Improvise, Adapt & Overcome: Successful Surgery-Sparing Prosthetic Hip Infection Antibiotic Suppression During COVID-19 Crisis.

CASE: A 79-year-old active male presented during the first COVID-19 pandemic surgery moratorium with late Staphylococcus lugdunensis periprosthetic total hip arthroplasty infection. Due to the unprecedented circumstances, novel treatment of IV and oral antibiotic suppression was trialed without preceding surgical intervention. At latest follow-up, the patient has two-year revision-free survival with normalization of inflammatory markers and MRI findings, and resolution of clinical symptoms. CONCLUSION: We report a novel surgery-sparing treatment for periprosthetic hip infection. Judicious caution should be used in the application of similar therapies, as host and organism characteristics likely contributed substantially to the success of this case.

Long-term functional and structural outcome of rotator cuff repair in patients 60 years old or less.

Background: The long-term outcomes of rotator cuff repair (RCR) have not been well studied. The purpose of this study was to evaluate long-term functional and structural outcomes after RCR in younger patients. Methods: A total of 49 patients (34 [69%] male) with a mean age of 51 ± 6 years were evaluated preoperatively, and at short- and long-term follow-ups (minimum 15 years). There were 13 (27%) small, 17 (35%) medium, 14 (29%) large, and 5 (10%) massive tears. 15 (31%) had an acute repair of a traumatic tear. Long-term evaluation included physical examination, plain radiographs, ultrasound, and patient reported outcome measures (PROMs) (visual analog scale pain, Disability of Arm, Shoulder and Hand, Simple Shoulder Test, American Shoulder and Elbow Surgeons score, and Short Form-36). Statistical analysis was performed to determine associations between preoperative and intraoperative factors and long-term functional and structural outcome. Results: There were significant improvements in the mean short- and long-term PROMs compared to preoperatively that exceeded reported minimal clinically important differences and substantial clinical benefits. There was a slight decrease in the PROMs from the short-term to long-term follow-up. Male sex and traumatic rotator cuff tears were associated with better long-term outcomes. The number of medical co-morbidities was associated with worse long-term outcomes. Smaller initial tear size was associated with better long-term outcomes. There were 15 (31%) full thickness and 9 (18%) partial thickness recurrent rotator cuff tears, 17 (35%) had rotator cuff tear arthropathy (2 Hamada grade 1, 15 Hamada grade 2), 5 (10%) had revision surgery (2 revision RCR, 2 anatomic total shoulder, and 1 reverse total shoulder), and 13 (26%) had subsequent contralateral RCR. There were weak correlations between the presence of arthropathy and DASH (r = 0.34; P = .02) and visual analog scale pain (r = 0.29; P = .049). There were no significant correlations between the structural outcomes (recurrent rotator cuff tear, recurrent full thickness tear, acromiohumeral space, and critical shoulder angle,) and the PROMs. Discussion and Conclusion: Long-term follow-up of RCR in this relatively young patient cohort demonstrated substantial and durable patient reported functional outcome and improvement despite considerable structural deterioration. This suggests that while RCR does not arrest the progression of rotator cuff disease it may delay this progression and that patients adapt to the structural changes as they age.

Association of tensor fascia lata hypertrophy and fatty infiltration in the presence of abductor tendon tears: a radiographic study.

Hip abductor tendon tears of the gluteus medius and minimus are becoming a well-recognized source of pain and dysfunction, primarily in middle-age females. Like the rotator cuff, fatty infiltration (FI) can occur after tearing of these tendons. While the association of TFL hypertrophy after abductor tendon tears has been established, its association with FI has not been well studied. Our hypothesis is that hypertrophy of the TFL will be associated with FI of the abductors. All patients >18 years old undergoing primary surgical repair for a confirmed tears on MRI, without a history of prior hip surgery or osteoarthritis, were included. The following measurements were obtained from MRI: TFL cross-sectional area, TFL:sartorius volume ratio, and modified Goutallier grade of gluteus medius and minimus. Seventy patients met inclusion criteria and were divided in two groups, those with (n = 28) and those without FI (n = 42) of the abductors. The FI group was on average older (65 versus 58 years, P < 0.00016). TFL hypertrophy and TFL:sartorius volume ratio were significantly associated with FI (P= 0.00069). Following abductor tendon tear and subsequent FI, there exists significant TFL hypertrophy in patients without a prior history of hip surgery in our patient cohort.

