A matched cohort study between cementless TKA and cemented TKA shows a reduction in tourniquet time and manipulation rate.

INTRODUCTION: Cementless total knee arthroplasty (TKA) is now becoming more acceptable with the advent of newer ongrowth constructs and better initial fixation. It has been proposed that cementless TKA may save OR time and result in a lower incidence of manipulation. This study was designed to assess the difference between cemented and cementless TKA. METHODS: Our hospital statistician performed a matched cohort analysis between 127 cementless TKAs and 127 cemented TKRs performed by a single surgeon. Patients were matched on age and BMI. Mean tourniquet time between the cemented and cementless TKAs was assessed as well as the rate of manipulation between these groups. Of note, a tourniquet was routinely used in both the cementless and cemented cohorts to reduce confounding bias. RESULTS: A total of 127 cementless TKAs with a mean age of 60.8 years and mean BMI 32.2 were compared to 127 cemented TKAs with a mean age of 61.5 years and mean BMI of 32.2 at an average follow-up of 2.0 years. There was a statistically significant reduction in tourniquet time in the cementless TKA cohort at 45.7 min compared to the cemented TKA cohort at 54.8 min (p = 0.001). Estimated blood loss was similar in both the cementless (179.5 ml) and cemented (196 ml) cohorts (p = 0.3) and postoperative outcomes, including UCLA score.In addition, the cementless TKA cohort had a manipulation rate of 0% compared to 3.1% for the cemented TKA group (p = 0.044). DISCUSSION AND CONCLUSION: While cementless and cemented TKA have shown similar PROMs and survivorship, we demonstrated a significant reduction in tourniquet time with cementless TKRs, with similar estimated blood loss, and a lower incidence of manipulation with cementless TKRs in this matched cohort study. The increased cost of a cementless implant may be negated if one considers the cost savings of not using cement, the cost savings of not performing manipulations, and the shorter operative time.

Mid-level constraint may correct coronal plane imbalance without compromising patient function in patients with severe osteoarthritis.

INTRODUCTION: Mid-level constraint (MLC) in Total Knee Arthroplasty (TKA) offer surgeons the opportunity to obtain a well-balanced varus-valgus balance in the setting of slight ligament imbalance. As such, we sought to evaluate patient reported outcome measures (PROMs), alignment correction, and rate of revision between the MLC group and a cohort of posterior stabilized (PS) knees in a cohort of patients with preoperative degenerative arthritis. MATERIALS/METHODS: We performed a retrospective review of 57 MLC knees and 96 PS knees from a single manufacturer that were implanted by a single surgeon. We found the average age (68.91 vs. 68.40, p = 0.72), average BMI (30.88 vs. 29.14, p = 0.10), and gender breakdown (25:32 vs. 28:69, p = 0.08) to be comparable between the two cohorts. The latest follow-up was 4.0 years in the MLC group and 3.8 years in the PS group, p = 0.26. RESULTS: The two cohorts inherently resulted in significantly different preoperative deformities (MCL knees: average varus deformity 13.75°, average valgus deformity 12.37°; PS knees average varus deformity 15.14°, average valgus deformity 10.8°). There were more valgus knees in the MLC group (36 vs. 22 (p < 0.001), respectively), but the postoperative alignment was the same. MLC cohort: preoperative varus group had 4.74° of valgus postoperatively, preoperative valgus group had 5.43° of valgus postoperatively. PS cohort: preoperative varus group had 5.40° of valgus postoperatively, preoperative valgus group had 4.80° of valgus postoperatively. We found a significant difference in Knee Injury and Osteoarthritis Outcome Score (KSCRS-Total) between the two groups (MLC 163.9 vs. PS 132.8, p = 0.003). There was no significant difference in terms of Range of Motion (ROM) (MLC 121° vs. PS 122°, p = 0.58), anterior knee pain (MLC 1.75 vs. PS 1.81, p = 0.39), or Pain VAS (MLC 25.1 vs. PS 28.6, p = 0.46). There was similar rate of revision between the cohorts (3.5% MLC vs. 2.10% PS, p = 0.13). There was no significant difference in manipulation rate (8.78% MLC vs. 9.40% PS, p = 0.38). CONCLUSION/DISCUSSION: This study demonstrated that the use of MLC in TKA allows surgeons to correct preoperative deformities with equal or improved functional outcomes compared to PS knees. In general, we recommend that surgeons try to balance the knee and use the least amount of constraint possible but should consider MLC when needed and use such implants if they are unable to balance the varus-valgus gap.

Lack of early dislocation for dual mobility vs. fixed bearing total hip arthroplasty: A multi-center analysis of comparable cohorts.

