Reporting of Full-Length Femur Imaging to Detect Incomplete Atypical Femur Fractures: 2023 Official Positions of the International Society for Clinical Densitometry.

Incomplete atypical femur fractures (iAFFs) are associated with the long-term use of anti-resorptive therapies. Although X-rays are typically used to screen for iAFFs, images from dual-energy X-ray absorptiometry (DXA) offer an alternate method for detecting iAFFs. Although a previous 2019 ISCD Official Position on this subject exists, our task force aimed to update the literature review and to propose recommendations on reporting findings related to iAFFs that may be observed on DXA images. The task force recommended that full-length femur imaging (FFI) from DXA can be used as a screening tool for iAFFs. The presence of focal lateral cortical thickening and transverse lucencies should be reported, if identified on the FFI. This task force proposed a classification system to determine the likelihood of an iAFF, based on radiographic features seen on the FFI. Lastly, the task force recommended that the clinical assessment of prodromal symptoms (pain) is not required for the assessment of FFI.

DXA Reporting Updates: 2023 Official Positions of the International Society for Clinical Densitometry.

INTRODUCTION: Professional guidance and standards assist radiologic interpreters in generating high quality reports. Initially DXA reporting Official Positions were provided by the ISCD in 2003; however, as the field has progressed, some of the current recommendations require revision and updating. This manuscript details the research approach and provides updated DXA reporting guidance. METHODS: Key Questions were proposed by ISCD established protocols and approved by the Position Development Conference Steering Committee. Literature related to each question was accumulated by searching PubMed, and existing guidelines from other organizations were extracted from websites. Modifications and additions to the ISCD Official Positions were determined by an expert panel after reviewing the Task Force proposals and position papers. RESULTS: Since most DXA is now performed in radiology departments, an approach was endorsed that better aligns with standard radiologic reports. To achieve this, reporting elements were divided into required minimum or optional. Collectively, required components comprise a standard diagnostic report and are considered the minimum necessary to generate an acceptable report. Additional elements were retained and categorized as optional. These optional components were considered relevant but tailored to a consultative, clinically oriented report. Although this information is beneficial, not all interpreters have access to sufficient clinical information, or may not have the clinical expertise to expand beyond a diagnostic report. Consequently, these are not required for an acceptable report. CONCLUSION: These updated ISCD positions conform with the DXA field's evolution over the past 20 years. Specifically, a basic diagnostic report better aligns with radiology standards, and additional elements (which are valued by treating clinicians) remain acceptable but are optional and not required. Additionally, reporting guidance for newer elements such as fracture risk assessment are incorporated. It is our expectation that these updated Official Positions will improve compliance with required standards and generate high quality DXA reports that are valuable to the recipient clinician and contribute to best patient care.

Reporting Fewer Than Four Vertebrae: 2023 Official Positions of the International Society for Clinical Densitometry.

The precision for spine bone mineral density (BMD) worsens as vertebrae are excluded, so recommendations are needed for least significant change (LSC) for spine BMDs based on fewer than 4 vertebrae. The task force recommends re-analysis of each facility's L1-L4 in-house precision study to determine the precision in order to calculate the LSC for each combination of 2 or 3 reported vertebrae. The task force recommended not reporting spine BMDs based on single vertebral bodies for either the diagnosis or monitoring of osteoporosis. Specific data for studies assessing the precision of two non-contiguous vertebrae are mixed, but ultimately the task force recommended that spine BMD based on 2 non-contiguous vertebrae can be used for the diagnosis and monitoring of osteoporosis.

Bilateral hip DXA Reporting: 2023 Official Positions of the International Society for Clinical Densitometry.

