A patients' view of OA: the Global Osteoarthritis Patient Perception Survey (GOAPPS), a pilot study.

BACKGROUND: Globally, osteoarthritis (OA) is the third condition associated with disability. There is still poor treatment in OA but science holds the key to finding better treatments and a cure. It is essential to learn what's important to patients from them to implement the most effective OA management. The OA Patients Task Force, conducted the Global OA Patient Perception Survey (GOAPPS)-the first global survey made by patients to analize the quality of life (QoL) & patient perceptions of care. The goal was to collect data on OA patients' perception of OA to understand patients' needs and expectations to improve OA management. METHODS: Observational, cross-sectional study by online survey data collection from six countries, translated into three languages. The questionnaire was comprised of 3 sections: patient demographics and clinical symptomology characteristics; relationship with physicians: perception of attention, treatment, and information provided; and OA impact on daily activity and QoL. The results of the survey were evaluated using the Limited Data Set. The survey results were analyzed using descriptive statistics to characterize the patients' answers. Additionally, Cronbach's alpha was calculated to determine internal consistency validity. RESULTS: A total of 1512 surveys were completed in 6 countries. 84.2% of respondents reported pain/tenderness and 91.1% experienced limitations to physical activities. 42.3% of patients were not satisfied with their current OA treatment. 86% had comorbidities, especially hypertension, and obesity. 51.3 and 78% would like access to additional drug or additional non-drug/non-surgical treatments respectively. 48.2% of patients perceived their QoL to be affected by OA. The Cronbach's alpha was 0.61. CONCLUSIONS: OA has a significant impact on patients' daily activities and their desire to play an active role in managing this disease. Patients are seeking additional treatments, especially no pharmacological/no surgical treatments stressing the need for investing in clinical research, implementing OA preventive measures, and managing interventions to improve the healthcare value chain in OA.

Global management of patients with knee osteoarthritis begins with quality of life assessment: a systematic review.

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent form of chronic joint disease associated with functional restrictions and pain. Activity limitations negatively impact social connectedness and psychological well-being, reducing the quality of life (QoL) of patients. The purpose of this review is to summarize the existing information on QoL in KOA patients and share the reported individual factors, which may influence it. METHODS: We conducted a systematic review examining the literature up to JAN/2017 available at MEDLINE, EMBASE, Cochrane, and PsycINFO using KOA and QOL related keywords. Inclusion criteria were QOL compared to at least one demographic factor (e.g., age, gender), lifestyle factor (e.g., functional independence), or comorbidity factor (e.g., diabetes, obesity) and a control group. Analytical methods were not considered as part of the original design. RESULTS: A total of 610 articles were reviewed, of which 62 met inclusion criteria. Instruments used to measure QoL included: SF-36, EQ-5D, KOOS, WHOQOL, HAS, AIMS, NHP and JKOM. All studies reported worse QoL in KOA patients when compared to a control group. When females were compared to males, females reported worse QOL. Obesity as well as lower level of physical activity were reported with lower QoL scores. Knee self-management programs delivered by healthcare professionals improved QoL in patients with KOA. Educational level and higher total mindfulness were reported to improve QoL whereas poverty, psychological distress, depression and lacking familial relationships reduce it. Surgical KOA interventions resulted in good to excellent outcomes generally; although, results varied by age, weight, and depression. CONCLUSION: KOA has a substantial impact on QoL. In KOA patients, QoL is also influenced by specific individual factors including gender, body weight, physical activity, mental health, and education. Importantly, education and management programs designed to support KOA patients report improved QoL. QoL data is a valuable tool providing health care professionals with a better comprehension of KOA disease to aid implementation of the most effective management plan.

Label-free protein profiling of adipose-derived human stem cells under hyperosmotic treatment.

Our previous work suggested that treatment of cells with hyperosmotic media during 2D passaging primes cells for cartilage tissue engineering applications. Here, we used label-free proteomic profiling to evaluate the effects of control and hyperosmotic treatment environments on the phenotype of multipotent adipose-derived stem cells (ASCs) cultivated with a chondrogenic growth factor cocktail. Spectra were recorded in a data-independent fashion at alternate low (precursor) and high (product) fragmentation voltages (MS(E)). This method was supplemented with data mining of accurate mass and retention time matches in precursor ion spectra across the experiment. The results indicated a complex cellular response to osmotic treatment, with a number of proteins differentially expressed between control and treated cell groups. The roles of some of these proteins have been documented in the literature as characteristic of the physiological states studied, especially aldose reductase (osmotic stress). This protein acted as a positive control in this work, providing independent corroborative validation. Other proteins, including 5'-nucleotidase and transgelin, have been previously linked to cell differentiation state. This study demonstrates that label-free profiling can serve as a useful tool in characterizing cellular responses to chondrogenic treatment regimes, recommending its use in optimization of cell priming protocols for cartilage tissue engineering.

Video assistance for surgical pulmonary embolectomy.

Surgical pulmonary embolectomy is one of the treatment options for massive pulmonary embolism. At our institute, we have recently adopted a strategy of video assistance for better visualization and clearance of distal pulmonary emboli. Here, we describe our experience.

