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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120270, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34438115

RESUMO

Hypochlorite plays a significant role in physiological processes, particularly regulation of lysosomal functions, and is involved in various diseases. Thus, it is crucial to develop highly sensitive and selective molecule tools to detect HClO in lysosomes. Herein, a novel 2H-benzo[h]chromene-pyridine derivative (1) was synthesized through condensation reaction, which exhibited a notable deep-red emission at 640 nm in pure water. This deep-red emission was specifically quenched by adding ClO-. The response of probe 1 toward ClO- was rapid (within 10 s), sensitive (detection limit of 0.012 µM), and effective over a wide range of pH (1.0-12.0). Due to the existence of morpholine as the lysosome-targeting unit, the probe was successfully utilized to monitor lysosomal ClO-. Moreover, the probe 1 was also applied to detecting ClO- in zebrafish.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Animais , Humanos , Lisossomos , Imagem Óptica , Água , Peixe-Zebra
2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21265753

RESUMO

BackgroundData on COVID-19 vaccine effectiveness (VE) among healthcare workers (HCWs) during periods of delta variant predominance are limited. MethodsWe followed a population of urban Massachusetts HCWs (45% non-White) subject to epidemiologic surveillance. We accounted for covariates such as demographics and community background infection incidence, as well as information bias regarding COVID-19 diagnosis and vaccination status. Results and DiscussionDuring the study period (December 16, 2020 to September 30, 2021), 4615 HCWs contributed to a total of 1,152,486 person-days at risk (excluding 309 HCWs with prior infection) and had a COVID-19 incidence rate of 5.2/10,000 (114 infections out of 219,842 person-days) for unvaccinated person-days and 0.6/10,000 (49 infections out of 830,084 person-days) for fully vaccinated person-days, resulting in an adjusted VE of 82.3% (95% CI: 75.1-87.4%). For the secondary analysis limited to the period of delta variant predominance in Massachusetts (i.e., July 1 to September 30, 2021), we observed an adjusted VE of 76.5% (95% CI: 40.9-90.6%). Independently, we found no re-infection among those with prior COVID-19, contributing to 74,557 re-infection-free person-days, adding to the evidence base for the robustness of naturally acquired immunity.

4.
Am J Nephrol ; : 1-10, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749369

RESUMO

INTRODUCTION: Transplant glomerulopathy (TG) is a morphological lesion resulting from chronic glomerular endothelium injury, and it is strongly associated with poor graft survival. TG coexisting with focal segmental glomerulosclerosis (FSGS) can be found in renal allograft biopsies, but few related studies are available. METHODS: Consecutive kidney transplant recipients with biopsy-proven TG were studied retrospectively. Patients concomitant with FSGS were identified and compared with those without FSGS. The influence of FSGS on allograft outcomes was assessed using univariate and multivariate Cox regression models. RESULTS: Of the 66 patients with TG, 40 (60.6%) had concomitant FSGS. TG patients with FSGS had higher proteinuria (median, 2.6 vs. 0.8 g/24 h, p < 0.001) and serum creatinine levels (median, 2.5 vs. 2.1 mg/dL, p = 0.04), lower serum albumin levels, higher chronic glomerulopathy (cg) score, larger glomerular tuft area, lower number of podocytes, and higher incidences of podocyte hyperplasia, pseudotubule formation, and diffuse foot process effacement than those without FSGS (all p < 0.05). The kidney allograft loss rate of patients with FSGS was higher than that of patients without FSGS (65.7% vs. 37.5%, p = 0.03). The presence of FSGS was independently associated with allograft loss in TG (hazard ratio (HR) = 3.42, 95% confidence interval (CI): 1.30-8.98, p = 0.01). Other independent predictors were proteinuria (HR = 1.18, 95% CI: 1.02-1.37, p = 0.02), estimated glomerular filtration rate (HR = 0.94, 95% CI: 0.91-0.97, p < 0.001), and panel reactive antibody (HR = 3.99, 95% CI: 1.14-13.99, p = 0.03). Moreover, FSGS (odds ratio (OR) = 4.39, 95% CI: 1.29-14.92, p = 0.02) and cg (OR = 5.36, 95% CI: 1.56-18.40, p = 0.01) were independent risk factors for proteinuria. CONCLUSION: In this cohort of patients with TG, the presence of FSGS was strongly associated with more severe clinicopathological features and worse allograft survival.

