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The Bone & Joint Journal
Vol. 103-B, Issue 6 Supple A | Pages 87 - 93
1 Jun 2021
Chalmers BP Elmasry SS Kahlenberg CA Mayman DJ Wright TM Westrich GH Imhauser CW Sculco PK Cross MB

Aims. Surgeons commonly resect additional distal femur during primary total knee arthroplasty (TKA) to correct a flexion contracture, which leads to femoral joint line elevation. There is a paucity of data describing the effect of joint line elevation on mid-flexion stability and knee kinematics. Thus, the goal of this study was to quantify the effect of joint line elevation on mid-flexion laxity. Methods. Six computational knee models with cadaver-specific capsular and collateral ligament properties were implanted with a posterior-stabilized (PS) TKA. A 10° flexion contracture was created in each model to simulate a capsular contracture. Distal femoral resections of + 2 mm and + 4 mm were then simulated for each knee. The knee models were then extended under a standard moment. Subsequently, varus and valgus moments of 10 Nm were applied as the knee was flexed from 0° to 90° at baseline and repeated after each of the two distal resections. Coronal laxity (the sum of varus and valgus angulation with respective maximum moments) was measured throughout flexion. Results. With + 2 mm resection at 30° and 45° of flexion, mean coronal laxity increased by a mean of 3.1° (SD 0.18°) (p < 0.001) and 2.7° (SD 0.30°) (p < 0.001), respectively. With + 4 mm resection at 30° and 45° of flexion, mean coronal laxity increased by 6.5° (SD 0.56°) (p < 0.001) and 5.5° (SD 0.72°) (p < 0.001), respectively. Maximum increased coronal laxity for a + 4 mm resection occurred at a mean 15.7° (11° to 33°) of flexion with a mean increase of 7.8° (SD 0.2°) from baseline. Conclusion. With joint line elevation in primary PS TKA, coronal laxity peaks early (about 16°) with a maximum laxity of 8°. Surgeons should restore the joint line if possible; however, if joint line elevation is necessary, we recommend assessment of coronal laxity at 15° to 30° of knee flexion to assess for mid-flexion instability. Further in vivo studies are warranted to understand if this mid-flexion coronal laxity has negative clinical implications. Cite this article: Bone Joint J 2021;103-B(6 Supple A):87–93


The Bone & Joint Journal
Vol. 105-B, Issue 12 | Pages 1265 - 1270
1 Dec 2023
Hurley ET Sherman SL Chahla J Gursoy S Alaia MJ Tanaka MJ Pace JL Jazrawi LM

Aims. The aim of this study was to establish consensus statements on medial patellofemoral ligament (MPFL) reconstruction, anteromedialization tibial tubercle osteotomy, trochleoplasty, and rehabilitation and return to sporting activity in patients with patellar instability, using the modified Delphi process. Methods. This was the second part of a study dealing with these aspects of management in these patients. As in part I, a total of 60 surgeons from 11 countries contributed to the development of consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered unanimous. Results. Of 41 questions and statements on patellar instability, none achieved unanimous consensus, 19 achieved strong consensus, 15 achieved consensus, and seven did not achieve consensus. Conclusion. Most statements reached some degree of consensus, without any achieving unanimous consensus. There was no consensus on the use of anchors in MPFL reconstruction, and the order of fixation of the graft (patella first versus femur first). There was also no consensus on the indications for trochleoplasty or its effect on the viability of the cartilage after elevation of the osteochondral flap. There was also no consensus on postoperative immobilization or weightbearing, or whether paediatric patients should avoid an early return to sport. Cite this article: Bone Joint J 2023;105-B(12):1265–1270


Bone & Joint Research
Vol. 4, Issue 8 | Pages 128 - 133
1 Aug 2015
Kuwashima U Okazaki K Tashiro Y Mizu-Uchi H Hamai S Okamoto S Murakami K Iwamoto Y

