Role of preoperative pain, muscle function, and activity level in discharge readiness after fast-track hip and knee arthroplasty.

BACKGROUND AND PURPOSE: The concept of fast-track surgery has led to a decline in length of stay after total hip arthroplasty (THA) and total knee arthroplasty (TKA) to about 2-4 days. However, it has been questioned whether this is only achievable in selected patients-or in all patients. We therefore investigated the role of preoperative pain and functional characteristics in discharge readiness and actual LOS in fast-track THA and TKA. METHODS: Before surgery, hip pain (THA) or knee pain (TKA), lower-extremity muscle power, functional performance, and physical activity were assessed in a sample of 153 [corrected] patients and used as independent variables to predict the outcome (dependent variable) ­ readiness for hospital discharge ­ for each type of surgery. Discharge readiness was assessed twice daily by blinded assessors RESULTS: Median discharge readiness and actual length of stay until discharge were both 2 days. Univariate linear regression followed by multiple linear regression revealed that age was the only independent predictor of discharge readiness in THA and TKA, but the standardized coefficients were small (≤ 0.03). INTERPRETATION: These results support the idea that fast-track THA and TKA with a length of stay of about 2-4 days can be achieved for most patients independently of preoperative functional characteristics.

No effect of fibrin sealant on drain output or functional recovery following simultaneous bilateral total knee arthroplasty: a randomized, double-blind, placebo-controlled study.

BACKGROUND AND PURPOSE: Blood loss after total knee arthroplasty (TKA) may lead to anemia, blood transfusions, and increased total costs. Also, bleeding into the periarticular tissue may cause swelling and a reduction in quadriceps strength, thus impairing early functional recovery. In this randomized, double-blind, placebo-controlled study, we analyzed the possible effect of fibrin sealant on blood loss and early functional recovery in a fast-track setting. METHODS: 24 consecutive patients undergoing bilateral simultaneous TKA were included. 10 mL of fibrin sealant (Evicel) was sprayed onto one knee whereas the contralateral knee had saline. Drain output, the primary outcome, was measured from knee drains removed exactly 24 h after surgery. Secondary outcomes (knee swelling, pain, strength of knee extension, and range of movement (ROM)) were evaluated up to 21 days after surgery. RESULTS: The drain output in knees treated with fibrin sealant and placebo was similar (582 mL and 576 mL, respectively). Likewise, no statistically significant differences were found between groups regarding swelling, pain, strength of knee extension, and ROM. INTERPRETATION: Fibrin sealant as a local hemostatic in TKA showed no benefit in reducing drain output or in facilitating early functional recovery when used with a tourniquet, tranexamic acid, and a femoral bone plug.

The tumor biological significance of RNF43 and LRP1B in gastric cancer is complex and context-dependent.

Gastric cancer (GC) is the fifth most common cancer in the world with a poor prognosis. Both RNF43 and LRP1B function as tumor suppressors in the Wnt signaling pathway and have been described to be frequently mutated in GC. In this study of a large and well characterized cohort of 446 GCs we explored the significance of expression of RNF43 and LRP1B and their correlations with clinicopathological patient characteristics. Immunostaining of whole mount tissue sections was documented with the histoscore. Dichotomized at the median, we separated the cohort into a low/negative and a high/positive group of RNF43 and LRP1B expression, respectively. Apart from the entire cohort, we also examined the intestinal and diffuse type GCs separately. Regarding the entire cohort, the expression of RNF43 and LRP1B correlated significantly with the Lauren phenotype and with each other. Interestingly, differences were noted regarding RNF43 between the intestinal and diffuse type GCs. Survival analysis of the intestinal type GCs showed that RNF43 low/negative GCs tended to have a better outcome compared with RNF43 high/positive GCs [24.5 months overall survival (OS) and 25.0 months tumor-specific survival (TSS) vs. 14.1 months OS and 17.9 months TSS, respectively]. To the contrary, diffuse type GCs with RNF43 low/negative had a worse outcome compared with RNF43 high/positive GCs (12.9 months OS and 18.2 months TSS vs. 17.1 months OS and 21.5 months TSS, respectively). On multivariate analysis, RNF43 low/negative versus high/positive was an independent prognosticator of survival in diffuse type GC (hazard ratio 2.393 for OS and 2.398 for TSS). These data support the contention that the expression and biological effect of RNF43 and LRP1B in GC is context-dependent.