5.
Ann Surg Oncol ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751872

RESUMO

BACKGROUND: Esophageal carcinoma (EC) is the sixth most common cause of cancer-related mortality worldwide. Studying the associations of the tumor microenvironment (TME) with pathology and prognosis would illustrate the underlying mechanism of prognostic prediction and provide novel targets for immunotherapy in the treatment of EC. METHODS: Transcriptomic profiles of 159 EC patients were obtained from The Cancer Genome Atlas (TCGA) database. Stromal and immune scores were calculated using the ESTIMATE algorithm. Differentially expressed genes (DEGs) were identified by the optimal score cutoff. Functional enrichments were analyzed by DAVID, while prognostic genes were explored using the Kaplan-Meier method. Validation analysis was performed using immunohistochemistry in tissue microarrays containing samples from 145 EC patients. Multiplex immunofluorescence staining was performed to detect a panel of 6 immune markers, including T-cell immunoreceptor with Ig and ITIM domains (TIGIT), in 90 EC patients. RESULTS: Immune scores significantly increased with increasing age, while stromal scores were dramatically elevated with increasing tumor stage. Fifteen TME-related DEGs including allograft inflammatory factor 1 (AIF1) were identified as prognostic factors of EC. Furthermore, the validation cohort indicated that AIF1 was negatively associated with the prognosis of esophageal squamous cell carcinoma patients. Subsequent analyses suggested that AIF1 may affect immune infiltrates, including T cells and natural-killer cells. Moreover, a correlation between AIF1 and TIGIT was identified. CONCLUSIONS: These results indicate that the TME-related gene AIF1 is a promising predictor of prognosis and is related to immune infiltrates and TIGIT expression in EC. However, further mechanistic studies are needed.

6.
Thorac Cancer ; 12(22): 3019-3031, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34596346

RESUMO

BACKGROUND: There is only limited knowledge of the treatment responses and clinical outcomes of immune checkpoint inhibitors (ICIs) in driver gene-negative non-small cell lung cancer (NSCLC) patients with brain metastases (BM). This study aims to assess the efficacy of immunotherapy in these patients in a real world setting. METHODS: NSCLC-BM patients without driver gene mutations who received ICIs were retrospectively identified between July 2017 and December 2019. The primary observation endpoint was intracranial objective response rate (iORR), and secondary objectives were objective response rate (ORR), intracranial and systemic progression-free survival (iPFS, PFS), and overall survival (OS). RESULTS: We reviewed 1578 patients with lung cancer and BM. According to the exclusion criteria, 41 patients were finally enrolled. Among these 41 patients, iORR was 36.6% (95% confidence interval [CI] = 21.2%-52.0%), whereas iPFS was 6.8 (95% CI = 3.32-10.35) months. Additionally, ORR, PFS, and OS were 24.4% (95% CI = 10.7%-38.1%), 6.2 (95% CI = 4.57-7.83) months and 13.7 (95% CI = 11.20-16.26) months, respectively. ICIs combined with concurrent radiotherapy group exhibited preferred iORR (p = 0.030) compared with no radiotherapy group, and ICIs plus chemotherapy showed improved OS (p = 0.024) compared to ICI monotherapy. Moreover, the lines of ICI treatment ≥2 (p = 0.005) and derived neutrophil-to-lymphocyte ratio (dNLR) ≥3 (p = 0.010) were independently negative factors for OS. CONCLUSION: In NSCLC-BMs patients lacking driver genes, ICIs exhibited an effective drug regime. A combination of ICIs with concurrent radiotherapy showed a better intracranial response, whereas ICIs plus chemotherapy were associated with superior OS.

