Yunmen (LU 2) combined with neck-seven-acupoint acupuncture for arm numbness caused by cervical spondylotic radiculopathy: A case report.

RATIONALE: Cervical spondylotic radiculopathy (CSR) is a common sensory, motor, and reflex disorder. Numbness, a common subjective symptom of CSR, lacks objective quantitative indicators and recognized effective treatments, but is also difficult to recover from. We present a case report describing a traditional acupuncture treatment for CSR, utilizing a special acupuncture method and point, namely the Yunmen point. PATIENT CONCERNS: A 40-year-old woman presented with unilateral arm numbness caused by CSR. DIAGNOSES: A diagnosis of CSR was made in the orthopedic department of a local hospital. INTERVENTIONS: We attempted acupuncture at the Yunmen (LU 2) acupoint combined with neck-seven-acupoint under computed tomographic guidance. OUTCOMES: After 10 times treatment sessions, the patient no longer experienced weakness, coldness, or numbness in the affected upper limb. In addition, the stiffness in the neck and shoulders was reduced. On physical examination, the patient's left brachial plexus traction test was negative; reassessment of the CSR-20-point score scale showed a perfect score, and the visual analog scale score was 0. LESSONS: Our report indicates that acupuncture at the LU 2 acupoint combined with neck-seven-acupoint is effective in treating numbness and coldness of the arm, and other neurological symptoms caused by cervical spondylosis. Moreover, with the appropriate acupuncture technique, the risk of acupuncture at the LU 2 acupoint can be minimized.

Corrigendum: Quercetin Attenuates Atherosclerosis via Modulating Oxidized LDL-Induced Endothelial Cellular Senescence.

[This corrects the article DOI: 10.3389/fphar.2020.00512.].

Quercetin Attenuates Atherosclerosis via Modulating Oxidized LDL-Induced Endothelial Cellular Senescence.

BACKGROUND AND AIMS: Endothelial senescence is an important risk factor leading to atherosclerosis. The mechanism of quercetin against endothelial senescence is worth exploring. METHODS: Quercetin (20 mg/kg/d) was administered to ApoE-/- mice intragastrically to evaluate the effectiveness of quercetin on atherosclerotic lesion in vivo. In vitro, human aortic endothelial cells (HAECs) were used to assess the effect of quercetin on cellular senescence induced by oxidized low-density lipoprotein (ox-LDL). Transcriptome microarray and quantitative RT-PCR was conducted to study the pharmacological targets of quercetin. RESULTS: ApoE-/- mice demonstrated obvious lipid deposition in arterial lumina, high level of serum sIcam-1 and IL-6, and high density of Vcam-1 and lower density of Sirt1 in aorta. Quercetin administration decreased lipid deposition in arterial lumina, serum sIcam-1, and IL-6 and Vcam-1 in aorta, while increased the density of Sirt1 in aorta of ApoE-/- mice. In vitro, quercetin (0.3, 1, or 3 µmol/L) decreased the expression of senescence-associated ß-galactosidase and improved cell morphology of HAECs. And quercetin decreased the cellular apoptosis and increased mitochondrial membrane potential (ΔΨm) in dose-dependent manner, and decreased ROS generation simultaneously. Transcriptome microarray suggested 254 differentially expressed (DE) mRNAs (110 mRNAs were upregulated and 144 mRNAs were downregulated) in HAECs after quercetin treatment (fold change > 1.5, P < 0 .05, Que vs Ox-LDL). GO and KEGG analysis indicated nitrogen metabolism, ECM-receptor interaction, complement, and coagulation cascades, p53 and mTOR signaling pathway were involved in the pharmacological mechanisms of quercetin against ox-LDL. CONCLUSIONS: Quercetin alleviated atherosclerotic lesion both in vivo and in vitro.

Guizhi Decoction () Inhibits Cholinergic Transdifferentiation by Regulating Imbalance of NGF and LIF in Salt-Sensitive Hypertensive Heart Failure Rats.

