Research on vitamin D in patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) is limited. We aimed to compare the vitamin D parameters of patients with NTM-PD to those of a healthy ...control group, and to assess the possible predictive markers for a clinical response. We prospectively enrolled 53 patients with NTM-PD between January 2014 and December 2016. The clinical data and vitamin D indices, including total, free, bioavailable 25-(OH)D, and vitamin D binding protein (VDBP) genotyping, were measured at baseline and six months after enrollment. An external dataset of 226 healthy controls was compared with the NTM-PD group. The mean age of subjects was 53 years; 54.5% were male. The NTM-PD group was older, predominantly female, and had a lower body mass index (BMI) than the controls. The proportion of patients with vitamin D concentration <50 nmol/L was 52.8% in the NTM-PD group and 54.9% in the control group (p = 0.789). The bioavailable 25-(OH)D concentrations of the NTM-PD group and the controls were similar (6.9 nmol/L vs. 7.6 nmol/L, p = 0.280). In the multivariable analysis, bioavailable 25-(OH)D concentrations were associated with NTM-PD, adjusting for age, sex, BMI, and VDBP levels. Bioavailable 25-(OH)D concentrations were significantly associated with susceptibility to NTM-PD, but not with treatment outcomes. Lower bioavailable 25-(OH)D might be a risk factor for NTM-PD.
We previously reported that the prognosis of microsatellite instability high (MSI‐H) gastric cancer is similar to that of MSI‐low/microsatellite stable (MSI‐L/MSS) gastric cancer. The reason for this ...seemed to be related to the effects of chemotherapy. To verify this hypothesis, we expanded the study population and reanalyzed the prognosis of MSI‐H gastric cancer. Data from 1,276 patients with Stage II and III gastric cancer who underwent gastrectomy with curative intent between January 2005 and June 2010 were reviewed. The prognosis of MSI‐H tumors in comparison with MSI‐L/MSS tumors was analyzed, according to the administration of chemotherapy and other clinicopathologic features. A total of 361 (28.3%) patients did not receive chemotherapy (MSI‐H = 47 and MSI‐L/MSS = 314), whereas 915 (71.7%) patients did receive chemotherapy (MSI‐H = 58 and MSI‐L/MSS = 857). The hazard ratio of MSI‐H versus MSI‐L/MSS was 0.49 (95% confidence interval: 0.26–0.94, p = 0.031) when chemotherapy was not received and 1.16 (95% confidence interval: 0.78–1.71, p = 0.466) when chemotherapy was received. In subgroup analyses, the prognosis of MSI‐H was better in Stage III, women, with lymph node metastasis, and undifferentiated histology subgroups when chemotherapy was not received. However, in patients treated with chemotherapy, prognosis was worse for MSI‐H tumors in Stage III, undifferentiated histology, and diffuse type subgroups of gastric cancer. In conclusion, MSI‐H tumors were associated with a good prognosis in Stage II and III gastric cancer when patients were treated by surgery alone, and the benefits of MSI‐H status were attenuated by chemotherapy.
What's new?
The frequency of microsatellite instability (MSI) in gastric cancer is associated with prognosis, with high frequency (MSI‐H) generally linked to good prognosis. Importantly, however, the ability of MSI frequency to predict patient outcome in gastric cancer may be influenced by chemotherapy. The authors of the present study tested that hypothesis by analyzing data on stage II and stage III gastric cancer patients who underwent gastrectomy. The prognostic benefits conferred by MSI‐H status were found to be significantly reduced among patients who received chemotherapy following surgery. Certain clinico‐pathological characteristics also modified the association of MSI‐H with gastric cancer prognosis.
Background
The association between leukapheresis (LK) as a treatment option for hyperleukocytosis (HL) in patients with acute myeloid leukemia (AML) remains controversial.
Methods
Data were extracted ...from the electronic medical record for 2801 patients with AML between April 2009 and December 2019. LK was performed when the leukocyte count was ≥100 × 109/L at the time initial bone marrow examination.