Effect of knee joint icing on knee extension strength and knee pain early after total knee arthroplasty: a randomized cross-over study.

OBJECTIVE: To investigate the acute effect of knee joint icing on knee extension strength and knee pain in patients shortly after total knee arthroplasty. DESIGN: A prospective, single-blinded, randomized, cross-over study. SETTING: A fast-track orthopaedic arthroplasty unit at a university hospital. PARTICIPANTS: Twenty patients (mean age 66 years; 10 women) scheduled for primary unilateral total knee arthroplasty. INTERVENTIONS: The patients were treated on two days (day 7 and day 10) postoperatively. On one day they received 30 minutes of knee icing (active treatment) and on the other day they received 30 minutes of elbow icing (control treatment). The order of treatments was randomized. MAIN OUTCOME MEASURES: Maximal knee extension strength (primary outcome), knee pain at rest and knee pain during the maximal knee extensions were measured 2-5 minutes before and 2-5 minutes after both treatments by an assessor blinded for active or control treatment. RESULTS: The change in knee extension strength associated with knee icing was not significantly different from that of elbow icing (knee icing change (mean (1 SD)) -0.01 (0.07) Nm/kg, elbow icing change -0.02 (0.07) Nm/kg, P = 0.493). Likewise, the changes in knee pain at rest (P = 0.475), or knee pain during the knee extension strength measurements (P = 0.422) were not different between treatments. CONCLUSIONS: In contrast to observations in experimental knee effusion models and inflamed knee joints, knee joint icing for 30 minutes shortly after total knee arthroplasty had no acute effect on knee extension strength or knee pain.

Loss of knee-extension strength is related to knee swelling after total knee arthroplasty.

OBJECTIVE: To examine whether changes in knee-extension strength and functional performance are related to knee swelling after total knee arthroplasty (TKA). DESIGN: Prospective, descriptive, hypothesis-generating study. SETTING: A fast-track orthopedic arthroplasty unit at a university hospital. PARTICIPANTS: Patients (N=24; mean age, 66y; 13 women) scheduled for primary unilateral TKA were investigated 1 week before surgery and on the day of hospital discharge 2.4 days postsurgery. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We assessed all patients for knee-joint circumference, knee-extension strength, and functional performance using the Timed Up & Go, 30-second Chair Stand, and 10-m fast speed walking tests, together with knee pain during all active test procedures. RESULTS: All investigated variables changed significantly from pre- to postsurgery independent of knee pain. Importantly, knee circumference increased (knee swelling) and correlated significantly with the decrease in knee-extension strength (r=-.51; P=.01). Reduced fast-speed walking correlated significantly with decreased knee-extension strength (r=.59; P=.003) and decreased knee flexion (r=.52; P=.011). Multiple linear regression showed that knee swelling (P=.023), adjusted for age and sex, could explain 27% of the decrease in knee-extension strength. Another model showed that changes in knee-extension strength (P=.009) and knee flexion (P=.018) were associated independently with decreased performance in fast-speed walking, explaining 57% of the variation in fast-speed walking. CONCLUSIONS: Our results indicate that the well-known finding of decreased knee-extension strength, which decreases functional performance shortly after TKA, is caused in part by postoperative knee swelling. Future studies may look at specific interventions aimed at decreasing knee swelling postsurgery to preserve knee-extension strength and facilitate physical rehabilitation after TKA.

The role of pain for early rehabilitation in fast track total knee arthroplasty.