OBJECTIVE: To observe the imbalance of anatomical and functional innervation factors of sympathetic nerves, nerve growth factor (NGF) and leukemia inhibitory factor (LIF), in salt-sensitive hypertensive heart failure rats and to explore the effects of treatment with Guizhi Decoction () on sympathetic remodeling by inhibiting cholinergic transdifferentiation. METHODS: SS-13BN and Dahl salt-sensitive (DS) rats were divided into 3 groups: SS-13BN group (control group, n=9), DS group (model group, n=9) and GS group (Guizhi Decoction, n=9). After 10 weeks of a high-salt diet, the GS group rats were given Guizhi Decoction and other two groups were given saline at an equal volume as a vehicle. After 4 weeks' intragastric administration, rats were executed to detect the relevant indicators. Echocardiography and plasma n-terminal pro-B type natriuretic peptide (NT-proBNP) levels were used to assess cardiac function. Noradrenaline (NA) levels in the plasma and myocardium were detected to evaluate the sympathetic function. NGF and LIF expression were detected in the myocardium by Western blot or quantitative real-time PCR. Double immunofluorescence or Western blot was used to detect tyrosine hydroxylase (TH), choline acetyltransferase (CHAT) and growth associated protein 43 (GAP43) in order to reflect anatomical and functional changes of sympathetic nerves. RESULTS: DS group had anatomical and functional deterioration of sympathetic nerves in the decompensation period of heart failure compared with SS-13BN group. Compared with the DS group, Guizhi Decoction significantly decreased the expression of LIF mRNA/protein (P<0.01), increased the expression of NGF (P<0.05 or P<0.01), enhanced the levels of TH+/GAP43+ and TH+/CHAT+ positive nerve fibers (P<0.01), and improved the protein expression of TH and GAP43 in left ventricle, but had no effect on CHAT (P>0.05). Guizhi Decoction inhibited inflammatory infiltration and collagen deposition of myocardial injury, increased the content of myocardial NA (P<0.05), reduced the plasma NA level (P<0.01), improved cardiac function (P<0.01), and improved weight and blood pressure to some extent (P<0.05), compared with DS group. CONCLUSIONS: Guizhi Decoction could inhibit cholinergic transdifferentiation of sympathetic nerves, improve the anatomical and functional denervation of sympathetic nerves, and delay the progression of decompensated heart failure. The mechanism may be associated with the correction of the imbalance of NGF and LIF.

Medicated thread moxibustion for alopecia areata: A case report.

RATIONALE: According to the literature reports and clinical studies on alopecia areata (AA) from 2008 to 2018, most clinical treatments have been oral drugs and external ointments. At present, systemic immunosuppressive therapy has been widely used in AA, but there are various side effects such as elevated liver enzymes, gastrointestinal discomfort, poor drug compliance, and repeated illness. We present a case report describing a traditional medicine treatment for AA that uses an ethnic therapy of Zhuang medicine, a kind of Traditional Chinese Medicine, namely, medicated thread moxibustion. PATIENT CONCERNS: A 36-year-old man endured AA after going through a family misfortune. Half a year ago, his father passed away suddenly. Since then, he suffered continuous anguish, alcoholism and hair loss, especially in the past 2 months. A coin-shaped area of hair loss began to appear at the top of his head and gradually expanded to the surrounding region. DIAGNOSES: A diagnosis of AA was made in the dermatology department of a local hospital. INTERVENTIONS: The patient was treated with the medicated thread moxibustion method of Traditional Zhuang Medicine at the Kuihua (special points of Zhuang medicine), Zusanli (ST 36), Xuehai (SP 10), Baihui (DU 20), and Taichong (LR 3) points every other day for 4 weeks. OUTCOMES: The area of hair loss showed slight improvement after 1 week of treatment. Only just a sprinkling of wooly hairs, whose color and thickness were similar to those of fine facial hairs, began to emerge sporadically from the follicles; they could be seen only in a bright light. When the patient saw the obvious curative effect, we continued the treatment for 2 weeks with the patient's consent. Three weeks later, the patchy AA area was covered with small cotton-like hairs of different lengths and uneven colors. LESSONS: The medicated thread moxibustion method of Zhuang medicine can be an effective alternative treatment in patients with AA.

Exploring the structure, bonding and stability of noble gas compounds promoted by superhalogens. A case study on HNgMX3 (Ng = Ar-Rn, M = Be-Ca, X = F-Br) via combined high-level ab initio and DFT calculations.

A series of complexes (HNgMX3), formed from superhalogen MX3 (M = Be-Ca, X = F-Br) noble gas (Ar-Rn) and the hydrogen atom, were investigated via combined high-level ab initio and DFT calculations. The high vertical electron detachment energy (VDE) of the superhalogen part will lead to charge transfer from the noble gas hydride to it. This charge transfer gives rise to attractive ionic interaction between the two components and to the existence of these complexes as local minima on the potential energy surface eventually. However, the VDE value of the superhalogen part is not always monotonically correlated with the thermodynamic/kinetic stability of the whole complexes. Therefore the superhalogen itself might not be enough to provide information for the correct prediction of the properties of the whole composites. Although there are exothermic channels of dissociation, the existence of energy barrier might ensure the existence of these Ng hydrides under certain conditions. Our analysis indicates the existence of two important factors, functioning in opposite directions, for the energy barriers along the exothermic channel. To achieve a high energy barrier, the attractive interaction between superhalogen and the H atom in the TS, which lowers the barrier, needs to be suppressed effectively. An understanding of the superhalogen-based composites will provide valuable information on the functional properties and potential application of superhalogens. The details of the interaction between different parts of these composites should be one of the areas of focus in these studies.

Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota.

BACKGROUND: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect. METHODS: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota. RESULTS: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF. CONCLUSIONS: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.

A NiFe Alloy Reduced on Graphene Oxide for Electrochemical Nonenzymatic Glucose Sensing.

A NiFe alloy nanoparticle/graphene oxide hybrid (NiFe/GO) was prepared for electrochemical glucose sensing. The as-prepared NiFe/GO hybrid was characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). The results indicated that NiFe alloy nanoparticles can be successfully deposited on GO. The electrochemical glucose sensing performance of the as-prepared NiFe/GO hybrid was studied by cyclic voltammetry and amperometric measurement. Results showed that the NiFe/GO-modified glassy carbon electrode had sensitivity of 173 µA mM-1 cm-2 for glucose sensing with a linear range up to 5 mM, which is superior to that of commonly used Ni nanoparticles. Furthermore, high selectivity for glucose detection could be achieved by the NiFe/GO hybrid. All the results demonstrated that the NiFe/GO hybrid has promise for application in electrochemical glucose sensing.

Theoretical study of Ni+ assisted C-C and C-H bond activations of propionaldehyde in the gas phase.

The reactions of Ni+ with propionaldehyde in the gas phase have been systematically investigated using density functional theory at the B3LYP/def2-TZVP level. The decomposition reaction mechanism has been identified. Our calculations indicated that Ni+ can assist decomposition of propionaldehyde to form Ni+CO and C2H6 through two types of reaction channel: C-C bond activation and C-H bond activation. In addition, charge decomposition analysis (CDA) was carried out to obtain a deeper understanding for orbital interaction of the initial complex. The bonding properties of the species involved were discussed by means of diverse analysis methods including electron localization function (ELF) and atoms in molecules (AIM).

[Synthesis of novel curcumin mimics and preliminary evaluation for their antitumor activity].

Curcumin has been reported to possess antitumor activity with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. In order to overcome these limitations and discover novel small molecules with potential antitumor activity, 29 curcumin mimics were synthesized, which were confirmed by 1H NMR and HR-MS, and their cytotoxic property was evaluated against five human cancer cell lines in vitro. Compounds 16, 18 and 19 exhibited good cytotoxic property, their IC50 value were even below 5 micromol x L(-1) to some cancer cell lines, 5-9 times better than curcumin.

Mechanistic exploration of the catalytic cycles for the CO oxidation by O2 over FeO(1-3) application of the energetic span model.

Carbon monoxide (CO) and oxygen (O2) catalyzed by small neutral iron oxide clusters (FeO(1-3)) was investigated at the density functional level of theory using the Becke-Perdew-Wang functional (BPW91). Three reaction pathways along with singlet, triplet and quintet states were calculated for ascertaining the presence of some spin inversion during the catalytic cycle. The catalytic cycle was found to be "two state reactivity" resulting from the crossing among the multistate energetic profiles. The Landau-Zener equation was used to calculate the thermally-averaged spin transition probabilities for the non-adiabatic surface crossing reaction. In order to predict the efficiency of catalyst the energetic span model developed by Kozuch was implemented, whereas this model is not suitable for handling the diabatic reaction, this feature we must take into consideration. To this end, a kinetic assessment is carried out with an expansion of the energetic span model, including the spin-crossing effects. This approximation enables one to measure the efficiency of catalytic cycle including spin-crossing effects by quantum mechanical computation.

Comparison of disease activity in SPMS and PPMS in the context of multicenter clinical trials.

BACKGROUND: Retrospective single center natural history studies have shown that times to reach disability milestones and ages at which they are reached are similar in primary (PPMS) and secondary (SPMS) progressive multiple sclerosis suggesting that they may be phenotypic variations of the same disease. OBJECTIVE: Here we compared longitudinal disease activity in SPMS and PPMS in the context of international multicenter clinical trials. METHODS: We analyzed all objective outcome measures that were systematically collected over 2 years for all subjects randomized to placebo arms in one SPMS and one PPMS clinical trial over the last decade. Conventional and exploratory definitions of clinical disease activity were used. Disease activity was analyzed in 3 different categories intermittent activity, progression, and improvement. Conventional MRI measures and one patient reported outcome measure of quality of life were included when available for comparison. Heat maps were drawn for all results followed by hierarchical clustering. RESULTS: There were 101 outcome variables from 206 SPMS subjects and 79 outcome variables from 135 PPMS subjects. The comparison revealed that SPMS and PPMS subjects exhibited similar disease activity over 2 years in all but two of the variables in common worsening in the EDSS sensory system was more common in PPMS while worsening on the 9 hole PEG was more common in SPMS. Intermittent activity was the most common pattern of disease activity in SPMS and PPMS. Clinical worsening and improvement occurred at similar frequency in both. CONCLUSION: Longitudinal disease activity was nearly identical in SPMS and PPMS subjects in the context of the two multicenter international clinical trials we examined.