Objectives. Because there have been no standard methods to determine pre-operatively the thickness of resection of the proximal tibia in unicompartmental knee arthroplasty (UKA), information about the relationship between the change of limb alignment and the joint line elevation would be useful for pre-operative planning. The purpose of this study was to clarify the correlation between the change of limb alignment and the change of joint line height at the medial compartment after UKA. Methods. A consecutive series of 42 medial UKAs was reviewed retrospectively. These patients were assessed radiographically both pre- and post-operatively with standing anteroposterior radiographs. The thickness of bone resection at the proximal tibia and the distal femur was measured radiographically. The relationship between the change of femorotibial angle (δFTA) and the change of joint line height, was analysed. Results. The mean pre- and post-operative FTA was 180.5° (172.2° to 184.8°) and 175.0° (168.5° to 178.9°), respectively. The mean δFTA was 5.5° (2.3° to 10.1°). The joint line elevation of the tibia (JLET) was 4.4 mm (2.1 to 7.8). The δFTA was correlated with the JLET (correlation coefficient 0.494, p = 0.0009). Conclusions. This study indicated that there is a significant correlation between the change of limb alignment and joint line elevation. This observation suggests that it is possible to know the requirement of elevation of the joint line to obtain the desired correction of limb alignment, and to predict the requirement of bone resection of the proximal tibia pre-operatively. Cite this article: Bone Joint Res 2015;4:128–133


The Bone & Joint Journal
Vol. 99-B, Issue 2 | Pages 204 - 210
1 Feb 2017
Xu J Jia Y Kang Q Chai Y

Aims. To present our experience of using a combination of intra-articular osteotomy and external fixation to treat different deformities of the knee. Patients and Methods. A total of six patients with a mean age of 26.5 years (15 to 50) with an abnormal hemi-joint line convergence angle (HJLCA) and mechanical axis deviation (MAD) were included. Elevation of a tibial hemiplateau or femoral condylar advancement was performed and limb lengthening with correction of residual deformity using a circular or monolateral Ilizarov frame. Results. At a mean follow-up of 2.8 years (1.5 to 4.1), the mean HJLCA improved from 15.6° (10° to 23°) pre-operatively to 0.4° (0° to 2°). The mean MAD improved from 70.0 mm (20.1 to 118.5) pre-operatively to 9.1 mm (3 to 15). The mean tibiofemoral angle improved from 31.0° (8° to 54°) pre-operatively to 4.9° (2° to 8°). The mean limb-length discrepancy decreased from 6.3 cm (2.9 to 13.6) pre-operatively to 1.1 cm (0 to 5). All osteotomies and distraction zones healed without complications. Conclusion. The use of intra-articular corrective osteotomies combined with the Ilizarov technique allowed correction of deformities of the knee joint with satisfactory HJLCA and overall mechanical axis in six patients with a good functional and cosmetic outcome in the short term. Cite this article: Bone Joint J 2017;99-B:204–10


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1065 - 1070
1 Aug 2011
Tanavalee A Honsawek S Rojpornpradit T Sakdinakiattikoon M Ngarmukos S

We compared inflammation in the knee after total knee replacement (TKR) for primary osteoarthritis between two groups of patients undergoing joint replacement with and without synovectomy. A total of 67 patients who underwent unilateral TKR were randomly divided into group I, TKR without synovectomy, and group II, TKR with synovectomy. Clinical outcomes, serial serum inflammatory markers (including interleukin-6 (IL-6), CRP and ESR) and the difference in temperature of the skin of the knee, compared with the contralateral side, were sequentially evaluated until 26 weeks after surgery. Pre-operatively, there were no statistically different clinical parameters between groups I and II. At the 26-week follow-up, both groups had a similarly significantly improved American Knee Society clinical score (p < 0.001) and functional score (p < 0.001) with no differences between the groups. Similar changes in serial inflammatory markers were found in both groups, including mean peak levels of IL-6 (189 pg/ml (. sd. 53.4) versus 201 pg/ml (. sd. 49.4) for groups I and II, respectively) and CRP (91 mg/L (. sd. 24.1) versus 88 mg/L (. sd. 23.4), respectively) on the first post-operative day, returning to pre-operative values at two and six weeks, respectively. The mean peak level of ESR for the respective two groups was 46 mm/hr versus 48 mm/hr at two weeks, which had still not returned to its pre-operative mean value at 26 weeks. The elevation in the skin temperature appeared to mirror the peak elevation of the ESR, with a range of 2.5° C to 4.5° C with some reduction at 26 weeks but still exceeding the pre-operative value. We concluded that synovectomy at the time of TKR does not provide any benefit to the clinical outcome or shorten the duration of the inflammatory response after surgery


