Few simple and effective tools are available for determining the prognosis of 30-day survivors after acute myocardial infarction. We aimed to assess whether the simple age, creatinine, and ejection ...fraction (ACEF) score could predict 1-year mortality of 12,000 post–myocardial infarction 30-day survivors who underwent percutaneous coronary intervention. The ACEF score was computed as follows: (age/ejection fraction) + 1, if the serum creatinine was >2 mg/dl. Accuracy was defined through receiver-operating characteristics analysis and area under the curve (AUC) evaluation. Twelve risk factors were selected and ranked according to their AUC value. Age, ejection fraction, and serum creatinine levels indicated the best AUC value. The ACEF score was significantly higher in the nonsurvivors (1.95 ± 0.82 vs 1.28 ± 0.50; p <0.001) and was an independent predictor of 1-year mortality (adjusted hazard ratio 2.26; p <0.001). The best accuracy was achieved by a prediction model including 12 risk factors (AUC = 0.80), but this did not significantly differ compared with the AUC (0.79) of the ACEF score (p = ns). Adjusted hazard ratios for 1-year mortality were 1 (reference), 3.11 (p <0.001), and 10.38 (p <0.001) for the ACEFLOW (ACEF score <1.0), ACEFMID (ACEF score 1.0 to 1.39), and ACEFHIGH (ACEF score ≥1.4) groups, respectively. The ACEF score may be a novel valid model to stratify the 1-year mortality risk in 30-day survivors who underwent percutaneous coronary intervention after acute myocardial infarction.
Natural killer (NK) cells are key effectors in cancer immunosurveillance, eliminating a broad spectrum of cancer cells without major histocompatibility complex (MHC) specificity and graft-versus-host ...diseases (GvHD) risk. The use of allogeneic NK cell therapies from healthy donors has demonstrated favorable clinical efficacies in treating diverse cancers, particularly hematologic malignancies, but it requires cytokines such as IL-2 to primarily support NK cell persistence and expansion. However, the role of IL-2 in the regulation of activating receptors and the function of NK cells expanded for clinical trials is poorly understood and needs clarification for the full engagement of NK cells in cancer immunotherapy. Here, we demonstrated that IL-2 deprivation significantly impaired the cytotoxicity of primary expanded NK cells by preferentially downregulating NKp30 but not NKp46 despite their common adaptor requirement for expression and function. Using NK92 and IL-2-producing NK92MI cells, we observed that NKp30-mediated cytotoxicity against myeloid leukemia cells such as K562 and THP-1 cells expressing B7-H6, a ligand for NKp30, was severely impaired by IL-2 deprivation. Furthermore, IL-2 deficiency-mediated NK cell dysfunction was overcome by the ectopic overexpression of an immunostimulatory NKp30 isoform such as NKp30a or NKp30b. In particular, NKp30a overexpression in NK92 cells improved the clearance of THP-1 cells
without IL-2 supplementation. Collectively, our results highlight the distinct role of IL-2 in the regulation of NKp30 compared to that of NKp46 and suggest NKp30 upregulation, as shown here by ectopic overexpression, as a viable modality to harness NK cells in cancer immunotherapy, possibly in combination with IL-2 immunocytokines.
In this study, N,N-dimethylformamide (DMF), which is a non-volatile solvent, was selected to dissolve polystyrene (PS) (190,000g/mol) and the concentration of the PS solution (∼35wt%) was maximized ...to retard the evaporation of the solvent under electrospinnable conditions. Unlike the porous morphology observed on the surface of the fibers electrospun from the PS solution in tetrahydrofuran (volatile solvent), the electrospun PS fibers obtained from the highly viscous solution of PS in DMF exhibited an intriguing surface morphology with numerous protuberances. The contact angle measurements indicated that the electrospun fibrous membranes were superhydrophobic with a water contact angle of 154.2±0.7°. This superhydrophobicity was attributed to the combined effects of the regular nanostructural protuberant morphology formed on the surfaces of the individual fibers during electrospinning and the microstructural surface roughness of the electrospun membrane itself.
