The purpose of this study is to report a unique overgrowth syndrome and discuss the insights into the complex orthopaedic management.

Written consent to report this case was granted. The patient's condition, wrongly diagnosed as Proteus syndrome, is characterised by a genetic mutation in PIK3CA, a critical regulator of cell growth. This lead to unregulated cellular division of fibroblasts isolated to the lower limbs. The legs weighed 117 kg, with a circumference of >110 cm. In addition to lower limb overgrowth, numerous musculoskeletal and organ pathologies have been encountered since birth requiring treatment from a wide variety of healthcare specialists and basic scientists. At 32 years, the patient developed septicaemia secondary to an infected foot ulcer. Amputation had been discussed in the elective setting, however the presence of sepsis expedited surgery. The above knee amputation took 9 hours and four assistants including a plastic surgeon. A difficult dissection revealed a deep subcutaneous fatty layer that integrated with deep muscle, massive hypertrophy of cutaneous nerves and the sciatic nerve and ossification within the distal quarter of the quadriceps muscles requiring osteotomy. The lower limb osteology was grossly aberrant. The size of the amputated limb did not permit use of a tourniquet and cell salvage reintroduced 10.5 litres of blood with a further 6 units of red cells intra-operatively. The leg stump successfully took to a split-skin graft. A unique phenomenon was witnessed post-operatively whereby the stump continued to grow due to upregulation of fibroblasts secondary to trauma. Targeted genetic therapies have been successfully developed to suppress this stump growth.

This unique and unclassified overgrowth syndrome was caused by a mutation in the PIK3CA gene. Orthopaedic management of the oversized limb was complex requiring multiple surgeons and prolonged general anesthetic. A multi-disciplinary approach to this condition is required for optimizing outcomes in these patients.

Aberrant infrapatellar fat metabolism is a notable feature provoking inflammation and fibrosis in the progression of osteoarthritis (OA). Irisin, a secretory subunit of fibronectin type III domain containing 5 (FNDC5) regulate adipose morphogenesis, energy expenditure, skeletal muscle, and bone metabolism. This study aims to characterize the biological roles of Irisin signaling in an infrapatellar fat formation and OA development. Injured articular specimens were harvested from 19 patients with end-stage knee OA and 11 patients with the femoral neck fracture. Knee joints in mice that overexpressed Irisin were subjected to intra-articular injection of collagenase to provoke OA. Expressions of Irisin, adipokines, and MMPs probed with RT-quantitative PCR. Infrapatellar adiposity, articular cartilage damage, and synovial integrity verified with histomorphometry and immunohistochemistry. Infrapatellar adipose and synovial tissues instead of articular cartilage exhibited Irisin immunostaining. Human OA specimens showed 40% decline in Irisin expression than the non-OA group. In vitro, the gain of Irisin function enabled synovial fibroblasts but not chondrocytes to display minor responses to the IL-1β provocation of MMP3 and MMP9 expression. Of note, Irisin signaling reduced adipogenic gene expression and adipocyte formation of mesenchymal progenitor cells. In collagenase-mediated OA knee pathogenesis, forced FNDC5 expression in articular compromised the collagenase-induced infrapatellar adipose hypertrophy, synovial hypercellularity, and membrane hyperplasia. These adipose-regulatory actions warded off the affected knees from cartilage destruction and gait aberrance. Likewise, intra-articular injection of Irisin recombinant protein mitigated the development of infrapatellar adiposity and synovitis slowing down the progression of cartilage erosion and walking profile irregularity. Affected joints and adipocytes responded to the Irisin recombinant protein treatment by reducing the expressions of cartilage-deleterious adipokines IL-6, leptin, and adiponectin through regulating PPAR&gamma, function. Irisin dysfunction is relevant to the existence of end-stage knee OA. Irisin signaling protects from excessive adipogenesis of mesenchymal precursor cells and diminished inflammation and cartilage catabolism actions aggravated by adipocytes and synovial cells. This study sheds emerging new light on the Irisin signaling stabilization of infrapatellar adipose homeostasis and the perspective of the therapeutic potential of Irisin recombinant protein for deescalating knee OA development