The Bone & Joint Journal
Vol. 98-B, Issue 1_Supple_A | Pages 84 - 88
1 Jan 2016
Vince K

The term mid-flexion instability has entered the orthopaedic literature as a concept, but has not been confirmed as a distinct clinical entity. The term is used freely, sometimes as a synonym for flexion instability. However, the terms need to be clearly separated. A cadaver study published in 1990 associated joint line elevation with decreased stability at many angles of flexion, but that model was not typical of clinical scenarios. The literature is considered and it is proposed that the more common entity of an uncorrected flexion contracture after a measured resection arthroplasty technique is more likely to produce clinical findings that suggest instability mid-flexion. It is proposed that the clinical scenario encountered is generalised instability, with the appearance of stability in full extension from tight posterior structures. This paper seeks to clarify whether mid-flexion instability exists as an entity distinct from other commonly recognised forms of instability. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):84–8


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1238 - 1247
1 Oct 2019
Soreide E Denbeigh JM Lewallen EA Thaler R Xu W Berglund L Yao JJ Martinez A Nordsletten L van Wijnen AJ Kakar S

Aims. Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function. Materials and Methods. A total of 18 New Zealand rabbits underwent bilateral anterior cruciate ligament reconstruction by autograft, FiberTape, or FiberTape-augmented autograft. Primary outcomes were biomechanical assessment (n = 17), microCT (µCT) assessment (n = 12), histological evaluation (n = 12), and quantitative polymerase chain reaction (qPCR) analysis (n = 6). Results. At eight weeks, FiberTape alone or FiberTape-augmented autograft demonstrated increased biomechanical stability compared with autograft regarding ultimate load to failure (p = 0.035), elongation (p = 0.006), and energy absorption (p = 0.022). FiberTape-grafted samples also demonstrated increased bone mineral density in the bone tunnel (p = 0.039). Histological evaluation showed integration of all grafts in the bone tunnels by new bone formation, and limited signs of inflammation overall. A lack of prolonged inflammation in all samples was confirmed by quantification of inflammation biomarkers. However, no regeneration of ligament-like tissue was observed along the suture tape materials. Except for one autograft failure, no adverse events were detected. Conclusion. Our results indicate that FiberTape increases the biomechanical performance of intra-articular ligament reconstructions in a verified rabbit model at eight weeks. Within this period, FiberTape did not adversely affect bone tunnel healing or invoke a prolonged elevation in inflammation. Cite this article: Bone Joint J 2019;101-B:1238–1247


The Bone & Joint Journal
Vol. 96-B, Issue 12 | Pages 1644 - 1648
1 Dec 2014
Abdel MP Pulido L Severson EP Hanssen AD

Instability in flexion after total knee replacement (TKR) typically occurs as a result of mismatched flexion and extension gaps. The goals of this study were to identify factors leading to instability in flexion, the degree of correction, determined radiologically, required at revision surgery, and the subsequent clinical outcomes. Between 2000 and 2010, 60 TKRs in 60 patients underwent revision for instability in flexion associated with well-fixed components. There were 33 women (55%) and 27 men (45%); their mean age was 65 years (43 to 82). Radiological measurements and the Knee Society score (KSS) were used to assess outcome after revision surgery. The mean follow-up was 3.6 years (2 to 9.8). Decreased condylar offset (p < 0.001), distalisation of the joint line (p < 0.001) and increased posterior tibial slope (p < 0.001) contributed to instability in flexion and required correction at revision to regain stability. The combined mean correction of posterior condylar offset and joint line resection was 9.5 mm, and a mean of 5° of posterior tibial slope was removed. At the most recent follow-up, there was a significant improvement in the mean KSS for the knee and function (both p < 0.001), no patient reported instability and no patient underwent further surgery for instability. . The following step-wise approach is recommended: reduction of tibial slope, correction of malalignment, and improvement of condylar offset. Additional joint line elevation is needed if the above steps do not equalise the flexion and extension gaps. Cite this article: Bone Joint J 2014;96-B:1644–8


