BACKGROUND AND PURPOSEThe safety and efficacy of tirofiban during endovascular therapy in patients undergoing intravenous thrombolysis with recombinant IV tPA remain unclear. This study aimed to ...investigate the safety and efficacy of intra-arterial tirofiban use during endovascular therapy in patients treated with IV tPA. MATERIALS AND METHODSUsing a multicenter registry, we enrolled patients with acute ischemic stroke who underwent endovascular therapy. Safety outcomes included postprocedural parenchymal hematoma type 2 and/or thick subarachnoid hemorrhage, intraventricular hemorrhage, and 3-month mortality. Efficacy outcomes included the successful reperfusion rate, postprocedural reocclusion, and good outcomes at 3 months (mRS scores of 0-2). The tirofiban effect on the outcomes was evaluated using a multivariable analysis while adjusting for potential confounders. RESULTSAmong enrolled patients, we identified 314 patients with stroke (279 and 35 patients in the no tirofiban and tirofiban groups, respectively) due to an intracranial artery occlusion who underwent endovascular therapy with intravenous thrombolysis. A multivariable analysis revealed no association of intra-arterial tirofiban with postprocedural parenchymal hematoma type and/or thick subarachnoid hemorrhage (adjusted OR, 1.07; 95% CI, 0.20-4.10; P = .918), intraventricular hemorrhage (adjusted OR, 0.43; 95% CI, 0.02-2.85; P = .467), and 3-month mortality (adjusted OR, 0.38; 95% CI, 0.04-1.87; P = .299). Intra-arterial tirofiban was not associated with good outcome (adjusted OR, 2.22; 95% CI, 0.89 -6.12; P = .099). CONCLUSIONSUsing intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.
This national survey was undertaken to propose the classification of extranodal natural killer (NK)/T-cell lymphoma (NTCL) subtypes and to clarify a clinical heterogeneity.
Two hundred and eighty ...patients newly diagnosed as NTCL were enrolled from 22 Korean medical centers. Two subsets were compared: one involving the upper aerodigestive tract (UAT) and another involving the non-upper aerodigestive tract (NUAT) region, which comprises the skin, gastrointestinal tract, and liver or soft tissues. Clinical prognostic factors, survival outcomes, and independent predictors for survival were compared between each subset.
NUAT-NTCL (59 patients) had significantly higher proportions of disseminated disease, aggressive biologic features, and unfavorable host reactions compared with UAT-NTCL (221 patients). NUAT-NTCL had shortened 5-year overall survival (OS) (22% versus 41%, P = 0.001). Ann Arbor staging, the International Prognostic Index, and the NTCL prognostic index failed to predict the OS of NUAT-NTCL, but did predict the OS in UAT-NTCL. Independent predictors for OS by multivariate analyses differed between each subset. In the NUAT subset, extranodal sites and regional nodes predicted the OS, while Ann Arbor staging, age, performance status, and lactate dehydrogenase level predicted the OS in the UAT subset.
NUAT-NTCL may represent a distinctive disease entity in terms of clinical factors, independent predictors, and survival outcomes.
Neutrino elastic scattering observation with NaI (NEON) is an experiment designed to detect neutrino-nucleus coherent scattering using reactor electron antineutrinos. NEON is based on an array of six ...NaI(Tl) crystals with a total mass of 13.3 kg, located at the tendon gallery that is 23.7 m away from a reactor core with a thermal power of 2.8 GW in the Hanbit nuclear power complex. The installation of the NEON detector was completed in December 2020, and since May 2021, the detector has acquired data at full reactor power. Based on the observed light yields of the NaI crystals of approximately 22, number of photoelectrons per unit keV electron-equivalent energy (keVee), and 6 counts/kg/keV/day background level at 2–6 keVee energy, coherent elastic neutrino-nucleus scattering (CE
ν
NS) observation sensitivity is evaluated as more than 3
σ
assuming 1-year reactor-on and 100 days reactor-off data, 0.2 keVee energy threshold, and 7 counts/keV/kg/day background in the signal region of 0.2
-
0.5 keVee. This paper describes the design of the NEON detector, including the shielding arrangement, configuration of NaI(Tl) crystals, and associated operating systems. The initial performance and associated sensitivity of the experiment are also presented.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor ...(FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. Heparin inhibited hMSC adhesion to PS-MBP-FGF2 but not to FN-coated surface. The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. hMSCs that were expanded on FN-coated surface differentiated into osteogenic and adipogenic cells more readily than those that were expanded on PS-MBP-FGF2. Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. Elucidation of the glycan structure on the cell membrane may help characterise hMSC function.