INTRODUCTION: This position development conference (PDC) Task Force examined the use and reporting of bilateral hip bone mineral density (BMD) measurements. This was deemed appropriate as increased availability of Dual-energy X-ray Absorptiometry (DXA) technology offering bilateral hip measurement resulted in more routine clinical use. The International Society for Clinical Densitometry Official Positions accept bilateral hip BMD measurement for clinical use but currently do not include recommendations for reporting those studies. METHODS: Four key questions regarding bilateral hip reporting were proposed by the PDC Steering Committee. Relevant literature was identified using PubMed. Questions included whether bilateral hip measurements are appropriate for diagnostic classification or monitoring, as well as which bilateral hip regions of interest should be reported for diagnosis and monitoring. Additionally, the appropriate nomenclature for bilateral hip acquisition was defined. RESULTS: The literature review demonstrated that bilateral hip measurement is appropriate and diagnostic classification should be based on the lowest T-score at the right or left side femoral neck or total hip; the mean T-score should not be used for diagnostic purposes. Mean bilateral total hip is preferred for BMD monitoring. The terms hip, or total hip were deemed appropriate nomenclature instead of femur or total proximal femur. CONCLUSION: Bilateral hip acquisition is clinically appropriate and reporting and nomenclature standards are offered herein when a bilateral hip study is acquired. In terms of future research, the impact of discordant hips on diagnosis and monitoring was identified as a significant knowledge gap.

Hip fractures in elderly patients with non-dialysis dependent chronic kidney disease: Outcomes in a Southeast Asian population.

ABSTRACT: Chronic kidney disease (CKD) causes bone and mineral disorders and alterations in vitamin D metabolism that contribute to greater skeletal fragility. Hip fracture in elderly is associated with significant morbidity and mortality. The aim of this study was to investigate the outcome of elderly patients with non-dialysis dependent CKD and hip fracture undergoing surgery.Retrospective study with IRB approval of patients above 65 years of age, with hip fractures admitted between June 2014 to June 2016 in a Southeast Asian cohort. Data collected included demographic variables and the haematological and biochemical parameters HBA1c, estimated glomerular filtration rate (eGFR), serum calcium, phosphorous, and 25(OH) Vitamin D. Co-morbidities investigated were ischemic heart disease, congestive heart failure, peripheral vascular disease, malignancy, chronic obstructive pulmonary disease, cerebro vascular accident, hypertension and hyperlipidaemia. All patients were followed up from index date to either death or June 1, 2018.Of the 883 patients, 725 underwent surgery and 334 had CKD. Death rates for CKD patients with hip fractures and those with normal renal function did not differ significantly [8.08% vs 6.54%, (HR= 1.33, 95% CI: 0.95, 1.86; P = .102)], whilst median hospital length of stay was significantly higher in CKD patients [10.5 vs 9.03 days (P = .003)]. Significant risk factors associated with higher risk of mortality in the elderly with hip fracture were male gender, age ≥80 years and serum albumin < 30 g/L (all, P < .0001).In summary, in elderly, non-dialysis dependent CKD patient with hip fracture we found that male gender, age ≥80 years, low serum albumin and eGFR < 30 mL/min/1.73 m2 were associated with higher risk of death. The hospital stay in the CKD group was also longer. Additional studies are needed to validate our findings.

Economic evaluation of patient-centered care among long-term cancer survivors.

