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1.
J Surg Oncol ; 130(1): 40-46, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38924626

ABSTRACT

INTRODUCTION: Patients with high-risk resected gastrointestinal stromal tumors (GIST) receiving adjuvant imatinib have improved recurrence-free survival (RFS), however whether a complete cytocidal effect exists is unknown. We investigated this using a normalized recurrence timeline measured from end of oncologic treatment (EOOT), defined as the later of resection or end of adjuvant therapy. METHODS: We reviewed patients with resected high-risk GIST at our cancer center from 2003 to 2018. RFS (measured from resection and EOOT), overall survival (OS), and time to imatinib resistance (TTIR) were analyzed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. The performance of the Memorial Sloan Kettering (MSK) GIST nomogram was assessed. RESULTS: We identified 86 patients with high-risk GIST with a median 106 months of postsurgical follow-up. One-third (n = 29; 34%) did not receive adjuvant imatinib, while 57 (66%) did for a median of 3 years. The MSK nomogram-predicted 5-year RFS for patients receiving adjuvant imatinib was similar to those who did not (29% vs. 31%, p = 0.64). When RFS was measured from EOOT, the MSK-predicted RFS was independently associated with EOOT RFS (hazard ratio 0.22, p = 0.02), while adjuvant imatinib receipt and duration were not. Neither receipt nor duration of adjuvant imatinib were associated with TTIR or OS (all p > 0.05). CONCLUSIONS: Treatment with adjuvant imatinib delays, but does not clearly impact ultimate recurrence, TTIR, or OS, suggesting many patients with high-risk GIST may receive adjuvant imatinib unnecessarily. Additional studies are needed to establish the benefit of adjuvant therapy versus initiating therapy at first radiographic recurrence.


Subject(s)
Antineoplastic Agents , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Imatinib Mesylate , Neoplasm Recurrence, Local , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/mortality , Imatinib Mesylate/therapeutic use , Female , Male , Middle Aged , Chemotherapy, Adjuvant , Antineoplastic Agents/therapeutic use , Aged , Gastrointestinal Neoplasms/surgery , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/mortality , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Survival Rate , Adult , Follow-Up Studies
2.
Cleft Palate Craniofac J ; : 10556656241256917, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778553

ABSTRACT

OBJECTIVE: This study aimed to determine the efficacy of gingivoperiosteoplasty (GPP) in preventing alveolar bone grafting (ABG) among children with cleft lip and palate (CLP). DESIGN/SETTING: Retrospective university hospital single center study. PATIENTS: Children with CLP treated with GPP from 2000-2015 were included. Those under eight years of age, without definitive conclusions regarding need for ABG or with incomplete data were excluded. INTERVENTIONS: Included patients were analyzed for demographics, cleft type, age at GPP, associated cleft surgery, use of nasoalveolar molding (NAM), indication for ABG, operating surgeon and presence of residual alveolar fistula. T-tests and Fisher's exact tests were utilized for statistical analysis. MAIN OUTCOME MEASURE: The need for ABG. RESULTS: Of the 1682 children identified with CLP, 64 underwent GPP and met inclusion criteria. 78% of patients with CLP who underwent GPP were recommended for ABG. Those who received GPP at a younger age (P = .004) and at the time of initial cleft lip repair (P = .022) were less likely to be recommended for ABG. Patients with complete CLP were more likely to be recommended for ABG than patients with cleft lip and alveolus only (P = .015). The operating surgeon impacted the likelihood of ABG (P = .004). Patient gender, race, ethnicity, laterality, and NAM were not significantly associated with recommendation for ABG. CONCLUSION: GPP does not preclude the need for ABG. Therefore, the success of ABG after GPP and maxillary growth restriction should be analyzed further to determine if GPP is a worthwhile adjunct to ABG in cleft care.