BACKGROUND: Dislocation is a major cause of morbidity and revision surgery following total hip arthroplasty (THA). To address such issues, dual mobility (DM) bearings were introduced as a more stable alternative to fixed-bearing (FB) prostheses. As such, we compared DM and FB systems in a cohort study in terms of dislocations, readmissions, and revisions. METHODS: A 27 multi-center retrospective review was performed of 664 DM and 218 FB cases from the same manufacturer with mean follow-up of 2.09 years and 1.83 years, respectively. Patient reported outcome measures (PROMs) including Harris Hip Score (HHS), SF12, EQ5D, and Lower Extremity Activity Score (LEAS) were evaluated as well as dislocation rates, readmissions, and revisions rates. We also performed a survivorship analysis through Kaplan-Meier estimator. Students t-test was used for normally distributed continuous data and Fisher exact test (P < 0.05) was used for discrete data. RESULTS: There were 0 dislocations in the DM (0%) group and 2 dislocations in the FB (0.92%) group (p = 0.06). Latest follow up HHS revealed a significant difference between groups (91.44 DM and 87.81 FB; p = 0.006). In addition, there was significant difference between DM and FB on SF12 Physical Component Score (PCS) (46.83 and 44.55, respectively, p = 0.015). Also, readmission rates at 30, 60 and 90 days remained lower for DM than for FB at each time point (1.05% vs. 2.75%, 1.81% vs. 2.75%, and 1.81% vs. 2.75, respectively). Overall, DM had a lower revision rate at 1.51% compared to 2.29% for FB (p = 0.24). The revision breakdown for DM revealed 0 (0%) for both Anatomic Dual Mobility (ADM) and Modular Dual Mobility (MDM) due to the acetabular component.) There was a difference, 14 (87.5%) for ADM and 2 (12.5%) due to the femoral component. The survivorship analysis revealed no significance difference between DM and FB at 4 years (97.90% and 97.26%, respectively). CONCLUSION: In comparison to patients who undergo FB THA, DM bearings have improved PROMs and a lower rate of dislocation, readmission, and revision.

Anatomic dual mobility compared to modular dual mobility in primary total hip arthroplasty: a matched cohort study.

BACKGROUND: Dual mobility (DM) has been used in primary total hip arthroplasty recently for their low dislocation rates, low revision rates, and improved patient functional outcomes. We compared 2 DM systems, anatomic dual mobility (ADM; Stryker, Mahwah, NJ) and modular dual mobility (MDM; Stryker, Mahwah, NJ), to determine differences in dislocation rates, revision rates, and patient outcome scores. METHODS: The study was a single-center matched retrospective review of prospectively collected data of patients who underwent primary total hip arthroplasty surgery with an ADM or MDM system by a single surgeon from 2012 to 2017. Demographics, operative details, postoperative patient-reported outcomes, and clinical outcomes were recorded. A Kaplan-Meier survivorship curve to compare survival time between groups was collected as well. RESULTS: Five hundred seventy-four patients were included in the study with 287 patients matched in each group with mean 2.86 years of follow-up. The dislocation rate in each cohort was 0%, the acetabular-specific revision rate was 0%, and in each cohort, overall revision rate in each cohort was 1.7%. In general, patient-reported outcomes were similar for each group (Harris Hip Score Pain (P = .919), Harris Hip Score Function (P = .736), Western Ontario and McMaster Universities Osteoarthritis Index (P = .139), Pain Visual Analog Scale (P = .146), Veterans RAND 12-Item Health Survey (P = .99), University of California, Los Angeles (P = .417), and Harris Hip Score Total (P = .136). There was a slight clinically insignificant increase in hip flexion between the cohorts favoring the ADM group (98.6 ± 9.8 vs 94.0 ± 9.7, P < .001). CONCLUSIONS: Both DM systems had similar patient-reported outcomes that were quite favorable. At 2.86 years of follow-up, neither the ADM nor MDM systems demonstrated dislocation, and both had low acetabular-specific and overall revision rates in this matched cohort study.

Levels of alpha1 acid glycoprotein and ceruloplasmin predict future albumin levels in hemodialysis patients.