The superficial zone (SFZ) of articular cartilage has unique structural and biomechanical features, and is important for joint long-term function. Previous studies have shown that TGF-β/Alk5 signaling upregulating PRG4 expression maintains articular cartilage homeostasis. However, the exact role and molecular mechanism of TGF-β signaling in SFZ of articular cartilage homeostasis are still lacking. In this study, a combination of in vitro and in vivo approaches were used to elucidate the role of Alk5 signaling in maintaining the SFZ of articular cartilage and preventing osteoarthritis initiation. Mice with inducible cartilage SFZ-specific deletion of Alk5 were generated to assess the role of Alk5 in OA development. Alterations in cartilage structure were evaluated histologically. The chondrocyte apoptosis and cell cycle were detected by TUNEL and Edu staining, respectively. Isolation, culture and treatment of SFZ cells, the expressions of genes associated with articular cartilage homeostasis and TGF-β signaling were analyzed by qRT-PCR. The effects of TGF-β/Alk5 signaling on proliferation and differentiation of SFZ cells were explored by cells count and alcian blue staining. In addition, SFZ cells isolated from C57 mice were cultured in presence of TGF-β1 or SB505124 for 7 days and transplanted subcutaneously in athymic mice. Postnatal cartilage SFZ-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. qRT-PCR and IHC results confirmed that Alk5 gene was effectively deleted in articular cartilage SFZ cells. Next, the PRG4-positive cells in articular cartilage SFZ were significantly decreased in Alk5 cKO mice compared with those in Cre-negative control mice. The mRNA expression of Aggrecan and Col2 were decreased, meanwhile, expression of Mmp13 and Adamts5 were significantly increased in articular cartilage SFZ cells of Alk5 cKO mice. In addition, Edu and TUNEL staining results revealed that slow-cell cycle cell number and increase the apoptosis positive cell in articular cartilage SFZ of Alk5 cKO mice compared with Cre-negative mice, respectively. Furthermore, all groups of SFZ cells formed ectopic solid tissue masses 1 week after transplantation. Histological examination revealed that the TGF-β1-pretreated tissues was composed of small and round cells and was positive for alcian blue staining, while the SB505124-pretreated tissue contained more hypertrophic cells though it did stain with alcian blue. TGF-β/alk5 signaling is an essential regulator of the superficial layer of articular cartilage by maintaining chondrocyte number, its differentiation properties, and lubrication function. Furthermore, it plays a critical role in protecting cartilage from OA initiation

From October 2005 to March 2014, we performed 46 arthroscopic surgeries for painful knee after knee arthroplasty. We excluded 16 cases for this study such as, unicompartmental knee arthroplasty, infection, patellar clunk syndrome, patellofemoral synovial hyperplasia, aseptic loosening, and follow-up period after arthroscopic surgery less than 6 months. Thirty cases matched the criteria. They had knee pain longer than 6 months after initial total knee arthroplasty (TKA), they had marked tenderness at medial and/or lateral tibiofemoral joint space, and also they complained walking pain with or without resting pain. Twenty one cases had initial TKA at our institute. In consideration of total number of TKA (n=489) in the period at our institute, incident rate of painful knee after initial TKA was 4.3%. Of 30 cases, 3 cases were male, and 27 cases were female. Types of implant were 4 in cruciate retaining type, 1 in cruciate substituting type, and 25 in posterior stabilized type. Age at the arthroscopy was 72 years old (51–87 years old), and period form initial TKA to pain perception was 18 months(1 – 144 months), and period from initial TKA to arthroscopic surgery was 29 months (6 – 125 months), and follow-up period after arthroscopy was 36 months (6 – 93 months). All arthroscopic debridement were performed through 3 portals, anteromedial, anterolateral, and proximal superomedial portal. Scar tissue impingements more than 5 mm wide were found in 87% of the cases both medial and lateral femorotibial joint spaces. Infrapatellar fat pad were covered with whitish scar tissue in all cases, and the scar tissue were connecting with the scar tissue which found at medial or lateral femorotibial joint spaces. We removed all scar tissue with motorized shaver or punches. At final follow-up, complete pain free in 63%, marked improvement in 3%, half improvement in 20%, slight improvement in 3%, and no change in 10% of the cases. Previously in the literatures, two reasons of the pain after total knee arthroplasty had been reported, patellar clunk syndrome, and patellar synovial hyperplasia. All cases reported this study had marked tenderness at tibiofemoral joint space. It was difficult to explain the tenderness by previously reported pathological mechanisms. We had to find another pathological mechanism to explain the pain of our cases. Painful knee due to scar tissue formation known as “infrapatellar contracture syndrome” after anterior cruciate ligament reconstruction surgery was previously reported. We hypothesized similar scar tissue formation should occur after TKA that caused painful knee. Continuity of the solid scar tissue between infrapatellar fat pad with the scar tissue at tibiofemoral joint space should be the cause of impingement at femorotibial joint even small size of scar tissue. From this study, we have to recognize that painful knee after TKA is not infrequent complication. And, if we could deny infection, and aseptic loosening in painful knee after TKA, arthroscopic debridement was good option to solve the pain. We could expect improvement of the pain more than half in 87% of cases