Results
A comparison between the patients with HL in the non‐LK (n = 1579) and LK (n = 208) groups revealed survival probabilities (%) of 93.2% and 90.4% (P = .130) for day 30 (D30), 85.4% and 84.2% (P = .196) for D60, and 83.6% and 80.8% (P = .258) for D90, respectively. After propensity score matching, a comparison between the patients with HL in the non‐LK (n = 192) and LK (n = 192) groups revealed survival probabilities (%) of 83.9% and 91.2% (P = .030) for D30, 75.0% and 84.9% (P = .015) for day 60 (D60), and 62.4% and 81.3% (P = .034) for day 90 (D90), respectively. After D150, the observed effect of LK appeared to be mitigated without a survival benefit.
Discussion
LK was associated with improved early survival outcomes at D30, D60, and D90 among patients with AML exhibiting HL. Thus, it may be considered a treatment option for reducing cell mass in such patients.
Impact of Brexit on G7 properties Yoon, Jae Ho; Nawrot, Katarzyna Anna
Applied economics,
12/2022, Volume:
54, Issue:
57
Journal Article
Peer reviewed
In this article, we adopted the Full Information Maximum Likelihood (FIML) Markov-switching model of Yoon to examine the contribution of the UK housing business cycle to the common G7 housing ...business cycle between housing price and GDP seeking to access the impact of Brexit on G7 properties. Taking a sample of G7 countries we investigated a period of over 50 years, using quarterly data from 1970:II to 2020:IV. Our findings demonstrate that UK GDP is a significant variable contributing to the G7 GDP growth, and furthermore that the UK housing price is a significant variable to the G7 housing prices. Considering common international housing business cycle, we found that the UK is not a significant variable for determining the common international housing business cycle between housing price and the real growth of output in the G7 countries. Finally, applying a FIML Markov-switching model to the G7 countries, we found a common international housing business cycle during the oil shock periods of the 1970s, the financial crisis in 2008, and COVID-19 pandemic. These findings are the first empirical evidence of the comparison of COVID-19 pandemic and other crises in terms of common international housing business cycle, thus providing significant input for policymakers.
Ventilator-induced lung injury (VILI) is an important critical care complication. Nuclear factor-κB (NF-κB) activation, a critical signaling event in the inflammatory response, has been implicated in ...the tracking of the lung injury. The present study aimed to determine the effect of simultaneous pretreatment with enteral aspirin and omega-3 fatty acid on lung injury in a murine VILI model. We compared the lung inflammation after the sequential administration of lipopolysaccharides and mechanical ventilation between the pretreated simultaneous enteral aspirin and omega-3 fatty acid group and the non-pretreatment group, by quantifying NF-κB activation using an in vivo imaging system to detect bioluminescence signals. The pretreated group with enteral aspirin and omega-3 fatty acid exhibited a smaller elevation of bioluminescence signals than the non-pretreated group (
= 0.039). Compared to the non-pretreated group, the pretreatment group with simultaneous enteral aspirin and omega-3 fatty acid showed reduced expression of the pro-inflammatory cytokine, tumor necrosis factor-α, in bronchoalveolar lavage fluid (
= 0.038). Histopathological lung injury scores were also lower in the pretreatment groups compared to the only injury group. Simultaneous pretreatment with enteral administration of aspirin and omega-3 fatty acid could be a prevention method for VILI in patients with impending mechanical ventilation therapy.
