the percentage of each immune population was calculated with respect to the total tumor cells. Mesenchymal GBMs displayed the highest percentage of microglia, macrophage, and lymphocyte infiltration. CD68+ and CD163+ cells were the most abundant cell populations in all four GBM subtypes, and a higher percentage of CD163+ cells was associated with a worse prognosis. We also compared our results to the relative composition of immune cell type infiltration (using RNA-seq data) across TCGA GBM tumors and validated our results obtained with immunohistochemistry with an external cohort and a different method. The results of this study offer a comprehensive analysis of the distribution and the infiltration of the immune components across the four commonly described GBM subgroups, setting the basis for a more detailed patient classification and new insights that may be used to better apply or design immunotherapies for GBM.

The Impact of Grammar on Mentalizing: A Training Study Including Children With Autism Spectrum Disorder and Developmental Language Disorder.

Training on complements in English, German, and Mandarin has been reported to trigger improvements on both complements and Theory of Mind (ToM), with typically developing (TD) pre-schoolers on the verge of developing these skills (Hale and Tager-Flusberg, 2003; Lohmann and Tomasello, 2003; Shuliang et al., 2014). In the current study, we build on the idea that increasing mastery of complementation holds the promise of enhancing ToM, and seek (i) to replicate the positive effects observed in previous work for this effect in French-speaking TD children, and (ii) to pilot extending this to clinical children, more specifically those with Autism Spectrum Disorder (ASD) and Developmental Language Disorder (DLD), through exploring whether improvement in the latter, clinical groups follows that of the TD group. Sixty children with ToM difficulties, 16 with ASD (aged 5;6-11;8), 20 with DLD (aged 4;8-9;0) and 24 typically developing children aged (2;9-5;3 years), participated in a 4-week training program. Half received training targeting sentential complements and half received a control training targeting lexical skills. Complementation training, but not lexical training, led to a significant direct increase in complements, and also had the indirect effect of significantly boosting belief reasoning. TD and clinical groups followed the same patterns of performance. These results confirm previous findings in other languages for TD, and further suggest promising new directions for therapeutic programs addressing ToM delays in populations of different aetiologies, namely the incorporation of a motivating training on complementation.

Tumors with TSC mutations are sensitive to CDK7 inhibition through NRF2 and glutathione depletion.

Tuberous sclerosis complex (TSC) is characterized by tumor development in the brain, heart, kidney, and lungs. In TSC tumors, loss of the TSC1/TSC2 protein complex leads to activation of mTORC1 with downstream effects on anabolism and cell growth. Because mTORC1 activation enhances mRNA transcription, we hypothesized that aberrant mTORC1 activation might confer TSC-null cell dependence on transcriptional regulation. We demonstrate that TSC1- or TSC2-null cells, in contrast to their wild-type counterparts, are sensitive to pharmacological inhibition of CDK7. Mechanistic studies revealed that CDK7 inhibition markedly reduces glutathione levels and increases reactive oxygen species due to reduced expression of NRF2 and glutathione biosynthesis genes. Treatment of both Tsc2+/ - mice and a TSC1-null bladder cancer xenograft model with a CDK7 inhibitor showed marked reduction in tumor volume and absence of regrowth in the xenograft model. These results suggest that CDK7 inhibition is a promising therapeutic approach for treatment of TSC-associated tumors and cancers with mutations in either TSC1 or TSC2.

Whole Exome Sequencing Identifies TSC1/TSC2 Biallelic Loss as the Primary and Sufficient Driver Event for Renal Angiomyolipoma Development.

Renal angiomyolipoma is a kidney tumor in the perivascular epithelioid (PEComa) family that is common in patients with Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM) but occurs rarely sporadically. Though histologically benign, renal angiomyolipoma can cause life-threatening hemorrhage and kidney failure. Both angiomyolipoma and LAM have mutations in TSC2 or TSC1. However, the frequency and contribution of other somatic events in tumor development is unknown. We performed whole exome sequencing in 32 resected tumor samples (n = 30 angiomyolipoma, n = 2 LAM) from 15 subjects, including three with TSC. Two germline and 22 somatic inactivating mutations in TSC2 were identified, and one germline TSC1 mutation. Twenty of 32 (62%) samples showed copy neutral LOH (CN-LOH) in TSC2 or TSC1 with at least 8 different LOH regions, and 30 of 32 (94%) had biallelic loss of either TSC2 or TSC1. Whole exome sequencing identified a median of 4 somatic non-synonymous coding region mutations (other than in TSC2/TSC1), a mutation rate lower than nearly all other cancer types. Three genes with mutations were known cancer associated genes (BAP1, ARHGAP35 and SPEN), but they were mutated in a single sample each, and were missense variants with uncertain functional effects. Analysis of sixteen angiomyolipomas from a TSC subject showed both second hit point mutations and CN-LOH in TSC2, many of which were distinct, indicating that they were of independent clonal origin. However, three tumors had two shared mutations in addition to private somatic mutations, suggesting a branching evolutionary pattern of tumor development following initiating loss of TSC2. Our results indicate that TSC2 and less commonly TSC1 alterations are the primary essential driver event in angiomyolipoma/LAM, whereas other somatic mutations are rare and likely do not contribute to tumor development.

