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The randomized phase II VELO trial showed that the addition of panitumumab to trifluridine/tipiracil significantly improves progression-free survival (PFS) as compared to trifluridine/tipiracil in third-line therapy in patients with refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC). With longer follow-up, final overall survival results and posttreatment subgroup analysis are presented. Sixty-two patients with refractory RAS WT mCRC were randomly assigned to receive, as third-line therapy, trifluridine/tipiracil alone (arm A) or in combination with panitumumab (arm B). Primary endpoint was PFS; secondary endpoints included overall survival (OS) and overall response rate (ORR). Median OS was 13.1 months (95% CI 9.5-16.7) in arm A compared to 11.6 months (95% CI 6.3-17.0) in arm B (HR: 0.96, 95% CI 0.54-1.71, P = .9). To evaluate the impact of subsequent lines of treatment, subgroup analysis was performed for the 24/30 patients in arm A, that received fourth-line therapy after disease progression. Median PFS was 4.1 months (95% CI 1.44-6.83) for 17 patients treated with anti-EGFR rechallenge as compared to 3.0 months (95% CI 1.61-4.31) for seven patients that received other therapies (HR: 0.29, 95% CI 0.10-0.85, P = .024). Median OS from the start of fourth-line treatment was 13.6 months (95% CI 7.2-20), and 5.1 months (95% CI 1.8-8.3) for patients treated with anti-EGFR rechallenge vs other therapies, respectively (HR: 0.30, 95% CI 0.11-0.81, P = .019). Final results of the VELO trial support the role of anti-EGFR rechallenge in the continuum of care of patients with RAS/BRAF WT mCRC.  相似文献   
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The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.  相似文献   
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Journal of Interventional Cardiac Electrophysiology - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, occurring in 1–2% of the general population. Catheter ablation...  相似文献   
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Clinical Rheumatology - Osteitis condensans ilii (OCI) is a benign condition characterised by triangular sclerosis of the iliac bone which may mimic radiographic sacroiliitis. Prevalence is...  相似文献   
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Diabetes technology has rapidly evolved, and insulin infusion pumps (IIPs) have gained worldwide acceptance in diabetes care. The safety of medical equipment is highly discussed, imposing complex challenges in its use. The accuracy of IIPs can be determined through laboratory tests, generally following the IEC 60601-2-24 protocol. Studies have evaluated the accuracy and precision of IIPs, and there are discrepant results. So, we conducted a Systematic Literature Review to assess the methodologies used to evaluate the accuracy of IIPs, organizing the findings in a compiled perspective. The methodology was based on Kitchenham and Biolchini guidelines, and when possible it was carried out the Bayesian meta-analyses to compare the accuracy of IIPs. Most studies used the microgravimetric technique to evaluate the device accuracy, and some proposed adaptations for the standard protocol. The variation of results was recurrent, and the establishment of a protocol, especially to evaluate patch pumps, is necessary. The present study gives enough data to understand the scenario of the IIPs evaluation, as well as the different protocols that can be explored for its evaluation. This highlights the need for a reliable, practical, and low-cost methodology to assist the evaluation of IIPs.

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Alzheimer's disease (AD) is a neurodegenerative disorder leading to cognitive deficits and cognitive decline. Since no cure or preventing therapy is currently available to counteract AD, natural‐derived compounds are investigated to find new potential neuroprotective agents for its treatment. In the present study, we tested the neuroprotective effect of lavender and coriander essential oils (EOs) and their main active constituent linalool, against the neurotoxicity elicited by Aβ1‐42 oligomers, a key molecular factor in the neurodegeneration of AD. Importantly, our findings on neuronally differentiated PC12 cells exposed to Aβ1‐42 oligomers are in accordance with previous in vivo studies reporting the neuroprotective potential of lavender and coriander EOs and linalool. We found that lavender and coriander EOs at the concentration of 10 μg/mL as well as linalool at the same concentration were able to improve viability and to reduce nuclear morphological abnormalities in cells treated with Aβ1‐42 oligomers for 24 hours. Lavender and coriander EOs and linalool also showed to counteract the increase of intracellular reactive oxygen species production and the activation of the pro‐apoptotic enzyme caspase‐3 induced by Aβ1‐42 oligomers. Our findings provide further evidence that these EOs and their main constituent linalool could be natural agents of therapeutic interest against Aβ1‐42‐induced neurotoxicity.  相似文献   
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Introduction:The relationship between chronic empyema and malignant tumors, most of which are lymphoma, has been recognized for many decades. Sarcomatoid carcinoma associated with chronic empyema is extremely rare, may metastasize to other organs in the early stage, and rapidly progresses to death. As far as we know, this was the first case report on sarcomatoid carcinoma associated chronic empyema.The patient''s main concerns and important clinical findings:A 59-year-old man presented to our hospital with a 9-year history of chronic empyema and a chief complaint of left chest wall pain for 5 months. The diagnostic contrast-enhanced computed tomography (CT) showed a large irregular soft tissue mass located on the left lower hemithorax at the margin of the empyema cavity extending to the adjacent chest wall and lung parenchyma. In addition, CT revealed pleural and pulmonary metastases surrounded by ground glass opacity.The main diagnosis, therapeutics interventions, and outcomes:The patient underwent CT guided percutaneous core needle biopsy (PCNB). The histopathological evaluation showed carcinomatous proliferation of pleomorphic spindle cells with extensive necrosis. Immunohistochemically, tumor cells were positive for cytokeratin and vimentin. The final histopathological diagnosis was sarcomatoid carcinoma underlying chronic empyema. The tumors showed rapid progression on serial simple radiography. Palliative treatments were performed, but the patient still developed severe dyspnea and died shortly after on day 16.Conclusion:Sarcomatoid carcinoma can occur very rarely as a complication of chronic empyema, and is more aggressive than usual. Early detection of developing malignancy during the follow-up of chronic empyema is an important factor for patient prognosis.  相似文献   
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