Background Granulocyte transfusions (GTs) have been used to treat infections in neutropenic patients undergoing chemotherapy or hematopoietic stem cell transplantation. However, there is persistent ...controversy regarding their outcomes. We aimed to analyze accumulated clinical and laboratory data from patients with acute myeloid leukemia (AML) who underwent GT at our institution in the last 10 years to determine optimal parameters to estimate the GT effect. We hypothesized that patients grouped according to prognostic factors would have inconsistent clinical outcomes. Materials and methods In this single-center retrospective study, we collected medical records of 219 GT-treated patients diagnosed with AML from 2009 to 2019. Prognostic factors, including clinical and laboratory parameters, were assessed. Serial measurements of laboratory parameters before and after GT were collected, and the area under the curve of the white blood cells (AUC-WBC) was calculated using the trapezoidal method. A prognostic scoring system using 8 factors from multivariate analysis was analyzed. The primary outcome was survival at 30 days (D30) after GT initiation. Results The 8 factors for the prognosis scoring system included secondary AML, mean AUC-WBC, prothrombin time, and levels of blood urea nitrogen (BUN), bilirubin, alanine aminotransferase (ALT), phosphorus, and lactate dehydrogenase (LDH). Patients were grouped into 4 risk groups (low, medium, high, and very high), and the D30 survival rates for each group were as follows: 87.6% (99/113), 55.9% (33/59), 21.1% (4/19), and 0% (0/19), respectively. Hematopoiesis, liver, and renal function affected the outcome. FLT3 mutation acted as a favorable factor for D30 survival. Conclusions GT response in patients with AML seemed to be reflected by 8 score markers, and GT was significantly effective in the low-risk group. We suggest that it is important to evaluate the risk assessment of patients before GT to achieve better outcomes.
Background Pyrazinamide (PZA) is a common drug that causes serious adverse events (SAEs). The aim of this study was to determine the incidence of and risk factors for SAEs due to PZA during ...first-line anti-tuberculosis treatment. Methods The medical records of patients with tuberculosis (TB) treated with PZA-containing regimens including first-line drugs-ethambutol, rifampicin, and isoniazid-from January 2003 to June 2016 were reviewed. SAEs were defined as side effects that led to drug discontinuation. The causative drug was determined based on the disappearance of the SAEs upon drug withdrawal and/or the recurrence of the same SAEs with re-challenge. Results Of 2,478 patients with TB, 16.4% experienced SAEs. The incidence of SAEs increased significantly as age increased, except with rifampin. PZA accounted for most SAEs (55.8%). Hepatotoxicity was the most common SAE due to PZA (44.5%), followed by gastrointestinal (GI) intolerance (23.8%). The risk of SAEs due to PZA increased significantly as age increased, when sex and comorbidities were adjusted (odds ratio, 1.013; 95% confidence interval, 1.004-1.023; P = 0.007). In the subgroup analysis, older age was an independent risk factor for GI intolerance but not for hepatotoxicity. Conclusion PZA was the most common drug associated with SAEs among the first-line anti-TB drugs, and old age was an independent factor for SAE occurrence. This study suggests that the early recognition of whether the causative agent is PZA may improve effective treatment compliance, particularly in elderly patients.
Cancer is heterogeneous among patients, requiring a thorough understanding of molecular subtypes and the establishment of therapeutic strategies based on its behavior. Gastric cancer (GC) is ...adenocarcinoma with marked heterogeneity leading to different prognoses. As an effort, we previously identified a stem-like subtype, which is prone to metastasis, with the worst prognosis. Here, we propose FNBP1 as a key to high-level cell motility, present only in aggressive GC cells. FNBP1 is also up-regulated in both the GS subtype from the TCGA project and the EMT subtype from the ACRG study, which include high portions of diffuse histologic type. Ablation of FNBP1 in the EMT-type GC cell line brought changes in the cell periphery in transcriptomic analysis. Indeed, loss of FNBP1 resulted in the loss of invasive ability, especially in a three-dimensional culture system. Live imaging indicated active movement of actin in FNBP1-overexpressed cells cultured in an extracellular matrix dome. To find the transcription factor which drives FNBP1 expression in an EMT-type GC cell line, the FNBP1 promoter region and DNA binding motifs were analyzed. Interestingly, the Sp1 motif was abundant in the promoter, and pharmacological inhibition and knockdown of Sp1 down-regulated FNBP1 promoter activity and the transcription level, respectively. Taken together, our results propose Sp1-driven FNBP1 as a key molecule explaining aggressiveness in EMT-type GC cells.
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