Background
Mammalian target of rapamycin (mTOR) inhibitor‐associated stomatitis (mIAS) is a frequent adverse event (AE) associated with mTOR inhibitor therapy and can impact treatment adherence. The ...objectives are to evaluate two steroid‐based mouthrinses for preventing/ameliorating mIAS in patients with metastatic breast cancer (MBC) treated with everolimus.
Materials and Methods
This prospective, randomized phase II study enrolled 100 postmenopausal patients with hormone receptor‐positive MBC within the US Oncology Network who were initiating therapy with an aromatase inhibitor + everolimus (AIE; 10 mg/day). Patients were randomized to prophylactic therapy with one of two oral rinses (Arm 1: Miracle Mouthwash MMW 480 mL recipe: 320 mL oral Benadryl diphenhydramine; Johnson & Johnson, New Brunswick, NJ, USA, 2 g tetracycline, 80 mg hydrocortisone, 40 mL nystatin suspension, water; or Arm 2: prednisolone P 15 mg/5 mL oral solution, 1.8% alcohol). Patients were instructed to swish/expectorate 10 mL of the assigned rinse for 1–2 minutes four times daily starting with day 1 of AIE treatment, for the first 12 weeks.
Results
A total of 100 patients received treatment (49 MMW; 51 P). The incidence of stomatitis/oral AEs during the first 12 weeks was 35% (n = 17/49) and 37% (19/51) in the MMW and P arms, respectively. The incidence of grade 2 oral AEs was 14% (7/49) and 12% (6/51) with MMW or P, respectively. There were two grade 3 oral AEs (MMW arm) and no grade 4 events. There was one everolimus dose reduction (MMW) and six dose delays (four MMW, two P) and one dose reduction + delay (MMW) during the first 12 weeks of treatment. No patients stopped steroid mouthwash therapy because of rinse‐related toxicity.
Conclusion
Prophylactic use of steroid‐containing oral rinses can prevent/ameliorate mIAS in patients with MBC treated with AIE. MMW + hydrocortisone is an affordable option, as is dexamethasone oral rinse.
Implications for Practice
This prospective phase‐II study showed that two steroid‐containing mouthrinses substantially reduced incidences of all‐grade and grade ≥2 stomatitis and related oral adverse events (AEs), and the number of everolimus dose‐delays and/or dose‐reduction in metastatic breast cancer (MBC) patients receiving everolimus treatment plus an aromatase inhibitor. Both oral rinses were well tolerated and demonstrated similar efficacy. Prophylactic use of steroid mouth rinse provides a cost‐effective option that substantially decreases the incidence and severity of mammalian target of rapamycin (mTOR) inhibitor‐associated stomatitis and related oral AEs as well as the need for dose modification in MBC patients undergoing treatment with an mTOR inhibitor.
摘要
背景。哺乳动物雷帕霉素靶向基因 (mTOR) 抑制剂相关口腔炎 (mlAS) 是一种与 mTOR 抑制剂疗法相关的常见不良反应(AE)，可能影响治疗依从性。本研究旨在评估两种基于类固醇的漱口液对于使用依维莫司进行转移性乳腺癌(MBC)治疗的患者预防/改善mlAS的效果。
材料和方法。这项前瞻性 II 期随机研究选取美国肿瘤网络中的 100 名激素受体阳性 MBC 的绝经后患者，均已开始芳香化酶抑制剂+依维莫司治疗(AIE; 10 mg/天)。患者随机接受使用其中一种漱口液的预防性治疗 组 1:神奇漱口水 (MMW)480 mL 处方:320 mL 口服苯海拉明(苯海拉明，强生公司，美国新泽西州新布伦瑞克)，2 g四环素，80 mg氢化可的松，40 mL制霉菌素混悬剂，水；或组 2:强的松龙(P)，15 mg/5 mL口服液， 1.8% 酒精浓度。按照指示，患者从 AIE 治疗第一天开始，含漱/吐出 10 mL指定漱口液，每次 1‐2 分钟，每日四次，持续治疗 12 周。
结果。总计 100 名患者接受了治疗(49 人使用 MMW；51 人使用 P)。使用 MMW 和 P 前 12 周的口腔炎/口腔AE发生率分别为 35% (n = 17/49) 和 37% (19/51)。使用 MMW 和 P 的二级口腔AE发生率分别为 14% (7/49) 和 12% (6/51)。另有两例三级口腔AE(MMW 组)，没有四级事件。在前 12 周治疗中，出现一例依维莫司剂量减少 (MMW) 和六例剂量延迟(4 例 MMW，2 例 P)，以及一例剂量减少+延迟(MMW)。没有患者因漱口液相关毒性而停止类固醇漱口水治疗。
结论。预防性使用含有类固醇的漱口液可以防止/改善接受 AIE 治疗的MBC患者的mIAS。MMW+氢化可的松和地塞米松漱口液都是价格合理的治疗选择。
对实践的启示:该前瞻性 II 期研究显示，两种含有类固醇的漱口液大幅度降低了各级别及二级(含)以上口腔炎和相关口腔不良反应的发生率，也减少了接受依维莫司治疗联合芳香酶抑制剂的转移性乳腺癌(MBC)患者中依维莫司剂量延迟和/或剂量减少的数量。两种漱口液都具备良好耐受性，且功效相似。
预防性使用类固醇漱口液提供了经济适用的选项，大幅度降低 mTOR 抑制剂相关口腔炎和相关口腔不良反应的发生率和严重程度，以及接受 mTOR 抑制剂治疗的MBC患者对剂量改变的需求。
Stomatitis is a frequent adverse event associated with mTOR inhibitor therapy. This article evaluates two steroid‐based mouthrinses for preventing or improving mTOR inhibitor‐associated stomatitis in patients with metastatic breast cancer treated with everolimus.