Effect of catheter ablation and periprocedural anticoagulation regimen on the clinical course of migraine in atrial fibrillation patients with or without pre-existent migraine: results from a prospective study.

BACKGROUND: We examined the influence of catheter ablation and periprocedural anticoagulation regimen on trajectory of migraine in atrial fibrillation patients with or without migraine history. METHODS AND RESULTS: Forty patients with (group 1: 64 ± 8 years; men 78%) and 85 (group 2: 61 ± 10 years; men 73%) without migraine history undergoing atrial fibrillation-ablation were enrolled. Migraine status and quality of life were evaluated using standardized questionnaires. Diffusion magnetic resonance imaging of brain was performed for all at pre and 24 hours post procedure. Catheter ablation was performed with (88, 70%) or without (37, 30%) continuous warfarin treatment. Fifty-four patients (11 and 43 from groups 1 and 2, respectively) had subtherapeutic international normalized ratio on procedure day. At 17 ± 5 months follow-up, from group 1, 25 (63%) reported no migraine, 10 (25%) had < 1, and 3 (8%) had 2 to 3 monthly symptoms. Intensity of pain decreased from baseline 7 (Q1-Q3, 4-8) to 2 (0-4) scale points at follow-up (P < 0.001) and duration of headache from median 8 (Q1-Q3, 4-15) to 0.5 (Q1-Q3, 0-2) hours (P < 0.001). Two patients from group 1 reported increased migraine severity and 2 from group 2 had new-onset migraine. Follow-up diffusion magnetic resonance imaging revealed new infarcts in 9.6% (12/125) patients; of which 11 had subtherapeutic preprocedural international normalized ratio on or off continuous warfarin. Quality of life improved significantly in patients with successful ablation, being more pronounced in group 1. CONCLUSIONS: In most patients, migraine symptoms improved substantially after catheter ablation. Interestingly, the only cases of new migraine and aggravation of pre-existent headache had subtherapeutic international normalized ratio during the procedure and new cerebral infarcts.

Efficacy of catheter ablation in nonparoxysmal atrial fibrillation patients with severe enlarged left atrium and its impact on left atrial structural remodeling.

INTRODUCTION: The effect of catheter ablation on severe left atrial enlargement especially in nonparoxysmal atrial fibrillation (NPAF) patients is not well understood. Whether reverse remodelling may occur after ablation has not been evaluated in this setting. METHODS AND RESULTS: Fifty consecutive patients with left atrial diameter (LAD) ≥50 mm, and LA volume >200 cc undergoing catheter ablation for drug-refractory NPAF were included in this study. Transthoracic echocardiographic measurements were performed at baseline and at 12-months postprocedure. Left ventricular end-diastolic and end-systolic dimensions were indexed by body surface area (LVEDDI, LVESDI). Electroanatomic mapping system (Carto or NavX system) and computed tomography (CT) were used for 3-dimensional reconstruction of the LA. All patients underwent posterior wall isolation and pulmonary vein (PV) antrum and extra PV trigger ablations. Long-term follow-up was monitored by event recordings, 7-day Holter monitors and office visits. The mean age was 65 ± 10 years, 78% male, persistent AF 22 (44%), longstanding AF 28 (56%), LAD diameter 56.9 ± 7.8 mm, left ventricular ejection fraction (LVEF) 53 ± 14 and median AF duration 72 (49-96) months. At 12-month follow-up, 27 patients (54%) remained arrhythmia-free off antiarrhythmic drugs. Significant reduction in LAD at follow-up (≥10% reduction) was observed in 52% (26/50) of the total population and among the 63% (17/27) of recurrence-free patients. Magnitude of LA reduction was identically distributed among the persistent and longstanding persistent AF cohorts (16 ± 12% vs 14 ± 16%, respectively, P = 0.15). A significant 20% improvement in LVEF (from 53 ± 14 to 58 ± 9, P = 0.03) was found in the overall population. Improvement was noted in recurrence-free patients. No significant change in LVEDDI and LVESDI was noted. After adjusting for baseline risk factors in a multivariable model, a reduction in LAD was identified as a strong predictor of long-term success (beta = -11.1, P = 0.013). Preexisting LA scarring was associated with increased LAD (beta = 2.7, P = 0.023). No periprocedural or long-term complications were reported. CONCLUSION: Our results show that atrial fibrillation ablation is effective in NPAF patients with severe LA enlargement and is associated with LA reverse remodeling and improvement in LVEF.