PURPOSE: To investigate the relationship between early functional mobility and pain intensity in a fast track program after total knee arthroplasty (TKA). METHODS: One hundred consecutive patients operated with TKA in an orthopaedic unit at a University hospital were prospectively studied. Measurements of independence in transfer and ambulation (Cumulated Ambulation Score), pain intensity (Verbal Analog Scale (VAS)), range of knee motion, functional mobility ('Timed Up & Go' (TUG) test), and walking distance were recorded daily from the first postoperative day until discharge. RESULTS: On the first postoperative day, 90% of the patients were able to walk independently with median pain intensity of < or =5 on VAS. Of these, 78% walked > 70 m. All patients walked independently on postoperative Day 2 with pain intensity of < or =4. On the day of discharge, all patients walked with crutches with pain intensity of < or =3, walking distance > 70 m, median range of motion 10-80 degrees , and median test time of the 'TUG' 19.2 s. The length of hospital stay was median 3 days. CONCLUSION: Pain has a limited influence on the functional recovery beyond the first postoperative day after TKA, thereby allowing early physiotherapy.

Timed up & go test score in patients with hip fracture is related to the type of walking aid.

UNLABELLED: Kristensen MT, Bandholm T, Holm B, Ekdahl C, Kehlet H. Timed Up & Go test score in patients with hip fracture is related to the type of walking aid. OBJECTIVE: To determine the relationship between Timed Up & Go (TUG) test scores and type of walking aid used during the test, and to determine the feasibility of using the rollator as a standardized walking aid during the TUG in patients with hip fracture who were allowed full weight-bearing (FWB). DESIGN: Prospective methodological study. SETTING: An acute orthopedic hip fracture unit at a university hospital. PARTICIPANTS: Patients (N=126; 90 women, 36 men) with hip fracture with a mean age +/- SD of 74.8+/-12.7 years performed the TUG the day before discharge from the orthopedic ward. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The TUG was performed with the walking aid the patient was to be discharged with: a walker (n=88) or elbow crutches (n=38). In addition, all patients also performed the TUG using a rollator. RESULTS: Patients who performed the TUG with a walker were on average 13.6 (95% confidence interval [CI], 11.2-16.1) seconds faster using a rollator compared with the walker (P<.001). Correspondingly, patients who performed the TUG with crutches were on average 3.5 (95% CI, 1.5-5.4) seconds faster using a rollator compared with elbow crutches (P=.001). In both patient groups, the between walking-aid scores were strongly correlated (r>.833, P<.001). CONCLUSIONS: TUG scores are significantly related to the type of walking aid used during the test in patients with hip fracture who are allowed FWB when discharged from the hospital, but all patients were able to perform the TUG using the rollator as a standardized walking aid. Our findings indicate the importance of using a standardized walking aid when evaluating changes or comparing TUG scores in patients with hip fracture.

A randomized phase II trial of concurrent chemoradiation with two doses of radiotherapy, 60Gy and 66Gy, concomitant with a fixed dose of oral vinorelbine in locally advanced NSCLC.

INTRODUCTION: In order to test the best performing radiation dose with a convenient chemotherapy schedule of an oral formulation of radio-sensitizing vinorelbine in inoperable locally advanced non-small cell lung cancer (NSCLC), we performed a randomized phase II trial based on a "pick the winner" design. METHODS: After 2 cycles of neoadjuvant chemotherapy, 117 patients with NSCLC stage IIB-IIIB in performance status 0-1 were randomized to radiotherapy 60Gy/30 fractions or 66Gy/33 fractions concurrent with a fixed dose of oral vinorelbine 50mg administered 3 times weekly. The primary endpoint was local progression free interval. A scheduled FDG-PET-CT-scan was performed 9months after randomization. The study was registered at ClinicalTrials.gov (NCT 00887783). RESULTS: Both arms were well tolerated. The local progression free interval at 9months was 54% in the 60Gy arm and 59% in the 66Gy arm (log rank test p=0.55). There was no statistically significant difference in overall survival. The median survival was 23.3 and 23.7months in the 60 and 66Gy arm, respectively. No significant difference in toxicity was observed. CONCLUSION: Both 60 and 66Gy administered concomitant with oral vinorelbine showed similar local control and overall survival, and was well tolerated. The pick the winner design choose 66Gy as the winning arm.

Acute esophagitis for patients with local-regional advanced non small cell lung cancer treated with concurrent chemoradiotherapy.

PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated radiotherapy (IMRT) and concomitant chemotherapy (CCT). METHODS: Between 2009 and 2013, 117 patients with stages IIB-IIIB NSCLC were treated in a multicenter randomized phase II trial with 2 cycles of induction chemotherapy followed by IMRT and CCT. The esophagitis was prospectively scored using the Common Toxicity Criteria 3.0. Clinical and dosimetric variables were analyzed for the correlation with grade ⩾2 esophagitis through logistic regression. RESULTS: Grade 2 esophagitis was experienced by 31 (27%). All models including gender, institution, a dosimetric parameter and a position parameter were significantly associated with esophagitis. The two models using the relative esophagus volume irradiated above 40 Gy (V40, OR=2.18/10% volume) or the length of esophagus irradiated above 40 Gy (L40, OR=4.03/5 cm) were optimal. The upper part of esophagus was more sensitive and females experienced more toxicity than men. CONCLUSION: V40 and L40 were most effective dosimetric predictors of grade ⩾2 esophagitis. The upper part of esophagus was more sensitive.

Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an epitope derived from indoleamine 2,3 dioxygenase.

PURPOSE: To investigate targeting of indoleamine 2,3 dioxygenase (IDO) enzyme using a synthetic peptide vaccine administered to patients with metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: In a clinical phase I study, we treated 15 HLA-A2-positive patients with stage III-IV NSCLC in disease stabilization after standard chemotherapy. Patients were treated with imiquimod ointment and subcutaneous vaccinations (100 µg IDO5 peptide, sequence ALLEIASCL, formulated in 900 µL Montanide). Primary endpoint was toxicity. Clinical benefit and immunity were assessed as secondary endpoints. RESULTS: No severe toxicity was observed. One patient developed a partial response (PR) after one year of vaccine treatment, whereas long-lasting stable disease (SD) ≥ 8.5 months was demonstrated in another six patients. The median overall survival (OS) was 25.9 months. Patients demonstrated significant improved OS (P = 0.03) when compared with the group of patients excluded because of HLA-A2 negativity. IDO-specific CD8(+) T-cell immunity was demonstrated by IFN-γ Elispot and Tetramer staining. Fluorescence-activated cell sorting analyses demonstrated a significant reduction of the Treg population (P = 0.03) after the sixth vaccine (2.5 months) compared with pretreatment levels. Furthermore, expression of IDO was detected in nine of ten tumor biopsies by immunohistochemistry. High-performance liquid chromatography analyses of kynurenine/tryptophan (Kyn/Trp) ratio in sera were performed. In long-term analyses of two clinical responding patients, the ratio of Kyn/Trp remained stable. CONCLUSIONS: The vaccine was well tolerated with no severe toxicity occurring. A median OS of 25.9 months was demonstrated and long-lasting PR+SD was seen in 47% of the patients.

Surgery-induced changes and early recovery of hip-muscle strength, leg-press power, and functional performance after fast-track total hip arthroplasty: a prospective cohort study.

BACKGROUND: By measuring very early changes in muscle strength and functional performance after fast-track total hip arthroplasty (THA), post-operative rehabilitation, introduced soon after surgery, can be designed to specifically target identified deficits. OBJECTIVES: Firstly, to quantify changes (compared to pre-operative values) in hip muscle strength, leg-press power, and functional performance in the first week after THA, and secondly, to explore relationships between the muscle strength changes, and changes in hip pain, systemic inflammation, and thigh swelling. DESIGN: Prospective, cohort study. SETTING: Convenience sample of patients receiving a THA at Copenhagen University Hospital, Hvidovre, Denmark, between March and December 2011. PARTICIPANTS: Thirty-five patients (65.9 ± 7.2 years) undergoing THA. MAIN OUTCOME MEASURES: Hip muscle strength, leg-press power, performance-based function, and self-reported disability were determined prior to, and 2 and 8 days after, THA (Day 2 and 8, respectively). Hip pain, thigh swelling, and C-Reactive Protein were also determined. RESULTS: Five patients were lost to follow-up. Hip muscle strength and leg press power were substantially reduced at Day 2 (range of reductions: 41-58%, P<0.001), but less pronounced at Day 8 (range of reductions: 23-31%, P<0.017). Self-reported symptoms and function (HOOS: Pain, Symptoms, and ADL) improved at Day 8 (P<0.014). Changes in hip pain, C-Reactive Protein, and thigh swelling were not related to the muscle strength and power losses. CONCLUSIONS: Hip muscle strength and leg-press power decreased substantially in the first week after THA - especially at Day 2 - with some recovery at Day 8. The muscle strength loss and power loss were not related to changes in hip pain, systemic inflammation, or thigh swelling. In contrast, self-reported symptoms and function improved. These data on surgery-induced changes in muscle strength may help design impairment-directed, post-operative rehabilitation to be introduced soon after surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT01246674.

