General Anesthesia Exposure in Infancy and Childhood: A 10-year Bibliometric Analysis.

PURPOSE: Heated discussions have divided health care providers and policymakers on the risks versus benefits of general anesthesia in pediatric populations. We conducted this study to provide a comprehensive bibliometric analysis of general anesthesia in this specific population over the past decade. DESIGN: We summarized and quantitatively analyzed the studies related to general anesthesia in children and infants over the past decade. METHODS: Using the Web of Science Core Collection as the data source, we analyzed the literature using CiteSpace software, focusing on authors, countries, institutions, keywords, and references to identify hotspots and predict research trends. FINDINGS: A total of 2,364 publications on pediatric anesthesia were included in the analysis. The number of related publications and citations steadily increased from 2013 to 2022. The United States was the leading country in terms of output, and University of Toronto was the primary contributing institution. Co-citation analysis revealed that over the past decade research has mainly focused on the long-term adverse effects of general anesthesia on neurodevelopment and acute perioperative crisis events. Keyword analysis identified infant sedation and drug selection and compatibility as promising areas for development. In addition, improving the quality of perioperative anesthesia will be a major research focus in the future. CONCLUSIONS: Recent research in pediatric anesthesia has focused on mitigating the adverse effects of general anesthesia in infants and young children and studying the pharmacological compatibility of anesthetics. Our study results would assist researchers and clinicians in understanding the current research status and optimizing clinical practice in this field.

Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

BACKGROUND: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life. RESULTS: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups. CONCLUSIONS: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

Impact of rhG-CSF on Clinical Efficacy and Immune Cell Subsets after Initial Induction Chemotherapy in AML.

BACKGROUND: The impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in acute myeloid leukemia (AML) is still controversial. The purpose of this study is to explore the impact of rhG-CSF administration on clinical efficacy and immune cell subsets after initial induction chemotherapy in AML. METHODS: The clinical efficacy and immune cell subsets were compared in the newly diagnosed patients with AML according to whether rhG-CSF was used after initial induction chemotherapy. Next, rhG-CSF stimulation experi-ments on leukemia cell lines and primary leukemia blasts were performed in vitro. RESULTS: There was no statistical difference between control group and rhG-CSF therapy group in complete remission rate and relapse free survival. The duration of agranulocytosis was significantly shortened in rhG-CSF therapy group compared with control group. The percentage of circulating monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) were significantly increased after the administration of rhG-CSF. Furthermore, it was found that rhG-CSF did not promote the proliferation of leukemia cell lines and primary leukemia blasts, but increased the proportion of M-MDSCs and Tregs in vitro. CONCLUSIONS: Administration of rhG-CSF after initial induction therapy of AML does not affect the clinical remission and relapse rate, but reduces the duration of agranulocytosis and increases the proportion of M-MDSCs and Tregs.

Recurrent ZNF83-E293V Mutation Promotes Bladder Cancer Progression through the NF-κB Pathway via Transcriptional Dysregulation of S100A8.

Urothelial carcinoma (UC) is the predominant form of bladder cancer. Significant molecular heterogeneity caused by diverse molecular alterations brings about large variations in the response to treatment in UC. An improved understanding of the genetic mechanisms underlying the development and progression of UC is essential. Through deep analysis of next-generation sequencing data of 99 UC patients, we found that 18% of cases had recurrent somatic mutations in zinc finger protein gene zinc finger protein 83 (ZNF83). ZNF83 mutations were correlated with poor prognosis of UC. We also found a hotspot mutation, p.E293V, in the evolutionarily well-conserved region of ZNF83. ZNF83-E293V increased tumor growth and reduced the apoptosis of UC cells compared to wild-type ZNF83 both in vitro and in mice xenografted tumors. ZNF83-E293V activated nuclear factor κB (NF-κB) more potently than did the wild-type protein owing to its decreased transcriptional repression for S100A8. The NF-κB inhibitors could pharmacologically block the tumor growth in mice engrafted with ZNF83-E293V-transfected UC cells. These findings provide a mechanistic insight and a potential therapeutic strategy for UC, which established a foundation for using the ZNF83-E293V mutation as a predictive biomarker of therapeutic response from NF-κB inhibitors.