7.
Ann Clin Transl Neurol ; 8(11): 2174-2183, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34716746

RESUMO

OBJECTIVE: New subtyping classification systems of Parkinson's disease (PD) have been proposed for phenotyping patients into three different subtypes: mild motor-predominant (PD-MMP), intermediate (PD-IM) and diffuse malignant (PD-DM). The quality of life (QoL) underlying the novel PD clinical subtypes is unknown. This study aimed explore the feasibility of the classification in Chinese PD patients and to investigate the potential heterogeneous determinants of QoL among the three subtypes. METHODS: 298 PD patients were enrolled, including 129 PD-MMP patients, 121 PD-IM patients and 48 PD-DM patients. All patients completed the QoL assessment, clinical evaluations and neuropsychological tests. Univariate linear analysis and multiple stepwise regression analysis were performed to identify determinants of QoL. RESULTS: Compared to PD-MMP patients, PD-IM and PD-DM patients had more impaired QoL. The Geriatric Depression Rating Scale (GDS) score, Non-Motor Symptoms Questionnaire (NMSQ) score, Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score and Epworth Sleepiness Score (ESS) were independent contributors to QoL in PD-MMP patients. The GDS score, ESS and sniffin' sticks screening 12 test score were independent contributors to QoL in PD-IM patients. The GDS score and Mini Mental State Examination score were independent contributors to QoL in PD-DM patients. INTERPRETATION: The new novel subtyping classification is feasible for Chinese PD patients. Although depression was the most crucial determinant for QoL in PD-MMP, PD-IM and PD-DM patients, the other contributors of QoL in the three subtypes were heterogeneous. These findings may prompt clinicians to target specific factors for improving QoL depending on PD subtypes.

8.
Signal Transduct Target Ther ; 6(1): 355, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34650034

RESUMO

This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).

9.
Zhongguo Fei Ai Za Zhi ; 24(10): 714-722, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34696543

RESUMO

With the development of precision medicine, therapies of targeting driver genes have significantly prolonged survival in advanced non-small cell lung cancer (NSCLC) patients. Among them, BRAF gene mutation is relatively rare, and the traditional regimen follows the treatment plan of NSCLC without driver gene mutation, which is far from meeting the clinical needs. In recent years, targeted therapy for NSCLC patients with BRAF V600E mutations has shown good efficacy when we are still exploring the better targeted therapies for other BRAF-mutated subtypes. Immunotherapy also showed positive antitumor activity in V600E and non-V600E subtypes of BRAF-mutated NSCLC. This article reviewed the progress of immunological and targeted therapy for patients with BRAF-mutated NSCLC.
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10.
Ann Clin Transl Neurol ; 8(10): 2096-2104, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34595848

RESUMO

OBJECTIVE: Little is known about the disease progression of Parkinson's disease patients with subjective cognitive complaint (PD-SCC). This longitudinal cohort study aims to compare the progression of clinical features and quality of life (QoL) in PD patients with normal cognition (NC), SCC, and mild cognitive impairment (MCI). METHODS: A total of 383 PD patients were enrolled, including 189 PD-NC patients, 59 PD-SCC patients, and 135 PD-MCI patients, with 1-7 years of follow-up. Linear mixed models were applied to evaluate longitudinal changes in motor symptoms, nonmotor features (cognitive impairment, depression, and excessive daytime sleepiness), and QoL in PD. RESULTS: At baseline, PD-SCC patients had lower Beck Depression Inventory (BDI) scores and Parkinson's Disease Questionnaire-39 (PDQ-39) scores than PD-NC patients (all p < 0.05). Longitudinal analyses revealed that the PD-SCC group exhibited faster progression in terms of BDI scores (p = 0.042) and PDQ-39 scores (p = 0.035) than the PD-NC group. The PD-MCI group exhibited faster progression rates in the Epworth Sleepiness Scale scores (p = 0.001) and PDQ-39 scores (p = 0.005) than the PD-NC group. In addition, the PD-SCC group exhibited a greater reduction in attention (Trail Making Test Part A, p = 0.047) and executive function (Stroop Color-Word Test, p = 0.037) than the PD-NC group. INTERPRETATION: PD-SCC patients exhibited faster deterioration of depression and QoL than PD-NC patients, and SCC may be an indicator of initial attention and executive function decline in PD. Our findings provided a more accurate prognosis in PD-SCC patients.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34668977

