The tourniquet's effects on skeletal muscle during total knee arthroplasty.

This study investigates the impact of perioperative tourniquet on skeletal muscle cells during total knee arthroplasty (TKA) and its effects on the gene expression of apoptotic, inflammatory, and angiogenic pathways. The randomized controlled trial included 44 patients undergoing TKA. The patients were randomized to undergo surgery with (n = 23) or without (n = 21) tourniquet. The tourniquet was inflated before skin incision and deflated before wound closure in the tourniquet group. Biopsies from the lateral vastus muscle were obtained from both groups before wound closure and 8 weeks after surgery. The messenger ribonucleic acid (mRNA) expression and protein levels of angiopoietin-like 4 (ANGPTL4), Hypoxia-inducible Factor 1α, and Vascular Endothelial Growth Factor Alpha (VEGF-A) in the biopsies were examined by reverse transcription-quantitative polymerase chain reaction and tissue microarray, respectively. Differences in mean values (ΔCt for mRNA expression and staining positivity for protein expression) were compared with t-tests. The apoptotic marker BID and the angiogenic marker VEGF-A were significantly lower in the tourniquet group compared to the control group (p = 0.03, p = 0.047). However, there was a significant upregulation of VEGF-A 8 weeks after surgery in the tourniquet group compared to perioperative biopsies (p = 0.002), indicating persistent changes. A significant upregulation in protein expression of the angiogenic marker ANGPTL4 was found perioperatively in the tourniquet group (p = 0.02). Our results demonstrate that the angiogenic gene expression is significantly altered by the tourniquet, the effects of which might contribute to postoperative interstitial edema, increased pain, and decreased muscle strength. These effects could lead to delayed rehabilitation and ultimately reduced patient satisfaction after TKA.

Surgical approach had minor association with femoral stem migration in total hip arthroplasty: radiostereometric analysis of 61 patients after 5-year follow-up.

BACKGROUND AND PURPOSE: Total hip arthroplasty (THA) is usually performed using 1 of 3 surgical approaches: direct lateral (DLA), posterior (PA), or anterior (AA). AA is different from DLA and PA owing to limited intraoperative visibility of the femoral canal. This could affect stem positioning and therefore migration. We aimed to perform an exploratory radiostereometric analysis (RSA) study with 3 groups for surgical approach assessing stem migration up to 5 years postoperatively. PATIENTS AND METHODS: 61 patients with unilateral osteoarthritis of the hip were included. 21 patients were allocated to the DLA, 20 to the PA, and 20 to the AA group. All patients received an uncemented, collarless, double-tapered, fully hydroxyapatite-coated Profemur Gladiator stem. Migration was measured with model-based RSA. Baseline RSA was on day 1 postoperatively. The follow-ups were at day 8, at 5 weeks, and at 3, 6, 12, 24, and 60 months after surgery. Generalized linear mixed models were used to analyze maximum total point motion (MTPM) migrations. RESULTS: Group mean differences in MTPM were 0.4 mm (95% confidence interval [CI] -1.5 to 2.4) for DLA vs. PA, 1.1 mm (CI -1.0 to 3.3) for AA vs. DLA, and 1.6 mm (CI -0.8 to 3.9) for AA vs. PA, when adjusted for sex and age as covariates. 2 stems in the AA group had excessive early migration. For all stems the migrations occurred mainly within 5-week follow-up and then stabilized. CONCLUSION: At 5-year follow-up, there were no statistically significant differences in stem migration associated with the 3 surgical approaches used in this study.

The extent of first-time THA revision is not associated with patient-reported outcomes at 1-year follow-up: a study of 426 aseptic revisions.

