Background Patients with interstitial lung disease (ILD) are occasionally positive for anti-neutrophil cytoplasmic antibodies (ANCAs). Differences between ILDs secondary to microscopic polyangiitis (MPA) and isolated ANCA-positive idiopathic interstitial pneumonia (IIP) remain unclear. The aim of this study was to explore the differences in clinical features and outcomes between MPA-associated ILDs and isolated ANCA-positive IIPs. Methods We reviewed 1338 ILDs patients with available ANCA results and retrospectively analysed 80 patients who were ANCA-positive. MPA-associated ILDs (MPA-ILDs group) and isolated ANCA-positive IIPs (ANCA-IIPs group) were compared. Results Among 80 patients with ANCA-positive ILDs, 31 (38.75%) had MPA-ILDs, and 49 (61.25%) had isolated ANCA-positive IIPs. Compared with ANCA-IIPs group, patients in MPA-ILDs group had a higher proportion of fever (p = 0.006) and higher neutrophil count (p = 0.011), erythrocyte sedimentation rate (ESR) (p < 0.001) and C-reactive protein (CRP) (p = 0.005). Multivariable analysis showed that ESR level was an independent risk factor for mortality in all 80 ANCA-positive ILDs patients (HR 1.028, p = 0.001). Survival in MPA-ILDs group was lower than that in ANCA-IIPs group, and further stratified analysis revealed that ANCA-IIPs patients with elevated ESR or CRP had a worse prognosis than those with normal inflammation markers, with 5-year cumulative survival rates of 60.00%, 86.90% and 100.00% in MPA-ILDs and ANCA-IIPs with and without elevated inflammation markers, respectively. Conclusions Among patients with ANCA-positive ILDs, the prognoses of ANCA-IIPs with normal inflammation markers, ANCA-IIPs with elevated inflammation markers and MPA-ILDs were sequentially poorer. Therefore, stratified treatment should be considered in the management of ILDs patients positive for ANCAs.
BackgroundTo determine the effects of noninvasive mechanical ventilation (NIV) compared with invasive mechanical ventilation (IMV) as the initial mechanical ventilation on clinical outcomes when used for treatment of acute respiratory failure (ARF) in immunocompromised patients.MethodsWe searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese Biomedical Literature Database (CBM) and other databases. Subgroup analyses by disease severity and causes of immunodeficiency were also conducted.ResultsThirteen observational studies with a total of 2552 patients were included. Compared to IMV, NIV was shown to significantly reduce in-hospital mortality (OR 0.43, 95 % CI 0.23 to 0.80, P value = 0.007) and 30-day mortality (OR 0.34, 95 % CI 0.20 to 0.61, P value < 0.0001) in overall analysis. Subgroup analysis showed NIV had great advantage over IMV for less severe, AIDS, BMT and hematological malignancies patients in reducing mortality and duration of ICU stay.ConclusionsThe overall evidence we obtained shows NIV does more benefits or at least no harm to ARF patients with certain causes of immunodeficiency or who are less severe.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0289-y) contains supplementary material, which is available to authorized users.
Background BCR-ABL1T315I mutations confer resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). Olverembatinib is a new potent BCR-ABL1 TKI with preclinical activity against T315I-mutated CML. In phase 1/2 studies, we explored the safety and efficacy of olverembatinib in Chinese adults with TKI-resistant CML in the chronic phase (CML-CP) and accelerated phase (CML-AP). Methods In the phase 1 study, olverembatinib was orally administered once every other day in 28-day cycles at 11 dose cohorts ranging from 1 to 60 mg, and we evaluated the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, efficacy, and pharmacokinetics of olverembatinib. In the phase 2 studies, olverembatinib was administered at the RP2D of 40 mg orally on alternate days for 28-day cycles. The primary outcome measure is major cytogenetic response (MCyR) and major hematologic response by the end of Cycle 12 in CML-CP and CML-AP, respectively. Fine and Gray's hazard models were used to identify covariates associated with responses. Results A total of 165 patients (> 80.0% of whom had received ≥ 2 TKIs) were enrolled in this study. Among 127 patients with CML-CP, the 3-year cumulative incidences of achieving MCyR, complete cytogenetic response (CCyR), major molecular response (MMR), MR4.0, and MR4.5 were 79.0, 69.0, 56.0, 44.0 and 39.0%, respectively. The highest response rates were observed in patients with a single T315I mutation. Among 38 patients with CML-AP, the 3-year cumulative incidences of achieving MCyR, CCyR, MMR, MR4.0, and MR4.5 were 47.4%, 47.4%, 44.7%, 39.3%, and 32.1%, respectively. In multivariate analyses, baseline BCR-ABL1 mutation status was significantly associated with cytogenetic and molecular responses. Common treatment-related adverse events included skin hyperpigmentation, hypertriglyceridemia, proteinuria, and severe thrombocytopenia. Conclusions Olverembatinib was well tolerated, with significant antileukemic activity in adults with TKI-resistant CML-CP and CML-AP, especially those with the T315I mutation. Trial registration: The phase 1 trial is registered at CTR20220566, and the two single-arm, open-label phase 2 studies are registered at ClinicalTrials.gov: NCT03883087 (CML-CP) and NCT03883100 (CML-AP).
The fast and cost-effective DNA extraction is critical for all DNA-based detections. Here, we fabricated a new kind of polyacrylamide microsphere (PAMMP) in various sizes with two methods, spot polymerization (large size but low yield) and modified inverse microemulsion polymerization (small size but high yield). The fabricated PAMMPs have strong autofluorescence (fPAMMPs), including both visible fluorescence (VF) and near-infrared fluorescence (NIRF), which can remain very stable in various stringent conditions including strong acid and alkali and high temperature. The fabricated fPAMMPs were also highly positively charged, which could be used to effectively capture various biomolecules such as IRDye 800-labeled streptavidin and DNA. We thus developed a new method for rapid extraction (3−5 min) of DNA from various samples including bacteria, mammalian cells, plant and animal solid tissues, and human blood plasma using fPAMMPs. Moreover, the DNA captured on fPAMMPs (fPAMMP@DNA) could be effectively detected by both normal and quantitative PCR amplifications. Finally, we showed that NaBH 4 treatment removed autofluorescence in fPAMMPs (PAMMPs), which could also be applied to DNA extraction and PCR detection. In conclusion, we here fabricated new kinds of fPAMMPs and PAMMPs, developed a new rapid DNA extraction method, and demonstrated their useful applications in PCR detection.
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