RESUMO

BACKGROUND: This phase II study evaluated camrelizumab in different PD-L1 expression cohorts of patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC; NCT03085069, registered March 21, 2017). METHODS: Patients who progressed during/after chemotherapy were enrolled and divided into four cohorts based on PD-L1 tumor proportion score (TPS). Patients with EGFR/ALK alterations and PD-L1 TPS ≥ 50% were also eligible. All enrolled patients received camrelizumab at 200 mg IV Q2W. The primary endpoint was objective response rate. RESULTS: A total of 146 patients were enrolled. As of data cutoff on Aug 20, 2020, the median follow-up was 29.5 months (95% CI 27.4-30.8). Objective response rate was 17.8% (95% CI 12.0-25.0) and improved with the increasing PD-L1 TPS (TPS < 1%, 12.2% [95% CI 5.7-21.8]; ≥ 1-< 25%, 19.4% [95% CI 7.5-37.5]; ≥ 25-< 50%, 36.4% [95% CI 10.9-69.2]; ≥ 50%, 23.3% [95% CI 9.9-42.3]). No response was observed in the five patients harboring EGFR mutations. Median progression-free survival was 3.2 months (95% CI 2.0-3.4), and patients with positive PD-L1 TPS had longer progression-free survival. Median overall survival was 14.8 months (95% CI 10.2-18.7). Treatment-related adverse events (TRAEs) of any grade occurred in 87.7% of patients, and 21.2% had grade ≥ 3 TRAEs. CONCLUSION: Camrelizumab showed improved efficacy compared with historical data of the second-line chemotherapy in pre-treated advanced/metastatic NSCLC. Patients with positive PD-L1 expression derived greater benefit from camrelizumab. Camrelizumab has a manageable safety profile.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34675989

RESUMO

Essential hypertension (EH) is a clinically frequent cardiovascular disease, with insidious onset, causing increased pressure load and neuroregulation disorders in patients. Long-term EH can cause left ventricular hypertrophy (LVH), which can lead to arrhythmia and even death. The soluble suppression of tumorigenicity 2 (sST2), matrix metalloproteinase-3 (MMP-3), and galectin-3 (Gal-3) in serum plays an important role in the occurrence, development, and prognosis of cardiovascular diseases. In our study, we divided EH patients into 3 levels and groups with or without LVH, according to their condition. The levels of sST2, MMP-3, and Gal-3 in the serum were measured in different groups of patients. Our results showed that the levels of sST2, MMP-3, and Gal-3 in the serum increased progressively with the level in different EH groups. The levels of sST2, MMP-3, and Gal-3 in the serum of the LVH group were higher than those of the NLVH group, and it is positively correlated with LVH-related indexes. The risk of developing and progressing to LVH in patients with EH can be determined by the method of measuring three indicators.

13.
Cancer Commun (Lond) ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34699693

RESUMO

BACKGROUND: Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line treatment in locally advanced or metastatic LSCC. METHODS: Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. RESULTS: The median duration of follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF-α, IFN-γ, IL-6, and IL-8, demonstrating an overlapping trend. CONCLUSION: The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