A chronic thromboembolic pulmonary hypertension catch-22 situation: inferior vena caval filter plays a pivotal role in an unlikely situation.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare clinical entity that occurs in a small subset of acute pulmonary embolism (PE) cases and is surgically cured by pulmonary endarterectomy. We report a case of a 44-year-old female with a complex history of CTEPH treated by thromboendarterectomy who presented with a subdural hematoma while on warfarin. The patient eventually recovered by a multidisciplinary approach, use of inferior vena caval filter, and effective anticoagulation management.

Effects of hypertonic (NaCl) two-dimensional and three-dimensional culture conditions on the properties of cartilage tissue engineered from an expanded mature bovine chondrocyte source.

Clinically relevant mature cartilage cells (chondrocytes) present challenges for use in cartilage tissue engineering applications, given their low capacity for cell division and tissue production. Since the in situ environment of chondrocytes is hypertonic relative to standard culture medium conditions, in this study we tested the hypothesis that using culture medium of a hypertonic, more physiologic osmolarity during both two-dimensional (2D) expansion of mature bovine chondrocytes (MBCs) and their subsequent encapsulation culture in three-dimensional (3D) agarose hydrogel constructs produces improved engineered tissue construct mechanical and biochemical properties. Results demonstrate that 2D expansion of MBCs in hypertonic (NaCl) medium before encapsulation yielded improved construct mechanical properties. However, 3D encapsulation culture of cells in hypertonic (NaCl) medium yielded poorer construct mechanical properties. Osmolarity-related differences in construct biochemical content and organization may have contributed to differences in mechanical properties, as construct glycosaminoglycan content correlated moderately with construct mechanical properties, and construct collagen distribution varied between 3D osmotic culture groups. Results of this study suggest that application of hypertonic (NaCl) medium during 2D mature chondrocyte expansion, but not 3D encapsulated chondrocyte culture, may serve as a convenient and inexpensive method for improving mechanical properties of expanded cell-seeded constructs.

Dependence of zonal chondrocyte water transport properties on osmotic environment.

OBJECTIVE: The increasing concentration of proteoglycans from the surface to the deep zone of articular cartilage produces a depth-dependent gradient in fixed charge density, and therefore extracellular osmolarity, which may vary with loading conditions, growth and development, or disease. In this study we examine the relationship between in situ variations in osmolarity on chondrocyte water transport properties. Chondrocytes from the depth-dependent zones of cartilage, effectively preconditioned in varying osmolarities, were used to probe this relationship. DESIGN: First, depth variation in osmolarity of juvenile bovine cartilage under resting and loaded conditions was characterized using a combined experimental/theoretical approach. Zonal chondrocytes were isolated into two representative "baseline" osmolarities chosen from this analysis to reflect in situ conditions. Osmotic challenge was then used as a tool for determination of water transport properties at each of these baselines. Cell calcium signaling was monitored simultaneously as a preliminary examination of osmotic baseline effects on cell signaling pathways. RESULTS: Osmotic baseline exhibits a significant effect on the cell membrane hydraulic permeability of certain zonal subpopulations but not on cell water content or incidence of calcium signaling. CONCLUSIONS: Chondrocyte properties can be sensitive to changes in baseline osmolarity, such as those occurring during OA progression (decrease) and de novo tissue synthesis (increase). Care should be taken in comparing chondrocyte properties across zones when cells are tested in vitro in non-physiologic culture media.

Low-serum media and dynamic deformational loading in tissue engineering of articular cartilage.

High-serum media have been shown to produce significant improvement in the properties of tissue-engineered articular cartilage when applied in combination with dynamic deformational loading. To mitigate concerns regarding the culture variability introduced by serum, we examined the interplay between low-serum/ITS-supplemented media and dynamic deformational loading. Our results show that low serum/ITS supplementation does not support the same level of tissue formation as compared to high serum controls. In free-swelling culture, using a combination of ITS with concentrations of FBS above 2% negated the beneficial effects of ITS. Although there were beneficial effects with loading and 0.2%FBS + ITS, these constructs significantly underperformed relative to 20%FBS constructs. At 2%FBS + ITS, the free-swelling construct stiffness and composition approached or exceeded that of 20%FBS constructs. With dynamic loading, the properties of 2%FBS + ITS constructs were significantly lower than free-swelling controls and 20%FBS constructs by day 42. By priming the chondrocytes in 20%FBS prior to exposure to low-serum/ITS media, we observed that low-serum/ITS media produced significant enhancement in tissue properties compared to constructs grown continuously in 20%FBS.

Chondrocyte nuclear response to osmotic loading.

Cartilage compression results in changes in the shape, volume as well as hydrostatic and osmotic pressure of chondrocytes in situ. For example, changes in the cellular osmotic environment have been shown to modulate chondrocyte biosynthesis and gene expression, however, the mechanosensing mechanisms mediating these responses are relatively unknown. Nuclear shape and size changes resulting from cell deformation have been suggested to alter cell functions, and as such we recently performed a study that reported that chondrocytes and their nuclei respond to osmotic loading with alterations in their size. In the current study, we focus on the potential role of the actin cytoskeleton in mediating the transmission of osmotic loading-induced cell size changes to the nucleus.