Identification of reproduction-related genes and pathways in the Culter alburnus H-P-G axis and characterization of their expression differences in malformed and normal gynogenetic ovaries.

This study applied RNA-seq technology to discover reproduction-related genes and pathways in female topmouth culter brain (including pituitary) and ovarian tissues. In functional analysis, 2479 and 2605 unigenes in the brain and ovary tissue were assigned to the "reproductive process" subcategory in addition to the 2660 and 2845 unigenes assigned to the "reproduction" subcategory. Twenty-three complete cDNA sequences were identified through the different gene expression (DGE) approach from five reproduction-related pathways (MAPK signaling pathway, neuroactive ligand-receptor interaction pathway, gonadotropin-releasing hormone signaling pathway, oocyte meiosis pathway, and steroid biosynthesis pathway). The expression levels of 16 candidate genes using qPCR in this study were in accordance with the results of transcriptome analysis. In addition, the expression levels of the FSH, 3ß-HSD, PGR, and NPYR genes in malformed gynogenetic ovaries were considerably low, which was consistent with the progress of oocytogenesis in the ovaries of topmouth culter. The high expression of these four genes in the ovaries of normal topmouth culter suggested they might involve in the preparation for the shift of oogenesis to ovulation. Hence, our work identified a set of annotated gene products that are candidate factors affecting reproduction in the topmouth culter H-P-G axis. These results could be essential for further research in functional genomics and genetic editing for topmouth culter reproduction.

Injection-seeded single-longitudinal-mode Ti:Sapphire laser with no active stabilization.

We report on the first injection-seeded nanosecond Ti:Sapphire laser that demonstrates a stable single-longitudinal-mode operation with no feedback loop for active cavity stabilization. The short cavity generates 6-mJ transform-limited pulses at a wavelength of 807 nm and with a slope efficiency of 43%. An intracavity dispersive prism makes a novel cavity design for injection-seeded lasers and provides pre-selection of the emission wavelength. In support of these experiments, we perform numerical simulations that include extra cavity losses. The simulation results are in good agreement with the outcome of the experiment and reveal the formation scenario of the laser mode.

Burden of infective endocarditis in an Australian cohort of people who inject drugs.

BACKGROUND: Infective endocarditis (IE) results in substantial morbidity and mortality in people who inject drugs (PWID). AIMS: To describe the burden of IE and its outcomes in PWID. METHODS: Retrospective cohort study of adults admitted to a tertiary referral centre in Melbourne, Australia, with IE due to injection drug use from 1997 to 2015. RESULTS: Ninety-seven PWID with 127 episodes of IE were identified with a median acute inpatient stay of 37 days (1-84). Admission to an intensive care unit was required in 67/127 (53%) episodes. Twenty-seven percent (34/127) of episodes occurred in patients with a previous episode of endocarditis. One third (43/127, 34%) of episodes involved left-sided cardiac valves. Antimicrobial treatment was completed in 88 (70%) episodes. Valve surgery was performed in 25/127 (20%) episodes. Predictors of surgery in univariable analysis were left-sided cardiac involvement (risk ratio (RR) 6.0), severe valvular regurgitation (RR 2.6) and cardiac failure (RR 2.2) (all P < 0.005). Twenty (16%) episodes resulted in death. Predictors of mortality on univariable analysis were left-sided cardiac involvement (RR 6.4), and not completing treatment (RR 0.12; both P < 0.001). The average estimated cost per episode was AU$74 168. CONCLUSIONS: IE causes a considerable burden of disease in PWID, with significant healthcare utilisation and cost. Surgery and death are not infrequent complications. In addition to ensuring completion of antimicrobial therapy, strategies such as opioid maintenance programmes may be useful in improving health outcomes for PWID.

Skeletal development of the chondrocranium in the tongue sole Cynoglossus semilaevis (Pleuronectiformes: Cynoglossidae).

