The outcomes and prognostic factors of patients who underwent reoperation for persistent/recurrent papillary thyroid carcinoma.

BACKGROUND: While the most suitable approach for treating persistent/recurrent papillary thyroid carcinoma (PTC) remains controversial, reoperation may be considered an effective method. The efficacy of reoperation in patients with locoregional persistent/recurrent PTC, especially those with unsatisfactory radioactive iodine (RAI) ablation results, is still uncertain. This study aimed to clarify the clinical management strategies for locoregional persistent/recurrent PTC and to explore factors that may affect long-term patient outcomes after reoperation. METHODS: In total, 124 patients who initially underwent thyroidectomy and variable extents of RAI therapy and finally received reoperation for locoregionally persistent/recurrent PTC were included. The parameters associated with recurrence-free survival (RFS) were analysed using a Cox proportional hazards model. RESULTS: Overall, 124 patients presented with structural disease after initial therapy and underwent secondary surgical resection, of whom 32 patients developed further structural disease during follow-up after reoperation. At the time of reoperation, metastatic lymph nodes with extranodal extension (P = 0.023) and high unstimulated thyroglobulin (unstim-Tg) levels after reoperation (post-reop) (P = 0.001) were independent prognostic factors for RFS. Neither RAI avidity nor the frequency and dose of RAI therapies before reoperation affected RFS. CONCLUSIONS: Reoperation is an ideal clinical treatment strategy for structural locoregional persistent/recurrent PTC, and repeated empirical RAI therapies performed prior to reoperation may not contribute to the long-term outcomes of persistent/recurrent PTC patients. Metastatic lymph nodes with extranodal extension and post-reop unstim-Tg > 10.1 ng/mL may predict a poor prognosis.

Colchicine for Coronary Heart Disease: A Meta-Analysis of Randomized Controlled Trials

BACKGROUND: The efficacy of colchicine administration for coronary heart disease remains controversial. We conducted a systematic review and meta-analysis to explore the influence of colchicine administration versus placebo on treatment efficacy for coronary heart disease. METHODS: We have searched PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through May 2021 for randomized controlled trials (RCTs) assessing the effect of colchicine administration versus placebo in patients with coronary heart disease. This meta-analysis was performed using the random-effects model. RESULTS: Six RCTs involving 6,321 patients were included in the meta-analysis. Overall, compared with control groups for coronary heart disease, colchicine intervention can significantly reduce major adverse cardiovascular events (odds ratio [OR] 0.74; 95% confidence interval [CI] 0.59 to 0.92; P = .006), but revealed no obvious impact on mortality (OR=0.93; 95% CI=0.63 to 1.36; P = .69), serious adverse events (OR 0.71; 95% CI 0.31 to 1.61; P = .41), or restenosis (OR 1.02; 95% CI 0.63 to 1.64; P = .95). CONCLUSIONS: Colchicine treatment may be effective to reduce major adverse cardiovascular events in patients with coronary heart disease.

High-Resolution Printable and Elastomeric Conductors from Strain-Adaptive Assemblies of Metallic Nanoparticles with Low Aspect Ratios.

Stretchable conductors capable of precise micropatterning are imperative for applications in various wearable technologies. Metallic nanoparticles with low aspect ratios and miniscule sizes are preferred over metallic nanowires or nanoflakes for such applications. However, nanoparticles tend to lose mutual contact during stretching. Therefore, they are rarely used alone in stretchable conductors. In this study, electronic inks comprising silver nanoparticles (AgNPs) for the high-resolution printing of stretchable conductors are reported. AgNPs are synthesized using aqueous polyurethane micelles, which are subsequently disentangled into polymeric chains in isopropanol to stabilize the inks. The ink rheology can be arbitrarily tuned to allow direct-write printing with a minimum feature width of 3 µm. Owing to the absence of extra surfactants, direct drying of such inks at room temperature provides the stretchable conductors with an initial conductivity of 8846 S cm-1 and conductivity of 1305 S cm-1 at 100% strain. This enhanced performance is attributed to the conductive percolations through assemblies of AgNPs adapting to the strain and is equivalent to those of stretchable conductors filled with Ag nanowires or flakes. These inks are promising for the scalable fabrication of highly integrated stretchable electronics.

[Research progress on sesquiterpenes and its pharmacological activities in genus Carpesium].