3.
HPB (Oxford) ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39242329

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAc) is a lethal malignancy, attributed in part to high rates of rapid recurrence (rrPDAc) following resection. We sought to characterize recurrence rates over time and investigate factors predictive of rrPDAc. METHODS: A regional multi-institutional cancer registry, augmented with data from the National Surgical Quality Improvement Program database, was queried for patients with PDAc from 1996 to 2020. rrPDAc was defined as recurrence within 6 months following curative-intent resection. RESULTS: We identified 924 patients who underwent resection for PDAc; rrPDAc occurred in 236 (26%) patients. Median incidence of rrPDAc was 25.3% (IQR 22-30.2%) per year. Median survival in rrPDAc, non-rapid recurrence, and no recurrence was 10.3, 25.2, and 56.1 months respectively (p < 0.001). Variables independently associated with greater odds of rrPDAc included surgical site infection (SSI) (OR 2.06) and nodal positivity (OR 2.05); adjuvant therapy was associated with lower odds (OR 0.38). Neoadjuvant chemotherapy did not alter risk of rrPDAc. Three-year post-recurrence survival was no different in rrPDAc versus those without. CONCLUSION: Despite therapeutic advances, incidence of rrPDAc remains unchanged. SSIs and nodal positivity are independently associated with increased risk of rrPDAc, while adjuvant chemotherapy is associated with lower risk. Strategies focused on preventing rapid recurrence may improve survival.

4.
Blood Cells Mol Dis ; 101: 102746, 2023 07.
Article in English | MEDLINE | ID: mdl-37150704

ABSTRACT

Coronavirus disease 2019 (COVID-19) is characterized by a pro-inflammatory state associated with organ failure, thrombosis, and death. We investigated a novel inflammatory biomarker, γ' fibrinogen (GPF), in 103 hospitalized patients with COVID-19 and 19 healthy controls. We found significant associations between GPF levels and the severity of COVID-19 as judged by blood oxygen saturation (SpO2). The mean level of GPF in the patients with COVID-19 was significantly higher than in controls (69.8 (95 % CI 64.8-74.8) mg/dL compared with 36.9 (95 % CI 31.4-42.4) mg/dL, p < 0.0001), whereas C-reactive protein (CRP), lactate dehydrogenase (LDH), and total fibrinogen levels were not significantly different between groups. Mean GPF levels were significantly highest in patients with severe COVID-19 (SpO2 ≤ 93 %, GPF 75.2 (95 % CI 68.7-81.8) mg/dL), compared to mild/moderate COVID-19 (SpO2 > 93 %, GPF 62.5 (95 % CI 55.0-70.0) mg/dL, p = 0.01, AUC of 0.68, 95 % CI 0.57-0.78; Youden's index cutpoint 62.9 mg/dL, sensitivity 0.64, specificity 0.63). In contrast, CRP, interleukin-6, ferritin, LDH, D-dimers, and total fibrinogen had weaker associations with COVID-19 disease severity (all ROC curves with lower AUCs). Thus, GPF may be a useful inflammatory marker of COVID-19 respiratory disease severity.


Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , Fibrinogen , Biomarkers , C-Reactive Protein/analysis , Patient Acuity , Retrospective Studies
5.
J Surg Res ; 287: 33-39, 2023 07.
Article in English | MEDLINE | ID: mdl-36868121

ABSTRACT

INTRODUCTION: An important component of plastic surgery residency training is independent cosmetic patient management. A resident cosmetic clinic was created at Oregon Health & Science University in 2007 to expand this experience. The cosmetic clinic has traditionally been most successful in offering nonsurgical facial rejuvenation with neuromodulators and soft tissue fillers. This study focuses on the demographics of the patient population and the treatments provided over a 5-year period and compares this experience to those of the same program's attending cosmetic clinics. METHODS: A retrospective chart review of all patients seen at Oregon Health & Science University's Plastic and Reconstructive Surgery Resident Cosmetic Clinic between January 1, 2017, and December 31, 2021 was performed. Patient demographics, type of injectable received (neuromodulator versus soft tissue filler), location of injection, and additional cosmetic procedures were evaluated. RESULTS: Two hundred patients met the study criteria, which included 114 seen in the resident clinic (RC), 31 seen in attending clinic (AC), and 55 patients seen in both. A primary analysis compared the two groups seen in the resident and attending only clinics. The average age of patients seen in the RC was younger, 45 versus 51.5 (P ≤ 0.05). There was a trend toward more patients in the RC being involved in healthcare as compared to those patients seen in the AC, but this difference was not found to be statistically significant. The median number of neuromodulator visits in the RC was 2 (1, 4) versus 1 (1, 2) in the AC (P ≤ 0.05) The most common location for neuromodulator injections in both clinics was the corrugators. CONCLUSIONS: Patients in the resident cosmetic clinic were younger females, most receiving neuromodulator injections. No statistically significant differences were identified in patient population, injections received, and location of injections between the two clinics, indicating a similar trainee skill set and patient care plan between the two clinics.


