Hemopoietic and Lymphoid Progenitor Cells in Human Umbilical Cord Blood

Human umbilical cord blood, which in the past was discarded with the placental tissue, provides a convenient source of fetal hemopoietic cells for scientific analysis and clinical use. Cord blood cells are immature compared to analogous populations in adult peripheral blood. Cord blood B lymphocytes display unique phenotypic and functional characteristics. The antigens CD1C, CD38, CD5, and CD23, although normally expressed on only a small percentage of circulating B cells in adults, are highly expressed on cord blood B cells. Recent studies have demonstrated that whereas cord blood B cells are functionally naive, their potential is similar to that of adult B cells if optimal T-cell help is available. Thus, the failure of B-cell responses in cord blood is due to the T cells. The functional abnormalities of T cells from newborns can be summarized as a dominance of the effects of TH0 cells. Thus, the cytokines produced are immunosuppressive rather than mediating helper activity for B cells. NK activity in cord blood is also depressed compared to that in adults. Cord blood is a very rich source of hemopoietic progenitor cells. The spectrum of progenitors shows a predominance of early progenitor cells when compared with bone marrow. These cells provide an alternative source to adult bone marrow for stem cells to use for hemopoietic reconstitution and as targets in the treatment of hereditary deficiencies by gene therapy. These features make cord blood a unique research tool to investigate hemopoietic ontogeny and a unique clinical tool for transplantation

Early radiographic osteoarthritis is associated with substantial changes in cartilage volume and tibial bone surface area in both males and females11Sources of support: National Health and Medical Research Council of Australia, Masonic Centenary Medical Research Foundation.

AbstractObjective: To describe the association between early radiographic osteoarthritis of the knee (ROA), knee cartilage volume and tibial bone surface area.Methods: Cross-sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26–61). Articular cartilage volume, bone area and volume were determined at the patella, medial tibial and lateral tibial compartments by processing images acquired in the sagittal plane using T1-weighted fat saturation MRI. ROA was assessed with a standing semiflexed radiograph and the OARSI atlas for joint space narrowing and osteophytosis. Both radiographs and MRIs were performed in the right knee and read by different observers.Results: ROA (predominantly grade 1) was present in 17% of subjects of which medial joint space narrowing was most common (14%) followed by medial osteophytes (6%). Grade one medial joint space narrowing was associated with substantial reductions in cartilage volume at both the medial and lateral tibial and patellar sites within the knee (adjusted mean difference 11–13%, all P<0.001) while grade one osteophytosis was associated with substantial increases in both lateral and medial tibial joint surface area (adjusted mean difference 10–16%, all P<0.001). In contrast, osteophytosis was not associated with a significant change in cartilage volume and joint space narrowing was not associated with a significant change in tibial bone area (all P>0.05).Conclusions: Early medial compartment ROA is associated with substantial reductions in cartilage volume and increases in bone area. These large changes, when combined with similar measurement error for MRI and radiographs, suggest that MRI may be superior at detecting and hence understanding early osteoarthritis of the knee in humans

Optimal sampling of MRI slices for the assessment of knee cartilage volume for cross-sectional and longitudinal studies

BACKGROUND: MRI slices of 1.5 mm thickness have been used in both cross sectional and longitudinal studies of osteoarthritis, but is difficult to apply to large studies as most techniques used in measuring knee cartilage volumes require substantial post-image processing. The aim of this study was to determine the optimal sampling of 1.5 mm thick slices of MRI scans to estimate knee cartilage volume in males and females for cross-sectional and longitudinal studies. METHODS: A total of 150 subjects had a sagittal T1-weighted fat-suppressed MRI scan of the right knee at a partition thickness of 1.5 mm to determine their cartilage volume. Fifty subjects had both baseline and 2-year follow up MRI scans. Lateral, medial tibial and patellar cartilage volumes were calculated with different samples from 1.5 mm thick slices by extracting one in two, one in three, and one in four to compare to cartilage volume and its rate of change. Agreement was assessed by means of intraclass correlation coefficient (ICC) and Bland & Altman plots. RESULTS: Compared to the whole sample of 1.5 mm thick slices, measuring every second to fourth slice led to very little under or over estimation in cartilage volume and its annual change. At all sites and subgroups, measuring every second slice had less than 1% mean difference in cartilage volume and its annual rate of change with all ICCs ≥ 0.98. CONCLUSION: Sampling alternate 1.5 mm thick MRI slices is sufficient for knee cartilage volume measurement in cross-sectional and longitudinal epidemiological studies with little increase in measurement error. This approach will lead to a substantial decrease in post-scan processing time

Do knee pain phenotypes have different risks of total knee replacement?