BACKGROUND AND PURPOSE: Studies evaluating pain and patient-reported outcome measures (PROMs) related to type of revision total hip arthroplasty (rTHA) are sparse. Our aim was to compare pain, physical function, quality of life, and patient satisfaction among different types of aseptic rTHA at 1-year follow-up. PATIENTS AND METHODS: We performed a retrospective study from an institutional registry with 426 primary THAs scheduled for rTHA in a fast-track setting between 2012 and 2021. Revisions were grouped by 4 types of surgery: head and/or liner exchange, cup revision, stem revision, and cup and stem revision. Pain during mobilization and at rest (NRS 0-10), physical function (HOOS-PS and HHS) and health-related quality of life (EQ-5D) were registered preoperatively, at 3 months, and 1 year postoperatively. Patient satisfaction was surveyed at the 1-year follow-up by 2 questions related to hip function and willingness to undergo the same surgery. RESULTS: With a response rate of 85%, all outcomes improved in the 4 groups but there were neither statistical nor clinical differences between types of rTHA at 1-year follow-up. NRS pain during mobilization improved overall by 2.7 (95% confidence interval 2.3-3.1) until 1-year follow-up, both being statistically significant and clinically relevant. The improvements were mainly seen at the 3-month follow-up, with minor progress observed at 1 year. About 80% reported improved hip function and willingness to undergo the surgery again at the 1-year follow-up. CONCLUSION: Significant improvements in NRS pain and PROMS were found in all groups after rTHA, with no group differences at 1 year. This is relevant preoperative information for both clinicians and patients eligible for rTHA.

Higher Dissatisfaction Rate Following Revision Compared With Primary Total Knee Arthroplasty: 1-Year Follow-up of 2151 Primary and 235 Aseptic Revision Surgeries.

Postoperative patient satisfaction is related to preoperative expectations. Information regarding expected results following surgery is therefore important. This study evaluated patient-reported outcome measures (PROMs) and patient satisfaction up to 1 year after primary and aseptic revision total knee arthroplasty (TKA). The study included 2151 primary and 235 aseptic revision TKA surgeries conducted between 2010 and 2018. Pain, Knee Injury and Osteoarthritis Outcome Score-Physical Function-Short Form and European Quality of Life-5 Dimension surveys were recorded preoperatively and at 8 weeks and 1 year. To determine satisfaction, patients were asked to rate their knee function compared with that before surgery and to answer whether they would undergo the surgery again given their current knowledge. Patients who had primary TKA improved in all PROMs in each follow-up up to 1 year, whereas patients who had revision TKA showed improvement at 8 weeks with no further improvement at 1 year. In terms of patient satisfaction, 88% of patients in the primary TKA group reported better knee function, and 87% were willing to have the surgery again at 1 year; the proportions were lower for patients who underwent revision TKA (66% and 68%, respectively). Aseptic revision TKA demonstrates inferior PROMs compared with those of primary TKA 1 year after surgery, and more than 30% of the patients who underwent revision TKA stated that they would not have their TKA revised or were uncertain, given the outcome of the procedure. Thus, patients who are candidates for revision TKA should be informed to expect less of an improvement following revision surgery than with the primary TKA. Our findings can facilitate the shared decision-making process by surgeons and patients based on realistic expectations of surgical outcomes. [Orthopedics. 2023;46(1):e52-e57.].

The indication for aseptic revision TKA does not influence 1-year outcomes: an analysis of 178 full TKA revisions from a prospective institutional registry.

BACKGROUND AND PURPOSE: Outcomes following revision total knee arthroplasty (TKA) may depend on the indication for revision surgery. We compared pain, patient-reported outcome measures (PROMs), and patient satisfaction among different indications for an aseptic TKA revision. PATIENTS AND METHODS: This was a retrospective study of prospective data from an institutional registry of 178 primary TKAs revised between 2012 and 2020. Patients were grouped by the main reason for their revision: loosening, malposition, instability, or stiffness. Pain during mobilization and at rest (NRS 0-10), physical function (KOOS-PS and KSS), and quality of life (EQ-5D) were surveyed preoperatively and at 2 months and 1 year postoperatively. Patient satisfaction was evaluated through questions related to knee function and their willingness to undergo the same surgery again at 1-year follow-up. RESULTS: Pain and PROMs improved in all groups and did not differ statistically significantly between the 4 groups at 1-year follow-up, but equivalence for pain was not confirmed between groups. Overall, pain during mobilization improved by 2.4 (95% CI 1.9-3.0) at 1-year follow-up, which was both clinically and statistically significant. Improvements were seen within 2 months of surgery, with no further improvements seen 1 year postoperatively. Approximately 2/3 of patients reported that their knee function had improved and would undergo the same surgery again, at 1-year follow-up. CONCLUSION: Statistically significant and clinically relevant improvements in pain and PROMs were seen in all 4 revision groups 1 year after revision TKA. These results may assist clinicians and patients during preoperative counselling.