This study provides a comprehensive description of chondrocranial development before, during and after larval metamorphosis in the tongue sole Cynoglossus semilaevis, a commercially valuable flatfish in China. Samples were collected at regular intervals ranging from 1 to 23 days post hatching (dph). Based on observations of cleared and double-stained specimens and images from sections stained with safranin O-fast green, major morphological events during early development were described. No cartilaginous structure was visible at hatching. From 2 dph onwards, cartilaginous structures such as the trabecular bar and some elements of the mandibular, hyoid and branchial arches appeared. At this time also, cartilaginous structures of the neurocranium started to form. Hypertrophic chondrocytes could be observed in many splanchnocranium elements at 5 dph. The start of ossification was indicated by alizarin red stain visible at 14 dph. At 17 dph, most of the cartilaginous skeleton was ossified. Soon after, the right eye started to migrate and pass through a slit beneath the dorsal-fin base and above the skull. Metamorphosis was complete at 20 dph, at which time the dorsal-fin base cartilage extended onto the anterior region of the head. Meanwhile, extremities of the hyoid and branchial arch elements remained cartilaginous. At 23 dph, endochondral ossification of the splanchnocranium was nearly complete. Unlike previous observations of other Pleuronectiformes, our study indicates that endochondral ossification of C. semilaevis skull cartilage occurs before metamorphosis.

Molecular Recalibration of PD-1+ Antigen-Specific T Cells from Blood and Liver.

Checkpoint inhibitors and adoptive cell therapy provide promising options for treating solid cancers such as HBV-related HCC, but they have limitations. We tested the potential to combine advantages of each approach, genetically reprogramming T cells specific for viral tumor antigens to overcome exhaustion by down-modulating the co-inhibitory receptor PD-1. We developed a novel lentiviral transduction protocol to achieve preferential targeting of endogenous or TCR-redirected, antigen-specific CD8 T cells for shRNA knockdown of PD-1 and tested functional consequences for antitumor immunity. Antigen-specific and intrahepatic CD8 T cells transduced with lentiviral (LV)-shPD-1 consistently had a marked reduction in PD-1 compared to those transduced with a control lentiviral vector. PD-1 knockdown of human T cells rescued antitumor effector function and promoted killing of hepatoma cells in a 3D microdevice recapitulating the pro-inflammatory PD-L1hi liver microenvironment. However, upon repetitive stimulation, PD-1 knockdown drove T cell senescence and induction of other co-inhibitory pathways. We provide the proof of principle that T cells with endogenous or genetically engineered specificity for HBV-associated HCC viral antigens can be targeted for functional genetic editing. We show that PD-1 knockdown enhances immediate tumor killing but is limited by compensatory engagement of alternative co-inhibitory and senescence program upon repetitive stimulation.

Acclimation of bloom-forming and perennial seaweeds to elevated pCO2 conserved across levels of environmental complexity.

Macroalgae contribute approximately 15% of the primary productivity in coastal marine ecosystems, fix up to 27.4 Tg of carbon per year, and provide important structural components for life in coastal waters. Despite this ecological and commercial importance, direct measurements and comparisons of the short-term responses to elevated pCO2 in seaweeds with different life-history strategies are scarce. Here, we cultured several seaweed species (bloom forming/nonbloom forming/perennial/annual) in the laboratory, in tanks in an indoor mesocosm facility, and in coastal mesocosms under pCO2 levels ranging from 400 to 2,000 µatm. We find that, across all scales of the experimental setup, ephemeral species of the genus Ulva increase their photosynthesis and growth rates in response to elevated pCO2 the most, whereas longer-lived perennial species show a smaller increase or a decrease. These differences in short-term growth and photosynthesis rates are likely to give bloom-forming green seaweeds a competitive advantage in mixed communities, and our results thus suggest that coastal seaweed assemblages in eutrophic waters may undergo an initial shift toward communities dominated by bloom-forming, short-lived seaweeds.

Clinical application of a gadolinium-based capsule as an MRI contrast agent in slow transit constipation diagnostics.