Objectives
This study aimed to examine the association between statin exposure and dementia risk in individuals with hypercholesterolaemia using data from the NHIS‐HEALS database between 2002 and ...2015.
Methods
Subjects were classified into statin exposure and statin nonexposure groups according to medication possession ratio. Dementia was defined as those with primary diagnostic dementia codes such as F00‐F03, G30, G31.1, G31.9 or G31.82. Cox proportional hazards regression models were adopted after stepwise adjustment for confounders to investigate the prospective association between statin exposure and dementia risk.
Results
During the follow‐up period (median follow‐up 11.7 years), 711 cases of dementia occurred, accounting for 11.5% of the total study population (statin exposure group, 8.2%; statin nonexposure group, 12.9%). Compared to the statin nonexposure group, fully adjusted hazard ratios (HRs) (95% confidence intervals CIs) for overall dementia in the statin exposure group were 0.63 (0.43–0.91) and 0.62 (0.50–0.78) in men and women, respectively. Compared to the statin nonexposure group, the HRs (95% CIs) for Alzheimer’s disease and related dementia, vascular dementia and other types of dementia in the statin exposure group were 0.54 (0.32–0.91), 2.45 (0.69–8.68) and 0.59 (0.32–1.07), respectively, in men and 0.53 (0.38–0.73), 1.29 (0.42–3.96) and 0.70 (0.51–0.96), respectively, in women.
Conclusions
Hypercholesterolaemic individuals exposed to statin had a lower risk of overall dementia and Alzheimer’s disease and related dementia in both sexes, and a lower risk of other types of dementia in women, than subjects who were not exposed to statins.
The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate ...changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer.
Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (n=92) undergoing PST with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24- or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.
A higher proportion of CD44+/CD24- tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24- and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24- tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.
The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.
Cancer immunotherapies targeting adaptive immune checkpoints have substantially improved patient outcomes across multiple metastatic and treatment-refractory cancer types. However, emerging studies ...have demonstrated that innate immune checkpoints, which interfere with the detection and clearance of malignant cells through phagocytosis and suppress innate immune sensing, also have a key role in tumour-mediated immune escape and might, therefore, be potential targets for cancer immunotherapy. Indeed, preclinical studies and early clinical data have established the promise of targeting phagocytosis checkpoints, such as the CD47-signal-regulatory protein α (SIRPα) axis, either alone or in combination with other cancer therapies. In this Review, we highlight the current understanding of how cancer cells evade the immune system by disrupting phagocytic clearance and the effect of phagocytosis checkpoint blockade on induction of antitumour immune responses. Given the role of innate immune cells in priming adaptive immune responses, an improved understanding of the tumour-intrinsic processes that inhibit essential immune surveillance processes, such as phagocytosis and innate immune sensing, could pave the way for the development of highly effective combination immunotherapy strategies that modulate both innate and adaptive antitumour immune responses.
The objective of this study is to construct a preoperative nomogram predicting lymph node metastasis (LNM) in early-cervical cancer patients.
Between 2009 and 2012, 493 early-cervical cancer patients ...received hysterectomy and pelvic/para-aortic lymphadenectomy. Patients who were diagnosed during 2009-2010 were assigned to a model-development cohort (n=304) and the others were assigned to a validation cohort (n=189). A multivariate logistic model was created from preoperative clinicopathologic data, from which a nomogram was developed and validated. A predicted probability of LNM<5% was defined as low risk.
Age, tumour size assessed by magnetic resonance imaging, and LNM assessed by positron emission tomography/computed tomography were independent predictors of nodal metastasis. The nomogram incorporating these three predictors demonstrated good discrimination and calibration (concordance index=0.878; 95% confidence interval (CI), 0.833-0.917). In the validation cohort, the discrimination accuracy was 0.825 (95% CI, 0.736-0.895). In the model-development cohort, 34% of them were classified as low risk and negative predictive value (NPV) was 99.0%. In the validation cohort, 38% were identified as low risk and NPV was 95.8%. Integrating the model-development and validation cohorts, negative likelihood ratio was 0.094 (95% CI, 0.036-0.248).
A robust nomogram predicting LNM in early cervical cancer was developed. This model may improve clinical trial design and help physicians to decide whether lymphadenectomy should be performed.
To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment.
We prospectively ...collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group.
Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00–2.83; p 0.05).
Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.
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