BACKGROUND—Ischemic postconditioning has been reported to reduce infarct size in patients with ST-segment–elevation myocardial infarction. However, cardioprotective effects of postconditioning have ...not been demonstrated in a large-scale trial.
METHODS AND RESULTS—We performed a multicenter, prospective, randomized, open-label, blinded end-point trial. A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction within 12 hours after symptom onset were randomly assigned to the postconditioning group or to the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow as followsThe angioplasty balloon was positioned at the culprit lesion and inflated 4 times for 1 minute with low-pressure (<6 atm) inflations, each separated by 1 minute of deflation. The primary end point was complete ST-segment resolution (percentage resolution of ST-segment elevation >70%) measured at 30 minutes after PCI. Complete ST-segment resolution occurred in 40.5% of patients in the postconditioning group and 41.5% of patients in the conventional PCI group (absolute difference, −1.0%; 95% confidence interval, −8.4 to 6.4; P=0.79). The rate of myocardial blush grade of 0 or 1 and the rate of major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) at 30 days did not differ significantly between the postconditioning group and the conventional PCI group (17.2% versus 22.4% P=0.20 and 4.3% versus 3.7% P=0.70, respectively).
CONCLUSION—Ischemic postconditioning did not improve myocardial reperfusion in patients with ST-segment–elevation myocardial infarction undergoing primary PCI with current standard practice.
CLINICAL TRIAL REGISTRATION—URLhttp://clinicaltrials.gov. Unique identifierNCT00942500.
Analyses of families affected by cold urticaria, immunodeficiency, and autoimmunity implicate mutations that activate phospholipase Cγ2 (PLCγ2), an enzyme pivotal to the translation of binding events ...at the cell surface to the intracellular milieu, as a cause of the disease.
The genetic dissection of unique inflammatory phenotypes can identify and elucidate immunologic pathways and mechanisms. Such investigations have ultimately led to findings whose significance extends beyond the monogenic diseases harboring the mutations. Examples include the recognition that
FOXP3
is essential for the differentiation of regulatory T cells in
Scurfy
mice and in patients with profound immune dysregulation,
1
–
4
the demonstration of a critical role for
AIRE
in thymic negative selection of T cells in patients with a specific autoimmune polyendocrinopathy,
5
and the identification of
NLRP3
as a critical regulator of interleukin-1 in families with cold-induced inflammation.
6
Cold-induced urticaria is a . . .
Imaging modalities for percutaneous coronary intervention (PCI), such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), have increased in the current PCI era. However, their ...clinical benefits in acute myocardial infarction (AMI) have not been fully elucidated. This study investigated the long-term outcomes of image-guided PCI in patients with AMI using data from the Korean Acute Myocardial Infarction Registry. A total of 9,271 patients with AMI, who underwent PCI with second-generation drug-eluting stents between November 2011 and December 2015, were retrospectively examined, and target lesion failure (TLF) at 3 years (defined as the composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was evaluated. From the registry, 2,134 patients (23.0%) underwent image-guided PCI (IVUS-guided: n = 1,919 20.6%; OCT-guided: n = 215 patients 2.3%). Based on propensity score matching, image-guided PCI was associated with a significant reduction in TLF (hazard ratio: 0.76; 95% confidence interval: 0.59-0.98, p = 0.035). In addition, the TLF incidence in the OCT-guided PCI group was comparable to that in the IVUS-guided PCI group (5.3% vs 4.7%, p = 0.903). Image-guided PCI, including IVUS and OCT, is associated with favorable clinical outcomes in patients with AMI at 3 years post-intervention. Additionally, OCT-guided PCI is not inferior to IVUS-guided PCI in patients with AMI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The morphology of an incompatible polymer blend composed of poly(
l-lactide) (PLLA) and poly(butylene succinate) (PBS) was examined by scanning and transmission electron microscopy, X-ray scattering, ...and X-ray photoelectron spectroscopy before and after the incorporation of an organoclay containing reactive functional groups, namely twice functionalized organoclay (TFC). TFC was prepared by treating Cloisite
® 25A with (glycidoxypropyl)trimethoxy silane. When a small amount of TFC was incorporated into the PLLA/PBS blend, the clay layers became fully exfoliated and were located mainly in the PLLA phase. At the low clay content, the dispersed phase had an almost constant domain size comparing with the PLLA/PBS blend, which decreased sharply as the clay content was further increased. When the clay content became high, the clay layers were dispersed not only in the PLLA phase but also in the PBS phase with intercalated/exfoliated coexisting morphology. The reactive TFC was found to play an important role in the blend similar to the in situ reactive compatibilizer. The specific interaction between the TFC and the polymer matrix was quantified by the Flory–Huggins interaction parameter, B, which was determined by combining the melting point depression and the binary interaction model. The morphology of the PLLA/PBS/clay composites was analyzed by considering the interaction parameter.