OBJECTIVES: To evaluate the economic outcomes associated with patient perceptions of patient-centered medical home (PCMH) characteristics among long-term cancer survivors in the United States. STUDY DESIGN: A retrospective analysis of the 2008 to 2012 Medical Expenditure Panel Survey. METHODS: A nationally representative sample of adult long-term cancer survivors (≥3 years since diagnosis) was categorized into either patient-centered care (PCC) or non-PCC groups based on responses to PCMH model hallmark attributes of "comprehensive care," "whole-person orientation," and "accessible care." The positive perception of all 3 attributes was defined as PCC. The patient perceptions, as well as patient characteristics, were measured at year 1 (baseline), with a propensity score model to balance baseline characteristics. Adjusted total healthcare utilization and healthcare expenditures in 2014 US$ at year 2 (follow-up) were compared between the PCC and non-PCC groups. RESULTS: A total of 4288 long-term cancer survivors were identified, with a mean (SD) age of 65.2 (13.8) years. The PCC group was associated with a reduction in mean adjusted healthcare expenditures at follow-up (savings of $1596 per cancer survivor; P = .020). These findings are driven by lower odds of hospitalization (odds ratio, 0.81; 95% CI, 0.66-0.99; P = .035) and lower hospitalization-related healthcare expenditures (PCC: $3323; 95% CI, $2727-$3918; non-PCC: $4912; 95% CI, $4039-$5785; P = .002) associated with PCC among the population who were 65 years and older. The whole-person orientation attribute had a major impact on reduced healthcare expenditures. CONCLUSIONS: The positive patient perception of PCMH characteristics was associated with reduced healthcare expenditures in adult long-term cancer survivors.

Similar radiological results with accelerometer-based navigation versus conventional technique in total knee arthroplasty.

BACKGROUND: The Zimmer iASSIST system is an accelerometer-based, portable navigation device for total knee arthroplasty (TKA) that does not require the use of a large console for alignment feedback as required in computer-assisted surgery. The purpose of this study was to determine the accuracy of the accelerometer-based system in component positioning and overall mechanical alignment. METHODS: Two groups of 30 patients each with primary osteoarthritis underwent TKA using either conventional method or Zimmer iASSIST navigation in 2013 was retrospectively studied. Patients were matched according to body mass index (BMI), gender and age. A senior arthroplasty surgeon performed all the operation using the same surgical approach. Perioperative and post-operative regimens were the same. All patients had standardized radiographs performed post-operatively to determine the lower limb mechanical alignment and component placement. RESULTS: There was no difference between the two groups for age, BMI, gender, side of operated knee and preoperative mechanical axis ( p > 0.05). There was no difference in the proportion of outliers for mechanical axis ( p = 0.38), coronal femoral angle ( p = 0.50), coronal tibia angle ( p = 0.11), sagittal femoral angle ( p = 0.28) and sagittal tibia angle ( p = 0.33). The duration of surgery, post-operative drop in haemoglobin level and transfusion incidence did not show statistically significant differences between the two groups ( p > 0.05). CONCLUSIONS: Our article showed that iASSIST was safe and remains a useful tool to restore mechanical axis. However, our data demonstrated no difference in lower limb alignment and component placement between the TKA that used accelerometer-based system and those that underwent conventional method.

Outcome following subluxation of mobile articulating spacers in two-stage revision total knee arthroplasty.

INTRODUCTION: Infection after total knee arthroplasty (TKA) is a severe complication. It is usually treated with two-stage revision and implantation of a cement spacer. Few studies describe the complications associated with a mobile articulating spacer. This study examined the subluxation of articulating antibiotic spacers in knees and correlated it with prospectively collected early outcome scores after implantation of a revision prosthesis. METHODS: Staged revisions for 72 infected primary total knee arthroplasties between 2004 and 2012 were examined. The mean age of the patients was 70.2 ± 10.8 years, with 40 right and 32 left knees. Sagittal and coronal subluxation was measured using radiographs prior to second-stage revision and grouped to be within (Group 1) or outside (Group 2) one standard deviation from the mean. Medical Outcomes Study Short Form-12 (SF-12), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Society Score (KSS) were obtained via patient-administered questionnaire. Statistical analysis was carried out to look at the correlation between subluxation and outcome. RESULTS: Significant improvements were observed between the interim outcome scores prior to implantation of a revision prosthesis and scores obtained after second-stage revision. Debonding occurred in 5.6%, and one dislocation was found. Mean coronal subluxation was 4.8 ± 5.5% of the tibia width, in the lateral direction. Coronal subluxation did not affect SF12, WOMAC or KSS outcome scores. Mean sagittal subluxation was 6.1 ± 16.4% posteriorly. However, sagittal subluxation had a significant influence on Knee Society Scores, with Group 2 having a lower mean Knee Society Function Score of 39.3 than Group 1 (60.2) (p = 0.045). Sagittal subluxation did not affect SF12 or WOMAC scores. CONCLUSION: Sagittal subluxation of the knee may influence the early to midterm outcome scores following a staged revision TKA for infection.