Subject(s)
Internship and Residency , Plastic Surgery Procedures , Surgery, Plastic , Female , Humans , Surgery, Plastic/education , Retrospective Studies , Neurotransmitter Agents
6.
J Surg Oncol ; 128(2): 271-279, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37095724

ABSTRACT

BACKGROUND: Pancreatic adenocarcinoma (PDAC) often impinges on the biliary tree and obstruction necessitates stent placement increasing the risk of surgical site infections (SSIs). We sought to explore the impact of neoadjuvant therapy on the biliary microbiome and SSI risk in patients undergoing resection. METHODS: A retrospective analysis was performed on 346 patients with PDAC who underwent resection at our institution from 2008 to 2021. Univariate and multivariate methods were utilized for analysis. RESULTS: Biliary stenting rates were similar between groups but resulted in increased bile culture positivity (97% vs. 15%, p < 0.001). Culture positivity did not differ between upfront resection or neoadjuvant chemotherapy (NAC) (77% vs. 80%, p = 0.60). NAC-alone versus neoadjuvant chemoradiotherapy did not impact biliary positivity (80% vs. 79%, p = 0.91), nor did 5-fluorouracil versus gemcitabine-based regimens (73% vs. 85%, p = 0.19). While biliary stenting increased incisional SSI risk (odds ratios [OR]: 3.87, p = 0.001), NAC did not (OR: 0.83, p = 0.54). Upfront resection, NAC, and chemoradiotherapy were not associated with biliary organism-specific changes or antibiotic resistance patterns. CONCLUSIONS: Biliary stenting is the greatest predictor for positive biliary cultures and SSIs in resected PDAC patients. Neither NAC nor radiotherapy impact bile culture positivity, speciation, rates, or antibiotic resistance patterns, and perioperative antibiotic prophylaxis should not differ.


Subject(s)
Adenocarcinoma , Biliary Tract , Microbiota , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Neoadjuvant Therapy/methods , Adenocarcinoma/pathology , Retrospective Studies , Biliary Tract/pathology , Pancreatic Neoplasms
7.
Heart Surg Forum ; 26(6): E842-E854, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38178345

ABSTRACT

OBJECTIVE: The ideal type of hospital to care for adult congenital heart disease (ACHD) patients is not well known. Hospital competitiveness, clinical volume and market structure can influence clinical outcomes. We sought to understand how hospital competitiveness affects clinical outcomes in ACHD patients in the era prior to the Adult Congenital Heart Association accreditation program. METHODS: Patient discharges with ACHD diagnosis codes were filtered between 2006-2011 from an all-payer inpatient healthcare database. Hospital-level data was linked to market structure patient flow. A common measure of market concentration used to determine market competitiveness-the Herfindahl-Hirschman Index (HHI)-was stratified into: more competitive (HHI ≤25th percentile), moderately competitive (HHI 25th to <75th percentile), and less competitive (HHI ≥75th percentile) hospital. Any complication, home discharge and mortality were analyzed with clustered mixed effects logistic regression. The combined impact of HHI and any complication on mortality by interaction was assessed. RESULTS: A total of 67,434 patient discharges were isolated. More competitive hospitals discharged the least number of patients (N = 15,270, 22.6%) versus moderately competitive (N = 36,244, 53.7%) and less competitive (N = 15,920, 23.6%) hospitals. The adjusted odds of any complication or home discharge were not associated with hospital competitiveness strata. Compared to more competitive hospitals, mortality at moderately competitive hospitals (Adjusted Odds Ratio (AOR) 0.79, 95% CI: 0.66-0.94) and less competitive hospitals (AOR 0.79, 95% CI: 0.63-0.98) were lower (p = 0.025). Age, race, elective admission, transfer status, and payer mix were all significantly associated with adjusted odds of any complication, home discharge and mortality (p ≤ 0.05). Having any complication independently increased the adjusted odds of mortality more than 6-fold (p < 0.001), and this trend was independent of HHI strata. Failure to rescue an ACHD patient from mortality after having any complication is highest at less competitive hospitals. Sensitivity analysis which excluded the transfer status variable, showed that any complication (p = 0.047) and mortality (p = 0.01) were independently associated with HHI strata. CONCLUSIONS: Whether lower competition allow hospitals to focus more on quality of care is unknown. Hospital competitiveness and outcome seem to have an inverse trend relationship among ACHD patients. Since medical care is frequently provided away from the home area, hospital selection is an important issue for ACHD patients. Further research is needed to determine why competitiveness is linked to surgical outcomes in this population.