Clinical Outcomes of Nonunions of Hindfoot and Ankle Fusions.

BACKGROUND: While nonunion after foot and ankle fusion surgery has been associated with poor outcomes, we are not aware of any longitudinal study on this subject. Thus, we prospectively evaluated the impact of nonunion on clinical outcomes of foot and ankle fusions and identified potential risk factors for nonunion after these procedures. METHODS: Using data from a randomized clinical trial on recombinant human platelet-derived growth factor-BB (rhPDGF-BB; Augment Bone Graft, BioMimetic Therapeutics), union was defined either by assessment of computed tomography (CT) scans at 24 weeks by a reviewer blinded to the type of treatment or by the surgeon's composite assessment of clinical and radiographic findings at 52 weeks and CT findings at 24 or 36 weeks. The nonunion and union groups (defined with each assessment) were then compared in terms of clinical outcome scores on the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale (AOFAS-AHS), Foot Function Index (FFI), and Short Form-12 (SF-12) as well as age, sex, body mass index (BMI), smoking status, diabetes status, work status, and arthrodesis site. RESULTS: Blinded CT assessment identified nonunion in 67 (18%) of 370 patients, and surgeon assessment found nonunion in 21 (5%) of 389 patients. Postoperatively, the nonunion group scored worse than the union group, regardless of the method used to define the nonunion, on the AOFAS-AHS and FFI, with mean differences of 10 and 12 points, respectively, when nonunion was determined by blinded CT assessment and 19 and 20 points when it was assessed by the surgeon. The nonunion group also had worse SF-12 Physical Component Summary scores. Differences between the union and nonunion groups were clinically meaningful for all outcome measures, regardless of the nonunion assessment method. The concept of an asymptomatic nonunion (i.e., imaging indicating nonunion but the patient doing well) was not supported. Patients with nonunion were more likely to be overweight, smokers, and not working. CONCLUSIONS: This prospective longitudinal study demonstrated poorer functional outcomes in patients with a nonunion after foot and ankle fusion, regardless of whether the diagnosis of nonunion was based on CT only or on combined clinical, radiographic, and CT assessment. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Importance of Sufficient Graft Material in Achieving Foot or Ankle Fusion.

BACKGROUND: Nonunion, an important complication following foot and ankle arthrodesis, causes substantial morbidity and disability. In patients undergoing hindfoot and ankle arthrodesis, autogenous bone graft (autograft) or a suitable alternative is often used to promote osseous fusion across the joint. This study assessed the importance of adequate graft material in the fusion space to achieve joint fusion during ankle and hindfoot arthrodesis. METHODS: This study used data from a previously published clinical trial of grafting material (recombinant human platelet-derived growth factor-BB with beta-tricalcium phosphate [rhPDGF-BB/ß-TCP] or autograft) for healing in hindfoot and ankle arthrodesis to correlate the amount of graft fill at 9 weeks with ultimate healing. Patients who received supplemental graft material for ankle or hindfoot arthrodesis for end-stage ankle or hindfoot arthritis were stratified according to nonunion risk factors and surgical fusion site. Patients underwent arthrodesis using standard rigid internal fixation. Graft fill was defined as "adequate" if the material occupied ≥50% of the cross-sectional area of the fusion space on a computed tomography (CT) scan made at 9 weeks. Fusion was defined as osseous bridging of ≥50% of each articulation on a CT scan made at 24 weeks. Three hundred and seventy-nine patients with 573 joints (383 managed with rhPDGF-BB/ß-TCP and 190 managed with autograft) that underwent arthrodesis had complete follow-up with 9-week and 24-week CT scans available. RESULTS: Overall, 472 (82%) of 573 joints had adequate graft fill; of those, 383 (81%) were successfully fused at 24 weeks compared with 21 (21%) of 101 joints without adequate graft fill (p < 0.0001). Absolute fusion rate differences (joints with adequate fill minus those without adequate fill) were consistent across joints (61% to 63%) and for graft materials. The overall odds ratio (OR) of successful fusion in joints with adequate graft fill compared with those without adequate graft fill was 16.4 (95% confidence interval, 9.6 to 27.9). CONCLUSIONS: This study demonstrates an association between the amount of graft material and successful hindfoot and ankle arthrodesis. Graft material filling of ≥50% of the fusion space at 9 weeks, regardless of type or origin, was associated with significantly higher fusion rates at 24 weeks. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated With rhPDGF-BB in Combination With a ß-TCP-Collagen Matrix.