BACKGROUND: As a traditional method for the assessment of colon dynamics, radio-opaque markers (ROMs) are limited in clinical use because of their ionizing radiation. We compared the accuracy and applicability of gadolinium-based capsules with ROMs in the measurement of colon dynamics in healthy controls and slow transit constipation (STC) patients. METHODS: Seven patients with STC and nine healthy controls under a normal diet orally consumed ROMs and gadolinium-based capsules simultaneously. All subjects underwent X-ray and magnetic resonance imaging (MRI). Healthy control images were acquired at 12, 24, and 48 h, and STC patient images were acquired at 24, 48, and 72 h. The scores based on the position of the labeling capsules and ROMs in the colon and the colon transit times (CTTs) in the two groups were compared. KEY RESULTS: The CTTs obtained via the ROMs were 34.7±17.4 and 67.3±6.5 h in the healthy controls and STC patients, respectively (P<.05). The CTTs obtained via MRI were 30.9±15.9 and 74.1±7.2 h in the healthy controls and STC patients, respectively (P<.05). The CTTs of the STC patients were significantly longer than the healthy controls. The correlation (rs ) between the scores based on the position of the labeling capsule and ROMs in the healthy group and the STC patients was .880 (P<.05) and .889 (P<.05), respectively. CONCLUSIONS AND INFERENCES: As a MRI contrast label, gadolinium-based capsules exhibit results comparable to ROMs in colon motility measurements.

Simulating Stable Isotope Ratios in Plumes of Groundwater Pollutants with BIOSCREEN-AT-ISO.

BIOSCREEN is a well-known simple tool for evaluating the transport of dissolved contaminants in groundwater, ideal for rapid screening and teaching. This work extends the BIOSCREEN model for the calculation of stable isotope ratios in contaminants. A three-dimensional exact solution of the reactive transport from a patch source, accounting for fractionation by first-order decay and/or sorption, is used. The results match those from a previously published isotope model but are much simpler to obtain. Two different isotopes may be computed, and dual isotope plots can be viewed. The dual isotope assessment is a rapidly emerging new approach for identifying process mechanisms in aquifers. Furthermore, deviations of isotope ratios at specific reactive positions with respect to "bulk" ratios in the whole compound can be simulated. This model is named BIOSCREEN-AT-ISO and will be downloadable from the journal homepage.

NUDT15 polymorphisms are better than thiopurine S-methyltransferase as predictor of risk for thiopurine-induced leukopenia in Chinese patients with Crohn's disease.

BACKGROUND: Thiopurine-induced leukopenia is the most common dangerous adverse event in Asians. NUDT15 R139C was recently proposed to be a promising biomarker for leukopenia with thiopurine therapy in Asians, but this has not been replicated in the Chinese population. AIM: To investigate the influence of NUDT15 R139C, thiopurine S-methyltransferase (TPMT), 6-TGN and 6-MMPR on thiopurine-induced leukopenia in Chinese patients with Crohn's disease. METHODS: Clinical and epidemiological characteristics were reviewed from medical records. NUDT15 R139C and TPMT were genotyped. 6-TGN/6-MMPR concentrations were measured with high-performance liquid chromatography (HPLC). RESULTS: A total of 253 patients were included, 65 (25.7%) of whom experienced leukopenia. The median follow-up with thiopurine treatment was 38.0 weeks (range, 1-192 weeks). NUDT15 R139C was strongly associated with the incidence of leukopenia (70.2% mutation vs. 12.8% wild type; P=8.61×10-19 ; odds ratio, 10.80; 95% CI, 5.89-19.83). However, TPMT genotype was not found to be correlated with the incidence of leukopenia (P = 0.44). In subgroup of NUDT15 wild type, there was significant difference of 6TGN concentration between patients with and without leukopenia (413.0 (174.2-831.4) vs. 279.7 (77.3-666.9) pmol/8 × 108 RBC, P = 0.0055). In contrast, no association was found in patients with NUDT15 R139C variant alleles (P = 0.26). 6-MMPR was not correlated with leukopenia (P = 0.84). CONCLUSIONS: In Chinese patients, it is strongly recommended to detect NUDT15 genotype rather than TPMT before initiating thiopurine drugs. 6TGN concentration should be routinely monitored in CD patients with NUDT15 wild type. As for CT genotype, starting at low dose and careful monitoring for leukopenia and 6TGN levels is recommended.

Intracoronary infusion of Wharton's jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial.