Subject(s)
Heart Defects, Congenital , Humans , Adult , Heart Defects, Congenital/therapy , Hospitals , Hospitalization , Inpatients , Logistic Models
8.
Metabolomics ; 16(10): 106, 2020 10 06.
Article in English | MEDLINE | ID: mdl-33021695

ABSTRACT

INTRODUCTION: Approximately 1% of the world's population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet, a high-fat, low-carbohydrate diet. Despite the KD's success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation. OBJECTIVES: The goal of this study was to explore changes in the lipidome in hippocampal and cortical tissue from Kv1.1-KO model of epilepsy. METHODS: FT-ICR/MS analysis was utilized to examine nonpolar metabolome of cortical and hippocampal tissue isolated from a Kv1.1 channel knockout mouse model of epilepsy (n = 5) and wild-type mice (n = 5). RESULTS: Distinct metabolic profiles were observed, significant (p < 0.05) features in hippocampus often being upregulated (FC ≥ 2) and the cortex being downregulated (FC ≤ 0.5). Pathway enrichment analysis shows lipid biosynthesis was affected. Partition ratio analysis revealed that the ratio of most metabolites tended to be increased in Kv1.1-/-. Metabolites in hippocampal tissue were commonly upregulated, suggesting seizure initiation in the hippocampus. Aberrant mitochondrial function is implicated by the upregulation of cardiolipin, a common component in the mitochondrial membrane. CONCLUSION: Generally, our study finds that the lipidome is changed in the hippocampus and cortex in response to Kv1.1-KO indicating changes in membrane structural integrity and synaptic transmission.


Subject(s)
Epilepsy/metabolism , Lipid Metabolism/physiology , Animals , Diet, Ketogenic/methods , Disease Models, Animal , Epilepsy/diet therapy , Hippocampus/metabolism , Kv1.1 Potassium Channel/genetics , Kv1.1 Potassium Channel/metabolism , Male , Mice , Mice, Inbred ICR , Mice, Knockout
10.
Clin Orthop Relat Res ; 472(2): 489-96, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23690156