BACKGROUND: Ankle and hindfoot arthrodesis is often supplemented with autograft to promote bony union. Autograft harvest can lead to increased perioperative morbidity. Purified recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot fusion. This randomized controlled trial evaluated the efficacy and safety of rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate (ß-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions. METHODS: Seventy-five patients requiring ankle or hindfoot fusion were randomized 5:1 for rhPDGF-BB/ß-TCP-collagen (treatment, n = 63) or autograft (control, n = 12). Prospective analysis included 142 autograft control subjects from another clinical trial with identical study protocols. Standardized operative and postoperative protocols were used. Patients underwent standard internal fixation augmented with autograft or 0.3 mg/mL rhPDGF-BB/ß-TCP-collagen. Radiologic, clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary outcome was joint fusion (50% or more osseous bridging on computed tomography) at 24 weeks. Secondary outcomes included radiographs, clinical healing status, visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale score, Foot Function Index score, and Short Form-12 score. Noninferiority P values were calculated. RESULTS: Complete fusion of all involved joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63 (84%) rhPDGF-BB/ß-TCP-collagen-treated patients and 100 of 154 (65%) autograft-treated patients (P < .001). Mean time to fusion was 14.3 ± 8.9 weeks for rhPDGF-BB/ß-TCP-collagen patients versus 19.7 ± 11.5 weeks for autograft patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%) rhPDGF-BB/ß-TCP-collagen patients and 120 of 154 (78%) autograft patients (P < .001). Safety-related outcomes were equivalent. Autograft controls had 2 bone graft harvest infections. CONCLUSIONS: Application of rhPDGF-BB/ß-TCP-collagen was a safe, effective alternative to autograft for ankle and hindfoot fusions, eliminating the pain and morbidity associated with autograft harvesting. LEVEL OF EVIDENCE: Level I, prospective randomized study.

Rapid-Onset Diffuse Skeletal Fluorosis from Inhalant Abuse: A Case Report.

CASE: A thirty-year-old man presented with severely debilitating left hip pain and stiffness. Radiographs demonstrated diffuse osteosclerosis and heterotopic bone formation with near ankylosis of the left hip. The patient underwent successful joint-preserving surgery to restore hip range of motion. After disclosing a history of inhalant abuse, which was confirmed by elevated serum fluoride levels, he was diagnosed with diffuse skeletal fluorosis. CONCLUSIONS: To the best of our knowledge, we present the first reported case of diffuse skeletal fluorosis caused by inhalant abuse of 1,1-difluoroethane. Skeletal fluorosis is uncommon in the United States but is important to consider in the differential diagnosis when a patient presents with otherwise unexplained joint pain and osteosclerosis.

Recombinant human platelet-derived growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/ß-TCP): an alternative to autogenous bone graft.

BACKGROUND: Joint arthrodesis employing autogenous bone graft (autograft) remains a mainstay in the treatment of many foot and ankle problems. However, graft harvest can lead to perioperative morbidity and increased cost. We tested the hypothesis that purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) homodimer combined with an osteoconductive matrix (beta-tricalcium phosphate [ß-TCP]) would be a safe and effective alternative to autograft. METHODS: A total of 434 patients were enrolled in thirty-seven clinical sites across North America in a prospective, randomized (2:1), controlled, non-inferiority clinical trial to compare the safety and efficacy of the combination rhPDGF-BB and ß-TCP with those of autograft in patients requiring hindfoot or ankle arthrodesis. Radiographic, clinical, functional, and quality-of-life end points were assessed through fifty-two weeks postoperatively. RESULTS: Two hundred and sixty patients (394 joints) underwent arthrodesis with use of rhPDGF-BB/ß-TCP. One hundred and thirty-seven patients (203 joints) underwent arthrodesis with use of autograft. With regard to the primary end point, 159 patients (61.2% [262 joints (66.5%)]) in the rhPDGF-BB/ß-TCP group and eighty-five patients (62.0% [127 joints (62.6%)]) in the autograft group were fused as determined by computed tomography at six months (p < 0.05). Clinically, 224 patients (86.2%) [348 joints (88.3%)]) in the rhPDGF-BB/ß-TCP group were considered healed at fifty-two weeks, compared with 120 patients (87.6% [177 joints (87.2%)] in the autograft group (p = 0.008). Overall, fourteen of sixteen secondary end points at twenty-four weeks and fifteen of sixteen secondary end points at fifty-two weeks demonstrated statistical non-inferiority between the groups, and patients in the rhPDGF-BB/ß-TCP group were found to have less pain and an improved safety profile. CONCLUSIONS: In patients requiring hindfoot or ankle arthrodesis, treatment with rhPDGF-BB/ß-TCP resulted in comparable fusion rates, less pain, and fewer side effects as compared with treatment with autograft.