BACKGROUND: The use of adult stem cells is limited by the quality and quantity of host stem cells. It has been demonstrated that Wharton's jelly-derived mesenchymal stem cells (WJMSCs), a primitive stromal population, could integrate into ischemic cardiac tissues and significantly improve heart function. In this randomized, controlled trial, our aim was to assess the safety and efficacy of intracoronary WJMSCs in patients with ST-elevation acute myocardial infarction (AMI). METHODS: In a multicenter trial, 116 patients with acute ST-elevation MI were randomly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infarct artery at five to seven days after successful reperfusion therapy. The primary endpoint of safety: the incidence of adverse events (AEs) within 18 months, was monitored and quantified. The endpoint of efficacy: the absolute changes in myocardial viability and perfusion of the infarcted region from baseline to four months, global left ventricular ejection fraction (LVEF) from baseline to 18 months were measured using F-18-fluorodeoxyglucose positron emission computed tomography (F-18-FDG-PET) and 99mTc-sestamibi single-photon emission computed tomography (99mTc-SPECT), and two-dimensional echocardiography, respectively. RESULTS: During 18 months follow-up, AEs rates and laboratory tests including tumor, immune, and hematologic indexes were not different between the two groups. The absolute increase in the myocardial viability (PET) and perfusion within the infarcted territory (SPECT) was significantly greater in the WJMSC group [6.9 ± 0.6 % (95 %CI, 5.7 to 8.2)] and [7.1 ± 0.8 % (95 %CI, 5.4 to 8.8) than in the placebo group [3.3 ± 0.7 % (95 %CI, 1.8 to 4.7), P <0.0001] and 3.9 ± 0.6(95 %CI, 2.8 to 5.0), P = 0.002] at four months. The absolute increase in the LVEF at 18 months in the WJMSC group was significantly greater than that in the placebo group [7.8 ± 0.9 (6.0 to approximately 9.7) vs. 2.8 ± 1.2 (0.4 to approximately 5.1), P = 0.001]. Concomitantly, the absolute decreases in LV end-systolic volumes and end-diastolic volumes at 18 months in the WJMSC group were significantly greater than those in the placebo group (P = 0.0004, P = 0.004, respectively). CONCLUSIONS: Intracoronary infusion of WJMSCs is safe and effective in patients with AMI, providing clinically relevant therapy within a favorable time window. This study encourages additional clinical trials to determine whether WJMSCs may serve as a novel alternative to BMSCs for cardiac stem cell-based therapy. TRIAL REGISTRATION: Clinical Trials NCT01291329 (02/05/2011).

Diagnostic performance of microRNA-29a for colorectal cancer: a meta-analysis.

Previous studies have revealed that the expression level of microRNA-29a (miR-29a) was remarkably different in colorectal cancer (CRC) patients and healthy controls, indicating that miR-29a can be used as a diagnostic marker of CRC, but the results have been inconsistent. We conducted this meta-analysis to assess the diagnostic performance of blood-based miR-29a for CRC. We performed a systematic review of studies published over the past two decades to investigate the diagnostic performance of serum miR-29a for the diagnosis of CRC. QUADAS-2 was used to evaluate the quality of the studies. Performance characteristics (diagnostic sensitivity, specificity, and other measures of accuracy) were pooled and examined using random-effect models. Five studies, which included 281 CRC patients and 299 healthy controls, met the inclusion criteria. The summary estimates for miR-29a in CRC diagnoses showed a diagnostic sensitivity of 0.59 (95%CI = 0.53-0.65), a specificity of 0.89 (95%CI = 0.85-0.93), and a diagnostic odds ratio of 12.22 (95%CI = 5.07-29.44). The area under curve and Q value for the summary receiver operating characteristic curves were 0.9128 and 0.8453, respectively. In conclusion, miR-29a may be a novel potential biomarker for CRC diagnosis.

Damage modeling and statistical analysis of optics damage performance in MJ-class laser systems.

Modeling the lifetime of a fused silica optic is described for a multiple beam, MJ-class laser system. This entails combining optic processing data along with laser shot data to account for complete history of optic processing and shot exposure. Integrating with online inspection data allows for the construction of a performance metric to describe how an optic performs with respect to the model. This methodology helps to validate the damage model as well as allows strategic planning and identifying potential hidden parameters that are affecting the optic's performance.

Novel method to establish molecular identity using inter-simple sequence repeat markers in cotton (Gossypium hirsutum) cultivars.