Thigh and knee circumference, knee-extension strength, and functional performance after fast-track total hip arthroplasty.

OBJECTIVE: To (1) quantify changes in knee-extension strength and functional-performance at discharge after fast-track total hip arthroplasty (THA) and (2) investigate whether these changes correlate to changes in thigh and knee circumference (ie, swelling) or pain. DESIGN: A prospective, descriptive, hypothesis-generating study. SETTING: A special unit for fast-track hip and knee arthroplasty operations at a university hospital. PARTICIPANTS: Twenty-four patients (20 women and 4 men; ages 69 ± 6.1 years) scheduled for primary unilateral THA. METHODS: All patients were evaluated before surgery and on the day of hospital discharge. MAIN OUTCOME MEASURES: Knee-extension strength, thigh and knee joint circumference, hip pain, and functional performance (Timed Up & Go, 30-Second Chair Stand, and 10-Meter Walk tests). RESULTS: All investigated variables changed significantly from before to after surgery, except for hip pain. The average loss in knee-extension strength after surgery (32%, P = .01) did not correlate with increased thigh circumference (6%, P < .01) or knee circumference (3%, P < .01) or with reductions in functional performance: Timed Up & Go test (114%, P = .01), 30-Second Chair Stand test (36%, P = .01), and 10-Meter Walk test (50%, P < .01). Only the increase in knee circumference correlated significantly with reduced performance in the 10-Meter Walk test time (R = -0.59, P < .01), explaining 34% of the variance in the 10-Meter Walk test. No correlations between changes in hip pain and functional performance or knee-extension strength were found. Mean postoperative hospital stay was 2.1 days. CONCLUSIONS: Knee-extension strength is considerably reduced at discharge after THA, but the early strength reduction does not correlate with changes in thigh or knee circumferences. Because functional performance is also considerably reduced at discharge (unrelated to reduced knee-extension strength), other mechanisms such as fear, avoidance of movement, or decreased hip-muscle strength also may be involved.

ERCC1 and Ki67 in small cell lung carcinoma and other neuroendocrine tumors of the lung: distribution and impact on survival.

BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair mechanism. Ki67 is associated with the clinical course of several malignancies. The associations of ERCC1 and Ki67, clinical features and survival in small cell lung carcinoma (SCLC), typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LCNEC) were determined. MATERIALS AND METHODS: We included a consecutive series of 186 patients with SCLC treated with platinum-based chemotherapy and surgically treated patients with TC (n = 48), AC (n = 15) and LCNEC (n = 27). ERCC1 and Ki 67 were measured by immunohistochemistry and scored using published criteria. RESULTS: The expression of ERCC1 was different among the different tumor types (p < 0.001). For patient with limited disease as well as extensive disease SCLC, no association of ERCC1 expression with survival was observed (p = 0.59). However, only 10% of SCLC tumors expressed ERCC1. For TC and AC, ERCC1 positive patients had better survival than ERCC1 negative patients. ERCC1 had no prognostic impact for LCNEC. A difference of the percentage of Ki67 LI was observed for the different tumor types (p < 0.001). The difference between TC and AC was significant (p = 0.02), as was the difference between low grade (TC+AC) and high grade NE (LCNEC + SCLC) (p < 0.001). For all included patients, a correlation between Ki67 and ERCC1 was observed (RSquare = 0.19, p < 0.001). CONCLUSION: ERCC1 expression in SCLC treated with platinum-based chemotherapy has no impact on survival. High expression of ERCC1 in TC might represent a clue to the failure of platinum-based therapy in these patients. ERCC1 expression has prognostic impact in lung carcinoids. Ki 67 might be considered as a supplementary test to the histopatologic classification of NE tumors.