Prospective, randomized, multi-center feasibility trial of rhPDGF-BB versus autologous bone graft in a foot and ankle fusion model.

BACKGROUND: The increased morbidity and surgical time associated with harvesting autologous bone graft (ABG) have encouraged surgeons to develop synthetic orthobiologic alternatives. The recombinant form of platelet-derived growth factor (rhPDGF-BB), an angiogenic, mitogenic, and chemotactic cytokine, has been shown to significantly enhance bone formation in human periodontal osseous defects when combined with a tricalcium phosphate carrier (ß-TCP). The purpose of this prospective, controlled, randomized, multi-center feasibility clinical trial was to compare the safety and efficacy of this biosynthetic bone graft substitute (Augment™ Bone Graft) to ABG during ankle and hindfoot fusion. MATERIALS AND METHODS: Twenty adult subjects requiring ankle or hindfoot fusion from three U.S. centers were enrolled and randomized in a 2:1 ratio to receive Augment™ or ABG, respectively. Surgical approach and fixation techniques were standardized, and minimum followup was 9 months. The primary endpoint was radiographic osseous union, evaluated by a blinded independent radiologist. Secondary endpoints included assessment of clinical success, union rate by serial computed tomography (CT) examination, time to full weightbearing, AOFAS Ankle-Hindfoot Score (AOFAS), Foot Function Index (FFI), Short Form-12 (SF-12), and Visual Analog pain assessment Scale (Pain VAS). RESULTS: At 36 weeks, 77% (10/13) of the Augment™ and 50% (3/6) of the ABG patients were fused based on radiographic criteria. There were two nonunions in the Augment™ group (9%, 2/14). Healing rates based on 12 week CT scanning (50% osseous bridging) were 69% (9/13) in the Augment™ and 60% (3/5) in the ABG groups, respectively. All functional outcome measures (FFI, AOFAS, SF-12), as well as the VAS pain scores, improved in both groups over time. Surgical procedure times lasted an average 26 minutes longer for the ABG as compared to the Augment™ populations. There were no device related serious adverse events in this study. CONCLUSION: Based on the available data, the rate of radiographic union, time to full weightbearing, and outcomes scores between the Augment™ and ABG subjects appear comparable. Augment™ may represent a safe and efficacious treatment alternative to ABG during foot and ankle arthrodesis.

Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036.

Acquired resistance to ABL1 tyrosine kinase inhibitors (TKIs) through ABL1 kinase domain mutations, particularly the gatekeeper mutant T315I, is a significant problem for patients with chronic myeloid leukemia (CML). Using structure-based drug design, we developed compounds that bind to residues (Arg386/Glu282) ABL1 uses to switch between inactive and active conformations. The lead "switch-control" inhibitor, DCC-2036, potently inhibits both unphosphorylated and phosphorylated ABL1 by inducing a type II inactive conformation, and retains efficacy against the majority of clinically relevant CML-resistance mutants, including T315I. DCC-2036 inhibits BCR-ABL1(T315I)-expressing cell lines, prolongs survival in mouse models of T315I mutant CML and B-lymphoblastic leukemia, and inhibits primary patient leukemia cells expressing T315I in vitro and in vivo, supporting its clinical development in TKI-resistant Ph(+) leukemia.