Patient-reported outcome after primary and aseptic revision hip arthroplasty: 1-year follow-up of 3,559 primary and 406 revision THAs in an institutional registry.

Background and purpose - Patient-reported outcomes (PROMs) after primary total hip arthroplasty (THA) and revision THA are important information in the preoperative shared decision-making process. We present 1-year results on pain, function, and quality of life following primary and revision THA. Patients and methods - From 2010 to 2018, 3,559 primary THA and 406 revision THAs were included in our institutional quality registry. PROMs were registered preoperatively, 3 months, and 1 year after surgery, numeric rating scale (0-10) for pain during mobilization and at rest, healthrelated quality of life (EQ-5D), and a hip-specific physical function score (HOOS-PS). 2 anchor questions were asked 1 year after surgery concerning joint function and willingness to go through surgery again. Results - There were statistically significant improvements in all PROMs at the 3-month follow-up in both groups. All PROMs improved more in the primary group relative to the revision group. 1 year after surgery, pain during mobilization was reduced with a mean change of 5.1 (SD 2.6) for primary THA and 2.9 (SD 3.0) for revision THA. 93% of primary THA patients reported both better function 1 year after surgery and that they would have gone through surgery again, compared with 78% and 79% in the revision THA group. Interpretation - Primary THA patients reported better function and more pain relief than the revision THA group 1 year after surgery. Pain during mobilization shows the most marked improvement in both groups, which is important preoperative information for patients.

Muscular strength and function after total hip arthroplasty performed with three different surgical approaches: one-year follow-up study.

BACKGROUND: Surgical approach influences short-term muscular strength, and leg-strength asymmetry has been demonstrated after total hip arthroplasty (THA). We evaluated muscular strength, physical function and patient-reported outcome measures (PROMs) up to 12 months postoperatively, in patients operated on using 3 different surgical approaches. METHODS: 60 patients scheduled for primary THA were allocated to the direct lateral (DLA), posterior (PA) or anterior (AA) approach. The following parameters were evaluated: leg press and abduction strength, pain, 6-minute walking test, Harris Hip Score and Hip disability and Osteoarthritis Outcome Score - Physical Function Shortform (HOOS-PS). RESULTS: Abduction strength in the DLA group was significantly more reduced than the PA and AA groups 12 months postoperatively (p < 0.001). A significant interleg difference in abduction (p < 0.01) and leg press (p < 0.03) persisted in all groups up to 6 months, and up to 12 months in the DLA (p < 0.05). In the AA group, interleg difference in leg press was present up to 12 months (p = 0.01). Pain scores were higher in the DLA than the AA group at 6 months (p = 0.01). Patients in the PA group had better HOOS-PS score than those in the DLA group 3 months postoperatively (p = 0.02). No intergroup differences in pain or PROMs were found 12 months postoperatively. CONCLUSION: Patients operated via the DLA had reduced muscular strength, HOOS-PS scores and higher pain scores than those who underwent PA and AA type surgery. The non-operated leg was significantly stronger than the operated leg in all groups 6 months postoperatively and this persisted up to 12 months postoperatively for the DLA and AA groups. Clinical Trial Protocol number: ClinicalTrials.gov (NCT01506024).

A randomized controlled trial on maximal strength training in 60 patients undergoing total hip arthroplasty.

Background and purpose - Total hip arthroplasty (THA) patients have reduced muscle strength after rehabilitation. In a previous efficacy trial, 4 weeks' early supervised maximal strength training (MST) increased muscle strength in unilateral THA patients <65 years. We have now evaluated muscle strength in an MST and in a conventional physiotherapy (CP) group after rehabilitation in regular clinical practice. Patients and methods - 60 primary THA patients were randomized to MST or CP between August 2015 and February 2016. The MST group trained at 85-90% of their maximal capacity in leg press and abduction of the operated leg (4 × 5 repetitions), 3 times a week at a municipal physiotherapy institute up to 3 months postoperatively. The CP group followed a training program designed by their respective physiotherapist, mainly exercises performed with low or no external loads. Patients were tested pre- 3, 6, and 12 months postoperatively. Primary outcomes were abduction and leg press strength at 3 months. Other parameters evaluated were pain, 6-min walk test, Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Score (HOOS) Physical Function Short-form score. Results - 27 patients in each group completed the intervention. MST patients were substantially stronger in leg press and abduction than CP patients 3 (43 kg and 3 kg respectively) and 6 months (30 kg and 3 kg respectively) postoperatively (p ≤ 0.002). 1 year postoperatively, no intergroup differences were found. No other statistically significant intergroup differences were found. Interpretation - MST increases muscle strength more than CP in THA patients up to 6 months postoperatively, after 3 months' rehabilitation in clinical practice. It was well tolerated by the THA patients and seems feasible to conduct within regular clinical practice.