Effect of Acetabular Component Positioning on Functional Outcomes in Primary Total Hip Arthroplasty.

BACKGROUND: Acetabular component positioning is crucial to a successful total hip arthroplasty (THA). This study evaluated the effect of absolute acetabular component position as well as acetabular position relative to bony anatomy on patient-reported functional outcomes after primary THA. METHODS: Primary, press fit, hemispherical metal-on-polyethylene THA performed between 2003 and 2011 were analyzed. Western Ontario and McMaster Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), Short Form-12 scores, and radiographs between 2 and 3 years after the index procedure were assessed. RESULTS: Of the 1241 primary THA included, the mean abduction and anteversion angles were 44.4 ± 6.94 and 21.7 ± 11.9 degrees, respectively. The mean anterior and lateral overhang were 1.9 ± 3.6 and 2.5 ± 3.4 mm, respectively. There was no correlation between functional outcomes and acetabular inclination. A weak positive correlation between anteversion and HHS (P < .001) and WOMAC (P = .02) scores was found. For relative position, anterior overhang of the acetabular component beyond the bone resulted in inferior Short Form-12 physical function (P = .001), HHS (P = .004), and WOMAC (P < .001) scores compared to those with bony coverage. Mean HHS pain score was 41.20 ± 5.69 in patients with lateral overhang and 41.97 ± 5.04 in those who had bony coverage of the lateral edge of the acetabular component (P = .02). CONCLUSION: The tribology and biomechanics of acetabular component position have been extensively studied without examination of how it affects patient function. Although statistical significance was seen, clinical outcome scores were not sensitive enough to show a clinically significant effect of the absolute or relative position of the acetabular component.

Predicting low testosterone in aging men: a systematic review.

BACKGROUND: Physicians diagnose and treat suspected hypogonadism in older men by extrapolating from the defined clinical entity of hypogonadism found in younger men. We conducted a systematic review to estimate the accuracy of clinical symptoms and signs for predicting low testosterone among aging men. METHODS: We searched the MEDLINE and Embase databases (January 1966 to July 2014) for studies that compared clinical features with a measurement of serum testosterone in men. Three of the authors independently reviewed articles for inclusion, assessed quality and extracted data. RESULTS: Among 6053 articles identified, 40 met the inclusion criteria. The prevalence of low testosterone ranged between 2% and 77%. Threshold testosterone levels used for reference standards also varied substantially. The summary likelihood ratio associated with decreased libido was 1.6 (95% confidence interval [CI] 1.3-1.9), and the likelihood ratio for absence of this finding was 0.72 (95% CI 0.58-0.85). The likelihood ratio associated with the presence of erectile dysfunction was 1.5 (95% CI 1.3-1.8) and with absence of erectile dysfunction was 0.83 (95% CI 0.76-0.91). Of the multiple-item instruments, the ANDROTEST showed both the most favourable positive likelihood ratio (range 1.9-2.2) and the most favourable negative likelihood ratio (range 0.37-0.49). INTERPRETATION: We found weak correlation between signs, symptoms and testosterone levels, uncertainty about what threshold testosterone levels should be considered low for aging men and wide variation in estimated prevalence of the condition. It is therefore difficult to extrapolate the method of diagnosing pathologic hypogonadism in younger men to clinical decisions regarding age-related testosterone decline in aging men.

Accuracy of the modified Hardinge approach in acetabular positioning.