Background Muscarinic acetylcholine receptors (MR) are involved in multiple intestinal reflexes. The cellular localization of subtypes of MRs within enteric circuits mediating muscle and mucosal ...reflexes remains to be demonstrated. This study aimed to localize the three functionally significant subtypes of MRs in human colon.
Methods Reverse transcriptase‐PCR was used to determine expression levels of muscarinic receptor subtype (MRs) M1Rs, M2Rs and M3Rs in human colon. Indirect immunofluorescence and confocal microscopy was used to localize MRs in cryostat‐cut sections of human colon. Sections were double labeled for multiple cellular and neurochemical markers. Western blotting was used to confirm specificity of the muscarinic antisera used.
Key Results All three MR subtypes were expressed in human colon. Immunoreactivity (IR) for M2Rs and M3Rs was most abundant in circular and longitudinal muscle. M1R‐IR was most abundant on myenteric and submucosal nerve cells, both cholinergic and nitrergic. M3R‐IR was also present on populations on myenteric nerve cell bodies. Immunoreactivity for all three receptors was present on nerve fibers in the circular muscle.
Conclusions & Inferences In the human colon, subtypes of MRs were present on multiple cell types within the enteric circuits underlying motility, secretory and vasoactive reflexes. The cellular distribution for MRs found in this study agrees with data from functional studies, providing insight into the role MRs have in mediating enteric cholinergic neurotransmission.
The 3000 km2 Marcy anorthosite massif dominates the Adirondack Highlands (Grenville Province, New York). The Marcy massif was metamorphosed to granulite facies conditions, in places preserving ...igneous textures with metamorphic coronas and is most deformed near its margins. Historically, the relationship between anorthosite emplacement and metamorphism has been controversial, and many workers have argued that anorthosite emplacement coincided with metamorphism. Valley and O'Neil (1982) proposed that high-pressure metamorphic mineral assemblages in the anorthosite could not reflect the same event that formed wollastonite skarns adjacent to anorthosite, which have low δ18O and formed in the presence of meteoric water during shallow emplacement. This study presents new in-situ geochronology that constrains the timing of metamorphic mineral growth in Adirondack anorthosite to 1050-1035 Ma. The Zr source for metamorphic zircon growth was the breakdown of hemoilmenite and is texturally linked to high-pressure mineral assemblages. These data are consistent with previously determined ca. 1155 Ma magmatic ages and later granulite facies metamorphism during the 1090-1020 Ma Ottawan phase of the Grenvillian orogeny.
We estimated the seroprevalence of Heartland virus antibodies to be 0.9% (95% CI 0.4%-4.2%) in a convenience sample of blood donors from northwestern Missouri, USA, where human cases and infected ...ticks have been identified. Although these findings suggest that some past human infections were undetected, the estimated prevalence is low.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metabolic rate is a key component of energy budgets that scales with body size and varies with largescale environmental geographical patterns. Here we conduct an analysis of standard metabolic rates ...(SMR) of marine ectotherms across a 70° latitudinal gradient in both hemispheres that spanned collection temperatures of 0–30 °C. To account for latitudinal differences in the size and skeletal composition between species, SMR was mass normalized to that of a standard-sized (223 mg) ash-free dry mass individual. SMR was measured for 17 species of calcified invertebrates (bivalves, gastropods, urchins and brachiopods), using a single consistent methodology, including 11 species whose SMR was described for the first time. SMR of 15 out of 17 species had a mass-scaling exponent between 2/3 and 1, with no greater support for a 3/4 rather than a 2/3 scaling exponent. After accounting for taxonomy and variability in parameter estimates among species using variance-weighted linear mixed effects modelling, temperature sensitivity of SMR had an activation energy (Ea) of 0.16 for both Northern and Southern Hemisphere species which was lower than predicted under the metabolic theory of ecology (Ea 0.2–1.2 eV). Northern Hemisphere species, however, had a higher SMR at each habitat temperature, but a lower mass-scaling exponent relative to SMR. Evolutionary trade-offs that may be driving differences in metabolic rate (such as metabolic cold adaptation of Northern Hemisphere species) will have important impacts on species abilities to respond to changing environments.