BACKGROUND: Serum albumin concentration predicts mortality in hemodialysis (HD) patients. While serum albumin concentration correlates with serum concentration of C-reactive protein (CRP) and is dependent upon CRP in multiple regression models in cross sectional studies, CRP does not predict future albumin levels, possibly because CRP changes rapidly, yielding large month-to-month variability in CRP. If inflammation causes rather than is simply associated with hypoalbuminemia, then changes in the levels of acute phase proteins should precede changes in serum albumin concentration. METHODS: The levels of long-lived positive and negative acute-phase proteins (APPs) (C-reactive protein, ceruloplasmin, alpha1 acid glycoprotein, transferrin and albumin) were measured longitudinally in 64 HD patients and a regression model was constructed to predict future albumin levels. Normalized protein catabolic rate (nPCR) was measured monthly. The number of repeated measurements ranged from 9 to 39 in each patient (median 22 and a mean of 23 measurements). To construct a model that would predict serum albumin concentration at any time j, values of all longitudinally measured APPs, positive and negative at any time j - 1, approximately 30 days prior to time j, were used. Other demographic factors (such as, race, access type, and cause of renal failure) also were incorporated into the model. RESULTS: The model with the best fit for predicting serum albumin at time j included albumin, ceruloplasmin, and alpha1 acid glycoprotein measured at time j - 1. The only demographic variable with subsequent predictive value was diabetes. CONCLUSIONS: The finding that changes in the concentration of the long lived APPs measured one month earlier are associated with predictable changes in the future concentration of serum albumin suggest that changes in inflammation are likely to be causal in determining serum albumin concentration in hemodialysis patients.

Event history graphs for censored survival data.

A compact graphical device for combining survival and time-varying covariate information is proposed. The proposed graph contains the Kaplan-Meier estimator for right-censored data and a simultaneous display of the behaviour of time-dependent covariate(s) and the lifetime for each subject in the sample. The observed levels of time-dependent covariates are possibly subjected to an initial dimension reduction or smoothing step to produce a continuous covariate function. Values of this function are plotted on a horizontal bar for the length of the lifetime of the subject. Covariate information for censored data is also incorporated. The union of the horizontal bars forms the Kaplan-Meier estimator of the survival function. Our graphical method is implemented with a new S-plus function and demonstrated in several applications.

Initial virological and immunologic response to highly active antiretroviral therapy predicts long-term clinical outcome.

Little is known about the long-term clinical outcomes for human immunodeficiency virus (HIV)-infected patients who have received highly active antiretroviral therapy (HAART). Determining factors associated with long-term clinical outcomes early in the course of treatment may allow modifications to be made for patients who are at a greater risk of treatment failure. To evaluate these factors, we studied 213 HIV-infected patients who had received HAART for at least 115 weeks. In the univariate analysis, virological response, which was measured as the change in virus load from baseline at month 3 of treatment, was the single best predictor of clinical outcome (relative hazard, 0.722; P=.001), independent of virological suppression. In the multivariate analysis, virological response and immunologic response, which was measured as an increase in CD4 cell count of >200 cells/mm(3), resulted in better prediction of clinical outcomes than did use of either variable alone (P=.02). Our results indicate that changes in virus load and immunologic response together are good predictors of clinical outcome and can be assessed after the initiation of HAART, which would allow clinicians to identify patients early in the course of therapy who are at greater risk of negative outcome.

The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients. The HEMO Study Group.

BACKGROUND: Cross sectional studies have established that the serum albumin level is dependent on serum levels of acute-phase proteins (APPs) or cytokine levels in hemodialysis patients. While the acute-phase response is generally associated with acute inflammatory events, a cross sectional analysis relating laboratory values to outcomes assumes these values to be unchanging. The longitudinal relationship among laboratory measurements and how they vary over time in a population of patients are unknown. METHODS: Patients who were enrolled in the HEMO Study were recruited into an ancillary longitudinal study to establish the predictive effect of temporal variation in the levels of APPs and of temporal variation in normalized protein catabolic rate (nPCR) on the serum albumin concentration. nPCR was measured monthly using a double-pool method. The positive APPs-C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1-AG), and ceruloplasmin-and the negative APP-transferrin (Trf)-were measured in serum obtained before each dialysis session for six weeks and then monthly in 37 hemodialysis patients. A random coefficient regression analysis was used to assess the association of serum albumin with other measured parameters at each time point, as well as fixed patient characteristics. RESULTS: The within-subject coefficients of variation of albumin (median, range of 25th to 75th percentiles; median, 0.0614; range, 0.0485 to 0.0690) were significantly less than that of APPs (CRP, median, 0.878; range, 0.595 to 1.314, P < 0. 05; and alpha1 AG, median, 0.173; range, 0.116 to 0.247, P < 0.05). The levels of APPs and albumin varied considerably over time. The primary predictor of current albumin was the current CRP level (P = 0.0014). nPCR also was a significant predictor for albumin levels (P = 0.0440) after controlling for the effect of APPs, suggesting an effect of nPCR on serum albumin concentration irrespective of the acute-phase response. Age and the presence of an arteriovenous graft were significant predictors that were associated with reduced albumin. CONCLUSIONS: The acute-phase response is intermittent and is not a continuous feature in individual dialysis patients. Levels of APPs are the most powerful predictors for the levels of albumin concentration in hemodialysis in a longitudinal setting. Since variations in albumin are small, measurement of variations in APPs may provide greater insight into the dynamics of clinically relevant processes.