BACKGROUND: The surgical approach chosen for total hip arthroplasty (THA) may affect the positioning of the acetabular component. The purpose of this study was to examine the accuracy in orienting the acetabular component using the modified Hardinge approach. METHODS: We used our institutional arthroplasty database to identify patients with primary, press-fit, hemispherical acetabular components of a metal-on-polyethylene THA performed between 2003 and 2011. Patients with radiographs obtained 1-3 years after the index procedure were included for measurement of anteversion and inclination angles. Acceptable values of anteversion and abduction angles were defined as 15° ± 10° and 40° ± 10°, respectively. RESULTS: We identified 1241 patients from the database, and the modified Hardinge approach was used in 1010 of the patients included in our analysis. The acetabular component was anteverted in the acceptable zone in 54.1% of patients. The abduction angle was within the defined range in 79.2% of patients. Combined anteversion and abduction angles within the defined zone were present in 43.6% of patients. CONCLUSION: Consistent with studies examining accuracy from other approaches, our study reveals that the modified Hardinge approach was only moderately accurate in positioning the acetabular component in the acceptable zone.

BACKGROUND: Les fractures de la clavicule sont fréquentes, et le choix du traitement optimal ne fait pas l'unanimité. Selon la littérature récente, la fixation chirurgicale des fractures du tiers médial déplacées (FTMD) aiguës raccourcies de plus de 2 cm donnerait de meilleurs résultats. Nous avons voulu établir une corrélation entre la mesure du déplacement obtenue par radiographie simple et par tomodensitométrie (TDM) et la fiabilité inter- et intra-observateur des mesures radiographiques répétées. BACKGROUND: La voie d'abord choisie pour une arthroplastie totale de la hanche (ATH) pourrait influer sur le positionnement du composant cotyloïdien. La présente étude portait sur la précision de l'orientation du composant dans les interventions empruntant la voie de Hardinge modifiée. METHODS: À partir de la base de données sur les arthroplasties de notre établissement, nous avons cherché puis retenu les patients ayant subi une ATH entre 2003 et 2011 et ayant alors reçu une première prothèse métal sur polyéthylène avec composant cotyloïdien hémisphérique ajusté à la presse. Nous avons inclus les patients ayant subi des radiographies de 1 à 3 ans après l'intervention afin de mesurer les angles d'antéversion et d'abduction. Les valeurs jugées acceptables étaient respectivement de 15° ± 10° et de 40° ± 10°. RESULTS: Nous avons retenu 1241 patients sélectionnés à partir de la base de données; la voie employée pour 1010 d'entre eux était la voie de Hardinge modifiée. L'angle d'antéversion du cotyle était dans les limites acceptables chez 54,1 % des patients, l'angle d'abduction se trouvait dans les limites définies dans 79,2 % des cas, et les valeurs cibles étaient respectées pour les 2 paramètres chez 43,6 % des patients. CONCLUSION: Nous avons conclu que la précision du positionnement du composant cotyloïdien par la voie de Hardinge modifiée est tout au plus modérée, ce qui concorde avec d'autres études visant à évaluer la précision d'autres techniques.

Incentivizing health care behaviors in emerging adults: a systematic review.

PURPOSE: For emerging adults with chronic medical diseases, the transition from pediatric to adult health care is often a time of great upheaval, commonly associated with unhealthy self-management choices, loss to follow-up, and adverse outcomes. We conducted a systematic review to examine the use of incentive strategies to promote positive health-related behaviors in young adults with chronic medical diseases. METHODS: The Medline, CINAHL, Embase, PsycInfo, and Cochrane databases were searched through June 2014. Studies of any design where an incentive was used to achieve a target behavior or outcome in a pediatric or emerging adult population (age <30 years) with chronic medical conditions including addictions, were included. RESULTS: A total of 26 studies comprising 10,880 patients met our inclusion criteria after screening 10,305 abstracts and 301 full-text articles. Of these studies, 20 examined the effects of behavioral incentives on cigarette smoking or substance abuse, including alcohol; four studies explored behavioral incentives in the setting of HIV or sexual health; and two articles studied individuals with other chronic medical conditions. Seventeen articles reported a statistically significant benefit of the behavioral incentive on one or more outcomes, although only half reported follow-up after the incentive period was terminated. CONCLUSION: While the majority of studies reported positive outcomes, these studies focused on promoting the cessation of adverse behaviors rather than promoting positive behaviors. In addition, conclusions were limited by the high risk of bias present in the majority of studies, as well as lack of follow-up after the incentive period. Whether behavioral incentives facilitate the adoption of positive health choices in this population remains to be determined.

