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Systems involving Action associated with MiRNAs and also LncRNAs within Extracellular Vesicle inside Atherosclerosis.
BACKGROUND The treatment of acute lymphoblastic leukemia (ALL) in older adults and elderly patients is a challenge, and modern protocols include targeted therapy and immunotherapy in combination with attenuated or minimal chemotherapy. However, frail patients are excluded from these trials, and reports on the outcome of this subgroup of patients are scarce. Our objective was to analyze the outcome of unfit older adults and elderly patients with Philadelphia chromosome-negative ALL included in a prospective trial (ALL-07FRAIL). PATIENTS AND METHODS Older adults and elderly patients with Charlson Comorbidity Index (CCI) ≥ 4 were included. Induction therapy consisted of vincristine and dexamethasone, and maintenance therapy with mercaptopurine and methotrexate for 2 years. RESULTS Seventy-two patients with a median age of 67 years (range, 57-89 years) and a median CCI of 5 (range, 4-12) were included. The rates of early withdrawal, early death, resistance, and complete response (CR) were 5%, 10%, 31%, and 54%, respectively. Six patients with CR abandoned the study, 5 died in CR, and 23 relapsed (cumulative relapse incidence 75%). The medians of disease-free and overall survival (OS) were 6.9 months (95% confidence interval [CI], 0.3-13.5 months) and 7.6 months (95% CI, 6.3-8.9 months), respectively. The most frequent toxic events were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases). Eastern Cooperative Oncology Group score but not the CCI had significant impact on OS. CONCLUSION Complete remission with very attenuated chemotherapy can be attained in one-half of older or elderly infirm patients with ALL. These results suggest that some of these patients could benefit from the concomitant or subsequent use of immunotherapy and/or targeted therapy. INTRODUCTION The purpose of this study was to explore the outcomes of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) plus idarubicin (IDA) as a frontline treatment in adult patients with acute promyelocytic leukemia (APL). PATIENTS AND METHODS We analyzed the outcomes of ATRA and intravenous ATO plus IDA as a frontline induction therapy in 118 patients with APL with high-risk (HR) and standard-risk (SR) disease from January 2008 to December 2017. The medical records of 118 patients with APL (HR, n = 45; SR, n = 73) who received the frontline triple combination regimen at Henan Provincial People's Hospital and Tongji Hospital were retrospectively reviewed. Consolidation therapy comprised 6 cycles of ATO and ATRA plus IDA, and IDA was administered in 1 to 4 cycles of consolidation therapy based on the comparable clinical efficacy compared with 6 cycles and fewer side effects to myocardium without subsequent maintenance therapy. RESULTS Of 118 patients, there were 3 (2.5%) early deaths and 115 (97.5%)tion mutation status (P = .405 and P = .528, respectively). CONCLUSION The triple combination of ATRA and ATO plus IDA as both an induction and consolidation therapy for the HR and SR groups attained excellent outcomes, and this regimen was effective, safe, and easy, without maintenance therapy. The triple combination treatment might be a preferred frontline therapy for patients with APL, especially for those with HR or the APL fms-related tyrosine kinase 3 internal tandem duplication mutation. OBJECTIVES To describe the pharmacy administration and pharmaceutical care in a module hospital during the coronavirus disease 2019 (COVID-19) epidemic and provide reference for domestic and foreign pharmacists participating in the epidemic prevention and control. SETTING The study was performed in a Jianghan module hospital constructed at the Wuhan Convention and Exhibition Center in Wuhan, China. This is 1 of the first 3 module hospitals. PRACTICE DESCRIPTION One thousand eight hundred forty-eight patients were admitted to the Jianghan module hospital, and 1327 cases (71.81% of the total number) were cured and discharged. Pharmacists have successfully completed the tasks of purchase, storage, and free distribution of drugs worth ¥1.03 million (approximately $146,000), reviewed about 20,000 electronic orders, provided one-on-one online medication consultation for 484 patients, and held 5 lectures on rational drug use knowledge, which could help reduce irrational drug use and minimize the risk involved. PRACTcidence of drug-induced risks through medication review and guidance, thereby improving patient compliance and helping the patients rebuild their confidence in overcoming the disease. CONCLUSION The new COVID-19 module pharmaceutical care model has played an important role in overcoming the epidemic situation of COVID-19 in China and thus can be implemented on a broader scale. OBJECTIVE To emphasize adverse outcomes associated with applying adult immunization protocols to the pediatric population. CASE SUMMARY A 15-year-old female with no past medical history developed severe pain in her left arm and decreased range of motion 11 days after receiving an intramuscular injection of the human papillomavirus vaccine. Over the following month, she was treated with a short course of steroids for frozen shoulder and gabapentin for Parsonage-Turner syndrome. During the third visit to a specialist for severe pain and loss of left arm mobility, she was sent to the emergency department for further workup. An x-ray and magnetic resonance imaging of the left arm were suspicious for osteomyelitis. The diagnosis was confirmed by incision and drainage of the abscess and a bone biopsy. A 6-week course of antibiotic therapy was