Pain is the main impetus for osteoarthritis (OA) patients to seek healthcare including joint replacement. The pain experience in OA is heterogeneous and affected by factors across multiple domains-peripheral, psychological, and neurological. This indicates the existence of homogenous subgroups/phenotypes within OA patients with pain. We recently identified three pain phenotypes using a wide spectrum of pain-related factors, including structural damage on magnetic resonance imaging (MRI), emotional problems, number of painful sites, sex, body mass index, education level and comorbidities (i.e., Class 1: high prevalence of emotional problems and low prevalence of structural damage (25%); Class 2: low prevalence of emotional problems and high prevalence of structural damage (20%); Class 3: low prevalence of emotional problems and low prevalence of structural damage (55%)). This study was to examine whether the total knee replacement (TKR) risk over 12 years was different among these three pain phenotypes. Data on 963 participants (mean age 62.8 ± 7.4 years) from a population-based cohort study were utilised. Data on socio-demographic, psychological and comorbidities were collected. MRI of the right knee structural pathology was performed. TKR history was ascertained by linking to the Australian Orthopedic Association National Joint Replacement Registry. Latent class analysis and the Cox proportional hazards model were applied for the analysis. During the follow-up period, 41 right and 44 left TKRs in 67 participants were identified. In multivariable analyses, participants in Class 1 and 2 had a higher risk of having a TKR (Class 1 vs. Class 3, HR (hazard ratio) 4.81, 95%CI (confidence interval) 2.33-9.93; Class 2 vs. Class 3, HR 9.23, 95%CI 4.66-18.30). These associations were stronger in the imaged right knee but were also significant in the left knee. Participants within distinct pain phenotypes have different risks of TKR, suggesting that the identified phenotypes reflect distinct clinical subgroups with different prognoses. The risk for TKR was higher in Class 1 than that in Class 3, suggesting that pain/emotional status is a stronger driver for TKR than structural damage, and that selecting patients for TKR needs to be optimized in clinical practice

Patients' perceived health service needs for osteoarthritis (OA) care: a scoping systematic review

OBJECTIVE: To identify and synthesise evidence regarding patients' perceived health service needs related to osteoarthritis (OA). DESIGN: A comprehensive systematic scoping review of MEDLINE, PsycINFO, EMBASE and CINAHL (1990-2016) was performed to capture information regarding patient perceived health service needs related to OA. Risk of bias and quality of included articles were assessed. Relevant data were extracted and collated to provide a systematic review of the existing literature. RESULTS: Of the 1384 identified manuscripts, 21 were relevant to areas of patient perceived need, including needs related to medical care, pharmacologic therapy, physiotherapy and exercise therapy and alternative medicine. Key findings included (1) Symptom control drove the need for both conventional and complementary services. (2) An individualized relationship was sought with a practitioner knowledgeable in OA care and who adopted a holistic approach, whether providing conventional or alternative therapies. (3) Medications were required to obtain symptomatic relief, with use tempered by recognition of potential side effects and financial cost. (4) The need for allied health services was recognised, although patient and system issues were barriers to uptake. (5) Patient's attitudes towards joint replacement, orthoses and physical aids were influenced by patient preferences and previous healthcare experiences. CONCLUSION: Patient perceived needs are similar to those suggested by clinical guideline recommendations. Better aligning patient perceived needs with healthcare requirements may improve OA outcomes and optimise healthcare system utilisation

Patients’ perceived needs for medical services for non-specific low back pain: A systematic scoping review

Background: An improved understanding of patients’ perceived needs for medical services for low back pain (LBP) will enable healthcare providers to better align service provision with patient expectations, thus improving patient and health care system outcomes. Thus, we aimed to identify the existing literature regarding patients’ perceived needs for medical services for LBP. Methods: A systematic scoping review was performed of publications identified from MEDLINE, EMBASE, CINAHL and PsycINFO (1990–2016). Descriptive data regarding each study, its design and methodology were extracted and risk of bias assessed. Aggregates of patients’ perceived needs for medical services for LBP were categorised. Results: 50 studies (35 qualitative, 14 quantitative and 1 mixed-methods study) from 1829 were relevant. Four areas of perceived need emerged: (1) Patients with LBP sought healthcare from medical practitioners to obtain a diagnosis, receive management options, sickness certification and legitimation for their LBP. However, there was dissatisfaction with the cursory and superficial approach of care. (2) Patients had concerns about pharmacotherapy, with few studies reporting on patients’ preferences for medications. (3) Of the few studies which examined the patients’ perceived need of invasive therapies, these found that patients avoided injections and surgeries (4) Patients desired spinal imaging for diagnostic purposes and legitimation of symptoms. Conclusions: Across many different patient populations with data obtained from a variety of study designs, common themes emerged which highlighted areas of patient dissatisfaction with the medical management of LBP, in particular, the superficial approach to care perceived by patients and concerns regarding pharmacotherapy. Patients perceive unmet needs from medical services, including the need to obtain a diagnosis, the desire for pain control and the preference for spinal imaging. These issues need to be considered in developing approaches for the management of LBP in order to improve patient outcomes