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 622 - 634
1 Jun 2023
Simpson CJRW Wright E Ng N Yap NJ Ndou S Scott CEH Clement ND

Aims

This systematic review and meta-analysis aimed to compare the influence of patellar resurfacing following cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasty (TKA) on the incidence of anterior knee pain, knee-specific patient-reported outcome measures, complication rates, and reoperation rates.

Methods

A systematic review of MEDLINE, PubMed, and Google Scholar was performed to identify randomized controlled trials (RCTs) according to search criteria. Search terms used included: arthroplasty, replacement, knee (Mesh), TKA, prosthesis, patella, patellar resurfacing, and patellar retaining. RCTs that compared patellar resurfacing versus unresurfaced in primary TKA were included for further analysis. Studies were evaluated using the Scottish Intercollegiate Guidelines Network assessment tool for quality and minimization of bias. Data were synthesized and meta-analysis performed.


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 28 - 37
1 Jan 2024
Gupta S Sadczuk D Riddoch FI Oliver WM Davidson E White TO Keating JF Scott CEH

Aims

This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults.

Methods

This is a retrospective cohort study of 182 displaced TPFs in 180 patients aged ≥ 60 years, over a 12-year period with a minimum follow-up of one year. The mean age was 70.7 years (SD 7.7; 60 to 89), and 139/180 patients (77.2%) were female. Radiological assessment consisted of fracture classification; pre-existing knee osteoarthritis (OA); reduction quality; loss of reduction; and post-traumatic OA. Fracture depression was measured on CT, and the volume of defect estimated as half an oblate spheroid. Operative management, complications, reoperations, and mortality were recorded.


The Bone & Joint Journal
Vol. 96-B, Issue 11 | Pages 1503 - 1509
1 Nov 2014
Ritter MA Davis KE Small SR Merchun JG Farris A

The relationship between post-operative bone density and subsequent failure of total knee replacement (TKR) is not known. This retrospective study aimed to determine the relationship between bone density and failure, both overall and according to failure mechanism. All 54 aseptic failures occurring in 50 patients from 7760 consecutive primary cemented TKRs between 1983 and 2004 were matched with non-failing TKRs, and 47 failures in 44 patients involved tibial failures with the matching characteristics of age (65.1 for failed and 69.8 for non-failed), gender (70.2% female), diagnosis (93.6% OA), date of operation, bilaterality, pre-operative alignment (0.4 and 0.3 respectively), and body mass index (30.2 and 30.0 respectively). In each case, the density of bone beneath the tibial component was assessed at each follow-up interval using standardised, calibrated radiographs. Failing knees were compared with controls both overall and, as a subgroup analysis, by failure mechanism. Knees were compared with controls using univariable linear regression. Significant and continuous elevation in tibial density was found in knees that eventually failed by medial collapse (p < 0.001) and progressive radiolucency (p < 0.001) compared with controls, particularly in the medial region of the tibia. Knees failing due to ligamentous instability demonstrated an initial decline in density (p = 0.0152) followed by a non-decreasing density over time (p = 0.034 for equivalence). Non-failing knees reported a decline in density similar to that reported previously using dual-energy x-ray absorptiometry (DEXA). Differences between failing and non-failing knees were observable as early as two months following surgery. This tool may be used to identify patients at risk of failure following TKR, but more validation work is needed. Cite this article: Bone Joint J 2014;96-B:1503–9


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1062 - 1066
1 Dec 2021
Krasin E Gold A Morgan S Warschawski Y

Aims

Hereditary haemochromatosis is a genetic disorder that is caused by several known mutations in the human homeostatic iron regulator protein (HFE) gene. Abnormal accumulation of iron causes a joint disease that resembles osteoarthritis (OA), but appears at a relatively younger age and is accompanied by cirrhosis, diabetes, and injury to other organs. Increased serum transferrin saturation and ferritin levels are known markers of haemochromatosis with high positive predictive values.