ABSTRACT

BACKGROUND: Impingement of the femoral neck with the acetabular component after metal-on-metal hip resurfacing arthroplasty (HRA) is a possible cause of edge loading and accelerated bearing wear. No attempt has been made to correlate radiographic impingement signs and blood metal ion levels. QUESTIONS/PURPOSES: We (1) compared serum cobalt (CoS) and chromium (CrS) concentrations between patients with and without radiographic impingement signs treated with unilateral HRA, (2) determined whether divot depth on the femoral neck correlated with CoS and CrS, and (3) assessed the predictive value of radiographic impingement signs for high levels of CoS and CrS. METHODS: A retrospective radiographic review of 141 patients with CoS and CrS analyses yielded 21 patients with and 120 without radiographic impingement signs (controls). Radiographic measurements included divot depth and orientation of the acetabular component to compute the contact patch to rim distance, a measure of functional head coverage. We defined a patient as having radiographic impingement signs if a remodeling of the femoral neck cortex showed a depression matching the predicted path of an impinging acetabular component. CoS and CrS were analyzed by inductively coupled plasma mass spectrometry and the radiographs were taken within 12 months of the last blood draw. RESULTS: Median CoS and CrS were greater in the impingement group than in controls in patients with less than 10-mm contact patch to rim distances. Divot depth did not correlate with CoS or CrS. In predicting elevated ion levels (≥ 7 µg/L), the presence of a radiographic impingement sign showed a sensitivity of 50% for CoS and 33% for CrS and a specificity of 87% for both CoS and CrS. CONCLUSIONS: Radiographic impingement signs influenced CoS and CrS only when the functional head coverage was insufficient due to poor socket positioning. Radiographic impingement signs alone were not a good predictor of elevated metal ion levels.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/instrumentation , Chromium/blood , Cobalt/blood , Femoracetabular Impingement/blood , Femur Neck/surgery , Hip Joint/surgery , Hip Prosthesis , Metal-on-Metal Joint Prostheses , Acetabulum/diagnostic imaging , Acetabulum/surgery , Adolescent , Adult , Aged , Biomarkers/blood , Female , Femoracetabular Impingement/diagnostic imaging , Femoracetabular Impingement/etiology , Femur Neck/diagnostic imaging , Hip Joint/diagnostic imaging , Humans , Ions , Logistic Models , Male , Mass Spectrometry , Middle Aged , Odds Ratio , Predictive Value of Tests , Prosthesis Design , Radiography , Retrospective Studies , Treatment Outcome , Young Adult
11.
J Trauma Acute Care Surg ; 96(3): 482-486, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37700441

ABSTRACT

BACKGROUND: Impaired coagulation is associated with elevated risk of mortality in trauma patients. Prior studies have demonstrated increased mortality in patients with hyperfibrinolysis (HF) and fibrinolysis shutdown (SD). In addition, prior studies have demonstrated no effect of tranexamic acid (TXA) on fibrinolysis phenotypes. We examined the association of admission fibrinolysis phenotype with traumatic brain injury (TBI) patient outcomes. METHODS: Data were extracted from a placebo-controlled multicenter clinical trial. Patients ≥15 years with TBI (Glasgow Coma Scale score, 3-12) and systolic blood pressure ≥90 mm Hg were randomized in the out-of-hospital setting to receive placebo bolus/placebo infusion (Placebo), 1 gram (g) TXA bolus/1 g TXA infusion (bolus maintenance [BM]); or 2 g TXA bolus/placebo infusion (bolus only [BO]). Fibrinolysis phenotypes on admission were determined by clot lysis at 30 minutes (LY30): SD, ≤0.8%; physiologic, 0.9% to 2.9%; HF, ≥3%. Logistic regression was used to control for age, sex, penetrating injury, Injury Severity Score, maximum head AIS, and TXA treatment group. RESULTS: Seven hundred forty-seven patients met inclusion criteria. Fibrinolysis shutdown was the most common phenotype in all treatment groups and was associated with increased age, Injury Severity Score, and presence of intracranial hemorrhage (ICH). Inpatient mortality was 15.2% for SD and HF, and 10.6% for physiologic ( p = 0.49). No differences in mortality, disability rating scale at 6 months, acute kidney injury, acute respiratory distress syndrome, or multi-organ failure were noted between fibrinolysis phenotypes. CONCLUSION: SD is the most common phenotype expressed in moderate to severe TBI. In TBI, there is no association between fibrinolysis phenotype and mortality or other major complications. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.


Subject(s)
Antifibrinolytic Agents , Blood Coagulation Disorders , Brain Injuries, Traumatic , Tranexamic Acid , Humans , Fibrinolysis , Brain Injuries, Traumatic/complications , Blood Coagulation Disorders/etiology , Phenotype
12.
Res Sq ; 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38410443

ABSTRACT

Objective: To compare early pulmonary function tests (PFTs) in neonates with critical congenital heart disease (CHD) compared to a historical reference group. Design: Infants > 37 weeks gestation with critical CHD were studied within the first few days of life and prior to cardiac surgery and compared to data from a published reference group. Passive respiratory resistance (Rrs) and compliance (Crs) were measured with the single breath occlusion technique following specific acceptance criteria. The study was powered for a 30% difference in Rrs. Results: PFTs in 24 infants with CHD were compared to 31 historical reference infants. There was no difference in the Rrs between the groups. The infants with CHD had a significantly decreased Crs (1.02 ± 0.26 mL/cmH2O/kg versus 1.32 ± 0.36; (p < 0.05; mean ± SD)). Conclusions: Further prospective studies are required to quantify early PFTs in infants with CHD of different phenotypes.