The genus Carpesium plants contain many kinds of sesquiterpenes. Up to now, more than 201 sesquiterpene compounds have been isolated and identified, including 86 germacranolides, 30 eudesmanolides, 29 guaianolides, 23 sesquiterpene dimers, 9 pseudoguaianes, 9 carabranolides, 7 xanthanolides, 6 sesquiterpenes without lactone, 1 eremophilane and 1 tricyclo dodecane sesquiterpene. The reported sesquiterpenes possess a series of pharmacological properties, such as anti-tumor, anti-inflammatory, antibacterial, antiparasitic, insecticidal, and antiviral activities. This paper summarizes the 201 chemical structures and biological activities of sesquiterpenes in genus Carpesium, and provides the scientific basis for the further development and utilization.

Integrating Biomass into the Organonitrogen Chemical Supply Chain: Production of Pyrrole and d-Proline from Furfural.

Production of renewable, high-value N-containing chemicals from lignocellulose will expand product diversity and increase the economic competitiveness of the biorefinery. Herein, we report a single-step conversion of furfural to pyrrole in 75 % yield as a key N-containing building block, achieved via tandem decarbonylation-amination reactions over tailor-designed Pd@S-1 and H-beta zeolite catalytic system. Pyrrole was further transformed into dl-proline in two steps following carboxylation with CO2 and hydrogenation over Rh/C catalyst. After treating with Escherichia coli, valuable d-proline was obtained in theoretically maximum yield (50 %) bearing 99 % ee. The report here establishes a route bridging commercial commodity feedstock from biomass with high-value organonitrogen chemicals through pyrrole as a hub molecule.

Cervical Lymph Node Metastatic Status and Adjuvant Therapy Predict the Prognosis of Salivary Duct Carcinoma.

PURPOSE: Salivary duct carcinoma (SDC) is an aggressive malignancy that is not yet fully understood. We designed the present retrospective study to investigate the factors affecting the prognosis of SDC and the effects of adjuvant therapies on the clinical outcomes of patients. MATERIALS AND METHODS: Patients with SDC treated surgically from 2006 to 2016 were enrolled in the present retrospective cohort study. The demographic data, clinical pathologic characteristics, and follow-up results were recorded. The prognostic indicators of overall survival (OS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) were analyzed using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: The study sample included 66 patients, most of whom were male (81.8%). The 5-year OS, LRFFS, and DMFS for all patients was 52.5%, 63.9%, and 51.3%, respectively. Univariate analysis showed that stage N2-N3, lymph node involvement of levels IV and V, 8 or more positive lymph nodes, and extranodal extension were all negative prognostic indicators for OS. The only significant indicator on multivariate analysis was the number of positive lymph nodes. Multivariate analysis revealed that extracapsular invasion and no adjuvant radiotherapy were risk factors for LRFFS. In contrast, lesions involving both glands and 8 or more positive lymph nodes were prognostic factors for DMFS. Further subgroup analysis showed that radiotherapy was only useful for patients with locally advanced lesions for local control. CONCLUSIONS: Cervical lymph node metastatic status is an important factor in predicting the prognosis of SDC patients. Adjuvant radiotherapy is useful for local control, especially for patients with stage T4 disease but does not benefit OS and DMFS.

Determination of strobilurin fungicide residues in fruits and vegetables by nonaqueous micellar electrokinetic capillary chromatography with indirect laser-induced fluorescence.

A nonaqueous micellar electrokinetic capillary chromatography method with indirect LIF was developed for the determination of strobilurin fungicide residues in fruits and vegetables. Hydrophobic CdTe quantum dots (QDs) synthesized in aqueous phase were used as background fluorescent substance. The BGE solution, QD concentration, and separation voltage were optimized to obtain the best separation efficiency and the highest signal intensity. The optimal BGE solution consists of 40 mM phosphate, 120 mM sodium dodecyl sulfate, 15% v/v water and 15% v/v hydrophobic CdTe QDs in formamide, of which apparent pH is 9.5. The optimized separation voltage is controlled as 25 kV. The resultant detection limits of azoxystrobin, kresoxim-methyl, and pyraclostrobin are all 0.001 mg/kg, their linear dynamic ranges are 0.005-2.5 mg/kg, and the recoveries of the spiked samples are 81.7-96.1%, 86.5-95.7%, and 87.3-97.4%, respectively. This method has been proved to be sensitive enough to detect the aforementioned fungicides in fruits and vegetables at the maximum residue limits.