Tribocorrosion: Ceramic and Oxidized Zirconium vs Cobalt-Chromium Heads in Total Hip Arthroplasty.

BACKGROUND: This matched-cohort study aims to compare tribocorrosion between matched ceramic and cobalt-chromium femoral head trunnions and between matched Oxinium and cobalt-chromium femoral head trunnions. Secondary objectives were to investigate whether taper design, depth of trunnion, implantation time, age, body mass index, and gender have an effect on fretting and corrosion. METHODS: All hip prostheses retrieved between 1999 and 2015 at one center were reviewed, giving a total of 52 ceramic heads. These were matched to a cobalt-chromium cohort according to taper design, head size, neck length, and implantation time. The trunnions were examined by 2 observers using a 4-point scoring technique and scored in 3 zones: apex, middle, and base. The observers were blinded to clinical and manufacturing data where possible. A separate matched-cohort analysis was performed between 8 Oxinium heads and 8 cobalt-chromium heads, which were similarly scored. RESULTS: Ceramic head trunnions demonstrated a lower median fretting and corrosion score at the base zone (P < .001), middle zone (P < .001), and in the combined score (P < .001). Taper design had a significant effect on fretting and corrosion in the apex zone (P = .04) of the ceramic group, as well as the cobalt-chromium group (P = .03). Between Oxinium heads and cobalt-chromium heads, there was no significant difference in the fretting and corrosion score across all 3 zones (base: P = .22; middle: P = .92; and apex: P = .71) and for the combined score (P = .67). CONCLUSION: This study shows that ceramic head confers an advantage in trunnion fretting and corrosion. Taper design and implantation time were also significant factors for fretting and corrosion.

The Effect of Subluxation of Articulating Antibiotic Spacers on Bone Defects and Degree of Constraint in Revision Knee Arthroplasty.

This study investigated whether subluxation of articulating antibiotic spacers is associated with the bone defects found and constraint required when re-implanting the knee arthroplasty components. Staged revisions for infections of primary total knee arthroplasties between 2004 and 2012 were examined. Radiographic sagittal and coronal subluxations of 72 knees were measured prior to second stage revision. Coronal subluxation was found to be associated with increased requirement for constrained knee systems (P<0.035). Sagittal subluxation was associated with greater tibia bone defects (P<0.037). Careful surgical technique and monitoring of articulating spacers should be done to avoid subluxation after stage 1 revision. If subluxation of the articulating spacer is present, constrained revision knee systems as well as augments should be available at time of re-implantation.

Morphology and fixation pitfalls of a highly unstable intertrochanteric fracture variant.

PURPOSE: To describe a variant of intertrochanteric fracture not well-characterised in the existing classification systems. METHODS: 10 women and 2 men aged 59 to 98 (median, 80) years with intertrochanteric fractures characterised by a low intertrochanteric fracture, a basicervical fracture fragment, and a thin or fractured lateral wall with greater trochanteric comminution were reviewed. RESULTS: The 12 fractures were classified as A2.1 (n=1), A2.2 (n=7), A2.3 (n=1), and A3 (n=3) according to the AO/OTA classification, and as type 3 (n=2), type 5 (n=7), and type 6 (n=3) according to the Evans classification. The fractures were characterised by greater trochanter comminution and a coronal plane fracture extending into the greater trochanter resulting in a loss of superolateral support. Patients were treated with the Proximal Femoral Nail Antirotation (n=5), the Proximal Femur Locking Plate (n=6), or the reversed Less Invasive Stabilization System for distal femur (n=1). Within the mean follow-up period of 6 months, 3 patients with plating and one patient with nailing had mechanical failure defined as loss of alignment of >10º or screw cutout. CONCLUSION: This intertrochanteric fracture variant is highly unstable with a high failure rate. Loss of superolateral support rather than the medial calcar buttress is the main contributing factor to mechanical failure. Computed tomography is important in preoperative planning. Intramedullary nailing is more appropriate than extramedullary plating for such unstable fractures.