[Combined anterior and posterior surgeries for double column acetabular fracture].

OBJECTIVE: To explore the clinical effects and related factors of combined anterior and posterior surgeries in treatment of double column acetabular fracture. METHODS: From August 2007 to July 2009, 19 patients with double column acetabular fracture were treated. There were 13 males and 6 females, with a mean age of 39.6 years (ranged, 27 to 52 years). Among the patients, upper double column fracture was in 11 cases, lower double column fracture was in 8 cases and double column fracture involved sacroiliac joint in 1 case. The mean time from injury to operation was 5.8 days (ranged, 4 to 10 days). All patients were received combined anterior and posterior surgeries, reconstructed plate and fixed by screw. RESULTS: One patient was death, other patients were followed up from 12 to 18 months (with a mean time of 13.6 months). According to Harris standard, 9 cases got excellent results, 7 good cases and 2 fair. CONCLUSION: Combined anterior and posterior surgeries for double column acetabular fracture can get satisfactory effects.

An entropy-based nonparametric test for the validation of surrogate endpoints.

We present a nonparametric test to validate surrogate endpoints based on measure of divergence and random permutation. This test is a proposal to directly verify the Prentice statistical definition of surrogacy. The test does not impose distributional assumptions on the endpoints, and it is robust to model misspecification. Our simulation study shows that the proposed nonparametric test outperforms the practical test of the Prentice criterion in terms of both robustness of size and power. We also evaluate the performance of three leading methods that attempt to quantify the effect of surrogate endpoints. The proposed method is applied to validate magnetic resonance imaging lesions as the surrogate endpoint for clinical relapses in a multiple sclerosis trial.

Density functional study of S(N) 2 substitution reactions for CH(3) Cl + CX(1) X(2•-) (X(1) X(2) = HH, HF, HCl, HBr, HI, FF, ClCl, BrBr, and II).

A systematic investigation on the S(N) 2 displacement reactions of nine carbene radical anions toward the substrate CH(3) Cl has been theoretically carried out using the popular density functional theory functional BHandHLYP level with different basis sets 6-31+G (d, p)/relativistic effective core potential (RECP), 6-311++G (d, p)/RECP, and aug-cc-pVTZ/RECP. The studied models are CX(1) X(2•-) + CH(3) Cl → X(2) X(1) CH(3) C(•) + Cl(-) , with CX(1) X(2•-) = CH(2) (•-) , CHF(•-) , CHCl(•-) , CHBr(•-) , CHI(•-) , CF(2) (•-) , CCl(2) (•-) , CBr(2) (•-) , and CI(2) (•-) . The main results are proposed as follows: (a) Based on natural bond orbital (NBO), proton affinity (PA), and ionization energy (IE) analysis, reactant CH(2) (•-) should be a strongest base among the anion-containing species (CX(1) X(2•-) ) and so more favorable nucleophile. (b) Regardless of frontside attacking pathway or backside one, the S(N) 2 reaction starts at an identical precomplex whose formation with no barrier. (c) The back-S(N) 2 pathway is much more preferred than the front-S(N) 2 one in terms of the energy gaps [ΔE cent≠(front)-ΔE cent≠(back)], steric demand, NBO population analysis. Thus, the back-S(N) 2 reaction was discussed in detail. On the one hand, based on the energy barriers (ΔE cent≠ and ΔE ovr≠) analysis, we have strongly affirmed that the stabilization of back attacking transition states (b-TSs) presents increase in the order: b-TS-CI(2) < b-TS-CBr(2) < b-TS-CCl(2) < b-TS-CHI < b-TS-CHBr < b-TS-CHCl < b-TS-CF(2) < b-TS-CHF < b-TS-CH(2) . On the other hand, depended on discussions of the correlations of ΔE ovr≠ with influence factors (PA, IE, bond order, and ΔE def≠), we have explored how and to what extent they affect the reactions. Moreover, we have predicted that the less size of substitution (α-atom) required for the gas-phase reaction with α-nucleophile is related to the α-effect and estimated that the reaction with the stronger PA nucleophile, holding the lighter substituted atom, corresponds to the greater exothermicity given out from reactants to products.