Comparison of intramedullary and extramedullary fixation of stable intertrochanteric fractures in the elderly: a prospective randomised controlled trial exploring hidden perioperative blood loss.

BACKGROUND: Hip fracture is a severe and common injury that occurs predominantly in the elderly. Blood loss in the perioperative period is associated with a greater risk of dying in anaemic patients. The aim of the study was to explore the best way to treat stable intertrochanteric fractures, taking hidden blood loss into account. METHODS: This prospective, randomised blinded study included patients aged over 65 years with stable intertrochanteric fractures (Evans grades I and II). The patients were allocated to one of two groups treated via extramedullary or intramedullary fixation. Patient data were retrieved from electronic charts. Functional recovery was evaluated using the Functional Recovery Score of Zuckerman. Postoperative complications were also recorded. The formula of Nadler and Gross was used to calculate blood loss. RESULTS: There were 92 patients in the extramedullary and 106 in the intramedullary group. Age, sex, the cause of injury, the type of fracture, the observed blood loss, functional recovery, time to union, complications, and American Society of Anesthesiologists classification did not differ significantly between the two groups (all p-values > 0.05). The frequencies of lung infection, electrolyte imbalance, and hypoproteinemia differed between groups (all p-values < 0.05). Total and hidden blood loss were higher in the intramedullary group (p = 0.001). CONCLUSION: Extramedullary (compared with intramedullary) fixation of stable intertrochanteric fractures significantly reduces perioperative blood loss but affords similar functional outcomes and times to union. In view of the morbidity and complications associated with acute anaemia and transfusions, extramedullary fixation may be the optimal choice for treatment of stable fractures, being associated with reduced blood loss. TRIAL REGISTRATION: The study was retrospectively registered at the Chinese Clinical Trial Registry, number: ChiCTR-INQ-16009754 , trial registration date: 6th Nov. 2016.

Cerebellar encephalitis associated with anti-mGluR1 antibodies: a case report and comprehensive literature review.

Anti-metabotropic glutamate receptor 1 encephalitis is an uncommon autoimmune condition characterized by a subacute onset of cerebellar syndrome. Frequently, it also manifests as sleep disorders and cognitive or behavioral changes. While immunotherapy is the primary treatment approach, the disease remains poorly understood. Herein, we present a case of anti-metabotropic glutamate receptor 1 encephalitis, highlighting its primary cerebellar syndrome manifestation. The first magnetic resonance imaging scan showed no obvious abnormality. Lumbar puncture showed increased cerebrospinal fluid pressure, increased white blood cell count and protein level. The next-generation sequencing of cerebrospinal fluid showed Epstein-Barr virus infection, and the patient was diagnosed with viral cerebellar encephalitis. However, antiviral therapy was ineffective. Finally, anti-metabotropic glutamate receptor 1 was measured at 1:1,000, and the patient was definitely diagnosed with anti-metabotropic glutamate receptor 1 encephalitis. Therefore, clinicians should pay attention to such diseases to avoid misdiagnosis.

Robust Carbon Nitride Homojunction Photoelectrode for Solar-Driven Water Splitting.

Achieving intimate particle-to-particle and particle-to-substrate contacts is the first priority for fabricating high-quality photoelectrodes to ensure sufficient visible light absorption and efficient charge separation/transport. To achieve this goal, a seeding strategy is designed to construct a robust carbon nitride (CN) homojunction photoelectrode, in which vaporized precursors are condensed into a compact seeding layer at low temperatures, inducing the further deposition of the top layer. This optimized photoelectrode displays an excellent photocurrent density of 320 µA cm-2 in 0.1 M NaOH electrolyte at 1.23 VRHE (V vs reversible hydrogen electrode) under AM 1.5G illumination, with H2 and O2 evolution rates of 2.98 and 1.47 µmol h-1 cm-2, respectively. Characterizations show that both the robust contact and the homojunction of the double-layered CN film contribute to enhanced photoelectrochemical performance. This work may provide a new strategy for the design of high-performing CN photoelectrodes.

Influence of nano-Fe3O4 biochar on the methanation pathway during anaerobic digestion of chicken manure.