The detailed biomechanical mechanism of annulus fibrosus under abnormal loading is still ambiguous, especially at the micro and nano scales. This study aims to characterize the alterations of modulus at the nano scale of individual collagen fibrils in annulus fibrosus after in-situ immobilization, and the corresponding micro-biomechanics of annulus fibrosus. An immobilization model was used on the rat tail with an external fixation device. Twenty one fully grown 12-week-old male Sprague-Dawley rats were used in this study. The rats were assigned to one of three groups randomly. One group was selected to be the baseline control group with intact intervertebral discs (n=7). In the other two groups, the vertebrae were immobilized with an external fixation device that fixed four caudal vertebrae (C7-C10) for 4 and 8 weeks, respectively. Four K-wires were fixed in parallel using two aluminum alloy cuboids which do not compress or stretch the target discs. The immobilized discs were harvested and then stained with hematoxylin/eosin, scanned using atomic force microscopy to obtain the modulus at both nano and micro scales, and analyzed the gene expression with real-time quantitative polymerase chain reaction. Significance of differences between the study groups was obtained using a two-way analysis of variance (ANOVA) with Fisher's Partial Least-Squares Difference (PLSD) to analyze the combined influence of immobilization time and scanning region. Statistical significance was set at P≤0.05. Compared to the control group, the inner layer of annulus fibrosus presented significant disorder and hyperplasia after immobilization for 8 weeks, but not in the 4 week group. The fibrils in inner layer showed an alteration in elastic modulus from 91.38±20.19MPa in the intact annulus fibrosus to 110.64±15.58MPa (P<0.001) at the nano scale after immobilization for 8 weeks, while the corresponding modulus at the micro scale also underwent a change from 0.33±0.04MPa to 0.47±0.04MPa (P<0.001). The upregulation of collagen II from 1±0.03 in control to 1.22±0.03 in 8w group (P = 0.003) was induced after immobilization, while other genes expression showed no significant alteration after immobilization for both 4 and 8 weeks compared to the control group (P>0.05). The biomechanical properties at both nano and micro scales altered in different degrees between inner and outer layers in annulus fibrosus after immobilization for different times. Meanwhile, the fibril arrangement disorder and the upregulation of collagen II in annulus fibrosus were observed using hematoxylin/eosin staining and real-time RT-PCR, respectively. These results indicate that immobilization not only influenced the individual collagen fibril at the nano scale, but also suggested alterations of micro-biomechanics and cell response. This work provides a better understanding of IVD degeneration after immobilization and benefits to the clinical treatment related to disc immobilization

Patellofemoral complaints are the common and nagging problem after total knee arthroplasty. Crepitus occurs in 5% to over 20% of knee arthroplasty procedures depending on the type of implant chosen. It is caused by periarticular scar formation with microscopic and gross findings indicating inflammatory fibrous hyperplasia. Crepitus if often asymptomatic and not painful, but in some cases can cause pain. Patella “Clunk Syndrome” is less common and represents when the peripatella scarring is abundant and forms a nodule which impinges and “catches” on the implant's intercondylar notch. Patella Clunk was more common with early PS designs due to short trochlear grooves with sharp transition into the intercondylar notch. Clunks are very infrequent with modern PS implants. This syndrome has been reported in CR implants as well. Thorough debridement of the synovium and scarring at the time of arthroplasty is thought to reduce the occurrence of crepitus and clunks. Larger patella with better coverage of the cut bone may also be helpful. The diagnosis can be made on history and physical exam. X-rays are also helpful to assess patella tracking. MRI or ultrasound can be used to identify and confirm the diagnosis, but this is not mandatory. Painful crepitus and clunk syndrome that fail conservative management of NSAIDS and physical therapy may require surgery. Both crepitus and clunk can be treated with arthroscopic removal of the peripatella scar. Patella maltracking should also be assessed and treated. While recurrence may occur, it is uncommon

Introduction. When total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA) was indicated for the patient, it is important to perform the exact preoperative planning. Conventionally we created the plan based on the Xp films and transparent acetate sheets. Recntly, the digital radiographs and templating systems were introduced in hospitals and utilized for the preoperative planning. The purpose of this study is to investigate the accuracy of the digital templating by comparing the size of the implants between those chosen by the planning and those actually selected during the operation. Materials and methods. We investigated the plans of 715 knees with TKAs and 238 knees with UKAs between 2010 and 2014. There were 89 men and 438 women with average age of 72.1. There were 867 osteoarthritis, 46 rheumatoid arthritis, 39 osteonecrosis and 1 revision TKA. We created the preoperative planning using Electronic Picture and Communication system (PACS) and templating system (Advanced Case Plan 2.2 / Stryker). [Fig. 1] During the operation we have checked the actual femoral and tibial sizes of the implants, and compared them with preoperative plannings. Results. The exact matching of the sizes of the implants between the planning and the operation with TKAs were 59.4% for the femoral components, 52.7% for the tibial components and 32.4% for both components. [Fig. 2] While those figures with UKAs were 88.7%, 67.6% and 63.0% respectively. [Fig. 3] The matching within 1 size difference of the size of the implants between the planning and the operation were 92.4% with TKAs and 95.8% with UKAs. Discussion. Our study suggested that the digital templating of the TKAs and UKAs had satisfactory accuracy to use as preoperative planning for the operation. The accuracy was better in femur than that of tibia. The difference of the accuracy indicate the probable presence of the hyperplasia of the medial tibial condyle that we cut off to get good ligamtnt balancing. The accuracy of the UKAs was better than that of TKAs. During UKAs, we initially chose the predicted size of the devise and cut the bone, and then finally select the size of the implant. While during TKAs, we measure the size of the bone and then cut the bone. This difference of the operative procedure may result in the higher accuracy of UKAs. We conclude that digital templating for preoperative planning of TKAs and UKAs had satisfactory accuracy