A ratio test in active control non-inferiority trials with a time-to-event endpoint.

There are essentially two kinds of non-inferiority hypotheses in an active control trial: fixed margin and ratio hypotheses. In a fixed margin hypothesis, the margin is a prespecified constant and the hypothesis is defined in terms of a single parameter that represents the effect of the active treatment relative to the control. The statistical inference for a fixed margin hypothesis is straightforward. The outstanding issue for a fixed margin non-inferiority hypothesis is how to select the margin, a task that may not be as simple as it appears. The selection of a fixed non-inferiority margin has been discussed in a few articles (Chi et al., 2003; Hung et al., 2003; Ng, 1993). In a ratio hypothesis, the control effect is also considered as an unknown parameter, and the noninferiority hypothesis is then formulated as a ratio in terms of these two parameters, the treatment effect and the control effect. This type of non-inferiority hypothesis has also been called the fraction retention hypothesis because the ratio hypothesis can be interpreted as a retention of certain fraction of the control effect. Rothmann et al. (2003) formulated a ratio non-inferiority hypothesis in terms of log hazards in the time-to-event setting. To circumvent the complexity of having to deal with a ratio test statistic, the ratio hypothesis was linearized to an equivalent hypothesis under the assumption that the control effect is positive. An associated test statistic for this linearized hypothesis was developed. However, there are three important issues that are not addressed by this method. First, the retention fraction being defined in terms of log hazard is difficult to interpret. Second, in order to linearize the ratio hypothesis, Rothmann's method has to assume that the true control effect is positive. Third, the test statistic is not powerful and thus requires a huge sample size, which renders the method impractical. In this paper, a ratio hypothesis is defined directly in terms of the hazard. A natural ratio test statistic can be defined and is shown to have the desired asymptotic normality. The demand on sample size is much reduced. In most commonly encountered situations, the sample size required is less than half of those needed by either the fixed margin approach or Rothmann's method.

Improved program activities are associated with decreasing tuberculosis incidence in the United States.

OBJECTIVE: This study was conducted to determine whether improvements in tuberculosis (TB) program activities correlate with incident TB cases. METHODS: National TB surveillance data and program data from patients with pulmonary and laryngeal TB and their contacts were collected. These data were analyzed using regression models to assess the association between changes in incident TB cases and indicators of program performance (a time series of percent changes in program indices). RESULTS: A total of 1,361,113 contacts exposed to 150,668 TB patients were identified through contact investigations. From 1987 to 1992 (the period of TB resurgence and antedating increased funding), there was a decline in several measures used by TB programs for outcomes of contact investigations. From 1993 to 1998 (the period after increases in TB funds), there was an observable improvement in the program indices. Four program indices for contacts and two for TB cases (directly observed therapy and completion of therapy) were statistically associated (p < or = .01) with the decline in TB incident cases. CONCLUSIONS: These analyses suggest that expanded TB program activities resulted in the reduction in national TB cases and underscore the importance of treatment completion for TB disease and latent TB infection. Based on these results, we propose that further improvements in these activities will accelerate the decline of TB in the United States.

FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer.

On August 19, 2004, pemetrexed for injection (Alimta); Eli Lilly and Company, Indianapolis, IN, http://www.lilly.com) received accelerated approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had received prior chemotherapy. Approval was primarily based on a single, controlled, unblinded trial. Five hundred seventy-one protocol-eligible patients were randomized to receive either pemetrexed or docetaxel (Taxotere); Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharmaus.com). The primary efficacy end point was overall survival. The median survival times were 8.3 months in the pemetrexed arm and 7.9 months in the docetaxel arm. Neither superiority nor noninferiority for overall survival could be demonstrated, the latter because a reliable and consistent survival effect of docetaxel could not be estimated and because of significant crossover of pemetrexed-treated patients to docetaxel after tumor progression. Comparable response rates, 9.1% for pemetrexed and 8.8% for docetaxel, times to progressive disease, and progression-free survival times supported the conclusion that an effect of pemetrexed on survival was reasonably likely, however. In addition, pemetrexed was felt to have a more favorable safety profile than docetaxel. Of greatest importance, pemetrexed caused significantly less neutropenia, febrile neutropenia, neutropenic infections, and need for granulocyte/macrophage colony-stimulating factors.

Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.

PURPOSE: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. EXPERIMENTAL DESIGN: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. RESULTS: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. CONCLUSIONS: On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.