initiated after the biopsy results. The injury was attributed to overpenetration by the needle during the intramuscular injection she had received in the previous month. PRACTICE IMPLICATIONS As the number of states allowing pharmacists to vaccinate patients of all ages grows, pharmacists must be prepared to safely provide vaccinations to patients of varying sizes. Assessing body habitus while balancing the constant responsibilities of a community pharmacy will be a challenge. Introduction of a guidance document with specific needle lengths based on weight, age, and sex can address potential errors before they occur. INTRODUCTION Immune checkpoint pathway markers induce immune tolerance to non-small cell lung cancer (NSCLC). Therapeutic antibodies targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have demonstrated efficacy in tumors expressing relatively high PD-L1 levels. Minimally invasive endobronchial ultrasound-guided fine needle aspiration allows patients with inoperable tumors or comorbidities to attain a confirmatory diagnosis. The aims of the present study were to determine whether PD-L1 testing is equivalent to cytology and biopsy or resection specimens at different tumor proportion score cutoffs and for different NSCLC subtypes. MATERIALS AND METHODS Data were retrospectively collected for patients with paired NSCLC cytology and surgical resection specimens from May 4, 2007 to May 4, 2017. The Food and Drug Administration-approved Dako PD-L1 immunohistochemistry 22C3 pharmDx kit was used to measure PD-L1 on paired cytology cell block and biopsy or resection specimens, and the PD-L1 tumor proportion scores were recorded. Statistical analysis of categorical and continuous variables was performed using SAS, version 9.4. RESULTS A total of 53 paired cytology and resection samples (27 adenocarcinoma, 25 squamous cell carcinoma, and 1 unclassified) were analyzed. Supposing the resection specimen to reflect the true PD-L1 expression, the sensitivity, specificity, positive predictive value, negative predictive value, and overall agreement for the cytology method was 73.3%, 65.2%, 73.3%, 65.2%, and 69.8%, respectively. For high PD-L1 expression (≥50%), the cytology method demonstrated an overall agreement of 79.2%. The overall agreement between methods was 81.5% and 76% for cases of adenocarcinoma and squamous cell carcinoma, respectively. CONCLUSIONS NSCLC cytology samples from endobronchial ultrasound-guided fine needle aspiration are suitable for PD-L1 testing, especially using a high PD-L1 expression cutoff of ≥50% and for adenocarcinoma. INTRODUCTION One of the key features of the Bethesda System for Reporting Thyroid Cytopathology is the risk of malignancy (ROM), which guides management for each diagnostic category. However, calculation of the ROM can be challenging for indeterminate diagnoses because only a portion of cases will be resected for cytologic-histologic correlation (CHC) analyses. In the present study, we used the probability of cancer information from ThyroSeq, version 3, reports to calculate the molecular-derived (MD) ROM for indeterminate categories. MATERIALS AND METHODS Cytology cases with indeterminate BSRTC diagnoses and adequate molecular test results were retrieved from our cytopathology laboratory for a 12-month period. The probability of cancer information from the ThyroSeq, version 3, molecular reports were tabulated, and the mean ROM was calculated for each diagnostic category. The MDROM included noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) as a "malignant" outcome because it is considered a surgical disease. RESULTS A total of 361 cases had adequate material for molecular testing. The diagnostic distribution was as follows atypia of undetermined significance/follicular lesion of undetermined significance, 271 cases (75.1%), follicular neoplasm/suspicious for a follicular neoplasm, 59 cases (16.3%), and Hürthle cell type/suspicious for a follicular neoplasm, Hürthle cell type, 31 cases (8.6%). The corresponding estimated MDROMs were 14.9%, 32.6%, and 34.4%. A comparison with the CHC data was performed, and the 95% confidence intervals of the MDROMs overlapped well with the 2 endpoint CHC values. CONCLUSIONS Calculation of the MDROMs provides a new method to approximate the ROMs of indeterminate diagnoses and has the advantage of potentially evaluating all cases, not just those resected. Furthermore, for those using the same platform, interinstitutional comparisons will be possible. Chemical modifications of quinoline moiety have been recognized as a useful strategy to development of new drugs. Here, the cytotoxicity of a set of twenty-four 4-substituted quinolines (named HTI) was screened for their antitumor and antileishmanial potential in vitro, and the underlying mechanisms investigated. HTI 21 and HTI 22 exhibited the highest cytotoxicity, being selected to the subsequent studies. read more Both derivatives induced caspase-dependent apoptosis associated to the dissipation of the mitochondrial transmembrane potential (ΔΨ) and ROS generation. HTI-induced cell death was calcium dependent, associated to thiol oxidation and cysteine proteases activation. In isolated mitochondria, HTI derivatives promoted mitochondrial permeabilization by different mechanisms. The inhibition of BCL-2 by venetoclax enhanced the HTI-induced cytotoxicity. Regarding the inhibition of cysteine proteases type B of Leishmania mexicana, HTI 15 exhibited the most potent inhibitory activity through a linear non-competitive mechanism. These data highlight the therapeutic potential of 4-substituted quinolines as antitumor and antileishmanial drugs.
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