Plant molecular identity (ID) is used to describe molecular characteristics of plants, which should contain all of the necessary information. Using inter-simple sequence repeat (ISSR) primers, molecular ID can be described in a way that reflects the polymerase chain reaction (PCR) conditions, annealing temperature, and the bands obtained in PCR amplification. A new complete molecular ID system is described in this study, which can be easily used and expanded to include more information. Using three cotton cultivars, we analyzed the products of PCR with ISSR primers and discussed the strategy for establishing their molecular ID. Using the segmented naming method, we designate the simple names and the full name systems of these three cultivars.

Growth model for laser-induced damage on the exit surface of fused silica under UV, ns laser irradiation.

We present a comprehensive statistical model which includes both the probability of growth and growth rate to describe the evolution of exit surface damage sites on fused silica optics over multiple laser shots spanning a wide range of fluences. We focus primarily on the parameterization of growth rate distributions versus site size and laser fluence using Weibull statistics and show how this model is consistent with established fracture mechanics concepts describing brittle materials. Key growth behaviors and prediction errors associated with the present model are also discussed.

The prevalence and risk factors of OAB in middle-aged and old people in China.

AIMS: To evaluate the prevalence of associated risk factors of over active bladder (OAB) in people ≥40 years old in mainland of China. METHODS: A randomized community-based, cross-sectional study was performed on 10,160 residents (≥40 years old) in the mainland of China using a questionnaire. The overactive bladder symptom score (OABSS) was filled upon site. The chi-square test was used to determine the differences of prevalence between sex, age groups, body mass index (BMI) and people with and without diabetes mellitus (DM). RESULTS: A total of 9,805 (96.5%) subjects qualified for the final statistical analysis. The overall prevalence of OAB was 2.1% (209/9,805), of whom 1.0% had OABdry and 1.1% had OABwet . The prevalence of OAB was more common in men than in women over the age of 60 (4.6% vs. 2.6%, P < 0.05). The prevalence of OAB in subjects with DM was significantly higher than those without DM in patients with BMI ≥ 25 (P < 0.05). The subjects with a BMI over 29 were more likely to have OAB (3.2% vs. 1.8%, P < 0.05). CONCLUSIONS: In this population, the prevalence of OAB increased with age for both sexes, but was higher for males over 60 years of age. The study also showed that diabetics with BMI ≥ 25 and people suffering from obesity are more likely to have OAB.

A critical challenge: dosage-related efficacy and acute complication intracoronary injection of autologous bone marrow mesenchymal stem cells in acute myocardial infarction.

BACKGROUND: Previous studies showed improvement in heart function by injecting bone marrow mesenchymal stem cells (BMSCs) after AMI. Emerging evidence suggested that both the number and function of BMSCs decline with ageing. We designed a randomized, controlled trial to further investigate the safety and efficacy of this treatment. METHODS: Patients with ST-elevation AMI undergoing successful reperfusion treatment within 12 hours were randomly assigned to receive an intracoronary infusion of BMSCs (n=21) or standard medical treatment (n=22) (the numbers of patients were limited because of the complication of coronary artery obstruction). RESULTS: There is a closely positive correlation of the number and function of BMSCs vs. the cardiac function reflected by LVEF at baseline (r=0.679, P=0.001) and at 12-month follow-up (r=0.477, P=0.039). Six months after cell administration, myocardial viability within the infarct area by 18-FDG SPECT was improved in both groups compared with baseline, but no significant difference in the BMSCs compared with control groups (4.0±0.4% 95%CI 3.1-4.9 vs. 3.2±0.5% 95%CI 2.1-4.3, P=0.237). 99mTc-sestamibi SPECT demonstrated that myocardial perfusion within the infarct area in the BMSCs did not differ from the control group (4.4±0.5% 95%CI 3.2-5.5 vs. 3.9±0.6% 95%CI 2.6-5.2, P=0.594). Similarly, LVEF after 12 and 24 months follow-up did not show any difference between the two groups. In the BMSCs group, one patient suffered a serious complication of coronary artery occlusion during the BMSCs injection procedure. CONCLUSIONS: The clinical benefits of intracoronary injection of autologous BMSCs in acute STEMI patients need further investigation and reevaluation.