13.
J Perinatol ; 44(10): 1437-1441, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38750194

ABSTRACT

OBJECTIVE: To compare early pulmonary function tests (PFTs) in neonates with critical congenital heart disease (CHD) compared to a historical reference group. DESIGN: Infants ≥ 37 weeks gestation with critical CHD were studied within the first few days of life, prior to cardiac surgery, and compared to data from a published reference group of healthy term neonates without CHD, studied at the same institution. Passive respiratory resistance (Rrs) and compliance (Crs) were measured with the single breath occlusion technique following specific acceptance criteria. The study was powered for a 30% difference in Rrs. RESULTS: PFTs in 24 infants with CHD were compared to 31 historical reference infants. There was no difference in the Rrs between the groups. The infants with CHD had a significantly decreased Crs (1.02 ± 0.26 mL/cmH2O/kg versus 1.32 ± 0.36; (p < 0.05; mean ± SD)). CONCLUSIONS: Further prospective studies are required to quantify early PFTs in infants with CHD of different phenotypes.


Subject(s)
Heart Defects, Congenital , Respiratory Function Tests , Humans , Infant, Newborn , Heart Defects, Congenital/surgery , Heart Defects, Congenital/physiopathology , Pilot Projects , Male , Female , Preoperative Care/methods , Airway Resistance/physiology , Prospective Studies , Lung Compliance , Case-Control Studies
14.
Am J Surg ; 231: 55-59, 2024 May.
Article in English | MEDLINE | ID: mdl-37087362

ABSTRACT

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas. We evaluated the effect disease stage, surgical intervention, and institutional volume status plays in survival. METHODS: We queried the Oregon State Cancer Registry for patients with PACC from 1997 to 2018. Treatment and referral patterns were analyzed, and overall survival (OS) was evaluated with Kaplan-Meier and Cox-proportional hazard analysis. RESULTS: 43 patients were identified. Median OS was 33.1 and 7.1 months in those with locoregional and metastatic disease respectively (p â€‹= â€‹0.008). Surgical intervention was associated with improved OS (hazard ratio 0.28, p â€‹< â€‹0.0001). High volume center (HVC) care trended towards improving OS. While the majority of cases were diagnosed at low volume centers (74%), referral to HVCs was rare (n â€‹= â€‹4) and limited to advanced (stage III/IV) disease. CONCLUSION: Stage and surgical resection influence survival outcomes in PACC, more data is needed to delineate the impact of institutional volume status.

15.
Analyst ; 138(1): 137-43, 2013 Jan 07.
Article in English | MEDLINE | ID: mdl-23120748

ABSTRACT

In Part II of this series describing the use of polystyrene (PS) devices for microfluidic-based cellular assays: various cellular types and detection strategies are employed to determine three fundamental assays often associated with cells. Specifically, using either integrated electrochemical sensing or optical measurements with a standard multi-well plate reader, cellular uptake, production, or release of important cellular analytes are determined on a PS-based device. One experiment involved the fluorescence measurement of nitric oxide (NO) produced within an endothelial cell line following stimulation with ATP. The result was a four-fold increase in NO production (as compared to a control), with this receptor-based mechanism of NO production verifying the maintenance of cell receptors following immobilization onto the PS substrate. The ability to monitor cellular uptake was also demonstrated by optical determination of Ca(2+) into endothelial cells following stimulation with the Ca(2+) ionophore A20317. The result was a significant increase (42%) in the calcium uptake in the presence of the ionophore, as compared to a control (17%) (p < 0.05). Finally, the release of catecholamines from a dopaminergic cell line (PC 12 cells) was electrochemically monitored, with the electrodes being embedded into the PS-based device. The PC 12 cells had better adherence on the PS devices, as compared to use of PDMS. Potassium-stimulation resulted in the release of 114 ± 11 µM catecholamines, a significant increase (p < 0.05) over the release from cells that had been exposed to an inhibitor (reserpine, 20 ± 2 µM of catecholamines). The ability to successfully measure multiple analytes, generated in different means from various cells under investigation, suggests that PS may be a useful material for microfluidic device fabrication, especially considering the enhanced cell adhesion to PS, its enhanced rigidity/amenability to automation, and its ability to enable a wider range of analytes to be investigated, even analytes with a high degree of hydrophobicity.