14.
Orthop Surg ; 13(7): 1987-1999, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34523790

RESUMO

OBJECTIVE: The study introduced uniportal-bichannel spinal endoscopic system (UBiSES) and explored the feasibility of applying UBiSES to conduct lumbar foraminoplasty in percutaneous endoscopic transforaminal discectomy (PETD). METHODS: This is a cohort study. 36 patients confirmed as L5/S1 lumbar disc herniation (LDH) in our hospital from March, 2019 to November, 2019 were enrolled. 36 patients were divided into two groups named the UBiSES group (n = 18, male: female = 8:10) and the TESSYS group (n = 18, male: female = 10:8). The average age of the UBiSES group and the TESSYS group were 40.94 ± 12.39 years old and 39.78 ± 13.02 years old respectively. PETD via uniportal-bichannel foraminoplasty assisted by UBiSES was adopted on the UBiSES group while PETD via conventional foraminoplasty was performed on the TESSYS group. One experienced surgeon with more than 4000 cases of lumbar surgery performed PETD on all patients. The demographic data, the duration of working cannula placement (minutes), decompression time (minutes), radiation exposure time (seconds), complications, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) scores and modified MacNab criteria were recorded and analyzed. The magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to evaluate the radiographic improvement. RESULTS: PETD via lumbar foraminoplasty was successfully performed in all cases. The follow-up points were 3 months, 6 months, and 12 months. The average follow-up period of all patients was 15.78 ± 2.29 months. There was no statistic difference in age (P = 0.81), sex (P = 0.51) and follow-up (P = 0.14) between two groups. The duration of working cannula placement was 19.08 ± 2.30 min in the UBiSES group and 24.90 ± 4.71 min in the TESSYS group and there was significant difference between two groups (P < 0.05). There was no statistic difference in decompression time between the UBiSES group (44.18 ± 5.70 min) and the TESSYS group (47.46 ± 5.96 min) (P = 1.70). The radiation exposure time was 28.00 ± 4.70 s in the UBiSES group and 40.50 ± 5.73 s in the TESSYS group respectively, and has significant difference between two groups (P < 0.05). Furthermore, there was significant different in the duration of working cannula placement and radiation exposure time in male or female between the UBiSES group and the TESSYS group (P < 0.05). For male or female, no difference observed in decompression time and follow-up period between two groups. Postoperative VAS of low back and leg at every follow-up point (1 day, 3 months, 6 months, 12 months) was improved significantly in both groups compared with their preoperative VAS (P < 0.05). The postoperative ODI (3 months, 6 months, 12 months) has decreased significantly in both the UBiSES group and the TESSYS group compared with their preoperative ODI (P < 0.05). 94.44% patients received an excellent or good recovery in the UBiSES group and 88.89% for the TESSYS group. There was no poor result reported in both groups. The radiographic images showed satisfactory foraminoplasty and sufficient decompression of nerve in both groups. No postoperative complications were observed during follow-ups in the UBiSES group. Two patients in the TESSYS group experienced postoperative dysesthesia and the symptom was disappeared in 5 days and 7 days respectively with dexamethasone and neurotrophic drugs treatment. CONCLUSIONS: The original designed UBiSES could effectively and safely enlarge the foramen with an extensive surgical view and space under full-time and real-time visualization and get satisfactory efficacy.


Assuntos
Discotomia Percutânea/instrumentação , Endoscopia/instrumentação , Desenho de Equipamento , Foraminotomia/instrumentação , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Adulto , Estudos de Coortes , Avaliação da Deficiência , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor
15.
JAMA Oncol ; 7(11): 1617-1625, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34473194

RESUMO

Importance: Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system efficacy for patients with ALK-positive non-small cell lung cancer (NSCLC). Objective: To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor. Design, Setting, and Participants: This open-label, multicenter, randomized, phase 3 trial conducted in 120 centers in 21 countries enrolled 290 patients between July 25, 2016, and November 12, 2018. Eligible patients were 18 years of age or older and had advanced, recurrent, or metastatic ALK-positive NSCLC. Interventions: Patients were randomized (1:1) to ensartinib, 225 mg once daily, or crizotinib, 250 mg twice daily. Main Outcomes and Measures: The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Secondary end points included systemic and intracranial response, time to central nervous system progression, and overall survival. Efficacy was evaluated in the intent-to-treat (ITT) population as well as a prespecified modified ITT (mITT) population consisting of patients with central laboratory-confirmed ALK-positive NSCLC. Results: A total of 290 patients (149 men [51.4%]; median age, 54 years [range, 25-90 years]) were randomized. In the ITT population, the median PFS was significantly longer with ensartinib than with crizotinib (25.8 [range, 0.03-44.0 months] vs 12.7 months [range, 0.03-38.6 months]; hazard ratio, 0.51 [95% CI, 0.35-0.72]; log-rank P < .001), with a median follow-up of 23.8 months (range, 0-44 months) for the ensartinib group and 20.2 months (range, 0-38 months) for the crizotinib group. In the mITT population, the median PFS in the ensartinib group was not reached, and the median PFS in the crizotinib group was 12.7 months (95% CI, 8.9-16.6 months; hazard ratio, 0.45; 95% CI, 0.30-0.66; log-rank P < .001). The intracranial response rate confirmed by a blinded independent review committee was 63.6% (7 of 11) with ensartinib vs 21.1% (4 of 19) with crizotinib for patients with target brain metastases at baseline. Progression-free survival for patients without brain metastases was not reached with ensartinib vs 16.6 months with crizotinib as a result of a lower central nervous system progression rate (at 12 months: 4.2% with ensartinib vs 23.9% with crizotinib; cause-specific hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001). Frequencies of treatment-related serious adverse events (ensartinib: 11 [7.7%] vs crizotinib: 9 [6.1%]), dose reductions (ensartinib: 34 of 143 [23.8%] vs crizotinib: 29 of 146 [19.9%]), or drug discontinuations (ensartinib: 13 of 143 [9.1%] vs crizotinib: 10 of 146 [6.8%]) were similar, without any new safety signals. Conclusions and Relevance: In this randomized clinical trial, ensartinib showed superior efficacy to crizotinib in both systemic and intracranial disease. Ensartinib represents a new first-line option for patients with ALK-positive NSCLC. Trial Registration: ClinicalTrials.gov Identifier: NCT02767804.