Aims: To determine the prevalence of intraocular pressure (IOP) alterations following intravitreal injection of triamcinolone acetonide (IVTA) and to assess possible risk factors of IOP elevation in ...eyes receiving single and/or repeat injections. Methods: Retrospective, consecutive case series. 570 consecutive eyes of 536 patients who received a single IVTA injection (4 mg/0.1 ml) and a second set of 43 eyes of 40 patients who received a second injection. Retrospective review of all IVTA cases performed by three vitreoretinal surgeons over a 42 month period beginning in 2000. The main outcome measure was change in IOP defined as absolute value of IOP elevation (5 mm Hg or higher, 10 mm Hg or higher), and percentage of baseline (30% or higher increase from baseline IOP). Results: Of the 528 eyes receiving single injections, 281 (53.2%) had an IOP elevation; 267 eyes (50.6%) experienced an elevation of IOP of at least 30%, and 245 (45.8%) and 75 (14.2%) eyes had an increase of 5 mm Hg or 10 mm Hg or more, respectively. Baseline IOP greater than 16 mm Hg is a risk factor for post-injection IOP elevation. Of the 43 eyes which received a second injection, 28 (65.1%) experienced an increase in IOP of at least 30% of baseline. Filtering surgery was required in five (0.094%) of the single and one (2.3%) of repeat injection eyes. Conclusions: Elevated IOP after IVTA is common and patients should be monitored beyond 6 months post-injection. Patients with a baseline IOP more than 16 mm Hg or receiving a second injection should be carefully monitored for an elevated IOP.
Sjögren's syndrome (SjS) is a human autoimmune disease characterized by exocrine dysfunction resulting from chronic autoimmune attack primarily against the lacrimal and/or salivary glands. Although, ...we previously established a good correlation between SjS in humans and autoimmune exocrinopathy in NOD/LtJ mice an in-depth evaluation of lacrimal gland disease in the NOD/LtJ mouse has remained limited. This leaves a major gap in our understanding of the dacryoadenitis/keratoconjunctivitis sicca in this model. Here we characterize the development of the autoimmune dacryoadenitis in NOD/LtJ and NOD.B10- H2 b mice in comparison with age- and sex-matched nonautoimmune CD1 mice. We observed a decline in tear production beginning at 8 weeks of age in both NOD/LtJ and NOD.B10- H2 b mice, continuing throughout the 40 to 46 weeks studied. This correlated with a quantifiable increase in mixed T- and B-lymphocyte infiltrations in the extraorbital lacrimal glands. In addition, temporal differences in tear protein expression between NOD/LtJ and CD1 mice were identified using two-dimensional gel electrophoresis and tandem mass spectrometry. Thus, using this model we can identify potentially important pathophysiological mechanisms of the autoimmune attack and possible diagnostic markers for development of SjS-associated dacryoadenitis.
Abstract
Objective
Independent assessment of SARS-CoV-2 antigen (COV2Ag) tests remains important as varying performance between assays is common. We assessed the performance of a new high-throughput ...COV2Ag test compared to SARS-CoV-2 nucleic acid amplification tests (NAAT).
Methods
A total of 347 nasopharyngeal samples collected from January to October 2021 were assessed by NAAT as part of standard-of-care testing (CDC LDT or GeneXpert System, Cepheid) and COV2Ag using the ADVIA Centaur CoV2Ag assay (Siemens Healthineers).
Results
Among NAAT positive specimens we found 82.4% agreement and in NAAT negative specimens we found 97.3% agreement (overall agreement 85.6%). In symptomatic persons, COV2Ag agreed with NAAT 90.0% (n = 291), and in asymptomatic persons, 62.5% (n = 56). Agreement between positive NAAT and COV2Ag increased at lower cycle threshold (Ct) values.
Conclusion
The COV2Ag assay exceeded the World Health Organization minimum performance requirements of ≥ 80% sensitivity and ≥ 97% specificity. The COV2Ag assay is helpful for large scale screening efforts due to high-throughput and reduced wait times.
Multiple small-scale transcriptome studies have been undertaken for various members of the Penaeidae. Penaeid shrimp are important both as members of diverse ecosystems around the world and for their ...importance as commercial commodities. Of the many shrimps, the most important from this family is the Pacific whiteleg shrimp, Litopenaeus vannamei, as it is the primary shrimp used in worldwide aquaculture. The sequencing and analysis of 13 656 expressed sequence tags (ESTs) from this species is presented. ESTs were derived from multiple tissue-specific cDNA libraries with an emphasis being placed on those tissues with predicted immune function. Assembly of the sequences into non-overlapping clusters yielded 7466 putative unigenes (1981 contigs and 5485 singletons). Multiple approaches were taken to assign putative function to each transcript; sequence homology searches using BLASTX (Basic Local Alignment Search Tool: Translated query versus protein database) of the National Center for Biotechnology Information's (NCBI) GenBank Database and Gene Ontology annotation, and still a significant portion of the shrimp ESTs (62%) had no homology with known proteins in the public databases. The sequence and complete annotation of all ESTs is available at , a publicly accessible database. In addition to providing the basic resources for microarray construction, transcript profiling, and novel gene discovery, this study constitutes the largest combined analysis of ESTs from any shrimp species and is a prelude to an even larger effort aimed at identifying and depleting highly redundant genes from shrimp cDNA libraries toward the goal of sequencing 100 000 shrimp ESTs.
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