Randomized controlled trial of maximal strength training vs. standard rehabilitation following total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) alleviates pain, but muscle strength and function is reduced for a long period postoperatively. AIM: To investigate whether maximal strength training (MST) is more effective in improving muscle strength than standard rehabilitation (SR) after TKA. DESIGN: A randomized, controlled study. SETTING: Community physical therapy centers and University hospital research department. POPULATION: Forty-one adults <75 years with primary, unilateral osteoarthritis of the knee scheduled for TKA. METHODS: Participants were randomized to supervised MST of the lower extremities 3 times/week for 8 weeks and physiotherapy session1/week (N.=21) or to SR, including physiotherapy sessions/telephone contact 1/week and writing home exercise logs (N.=20). Maximal strength in leg press and knee extension, 6-minute walk test, patient-reported functional outcome score and pain were assessed preoperatively, 7 days, 10 weeks and 12 months postoperatively. RESULTS: The MST group exceeded preoperative levels of muscle strength in leg press and knee extension by 37% and 43%, respectively at 10 weeks' follow-up, and the increase was higher than in the SR group (P≤0.001). Strength differences persisted up to 12-months follow-up. At 12 months, both groups recovered to normative levels in the 6-Minute Walk Test, with no statistically significantly difference between the groups. CONCLUSIONS: Participants undergoing MST experienced superior increases in leg press and knee extension muscle strength compared with those managed with SR from 7-day to 10-week follow-up. The difference in muscle strength was maintained at 12-month follow-up. No differences in functional performance were found at any time-point. CLINICAL REHABILITATION IMPACT: Exercises after TKA should be performed with high intensity and target the operated leg specifically.

Load transfer in the proximal femur and primary stability of a cemented and uncemented femoral stem: An experimental study on cadaver femurs.

There are principally two fixation methods in total hip arthroplasty, cemented and uncemented. Both methods have in general good long-time survival. Studies comparing cemented and uncemented femoral stems indicate that the cemented stems perform somewhat better, at least in the elderly population. The aim of this study was to compare load transfer and the initial micromotion pattern for an uncemented and a cemented stem. A total of 12 human cadavers were tested in a hip simulator during single leg and stair climbing. Strain was measured on the proximal femur before and after implantation of the prostheses, and the values were presented as percentage of physiological strain. The micromovements between the stem and bone were measured and a total point motion was calculated. The results showed small statistically significant differences between the fixation methods, the largest difference being 8.1 percentage points. The uncemented stem had somewhat higher micromotion than the cemented stem, but less than 10 µm. Both stems thus had acceptable primary stability. The main finding of this study is the strain and micromotion pattern of a cemented and an uncemented stem of similar geometry is overall equal. There were small statistical significant differences between the two fixation methods regarding strain and micromotion levels. The differences are considered too small to be clinically relevant.

Muscular strength after total hip arthroplasty. A prospective comparison of 3 surgical approaches.

BACKGROUND AND PURPOSE: Minimizing the decrease in muscular strength after total hip arthroplasty (THA) might allow patients to recover faster. We evaluated muscular strength in patients who were operated on using 3 surgical approaches. PATIENTS AND METHODs: In a prospective cohort study, 60 patients scheduled for primary THA were allocated to the direct lateral, posterior, or anterior approach. Leg press and abduction strength were evaluated 2 weeks or less preoperatively, 2 and 8 days postoperatively, and at 6-week and 3-month follow-up. RESULTS: Differences in maximal strength change were greatest after 2 and 8 days. The posterior and anterior approaches produced less decrease in muscular strength than the direct lateral approach. 6 weeks postoperatively, the posterior approach produced greater increase in muscular strength than the direct lateral approach, and resulted in a greater increase in abduction strength than the anterior approach. At 3-month follow-up, no statistically significant differences between the groups were found. The operated legs were 18% weaker in leg press and 15% weaker in abduction than the unoperated legs, and the results were similar between groups. INTERPRETATION: The posterior and anterior approaches appeared to have the least negative effect on abduction and leg press muscular strength in the first postoperative week; the posterior approach had the least negative effect, even up to 6 weeks postoperatively. THA patients have reduced muscle strength in the operated leg (compared to the unoperated leg) 3 months after surgery.