16.
Ann Epidemiol ; 64: 96-101, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34517110

RESUMO

PURPOSE: To compare the effectiveness of COVID-19 mitigation strategies in two homeless shelters in Massachusetts during the pandemic. METHODS: We conducted a prospective cohort study that followed guests in two Massachusetts homeless shelters between March 30 and May 13, 2020, which adopted different depopulation strategies. One set up temporary tents in its parking lot, while the other decompressed its guests to a gym and a hotel. The outcome was assessed by comparing the odds ratios of positive SARS-CoV-2 RT-PCR assays. RESULTS: Guests residing at the shelter that used temporary tents had 6.21 times (95% CI = 1.86, 20.77) higher odds of testing positive for SARS-CoV-2 at follow-up after adjusting for loss to follow up, age, gender, and race. The daily COVID-19 symptoms checklist performed poorly in detecting positive infection. CONCLUSIONS: The study highlights the importance of depopulating shelter guests with stable and adequate indoor space to prevent SARS-CoV-2 transmission. Daily temperature and symptom checks should be combined with routine testing. With the rising homelessness due to mass unemployment and eviction crisis, our study supports further governmental assistance in decompressing homeless shelters during this pandemic.

17.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21263038

RESUMO

ObjectiveTo investigate COVID-19 vaccine efficacy (VE) among healthcare workers (HCWs) in an ethnically diverse community healthcare system, during its initial immunization campaign. MethodsHCWs of the system were retrospectively included from the beginning of a COVID-19 vaccination program (December 16, 2020) until March 31, 2021. Those with a prior COVID-19 infection before December 15 were excluded. The Occupational Health department of the system ran a COVID-19 screening and testing referral program for workers, consistently throughout the study period. A master database had been established and updated comprising of the demographics, COVID-19 PCR assays, and vaccinations of each HCW. Andersen-Gill extension of the Cox models were built to estimate the VE of fully/partially vaccinated person-days at risk. ResultsAmong the 4317 eligible HCWs, 3249 (75%) received any vaccination during the study period. Vaccinated HCWs were older, less likely to be Black/African American, Hispanic/Latino or identify as two or more races, and more likely to be medical providers. After adjusting for age, sex, race, and the statewide background incidence at the time of vaccination, we observed a VE of 80.2% (95% CI: 57.5-90.8%) for [greater double equals]14 days after the first dose of Pfizer/Moderna, and 95.5% (95% CI: 88.2-98.3%) among those fully vaccinated (i.e. [greater double equals]14 days after the second dose of Pfizer/Moderna or the single dose of J&J/Janssen). ConclusionCOVID-19 vaccine effectiveness in the real world is promising, and these data in concert with culturally appropriate may decrease vaccine hesitancy.

18.
Sci Rep ; 11(1): 19101, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580352

RESUMO

Obstructive sleep apnea (OSA) is a common cause of hypertension. Previous studies have demonstrated beneficial short-term effects of continuous positive airway pressure (CPAP) therapy on blood pressure. However, long-term antihypertensive effects of CPAP have not been properly verified. This study examined the longitudinal effect of CPAP therapy adherence on blood pressure among OSA patients. All patients diagnosed with OSA and undergoing subsequent CPAP therapy at a Kanagawa-area sleep clinic were clinically followed for 24 months to examine CPAP adherence, as well as longitudinal changes in blood pressure and body weight because it may become a confound factor for changes in blood pressure. The hours of CPAP usage were collected over the course of 30 nights prior to each follow-up visit (1st, 3rd, 6th, 12th, and 24th month). The relationship between CPAP adherence and blood pressure was analyzed using mixed-effect logistic regression models. A total of 918 OSA patients were enrolled in the study. We found a significant reduction in diastolic blood pressure among patients with good CPAP adherence during the 24-month follow-up period (ß = - 0.13, p = 0.03), when compared to the group with poor CPAP adherence. No significant association was found between CPAP adherence and weight loss (ß = - 0.02, p = 0.59). Long-term, good CPAP therapy adherence was associated with lower diastolic blood pressure without significant weight loss.