[Rehabilitation after total knee arthroplasty]. / Genoptraening efter total knaealloplastik.

The short- and long-term benefits of post-discharge physiotherapy regimens after total knee arthroplasty are debatable. A national survey including hospitals in Denmark that perform total knee arthroplasty showed a large variability in indication and regimen for post-knee arthroplasty rehabilitation. Since hospital stay duration has decreased considerably, the need for post-discharge physiotherapy may also have changed. Thus, the indication for and types of rehabilitation programmes need to be studied within the context of fast-track knee arthroplasty.

Different impact of excision repair cross-complementation group 1 on survival in male and female patients with inoperable non-small-cell lung cancer treated with carboplatin and gemcitabine.

PURPOSE: The excision repair cross-complementation group 1 (ERCC1) status was assessed in patients receiving carboplatin and gemcitabine for inoperable non-small-cell lung cancer (NSCLC). We analyzed the association between the ERCC1 status and the overall survival after the chemotherapy. PATIENTS AND METHODS: We retrospectively identified 163 patients with inoperable NSCLC and sufficient tumor tissue for ERCC1 analysis, who had received carboplatin and gemcitabine as first-line treatment. Immunohistochemistry was used to assess the expression of ERCC1. RESULTS: One hundred sixty-three patients were included. Seventy (42%) were ERCC1 positive. Patients treated with carboplatin and gemcitabine and having ERCC1-negative tumors had a significantly increased survival when compared to patients with ERCC1-positive tumors (median survival, 12.0 months v 8.2 months; P = .02). This difference was mainly seen in men, where those with ERCC1-negative tumors had a significantly increased survival compared to men with ERCC1-positive tumors (median survival, 11.8 months v 7.9 months; P = .005). Conversely, women who were ERCC1 negative did not have a survival advantage over ERCC1-positive women. CONCLUSION: We confirmed previous reports that ERCC1 expression is predictive for outcome in patients treated with carboplatin and gemcitabine. Patients with ERCC1-negative tumors had an increased survival compared to patients with ERCC1-positive tumors and this difference was mainly attributable to a survival difference among men.

Keitel Functional Test for patients with rheumatoid arthritis: translation, reliability, validity, and responsiveness.

BACKGROUND AND PURPOSE: The purpose of this study was to translate the German Keitel Functional Test (KFT) into Danish and test it for reliability, concurrent and predictive validity, and responsiveness in patients with rheumatoid arthritis (RA). METHODS: Translation of the KFT was performed according to international recommendations, and the translated version was tested twice by 2 observers for intraobserver and interobserver reliability, with a 1-week interval between assessments, in 20 patients with RA with stable disease activity. Validity was investigated by studying 2 patient groups: (1) 15 patients with long-lasting (median=6 years) active RA, tested before and after 2, 6, and 14 weeks of anti-tumor necrosis factor alpha (TNF-alpha) inhibitor therapy, and (2) 35 patients with early (median=0.25 year) RA, tested at years 0, 0.5, 1, and 2. Twenty-three patients in the early RA group also were tested at year 7. KFT, conventional clinical and biochemical markers of disease activity, and Health Assessment Questionnaire (HAQ) were used. RESULTS: The translated KFT showed good intraobserver reliability (intraclass correlation coefficients [ICC]=.90 and .95, coefficient of variation [CV]=3.5%) and interobserver reliability (ICC=.99 and .92, CV=3.5%), and the KFT correlated with several measures of disease activity and, most closely, with the HAQ. The KFT was, in contrast to clinical disease activity measures, not sensitive to changes over time. Only baseline KFT data were significantly related to functional changes over a long period of time as measured by the KFT, and only in the early RA group. DISCUSSION AND CONCLUSION: The Danish translation of the KFT showed good reliability, acceptable concurrent validity, very poor responsiveness, and inconclusive results concerning predictive validity. The results of this study do not support the use of the KFT for monitoring function in clinical practice, as an outcome measure in clinical trials, or as a predictor of functional changes.