Perioperative local infiltration anesthesia with ropivacaine has no effect on postoperative pain after total hip arthroplasty.

BACKGROUND AND PURPOSE: The local infiltration analgesia (LIA) technique has been widely used to reduce opioid requirements and to improve postoperative mobilization following total hip arthroplasty (THA). However, the evidence for the efficacy of LIA in THA is not yet clear. We determined whether single-shot LIA in addition to a multimodal analgesic regimen would reduce acute postoperative pain and opioid requirements after THA. PATIENTS AND METHODS: 116 patients undergoing primary THA under spinal anesthesia were included in this randomized, double-blind, placebo-controlled trial. All patients received oral opioid-sparing multimodal analgesia: etoricoxib, acetaminophen, and glucocorticoid. The patients were randomized to receive either 150 mL ropivacaine (2 mg/mL) and 0.5 mL epinephrine (1 mg/mL) or 150 mL 0.9% saline. Rescue analgesic consisted of morphine and oxycodone as needed. The primary endpoint was pain during mobilization in the recovery unit. Secondary endpoints were pain during mobilization on the day after surgery and total postoperative opioid requirements on the first postoperative day. RESULTS: The levels of pain during mobilization-both in the recovery unit and on the day after surgery-and consumption of opioids on the first postoperative day were similar in the 2 groups. INTERPRETATION: LIA did not provide any extra analgesic effect after THA over and above that from the multimodal analgesic regimen used in this study.

1-year follow-up of 920 hip and knee arthroplasty patients after implementing fast-track.

BACKGROUND: Fast-track has become a well-known concept resulting in improved patient satisfaction and postoperative results. Concerns have been raised about whether increased efficiency could compromise safety, and whether early hospital discharge might result in an increased number of complications. We present 1-year follow-up results after implementing fast-track in a Norwegian university hospital. METHODS: This was a register-based study of 1,069 consecutive fast-track hip and knee arthroplasty patients who were operated on between September 2010 and December 2012. Patients were followed up until 1 year after surgery. RESULTS: 987 primary and 82 revision hip or knee arthroplasty patients were included. 869 primary and 51 revision hip or knee patients attended 1-year follow-up. Mean patient satisfaction was 9.3 out of a maximum of 10. Mean length of stay was 3.1 days for primary patients. It was 4.2 days in the revision hip patients and 3.9 in the revision knee patients. Revision rates until 1-year follow-up were 2.9% and 3.3% for primary hip and knee patients, and 3.7% and 7.1% for revision hip and knee patients. Function scores and patient-reported outcome scores were improved in all groups. INTERPRETATION: We found reduced length of stay, a high level of patient satisfaction, and low revision rates, together with improved health-related quality of life and functionality, when we introduced fast-track into an orthopedic department in a Norwegian university hospital.

The migration pattern of the Charnley femoral stem: a five-year follow-up RSA study in a well-functioning patient group.

BACKGROUND: Implant stability is considered vital to long-time implant survival in total hip arthroplasty (THA), since loose implants are reported to be a major cause of hip revision. There is an association between early implant micromotion and increased risk of revision. More implant-specific data are needed to establish acceptable levels of early implant movement. MATERIALS AND METHODS: Thirty-five patients (36 hips) undergoing Charnley THA were followed with repeated clinical, radiographic, and radiostereometric analysis (RSA) over 5 years. Twenty-three patients attended 5 years postoperatively. RESULTS: The patient group was well functioning based on the radiological and clinical evaluations. The stems constantly moved up to 5 years postoperatively, with subsidence, retroversion, and varus tilt, based on the RSA. CONCLUSION: Continuous movement of the Charnley stem was observed up to 5 years postoperatively in a well-functioning patient group. The migration data presented herein could be useful when defining acceptable migration limits for certain types of cemented femoral stems.