19.
Front Oncol ; 11: 720044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504796

RESUMO

Objectives: To examine the long-term survival outcome of dabrafenib in combination with trametinib in Chinese patients with unresectable or metastatic acral/cutaneous melanoma with BRAF-V600 mutation and to explore potential predictors of effectiveness. Methods: This was a long-term follow-up of Chinese patients with unresectable or metastatic BRAF V600-mutant acral/cutaneous melanoma administered dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) in an open-label, multicenter, single-arm, phase IIa study (NCT02083354). Efficacy endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The impacts of baseline characteristics on PFS and OS were analyzed. Results: A total of sixty patients were included. The median age was 48 years, and 24 patients (40.0%) were male. Totally 12 individuals (20.0%) had acral melanoma, and 45 (75.0%) had failed previous systemic therapy. Up to July 2020, the median duration of follow-up was 37.0 (95% confidence interval [CI] 29.1-44.9) months. The updated ORR was 71.7% (95%CI 60.3%-83.1%). The 3-year OS rate was 28.8% (95%CI 19.1-43.6%) in the overall population, and 35.7% (95%CI 15.5-82.4%) in acral melanoma patients. The median DOR was 7.5 months (95%CI 4.5 to 10.5). Baseline normal lactic dehydrogenase (LDH), metastatic organ sites<3 and complete response to combination therapy with dabrafenib plus trametinib were associated with improved PFS and OS. Conclusion: Dabrafenib combined with trametinib confer long-term survival in Chinese patients with BRAF V600-mutant, unresectable or metastatic acral/cutaneous melanoma. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02083354, identifier NCT02083354.

20.
Transl Lung Cancer Res ; 10(8): 3594-3607, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34584859

RESUMO

Background: Currently, there is no standard context that conforms to the Chinese national framework for evaluating medical decisions regarding the treatment of lung cancer. Methods: This draft was formulated after a systematic review and a focus group discussion among 20 experts, who were senior physicians with extensive clinical experience from the Chinese Thoracic Oncology Group (CTONG) task force. Subsequently, a draft and a five-point Likert scale were sent to 300 CTONG working group members. These were modified according to feedback from a four-round modified Delphi approach. Hence, the first version of the 'Therapeutic option of lung cancer: CTONG scoring system' was formulated. Afterward, a corresponding questionnaire was designed to collect opinions on the weight allocation of various indicators. This was issued through the WeChat platform, "Oncology News" application and e-mails from October 23, 2020, to November 25, 2020. Participants from numerous occupations in cancer-related fields from various regions of China were included in the study. Overall and subgroup analyses regarding weight allocations were performed. The differences between participant-allocated and reference weights were considered to adjust the framework. Results: The framework contained four aspects and six indicators, including efficacy [progression-free survival (PFS)/overall survival (OS) and subsequent treatment], safety [treatment-related severe adverse event (SAE), dose adjustment], quality of life (Qol), and compensation. The reference weights were 50%, 5%, 10%, 5%, 10%, and 20% for each indicator. By November 25, 2020, 1,043 valid questionnaires had been obtained. The majority of the questionnaires were completed by physicians (86.5%). Subgroup analysis among the various groups showed an overall consistent trend. Besides, significant differences between the participant-allocated and reference weights were found among PFS/OS (difference: -11.5%), compensation (difference: -10.1%), and subsequent treatment (difference: 9.7%) indicators. After discussion, the final weight allocations were set at 45%, 10%, 15%, 5%, 10%, and 15% for PFS/OS, subsequent treatment, treatment-related SAE, dose adjustment, Qol, and compensation, respectively. Conclusions: The CTONG scoring system, as an objective evaluation model that involves multiple parameters, is a breakthrough method for evaluating the therapeutic value of lung cancer treatment options in China, which is worthy of further verification in future clinical practice.

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