Methods

We have retrospectively analyzed the iron studies of a cohort of 2,035 patients undergoing knee joint arthroplasty due to OA.


Bone & Joint Open
Vol. 2, Issue 8 | Pages 576 - 582
2 Aug 2021
Fuchs M Kirchhoff F Reichel H Perka C Faschingbauer M Gwinner C

Aims

Current guidelines consider analyses of joint aspirates, including leucocyte cell count (LC) and polymorphonuclear percentage (PMN%) as a diagnostic mainstay of periprosthetic joint infection (PJI). It is unclear if these parameters are subject to a certain degree of variability over time. Therefore, the aim of this study was to evaluate the variation of LC and PMN% in patients with aseptic revision total knee arthroplasty (TKA).

Methods

We conducted a prospective, double-centre study of 40 patients with 40 knee joints. Patients underwent joint aspiration at two different time points with a maximum period of 120 days in between these interventions and without any events such as other joint aspirations or surgeries. The main indications for TKA revision surgery were aseptic implant loosening (n = 24) and joint instability (n = 11).


Bone & Joint Research
Vol. 11, Issue 1 | Pages 32 - 39
27 Jan 2022
Trousdale WH Limberg AK Reina N Salib CG Thaler R Dudakovic A Berry DJ Morrey ME Sanchez-Sotelo J van Wijnen A Abdel MP

Aims

Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release.

Methods

A total of 24 rabbits underwent contracture-forming surgery with knee immobilization followed by remobilization surgery at eight weeks. At remobilization, one cohort underwent capsular release (n = 12), while the other cohort did not (n = 12). Both groups were divided into two subcohorts (n = 6 each) – one receiving IA injections of celecoxib, and the other receiving injections of vehicle solution (injections every day for two weeks after remobilization). Passive extension angle (PEA) was assessed in live rabbits at 10, 16, and 24 weeks, and disarticulated limbs were analyzed for capsular stiffness at 24 weeks.


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 34 - 44
1 Jan 2022
Beckers L Dandois F Ooms D Berger P Van Laere K Scheys L Vandenneucker H

Aims

Higher osteoblastic bone activity is expected in aseptic loosening and painful unicompartmental knee arthroplasty (UKA). However, insights into normal bone activity patterns after medial UKAs are lacking. The aim of this study was to identify the evolution in bone activity pattern in well-functioning medial mobile-bearing UKAs.

Methods

In total, 34 patients (13 female, 21 male; mean age 62 years (41 to 79); BMI 29.7 kg/m2 (23.6 to 42.1)) with 38 medial Oxford partial UKAs (20 left, 18 right; 19 cementless, 14 cemented, and five hybrid) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively, and at one and two years postoperatively. Changes in mean osteoblastic activity were investigated using a tracer localization scheme with volumes of interest (VOIs), reported by normalized mean tracer values. A SPECT/CT registration platform additionally explored cortical tracer evolution in zones of interest identified by previous experimental research.


Bone & Joint Research
Vol. 10, Issue 6 | Pages 363 - 369
1 Jun 2021
MacDonald DRW Neilly DW Elliott KE Johnstone AJ

Aims

Tourniquets have potential adverse effects including postoperative thigh pain, likely caused by their ischaemic and possible compressive effects. The aims of this preliminary study were to determine if it is possible to directly measure intramuscular pH in human subjects over time, and to measure the intramuscular pH changes resulting from tourniquet ischaemia in patients undergoing knee arthroscopy.

