We aimed to evaluate the impact in sleep quality and musculoskeletal pain of a Medium-Firm Mattress (MFM), and their relationship with objective sleep parameters in a group of institutionalized elders. The sample size included forty older adults with musculoskeletal pain. We did a clinical assessment at baseline and weekly trough the study period of four weeks. We employed the Pittsburgh Sleep Quality Index (PSQI) and Pain Visual Analog Scale (P-VAS). Additionally a sub-group of good sleepers, selected from PSQI baseline evaluation, were studied with actigraphy and randomized to MFM or High Firm Mattress (HFM), in two consecutive nights.We found a significant reduction of cervical, dorsal and lumbar pain. PSQI results did not change. The actigraphy evaluation found a significant shorter sleep onset latency with MFM, and a slightly better, but not statistically significant, sleep efficiency. The medium firmness mattress improved musculoskeletal pain and modified the sleep latency.
Causas de reintervenciones quirúrgicas por complicación postoperatoria en pacientes de una unidad de cuidados intensivos quirúrgicos sometidos a cirugía abdominal.Causes of reoperations in postoperative complications after abdominal surgery in a surgical intensive care unit.
Introduction: Obstructive sleep apnea (OSA) is a biological plausible risk factor for leukoaraiosis (LA). We tested the hypothesis that polysomnographic (PSG) and sleep-related variables are associated to LA in OSA patients. Methods: Cross-sectional study in which PSG records, medical histories and brain 1.5T MRI were collected from all consecutive patients who had attended a Sleep Medicine Center between 2009-2014. LA was graded from 0 to 9 with the ’Atherosclerosis Risk In Communities’ study scale. OSA was defined by The International Classification of Sleep Disorders, 2014, and its severity categorizing according to apnea-hypopnea index (AHI, <15 mild, 15 to <30 moderate, 30 to <45 severe and ≥45 very severe). A multinomial logistic regression was performed to describe the association between OSA severity and LA (divided into 2 groups: mild-to-moderate LA and non-to-minimal LA). The covariates for all regression models were age, gender, BMI, hypertension, ischemic stroke, myocardial infarction, diabetes and pack-year of smoking. Results: From 82 OSA patients (77% male; mean age 58±9 years, range 19-91), 54 (66%) had LA. Mild-to-moderate LA was found in 13 patients (8 mild and 5 moderate LA) and non-to-minimal LA in 69 (41 minimal and 28 non LA). Spearman’s correlation coefficient between AHI and LA grade was 0.41 (p<0.001). Furthermore, the higher OSA severity, the higher LA severity (p<0.001, for Jonckheere-Terpstra test for ordered alternatives). In the multinomial logistic regression model adjusted for cofounders, severe OSA patients had higher risk for mild or moderate LA (HR 12.8, 95% IC 1.2-141) compared to mild-to-moderate OSA patients. Additionally, self-reported habitual sleep duration from 7 to 9 hours (HR 0.36, 90% IC 0.14-0.90) and proportion of time in apnea/hypopnea over total sleep time (HR 1.04 for one unit increase, 90% IC 1.01-1.08) could be associated with the presence of LA (adjusted only for age and gender). In a multiple regression analysis with all the aforementioned variables, age (p=0.002), diabetes (p=0.003), and OSA severity (p=0.04) were predictors of the presence of LA. Conclusion: Patients with severe OSA had higher risk for mild to moderate LA when compared to patients with mild or moderate OSA.