Risk factors of surgical site infections in hip hemiarthroplasty: a single-institution experience over nine years.

INTRODUCTION: This study aims to describe the factors associated with surgical site infection (SSI) in elderly patients who underwent hip hemiarthroplasty following a hip fracture, in a single institution over a nine-year period. METHODS: All patients who underwent hip hemiarthroplasty between 1 January 2004 and 31 December 2012 in our hospital were included in the present study. The detection of SSI was carried out by a trained, independent infection control nurse using the United States Centers for Disease Control and Prevention criteria. Demographic and clinical data were collected retrospectively. Demographics and clinical factors were analysed for potential associations with SSI. RESULTS: Among the 1,320 patients who met the study inclusion criteria, a total 57 SSIs were documented, giving an infection rate of 4.3%. Patients who waited for more than one week for surgery had a statistically significantly higher risk of SSI (odds ratio 3.030, 95% confidence interval 1.075-8.545, p = 0.036). The presence of SSI was also significantly associated with increased length of hospital stay (p < 0.001). The two main microorganisms detected were methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, which accounted for 50.9% and 26.3% of the SSIs, respectively. CONCLUSION: We concluded that the number of days from admission to surgery is a main risk factor for the development of SSI. Steps should, therefore, be taken to prevent unnecessary delay of surgery in elderly patients requiring hip hemiarthroplasty.

An integrated optofluidic platform for Raman-activated cell sorting.

We report on integrated optofluidic Raman-activated cell sorting (RACS) platforms that combine multichannel microfluidic devices and laser tweezers Raman spectroscopy (LTRS) for delivery, identification, and simultaneous sorting of individual cells. The system allows label-free cell identification based on Raman spectroscopy and automated continuous cell sorting. Two optofluidic designs using hydrodynamic focusing and pinch-flow fractionation are evaluated based on their sorting design and flow velocity effect on the laser trapping efficiency at different laser power levels. A proof-of-principle demonstration of the integrated optofluidic LTRS system for the identification and sorting of two leukemia cell lines is presented. This functional prototype lays the foundation for the development of a label-free cell sorting platform based on intrinsic Raman markers for automated sampling and sorting of a large number of individual cells in solution.

Localized decrease of beta-catenin contributes to the differentiation of human embryonic stem cells.

Human embryonic stem cells (hESC) are pluripotent, and can be directed to differentiate into different cell types for therapeutic applications. To expand hESCs, it is desirable to maintain hESC growth without differentiation. As hESC colonies grow, differentiated cells are often found at the periphery of the colonies, but the underlying mechanism is not well understood. Here, we utilized micropatterning techniques to pattern circular islands or strips of matrix proteins, and examined the spatial pattern of hESC renewal and differentiation. We found that micropatterned matrix restricted hESC differentiation at colony periphery but allowed hESC growth into multiple layers in the central region, which decreased hESC proliferation and induced hESC differentiation. In undifferentiated hESCs, beta-catenin primarily localized at cell-cell junctions but not in the nucleus. The amount of beta-catenin in differentiating hESCs at the periphery of colonies or in multiple layers decreased significantly at cell-cell junctions. Consistently, knocking down beta-catenin decreased Oct-4 expression in hESCs. These results indicate that localized decrease of beta-catenin contributes to the spatial pattern of differentiation in hESC colonies.