Volatile fatty acids and ammonia nitrogen (AN) accumulate during anaerobic digestion (AD) of high N substrates, such as chicken manure (CM), causing decreases in methane yield. Previous research found that the addition of nano-Fe3O4 biochar can alleviate the inhibition caused by acids and ammonia and increase methane production. The mechanism of enhanced methane production in nano-Fe3O4 biochar-mediated AD of CM was explored in depth in this study. The results showed the lowest AN concentration in the control and nano-Fe3O4 biochar addition groups were 8,229.0 mg/L and 7,701.5 mg/L, respectively. Methane yield of volatile solids increased from 92.0 mL/g to 219.9 mL/g in the nano-Fe3O4 biochar treatment, which was attributed to the enrichment of unclassified Clostridiales and Methanosarcina. The mechanism of nano-Fe3O4 biochar in AD of CM under high AN level was to improve methane production by promoting syntrophic acetate oxidation and facilitating direct electron transfer between microorganisms.

Chemical genomics reveals targetable programs of human cancers rooted in pluripotency.

Overlapping principles of embryonic and tumor biology have been described, with recent multi-omics campaigns uncovering shared molecular profiles between human pluripotent stem cells (hPSCs) and adult tumors. Here, using a chemical genomic approach, we provide biological evidence that early germ layer fate decisions of hPSCs reveal targets of human cancers. Single-cell deconstruction of hPSCs-defined subsets that share transcriptional patterns with transformed adult tissues. Chemical screening using a unique germ layer specification assay for hPSCs identified drugs that enriched for compounds that selectively suppressed the growth of patient-derived tumors corresponding exclusively to their germ layer origin. Transcriptional response of hPSCs to germ layer inducing drugs could be used to identify targets capable of regulating hPSC specification as well as inhibiting adult tumors. Our study demonstrates properties of adult tumors converge with hPSCs drug induced differentiation in a germ layer specific manner, thereby expanding our understanding of cancer stemness and pluripotency.

[Evaluation of the effect of repairing unilateral cleft lip nose deformity with autogenous concha cartilage].

PURPOSE: To explore the effect of nasal deformity correction after unilateral cleft lip repair with autogenous concha cartilage transplantation. METHODS: Thirteen patients with nasal deformity after unilateral cleft lip surgery were collected, who were treated with autogenous concha cartilage and nasal septum deviation correction at the same time. Their chin-lifting photos were taken before operation, five days, one month and six months after operation. The nasal morphology was evaluated by subjective evaluation and objective measurement, and statistical analysis was performed using SPSS 21.0 software package. RESULTS: Subjective evaluation showed that there was significant difference in nasal morphology between prior to operation and 5 days postoperatively (P=0.000), but there was no significant difference between 5 days postoperatively and 1 month and 6 months postoperatively(P=0.110, 0.053). In objective measurement, there was no significant difference in the symmetry rate of nasal tip between prior to operation and 5 days, 1 month and 6 months after operation(P=0.051, 0.136, 0.204), but there was significant difference in the symmetry rate of nasal base, nasal columella, extranasal convex angle and nasal alar base inclination angle between prior to operation and 5 days postoperatively(P=0.000, 0.000, 0.000, 0.000). However, there was no significant difference in symmetry rate of the above four indexes between 5 days after operation and 1 month and 6 months after operation(P＞0.05). CONCLUSIONS: Autogenous concha cartilage transplantation can effectively improve the symmetry of nasal floor, columella and alar after operation, and the effect is stable half a year after operation.

Plastic bending in a semiconducting coordination polymer crystal enabled by delamination.

Coordination polymers (CPs) are a class of crystalline solids that are considered brittle, due to the dominance of directional coordination bonding, which limits their utility in flexible electronics and wearable devices. Hence, engineering plasticity into functional CPs is of great importance. Here, we report plastic bending of a semiconducting CP crystal, Cu-Trz (Trz = 1,2,3-triazolate), that originates from delamination facilitated by the discrete bonding interactions along different crystallographic directions in the lattice. The coexistence of strong coordination bonds and weak supramolecular interactions, together with the unique molecular packing, are the structural features that enable the mechanical flexibility and anisotropic response. The spatially resolved analysis of short-range molecular forces reveals that the strong coordination bonds, and the adaptive C-H···π and Cu···Cu interactions, synergistically lead to the delamination of the local structures and consequently the associated mechanical bending. The proposed delamination mechanism offers a versatile tool for designing the plasticity of CPs and other molecular crystals.