Subject(s)
Microfluidic Analytical Techniques/methods , Polystyrenes/chemistry , Animals , Biological Transport , Calcium/metabolism , Catecholamines/metabolism , Cattle , Cell Adhesion , Dimethylpolysiloxanes/chemistry , Electrochemistry , Endothelial Cells/cytology , Endothelial Cells/metabolism , Humans , Intracellular Space/metabolism , Microfluidic Analytical Techniques/instrumentation , Nitric Oxide/biosynthesis , PC12 Cells , Pulmonary Artery/cytology , Rats
16.
Analyst ; 138(1): 129-36, 2013 Jan 07.
Article in English | MEDLINE | ID: mdl-23120747

ABSTRACT

In Part I of a two-part series, we describe a simple and inexpensive approach to fabricate polystyrene devices that is based upon melting polystyrene (from either a Petri dish or powder form) against PDMS molds or around electrode materials. The ability to incorporate microchannels in polystyrene and integrate the resulting device with standard laboratory equipment such as an optical plate reader for analyte readout and pipets for fluid propulsion is first described. A simple approach for sample and reagent delivery to the device channels using a standard, multi-channel micropipette and a PDMS-based injection block is detailed. Integration of the microfluidic device with these off-chip functions (sample delivery and readout) enables high-throughput screens and analyses. An approach to fabricate polystyrene-based devices with embedded electrodes is also demonstrated, thereby enabling the integration of microchip electrophoresis with electrochemical detection through the use of a palladium electrode (for a decoupler) and carbon-fiber bundle (for detection). The device was sealed against a PDMS-based microchannel and used for the electrophoretic separation and amperometric detection of dopamine, epinephrine, catechol, and 3,4-dihydroxyphenylacetic acid. Finally, these devices were compared against PDMS-based microchips in terms of their optical transparency and absorption of an anti-platelet drug, clopidogrel. Part I of this series lays the foundation for Part II, where these devices were utilized for various on-chip cellular analysis.


Subject(s)
Microfluidic Analytical Techniques/instrumentation , Polystyrenes/chemistry , Dimethylpolysiloxanes/chemistry , Electrochemistry , Optical Devices
17.
Anal Bioanal Chem ; 405(10): 3013-20, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23340999

ABSTRACT

The use of microchip devices to study cellular systems is a rapidly growing research area. There are numerous advantages of using on-chip integrated electrodes to monitor various cellular processes. The purpose of this review is to give examples of advancements in microchip-based cellular analysis, specifically where electrochemistry is used for the detection scheme. These examples include on-chip detection of single-cell quantal exocytosis, electrochemical analysis of intracellular contents, the ability to integrate cell culture/immobilization with electrochemistry, and the use of integrated electrodes to ensure cell confluency in longer-term cell culture experiments. A perspective on future trends in this area is also given.


