ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality. 相似文献
Background: Thyrosin kinase inhibitors (TKIs) is approved for the first line treatment of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. This study performed to assess clinical effectiveness and safety of Erlova (generic form of Erlotinib). Methods: Somatic mutations of EGFR gene were studied in tumor tissue by polymerase chain reaction (PCR) and bi-directional sequencing in 513 chemonaive and histologically verified lung adenocarcinoma Iranian patients. Patients with EGFR mutation received Erlova at 150 mg/day as first line treatment. Primary endpoint was progression free survival (PFS). Results: About 21% (n=109) cases had EGFR mutation. Most EGFR mutations were occurred at exon 19. Among them, sixty nine patients treated with Erlova. Median PFS was 11.4 months and objective response rate (ORR) was about 88%. Most frequent treatment related adverse events was skin rash. Conclusion: Our findings showed Erlova had remarkable effectiveness. In mutation-positive patients with EGFR, Erlova can be used safely instead of other tyrosine-kinase inhibitors. 相似文献
Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF. 相似文献
Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.
Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.
Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity. 相似文献
BackgroundDuring aseptic revision total joint arthroplasty (TJA), one or more cultures may occasionally isolate an organism. The hypothesis of this study was that in a portion of patients undergoing revision arthroplasty for aseptic failure, culture may isolate an organism(s) that can be left untreated.MethodsAll patients undergoing revision TJA from 2000 to 2017 at two institutions were retrospectively reviewed. Patients were categorized as aseptic if they were appropriately investigated preoperatively and did not meet the 2018 International Consensus Meeting criteria. In the aseptic revision cohort, patients with a single positive culture or multiple cultures positive for different organisms (“organism-positive”) and patients who had negative intraoperative cultures (“organism-negative”) were compared based on demographics, comorbidities, operative details, subsequent reoperations, and periprosthetic joint infection (PJI).ResultsIn total, 3,234 International Consensus Meeting–negative aseptic revision TJAs were included, of which 215 patients (6.6%) were organism-positive, 196 (91.2%) had a single positive culture, and 19 (8.8%) were positive for 2 or more distinct organisms (ie, polymicrobial). The most prevalent organisms were coagulase-negative Staphylococci (37.5%), Staphylococcus epidermidis (9.6%), and Cutibacterium acnes (8.0%). Demographics and operative details were comparable between the groups. Using multiple regressions there was no association between culture positivity and the rate of reoperation or PJI.ConclusionIsolation of organisms by culture in patients undergoing revision for aseptic failure was not uncommon. As long as these patients were appropriately investigated preoperatively and PJI was excluded, these findings suggest that culture results may be ignored without subjecting patients to additional antimicrobial treatment. 相似文献
This article applies a qualitative approach to the 2017 dengue vaccine controversy involving Sanofi Pasteur’s Dengvaxia to understand vaccine hesitancy and related anxieties in contemporary Philippines. Through a multisited project that investigated the health aspirations and lived experiences of low- and middle-income Filipinos across urban and rural Philippines, this article distills the perspectives of both ordinary community members and health workers in local and national capacities regarding the controversy—and how it altered their perceptions toward vaccines, health care, and government. Our study reveals widespread mistrust and fear in the communities toward both the state and health institutions following the controversy, with frontline health workers bearing the brunt of the communities’ apprehensions, and the media partly responsible in fomenting these fears. Given the repetitive nature of health and vaccine controversies, this article suggests the importance of responsible journalism, well-calibrated crisis communications, and a people-centered health paradigm that involves exploring local contexts of vaccine hesitancy and mining people’s lived experiences in tackling present and future health crises—especially now in the advent of COVID-19 vaccinations. 相似文献