Abnormal dopamine receptor signaling allows selective therapeutic targeting of neoplastic progenitors in AML patients.

The aberrant expression of dopamine receptors (DRDs) in acute myeloid leukemia (AML) cells has encouraged the repurposing of DRD antagonists such as thioridazine (TDZ) as anti-leukemic agents. Here, we access patient cells from a Phase I dose escalation trial to resolve the cellular and molecular bases of response to TDZ, and we extend these findings to an additional independent cohort of AML patient samples tested preclinically. We reveal that in DRD2+ AML patients, DRD signaling in leukemic progenitors provides leukemia-exclusive networks of sensitivity that spare healthy hematopoiesis. AML progenitor cell suppression can be increased by the isolation of the positive enantiomer from the racemic TDZ mixture (TDZ+), and this is accompanied by reduced cardiac liability. Our study indicates that the development of DRD-directed therapies provides a targeting strategy for a subset of AML patients and potentially other cancers that acquire DRD expression upon transformation from healthy tissue.

Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics.

Natural products (NPs) encompass a rich source of bioactive chemical entities. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (McM25044) capable of selectively inhibiting human CSC function versus normal stem cell counterparts. Biochemical and molecular studies revealed that McM025044 exerts inhibition on human CSCs through the small ubiquitin-like modifier (SUMO) cascade, found to be hyperactive in a variety of human cancers. McM025044 impedes the SUMOylation pathway via direct targeting of the SAE1/2 complex. Treatment of patient-derived CSCs resulted in reduced levels of SUMOylated proteins and suppression of progenitor and stem cell capacity measured in vitro and in vivo. Our study overcomes a barrier in chemically inhibiting oncogenic SUMOylation activity and uncovers a unique role for SAE2 in the biology of human cancers.

NLRP3 inflammasome activation by estrogen promotes the progression of human endometrial cancer.

BACKGROUND: Activation of NLPR3 inflammasome is associated with the development and progression of some types of malignant tumors, but its role in endometrial cancer is unclear. This study aimed to investigate the expression and function of NLRP3 inflammasome in endometrial cancer. MATERIALS AND METHODS:  The expression levels of NLRP3, its inflammasome components and estrogen receptor ß in endometrial cancer and paired non-tumor tissues were detected. The effects of NLPR3 silencing or overexpression on the proliferation, migration, and invasion of Ishikawa and HEC-1A cells were determined. The impact of NLPR3 silencing on the growth of implanted tumors was determined in vivo. The effects of estrogen on NLPR3 inflammasome activation and Ishikawa cell proliferation were determined. RESULTS: The upregulation of NLRP3, ASC, caspase-1, and IL-1ß was associated with the progression of endometrial cancer and poor survival. NLPR3 silencing inhibited the proliferation, migration, and invasion of endometrial cancer cells while NLPR3 overexpression had opposite effects. NLPR3 silencing reduced IL-1ß and caspase-1 expression and the growth of implanted endometrial tumors, accompanied by decreased pro-IL-1ß maturation. Estrogen enhanced NLPR3, ERß, pro-IL-1ß, IL-1ß expression, and endometrial cancer cell proliferation, which were mitigated by treatment with ERß inhibitor but not ERα inhibitor. CONCLUSION: Our results suggest that estrogen acts through ERß to enhance the activation of NLPR3 inflammasome and promote the progression of endometrial cancer. NLPR3 inflammasome may be a new therapeutic target for endometrial cancer.

Severe bradyarrhythmia linked to left atrial dysfunction in Fabry disease-A cross-sectional study.