Methods

For patients undergoing short knee arthroscopic procedures, a sterile calibrated pH probe was inserted into the anterior fascial compartment of the leg after skin preparation, but before tourniquet inflation. The limb was elevated for three minutes prior to tourniquet inflation to 250 mmHg or 300 mmHg. Intramuscular pH was recorded at one-second intervals throughout the procedure and for 20 minutes following tourniquet deflation. Probe-related adverse events were recorded.


The Bone & Joint Journal
Vol. 102-B, Issue 11 | Pages 1527 - 1534
3 Nov 2020
Orita K Minoda Y Sugama R Ohta Y Ueyama H Takemura S Nakamura H

Aims

Vitamin E-infused highly cross-linked polyethylene (E1) has recently been introduced in total knee arthroplasty (TKA). An in vitro wear simulator study showed that E1 reduced polyethylene wear. However there is no published information regarding in vivo wear. Previous reports suggest that newly introduced materials which reduce in vitro polyethylene wear do not necessarily reduce in vivo polyethylene wear. To assist in the evaluation of the newly introduced material before widespread use, we established an in vivo polyethylene wear particle analysis for TKA. The aim of this study was to compare in vivo polyethylene wear particle generation between E1 and conventional polyethylene (ArCom) in TKA.

Methods

A total of 34 knees undergoing TKA (17 each with ArCom or E1) were investigated. Except for the polyethylene insert material, the prostheses used for both groups were identical. Synovial fluid was obtained at a mean of 3.4 years (SD 1.3) postoperatively. The in vivo polyethylene wear particles were isolated from the synovial fluid using a previously validated method and examined by scanning electron microscopy.


Aims

Enhanced perioperative protocols have significantly improved patient recovery following primary total knee arthroplasty (TKA). Little has been investigated the effectiveness of these protocols for revision TKA (RTKA). We report on a matched group of aseptic revision and primary TKA patients treated with an identical pain and rehabilitation programmes.

Methods

Overall, 40 aseptic full-component RTKA patients were matched (surgical date, age, sex, and body mass index (BMI)) to a group of primary cemented TKA patients. All RTKAs had new uncemented stemmed femoral and tibial components with metaphyseal sleeves. Both groups were treated with an identical postoperative pain protocol. Patients were followed for at least two years. Knee Society Scores (KSS) at six weeks and at final follow-up were recorded for both groups.


The Bone & Joint Journal
Vol. 102-B, Issue 6 Supple A | Pages 49 - 58
1 Jun 2020
Mullaji A

Aims

The aims of this study were to determine the effect of osteophyte excision on deformity correction and soft tissue gap balance in varus knees undergoing computer-assisted total knee arthroplasty (TKA).

Methods

A total of 492 consecutive, cemented, cruciate-substituting TKAs performed for varus osteoarthritis were studied. After exposure and excision of both cruciates and menisci, it was noted from operative records the corrective interventions performed in each case. Knees in which no releases after the initial exposure, those which had only osteophyte excision, and those in which further interventions were performed were identified. From recorded navigation data, coronal and sagittal limb alignment, knee flexion range, and medial and lateral gap distances in maximum knee extension and 90° knee flexion with maximal varus and valgus stresses, were established, initially after exposure and excision of both cruciate ligaments, and then also at trialling. Knees were defined as ‘aligned’ if the hip-knee-ankle axis was between 177° and 180°, (0° to 3° varus) and ‘balanced’ if medial and lateral gaps in extension and at 90° flexion were within 2 mm of each other.


The Bone & Joint Journal
Vol. 101-B, Issue 9 | Pages 1087 - 1092
1 Sep 2019
Garceau S Warschawski Y Dahduli O Alshaygy I Wolfstadt J Backstein D

Aims

The aim of this study was to assess the effects of transferring patients to a specialized arthroplasty centre between the first and second stages (interstage) of prosthetic joint infection (PJI) of the knee.

Patients and Methods

A search of our institutional database was performed to identify patients having undergone two-stage revision total knee arthroplasty (TKA) for PJI. Two cohorts were created: continuous care (CC) and transferred care (TC). Baseline characteristics and outcomes were collected and compared between cohorts.