Natural killer (NK) cells are innate lymphoid cells that provide early protection against cancer development via their selectivity to kill abnormal cells undergoing cellular transformation without ...the need for prior stimulation. Given the correlation between NK cell dysfunction and cancer prognosis, restoration of endogenous NK cells in the tumor microenvironment or adoptive transfer of NK cells with improved function holds great promise in cancer treatment. Furthermore, MHC-unrestricted tumor lysis by NK cells complements the MHC-restricted killing of tumor cells by cytotoxic T cells, thus positioning NK cells as an alternative or complementary therapeutic target for cancers that are refractory to T cell-based therapy. Although previous therapeutic strategies have focused on the manipulation of NK cell inhibitory receptors, recent advances in our understanding of NK cell activation have provided additional promising strategies to enhance NK cell reactivity against cancer. These approaches include targeting immunosuppressive mechanisms in the tumor microenvironment, such as immune checkpoint receptors, and further enhancing NK cell activation via modulation of intracellular checkpoint molecules or incorporation of tumor-directed chimeric antigen receptors. Thus, an in-depth understanding of NK cell activation will facilitate the optimal design of therapeutic strategies against refractory cancers, possibly in rational and synergistic combination with other therapies.
We performed the long-term follow-up of a large cohort of patients in a multicenter study receiving left main coronary artery (LMCA) revascularization.
Limited information is available on long-term ...outcomes for patients with unprotected LMCA disease who underwent coronary stent procedure or coronary artery bypass grafting (CABG).
We evaluated 2,240 patients with unprotected LMCA disease who received coronary stents (n = 1,102; 318 with bare-metal stents and 784 with drug-eluting stents) or underwent CABG (n = 1,138) between 2000 and 2006 and for whom complete follow-up data were available for at least 3 to 9 years (median 5.2 years). The 5-year adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction MI, or stroke; and target vessel revascularization TVR) were compared with the use of the inverse probability of treatment weighted method and propensity-score matching.
After adjustment for differences in baseline risk factors with the inverse probability of treatment weighting, the 5-year risk of death (hazard ratio HR: 1.13; 95% confidence interval CI: 0.88 to 1.44, p = 0.35) and the combined risk of death, Q-wave MI, or stroke (HR: 1.07; 95% CI: 0.84 to 1.37, p = 0.59) were not significantly different for patients undergoing stenting versus CABG. The risk of TVR was significantly higher in the stenting group than in the CABG group (HR: 5.11; 95% CI: 3.52 to 7.42, p < 0.001). Similar results were obtained in comparisons of bare-metal stent with concurrent CABG and of drug-eluting stent with concurrent CABG. In further analysis with propensity-score matching, overall findings were consistent.
During 5-year follow-up, stenting showed similar rates of mortality and of the composite of death, Q-wave MI, or stroke but higher rates of TVR as compared with CABG for patients with unprotected LMCA disease.
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