Subject(s)
Cells/chemistry , Electrochemical Techniques/methods , Microchip Analytical Procedures/methods , Animals , Electrochemical Techniques/instrumentation , Humans , Lab-On-A-Chip Devices
18.
Clin Orthop Relat Res ; 471(5): 1615-21, 2013 May.
Article in English | MEDLINE | ID: mdl-23184671

ABSTRACT

BACKGROUND: Component design, size, acetabular orientation, patient gender, and activity level have been suggested as factors leading to elevated metal ion concentrations after-on-metal hip resurfacing arthroplasty (MMHRA). The calculation of the contact patch to rim (CPR) distance integrates component size, design, and acetabular orientation and may be a good predictor of elevated metal ion levels. QUESTIONS/PURPOSES: We evaluated the effects and the predictive value of the CPR distance on serum cobalt (CoS) and chromium (CrS) ion levels. METHODS: We retrospectively studied 182 patients with Conserve Plus MMHRAs at a minimum of 12 months after surgery (median, 57 months; range, 12-165 months). CoS and CrS levels were analyzed using inductively-coupled plasma mass spectrometry. Multiple logistic regression was performed to determine which if any of the factors related to serum ion levels. RESULTS: Patients with CPR distances of 10 mm or less had a 37-fold increased risk of having elevated CoS of 7 µg/L or higher. Similarly, these patients had an 11-fold increased risk of having elevated CrS of 7 µg/L or higher. Sex and University of California Los Angeles activity scores did not influence the postoperative CoS and CrS levels. The negative predictive value for CPR distance less than 10 mm was 99.3% for CoS greater than 7 µg/L and 98.0% for CrS greater than 7 µg/L. CONCLUSIONS: Our observations suggest the CPR distance would be a useful indicator to determine which patients are at risk for elevated ion levels. Patients with CPR distances greater than 10 mm need not be monitored unless they become symptomatic.


Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip/instrumentation , Chromium/blood , Cobalt/blood , Hip Joint/surgery , Hip Prosthesis , Acetabulum/physiopathology , Adult , Aged , Arthroplasty, Replacement, Hip/adverse effects , Biomarkers/blood , Biomechanical Phenomena , Female , Hip Joint/physiopathology , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Prosthesis Design , Range of Motion, Articular , Recovery of Function , Retrospective Studies , Risk Factors , Spectrophotometry, Atomic , Time Factors , Treatment Outcome , Young Adult
19.
J Arthroplasty ; 28(6): 1010-4, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23433997

ABSTRACT

Degenerative hip conditions most commonly affect older patients. However, many cases occur in younger patients. Total hip arthroplasty is the conventional approach; however, hip resurfacing is a viable option. Fifty-three metal-on-metal resurfacings in 46 patients under age 30 were performed. Patients had a variety of etiologies, and were followed clinically and radiographically with mean follow-up of 98.2 months. Clinical scores and x-rays were compared pre-operatively and post-operatively. The last follow-up SF-12 and UCLA scores significantly improved post-operatively (P<0.0001). Range of motion scores also improved (P<0.001), and the mean Harris Hip Score was 88. There were 6 revisions. The Kaplan-Meier survivorship estimate at 8 years was 95%. Metal-on-metal hip resurfacing appears to be an effective procedure for younger patients. Longer-term data are needed for confirmation.


Subject(s)
Arthroplasty, Replacement, Hip/methods , Hip Prosthesis , Metal-on-Metal Joint Prostheses , Adolescent , Adult , Female , Follow-Up Studies , Humans , Male , Prosthesis Design , Prosthesis Failure , Retrospective Studies , Treatment Outcome , Young Adult
20.
J Arthroplasty ; 28(7): 1235-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23618754

ABSTRACT

Recent studies suggest that the tapered interface between stem and femoral head may be a substantial source of cobalt and chromium ion release after metal-on-metal (MOM) total hip arthroplasty (THA). This study compared patient ion levels after MOM hip resurfacing (HR) and MOM THA performed with identical acetabular components. 110 HRs were compared with 22 THAs. All had well-oriented components, unilateral implants, and serum ion studies beyond one year post-operatively. The HR group's median cobalt value was 1.11 µg/L vs. 2.86 µg/L for the THA patients. The HR group's median chromium value was 1.49 µg/L vs. 2.94 µg/L for THA. Significantly higher THA ion levels suggest a source of ions other than the MOM bearing itself.


Subject(s)
Arthroplasty, Replacement, Hip/instrumentation , Chromium/blood , Cobalt/blood , Hip Prosthesis , Prosthesis Design , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Ions , Male , Middle Aged , Prosthesis Failure , Retrospective Studies , Statistics, Nonparametric
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