BACKGROUND: Fabry disease (FD) is a lysosomal storage disorder caused by an enzymatic deficiency. Conduction abnormalities and bradyarrhythmias are common and can occur prior to the onset of left ventricular (LV) hypertrophy. We aimed to describe the clinical, electrocardiographic and echocardiographic, including left atrial (LA) function, determinants of bradyarrhythmic events in FD. HYPOTHESIS: Bradyarrhythmic events are frequent in patients with FD and are associated with LA dysfunction. METHODS: We designed a cross-sectional study that includes 53 FD patients (mean age, 45 years; 42% male). Clinical characteristics and electrocardiographic and echocardiographic data were collected. LA function was measured using biplane volumes and 2D speckle-tracking echocardiography. Bradyarrhythmic events were defined as pause of more than 2 seconds (sinus pause or atrioventricular block) recorded on Holter, severe bradycardia (≤ 40 bpm on ECG) or implantation of a permanent pacemaker. RESULTS: Six (11%) patients had installation of a pacemaker, 4 (8%) patients had cardiac pause and 2 (4%) patients had an episode of severe bradycardia. Patients with bradyarrhythmic events were older and had a lower resting heart rate. On echocardiography, a significantly higher LV mass, a lower LV ejection fraction, and a more affected LA reservoir function were found in those with bradyarrhythmic events. Patients also experienced tachyarrhythmias frequently. Atrial fibrillation occurred in 11 (21%) patients and ventricular tachycardia in 4 (8%) patients. CONCLUSIONS: Bradyarrhythmia are common manifestations of cardiac involvement in FD. Age, LV mass, LV ejection fraction and LA reservoir dysfunction can be useful markers associated with bradyarrhythmia.

Radiotherapy as salvage treatment of salivary duct carcinoma in major salivary glands without radical operations.

BACKGROUND: Salivary duct carcinoma (SDC) is an extremely rare and highly malignant carcinoma, and surgical radical resection is the most effective therapy. However, there were quite a proportion of patients receiving non-radical resections, and how to treat them remained controversial. Thus, the aim of this study is to evaluate whether postoperative radiotherapy could be a salvage treatment of SDC in major salivary glands without radical operations. PATIENTS AND METHODS: We identified 40 pathologically diagnosed SDC patients who came to our hospital and did not receive radical operations. Thirty-three patients received at least one treatment (remedial operation, postoperative radiotherapy and chemotherapy), and seven patients only chose observation and received no further treatment. The prognostic indicators of the local-regional control (LRC) and distant disease-free survival were analyzed using the Kaplan-Meier methods and the Cox proportional hazards regression models. RESULTS: Thirteen patients experienced local-regional recurrence or local progression, and distant metastases were observed in 15 patients. Through multivariate analysis, we found that postoperative radiotherapy was associated with better LRC, but this kind of treatment did not show significant efficacy in the prevention of distant metastasis. CONCLUSION: SDC is a rare, aggressive malignancy, and a substantial proportion of these patients experienced inadequate initial treatments. Although postoperative radiotherapy could not decrease distant metastases, it might help to improve LRC in patients with SDC.

Impaired Left Atrial Function in Fabry Disease: A Longitudinal Speckle-Tracking Echocardiography Study.

BACKGROUND: Fabry disease (FD) is characterized by the accumulation of sphingolipids in multiple organs, including the left atrium. It is uncertain if the left atrial (LA) reservoir, conduit, and contractile functions evaluated by speckle-tracking echocardiography are affected in Fabry cardiomyopathy and whether enzyme replacement therapy can improve LA function. METHODS: In this retrospective cohort study, LA strain, strain rates, and phasic LA volumes were studied in 50 patients with FD and compared with values in 50 healthy control subjects. RESULTS: All three LA phasic functions were altered. Peak positive strain (reservoir function) was 38.9 ± 14.9% versus 46.5 ± 10.9% (P = .004), and late diastolic strain (contractile function) was 12.6 ± 5.9% versus 15.6 ± 5.3% (P = .010). In 15 patients who started enzyme replacement therapy during the study, most of the LA parameters improved at 1-year follow-up (peak positive strain from 32.0 ± 13.5% to 38.0 ± 13.5%, P = .006), whereas there was a trend toward deterioration in 15 patients who never received treatment (peak positive strain from 47.3 ± 10.8% to 41.3 ± 9.3%, P = .058). Nine patients with FD (21%) experienced new-onset atrial fibrillation or stroke during 4-year follow-up. By univariate analysis, peak positive strain and early diastolic strain demonstrated significant associations with clinical events, surpassing conventional echocardiographic parameters and clinical characteristics. CONCLUSIONS: LA reservoir, conduit, and contractile functions by speckle-tracking echocardiography were all affected in FD. Enzyme replacement therapy improved LA function. LA strain parameters were associated with atrial fibrillation and stroke.