Patellofemoral complaints are the common and nagging problem after Total Knee Arthroplasty. Crepitus occurs in 5% to over 20% of knee arthroplasty procedure depending on the type of implant chosen. It is caused by periarticular scar formation with microscopic and gross findings indicating inflammatory fibrous hyperplasia. Crepitus if often asymptomatic and not painful, but in some cases can cause pain. Patella “Clunk Syndrome” is less common and represents a when the peripatella scarring is abundant and forms a nodule which impinges and “catches” on the implants intercondylar notch. Patella Clunk was more common with early PS designs due to short trochlear grooves with sharp transition into the intercondylar notch. Clunks are very infrequent with modern PS implants. This Syndrome has been reported in CR implants as well. Thorough debridement of the synovium and scarring at the time of Arthroplasty is thought to reduce the occurrence of crepitus and clunks. Larger patella with better coverage of the cut bone may also be helpful. The diagnosis can be made on history and physical exam. X-rays are also helpful to assess patella tracking. MRI or ultrasound can be used to identify and confirm the diagnosis but this is not mandatory. Painful crepitus and clunk syndrome that fail conservative management of NSAIDS and physical therapy may require surgery. Both crepitus and clunk can be treated with arthroscopic removal of the peripatella scar. Patella maltracking should also be assessed and treated. While recurrence may occur it is uncommon

To progress to a same day surgery program for arthroplasty, it is important that we examine and resolve the issues of why patients stay in the hospital. The number one reason is fear and anxiety for the unknown and for surgical pain. The need for hospital stay is also related to risk arising from comorbidities and medical complications. Patients also need an extended stay to manage the side effects of our treatment, including after-effects of narcotics and anesthesia, blood loss, and surgical trauma. The process begins pre-operatively with an appropriate orthopaedic assessment of the patient and determination of the need for surgery. The orthopaedic team must motivate the patient, and ensure that the expectations of the patient, family and surgeon are aligned. In conjunction with our affiliated hospitalist group that performs almost all pre-admission testing, we have established guidelines for patient selection for outpatient arthroplasty. The outpatient surgical candidate must have failed conservative measures, must have appropriate insurance coverage, and must be functionally independent. Previous or ongoing comorbidities that contraindicate the outpatient setting include: cardiac – prior revascularization, congestive heart failure, or valve disease; pulmonary – chronic obstructive pulmonary disease, or home use of supplemental oxygen; untreated obstructive sleep apnea – BMI >40 kg/m2; renal disease – hemodialysis or severely elevated serum creatinine; gastrointestinal – history or post-operative ileus or chronic hepatic disease; genitourinary – history of urinary retention or severe benign prostatic hyperplasia; hematologic – chronic Coumadin use, coagulopathy, anemia with hemoglobin <13.0 g/dl, or thrombophilia; neurological – history of cerebrovascular accident or history of delirium or dementia; solid organ transplant. Pre-arthroplasty rehabilitation prepares the patient for peri-operative protocols. Patients meet with a physical therapist and are provided with extensive educational materials before surgery to learn the exercises they will need for functional recovery. Enhancement of our peri-operative pain management protocols has resulted in accelerated rehabilitation. The operative intervention must be smooth and efficient, but not hurried. Less invasive approaches and techniques have been shown to decrease pain, reduce length of stay, and improve outcomes, especially in the short term. In 2014, 385 primary partial knee arthroplasty procedures (7 patellofemoral replacement, 13 lateral, and 365 medial) were performed by the author and his 3 associates at an outpatient surgery center. Of those, 348 (95%) went home the same day while 17 (5%) required an overnight stay, with 11 for convenience related to travel distance or later operative time and 6 for medical issues. Outpatient arthroplasty is safe, it's better for us and our patients, and it is here now. In an outpatient environment the surgeon actually spends more time with the patients and family in a friendly environment. Patients feel safe and well cared for, and are highly satisfied with their arthroplasty experience