Pretransplant systemic inflammation and acute rejection after renal transplantation.

BACKGROUND: There are presently no established pre-transplant tests that consistently identify patients who may be at increased risk for acute rejection episodes after renal transplantation. We studied whether pretransplant serum levels of C-reactive protein (CRP), a marker for the presence of systemic inflammation, would predict the occurrence of acute rejection episodes after renal transplantation. METHODS: Pretransplant serum was tested for CRP level in 97 consecutive renal transplant recipients. Time to acute rejection after transplantation was stratified by CRP level and compared using the Kaplan-Meier method. In addition, Cox regression multivariate analysis was performed to assess whether any pretransplant covariates could independently predict the subsequent occurrence of acute rejection episodes. RESULTS: Pretransplant mean CRP levels were higher in patients who subsequently had a rejection episode versus those who had no rejection (22.2+/-2.9 vs. 11.7+/-1.8 microg/ml, respectively, P=0.003). Patients less than the median CRP value had a significantly longer time to rejection compared to those with higher CRP levels (P=0.002). Similarly, patients within the lowest CRP quartile had longer times to rejection when compared with the highest quartile (P=0.006). Cox proportional hazards regression multivariate analysis identified CRP level as the only independent pretransplant risk factor for rejection identified (P=0.044). CONCLUSIONS: Pretransplant systemic inflammation as manifested by elevated serum CRP level independently predicts the risk of acute rejection after renal transplantation and may be useful in stratifying patients at the time of transplantation according to immunological risk. Thus, assessment of pretransplant systemic inflammatory status may be helpful in prospective individualization of immunosuppression therapy after renal transplantation.

S phase determination in intact colonic crypts by histone H3 messenger RNA in situ hybridization and confocal microscopy.

Proliferating cells have a restricted three-dimensional spatial distribution within the crypt, which is the proliferative unit of the colon. Accurate quantitative and spatial analyses of S phase cells in the colon have therefore been limited by histological techniques. To overcome these limitations, S phase cells in microdissected intact colonic crypts of control, modified-starved, and refed rats were labeled by histone H3 in situ hybridization and analyzed by confocal microscopy. High-resolution digital images of the crypt cell nuclei stained with cyanine nucleic acid and of the labeled S phase cells were produced from confocal microscopic optical crypt sections. The S phase labeling index (LI) per whole crypt significantly (P < 0.001) discriminated the proliferative differences between control, modified-starved, and refed rats and correlated (r = 0.92) with the LI determined from histological crypt sections of the same rats. The variance component of the LI attributable to differences between whole crypts, 0.44 (95% confidence interval, 0.38-0.51), was considerably smaller than that attributable to differences between histological crypt sections, 6.07 (95% confidence interval, 5.18-6.96). Confocal microscopy and histone H3 in situ hybridization of intact three-dimensional crypts enables precise in vitro quantitation and spatial analysis of the total and S phase crypt cells.

Histone H3 messenger RNA in situ hybridization correlates with in vivo bromodeoxyuridine labeling of S-phase cells in rat colonic epithelium.

Measurements of cell cycle phase fractions, particularly S-phase, are useful for studies of cell biology and carcinogenesis. Up-regulation of histone gene expression is tightly coupled to the G1-S-phase transition of the cell cycle, and mRNA levels rise 30-100-fold during S-phase. Labeling of histone H3 mRNA using in situ hybridization (ISH) was assessed as a measure of S-phase cells and compared with that found using in vivo 5-bromodeoxyuridine (BrdUrd) labeling in formalin-fixed rat colonic crypts under baseline, modified 72-h starvation, and 24-h refeeding conditions. The labeling index scored in single-labeled sections by histone H3 ISH tightly correlated with that found by in vivo BrdUrd labeling (r = 0.99, p < 0.0001) and clearly discriminated between the control, starved, and refed states (P < 0.001). In 180 crypt sections double labeled using histone H3 ISH and BrdUrd, 92% of 1572 labeled cells exhibited both nuclear BrdUrd and cytoplasmic histone H3 label. It is concluded that histone H3 ISH is an accurate measure of the S-phase fraction and provides an alternative to in vivo BrdUrd labeling in rat colon. This finding warrants validation in human studies.