Unilateral vs. bilateral total hip arthroplasty - the influence of medial femoral head offset and effects on strength and aerobic endurance capacity.

The purpose of the present study was to determine whether unilaterally operated total hip arthroplasty (THA) patients were superior to bilaterally operated THA patients with respect to aerobic endurance capacity, muscle strength and gait patterns 3-5 years after surgery, and to what extent medial femoral head offset (FO) influenced hip abductor strength. 10 unilaterally operated THA patients with normal FO (UNO), 10 bilaterally operated THA patients with normal FO (BNO) and 10 bilaterally operated THA patients with abnormal offset (BDO) participated in the study. Improved muscle strength in the healthy leg of the UNO did not result in differences compared to the BNO and the BDO in work efficiency, gait patterns or maximal oxygen consumption (VO2max ) A reduced FO in the BDO did not result in lower hip abduction strength compared to the BNO. However, a correlation between reduced FO and low abduction strength was found in the BDO (r=0.866, p=0.001). Future focus should be on the quality of rehabilitation.

A prospective randomised radiostereometric analysis trial of SmartSet HV and Palacos R bone cements in primary total hip arthroplasty.

BACKGROUND: Introduction of new bone cements into clinical practice should include radiostereometric studies. MATERIALS AND METHODS: A prospective randomised radiostereometric study was performed, comparing SmartSet HV and Palacos R acrylic bone cements (without antibiotics) using third-generation cementing techniques in primary total hip arthroplasty. Thirty-five patients (36 hips) undergoing Charnley total hip arthroplasty were randomised to receive either of the two cements and were followed with repeated clinical, radiographic and radiostereometric examinations over 24 months. Twenty-seven patients (28 hips) attended 2 years postoperatively. RESULTS: The mean distal translation observed was -0.15 mm for SmartSet HV and -0.16 mm for Palacos R. The mean rotation around the longitudinal axis was 0.9 degrees for SmartSet HV and 1.2 degrees for Palacos R. The Merle d'Aubigne Postel score was the maximum of 18 points for all patients in both groups. CONCLUSIONS: No statistically significant difference in stem fixation with use of SmartSet HV and Palacos R was found at 2-year follow-up.

Early maximal strength training is an efficient treatment for patients operated with total hip arthroplasty.

UNLABELLED: Husby VS, Helgerud J, Bjørgen S, Husby OS, Benum P, Hoff J. Early maximal strength training is an efficient treatment for patients operated with total hip arthroplasty. OBJECTIVE: To compare muscle strength, work efficiency, gait patterns, and quality of life in patients undergoing total hip arthroplasty (THA) randomly assigned to either maximal strength training or a conventional rehabilitation program. DESIGN: A randomized controlled study. SETTING: Research laboratory, rehabilitation center, and physical therapy clinic. PARTICIPANTS: Patients (N=24) with osteoarthritis as the main reason for THA were randomly assigned to perform maximal strength training (n=12) or conventional rehabilitation (n=12). INTERVENTIONS: The maximal strength training group (STG) performed maximal strength training in leg press and abduction with the operated leg only 5 times a week for 4 weeks in addition to the conventional rehabilitation program. The conventional rehabilitation group (CRG) received supervised physical therapy 3 to 5 times a week for 4 weeks. MAIN OUTCOME MEASURES: 1-repetition maximum (1RM) leg press strength, 1RM abduction strength, rate of force development (RFD), work efficiency, gait patterns, and quality of life. RESULTS: 1RM increased in the bilateral leg press (P<.002) and in the operated leg separately (P<.002) in the STG compared with the CRG. 1RM abduction strength in the operated leg (P<.002) and the healthy leg (P<.002) increased in the STG compared with the CRG. RFD increased in the STG compared with the CRG (P(g)=.030), followed by a trend towards increased peak force in the STG (P(g)=.053) (P(g) = probability for differences between groups). Work efficiency tended to improve in the STG compared with the CRG (P=.065). No differences in gait patterns were revealed between the groups after the training intervention. CONCLUSIONS: Early maximal strength training 1 week postoperatively is feasible and an efficient treatment to regain muscular strength for patients who have undergone THA, demonstrated by a significantly larger increase in muscular strength and a trend towards a better work efficiency in the STG compared with the CRG.