BackgroundTIGIT (T cell immunoreceptor with Ig and ITIM domains) is an exciting novel target for immuno-oncology which functions as an immune checkpoint on multiple immune cell types including memory CD8+, CD4+ Treg, and memory CD4+ cells. TIGIT upregulation on tumor infiltrating lymphocytes (TILs) has been observed in multiple cancer types and contributes to an immunosuppressive tumor microenvironment (TME). Interestingly, TIGIT is commonly co-expressed with PD-1 on Tregs in the TME, tumor antigen specific CD8+ T cells and CD8+ TILs, leading to weakened anti-tumor immune responses.1–2 To date, TIGIT inhibiting monoclonal antibodies (mAb) have shown little activity as a monotherapy in clinical and preclinical studies. 3–4 Therefore, current clinical trials are now focused on combining TIGIT mAbs with known commercial PD-1 or PD-L1 mAbs. A TIGIT-specific engineered toxin body (ETB) represents a wholly new approach to targeting TIGIT expressing cells including those co-expressing TIGIT and PD-1.MethodsETBs targeting TIGIT were designed to deplete TIGIT-expressing TILs, including Tregs, directly in the TME. ETBs are proteins that consist of an antibody fragment genetically fused to a proprietary de-immunized (DI) form of the Shiga-like toxin A subunit (SLTA). These proteins are specific for a cell surface receptor, and function through triggering rapid internalization upon binding, followed by an enzymatic and irreversible termination of ribosomal protein synthesis resulting in cellular apoptosis. Here we provide proof of concept for ETBs as a novel modality for the depletion of TIGIT-expressing immune cells.ResultsTIGIT-targeting ETBs exhibit potent in vitro cytotoxicity of TIGIT over-expressing cell lines (IC50<1nM). These ETBs also lead to apoptotic depletion of ex vivo TIGIT-expressing regulatory T cells (Tregs) from healthy donors. In mixed culture assays, TIGIT ETBs increase the proliferation of TIGIT negative T cells by depleting TIGIT-expressing T cells.ConclusionsStudies to assess pharmacodynamics and efficacy of TIGIT targeting ETBs using a double knock-in (TIGIT and PD-1) mouse tumor model are ongoing, but these early proof of concept in vitro data support the hypothesis that ETBs can deplete TIGIT positive immune cell populations including those co-expressing PD-1. It is possible that targeted TIGIT inhibition through ETB-induced cell death could tip the balance towards tumor regression by eliminating this novel checkpoint (and TIGIT/PD-1 co-expression) at the level of the TME.ReferencesJinhua X, Ji W, Shouliang C, Liangfeng Z. Expression of immune checkpoints in T cells of esophageal cancer patients. Oncotarget 2016;7(39):1–10.Blessin NC, Simon R, Kluth M, Fischer K, et al. Patterns of TIGIT expression in lymphatic tissue, inflammation and cancer. Dis Markers 2019;2019:1–13.Johnston RJ, Comps-Agrar L, Hackney J, Yu X, et al. The immunoreceptor TIGIT regulates anti-tumor and antiviral CD8(+) T effector function. Cancer Cell 2014;26(6):923–927.Bendell JC, Bedrad P, Bang Y-J, LoRusso P, et al. Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody Tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors. Proceedings: AACR Annual Meeting 2020; April 27–28, 2020 and June 22–24, 2020; Philadelphia, PA.
Engineered toxin bodies (ETBs) are next-generation immunotoxins that harbor an antibody-derived targeting domain and a cytotoxic payload derived from Shiga-like toxin-1 catalytic subunit A (SLTA). SLTA has been engineered to reduce innate immunogenicity and therefore increase the safety of ETBs whilst retaining potent cytotoxic properties. When targeted via a binding domain, SLTA is internalized and routes to the cytosol leading to irreversible ribosome inactivation and ultimately cell death. ETBs have been developed to treat a wide variety of cancers, including breast, lymphoma, multiple myeloma and PD-L1 positive solid tumors. This technology holds promise for non-oncology indications as well, particularly as a targeted and non-genotoxic conditioning regimen for hematopoietic stem cell (HSC) ablation to prepare patients for autologous stem cell transplant. c-KIT (CD117) is a well-known marker of hematopoietic stem and progenitor cells and is overexpressed in a high percentage of certain cancers including GIST, SCLC and AML. While tyrosine kinase inhibitors such as imatinib are effective therapies for c-KIT mutant GIST, resistance often occurs by the development of secondary mutations in the intracellular signaling domains. Thus, c-KIT represents a potential ETB target for both oncological and HSC transplant conditioning indications. Here we present data highlighting the in vitro potency and efficacy of CD117-targeting ETBs on cancer cell lines as well as on primary human CD34+ HSCs. CD117-targeted ETBs demonstrate exquisite specificity in vitro by killing only target positive CD34+ cells at picomolar potency while sparing the progenitors that lack CD117 expression. However, relatively low CD117 receptor levels on CD34+ HSCs prevent complete killing in vitro, limiting the observed efficacy. To overcome this challenge, an additional cytotoxic payload was conjugated to the ETB molecule to capitalize on ETBs’ unique internalization and routing properties to deliver a secondary mechanism of action. ETB-drug conjugates (ETB-DCs) exhibited improved cytotoxicity in vitro, especially in CD117-low target cells. Moving forward, we plan to explore both the ETB and the ETB-DC therapeutic index in vivo with a series of CD117+ tumor efficacy and HSC depletion models. Citation Format: Caleigh Howard, Shu Wiley, Wenzhao Dong, Andrea Mendiola, Veronica Partridge, Sara LeMar, Paul Amador, Amit K. Chaudhary, Joseph D. Dekker, Jay Zhao, Ross Durland, Aimee Iberg. c-KIT targeted ETBs for cancer therapy and HSC transplant conditioning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 335.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.