Autologous fat graft injections for the treatment of perianal fistulas in Crohn's disease: a systematic review and single-arm meta-analysis.

BACKGROUND: Crohn's perianal fistulas are often refractory to standard management. Fat graft injections are hypothesised to improve fistula healing rates. We evaluated the treatment efficacy of fat graft injections for Crohn's perianal fistulas in a systematic review (PRISMA). METHODS: We completed database searches of MEDLINE (Ovid), Embase, and PubMed. All studies published in English in full text or abstract, from January 2001 to August 2021, evaluating fat graft injections for Crohn's perianal fistulas were selected. Included randomized controlled trials, single-arm intervention trials, cohort studies, and case series; excluded single case reports. Primary outcome was pooled clinical healing, defined as non-draining treated fistulas, or closure, defined as closure of treated fistulas. Secondary outcomes were clinical healing, clinical closure, radiologic response, and adverse events. RESULTS: Of 1258 publications identified, 891 articles were assessed for eligibility, and 107 relevant for manuscript review. Forty-nine patients received fat graft injections for Crohn's perianal fistulas across four single-arm intervention trials. Clinical healing or closure was achieved in 74% in a pooled single-arm meta-analysis (95% confidence interval: 57%, 85%), with moderate heterogeneity between studies. Clinical healing was achieved in 20% and 60% at 3 and 12 months, respectively. Clinical closure was achieved in 83% at 6 months. Variable parameters were used to define radiologic response, with success rates from 20% to 67%. Minimal adverse events were reported. CONCLUSION: Fat graft injections show promise as a novel treatment for Crohn's perianal fistulas in this systematic review and meta-analysis. Assessment in controlled matched studies is warranted.

Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn's Perianal Fistulas.

BACKGROUND & AIMS: Higher anti-tumor necrosis factor-α (TNF) drug levels are associated with improved clinical healing of Crohn's perianal fistulas. It is unclear whether this leads to improved healing on radiologic assessment. We aimed to evaluate the association between anti-TNF drug levels and radiologic outcomes in perianal fistulising Crohn's disease. METHODS: A cross-sectional retrospective multicenter study was undertaken. Patients with perianal fistulising Crohn's disease on maintenance infliximab or adalimumab, with drug levels within 6 months of perianal magnetic resonance imaging were included. Patients receiving dose changes or fistula surgery between drug level and imaging were excluded. Radiologic disease activity was scored using the Van Assche Index, with an inflammatory subscore calculated using indices: T2-weighted imaging hyperintensity, collections >3 mm diameter, rectal wall involvement. Primary endpoint was radiologic healing (inflammatory subscore ≤6). Secondary endpoint was radiologic remission (inflammatory subscore = 0). RESULTS: Of 193 patients (infliximab, n = 117; adalimumab, n = 76), patients with radiologic healing had higher median drug levels compared with those with active disease (infliximab 6.0 vs 3.9 µg/mL; adalimumab 9.1 vs 6.2 µg/mL; both P < .05). Patients with radiologic remission also had higher median drug levels compared with those with active disease (infliximab 7.4 vs 3.9 µg/mL; P < .05; adalimumab 9.8 vs 6.2 µg/mL; P = .07). There was a significant incremental reduction in median inflammatory subscores with higher anti-TNF drug level tertiles. CONCLUSIONS: Higher anti-TNF drug levels were associated with improved radiologic outcomes on magnetic resonance imaging in perianal fistulising Crohn's disease, with an incremental improvement at higher drug level tertiles for both infliximab and adalimumab.

Prospective randomised controlled trial of adults with perianal fistulising Crohn's disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol.

INTRODUCTION: Perianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy. METHODS AND ANALYSIS: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18-80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate. ETHICS AND DISSEMINATION: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.

Optimizing the Double-Row Construct: An Untied Medial Row Demonstrates Equivalent Mean Contact Pressures in a Rotator Cuff Model.

BACKGROUND: The merits of a double-row rotator cuff repair (RCR) construct are well-established for restoration of the footprint and lateral-row security. The theoretical benefit of leaving the medial row untied is to prevent damage to the rotator cuff by tissue strangulation, and the benefit of suture tape is a more even distribution of force across the repair site. These benefits, to our knowledge, have not been evaluated in the laboratory. HYPOTHESIS: Leaving the medial row untied and using a suture bridge technique with suture tape will offer more even pressure distribution across the repair site without compromising total contact force. STUDY DESIGN: Controlled laboratory study. METHODS: A laboratory model of RCR was created using biomechanical research-grade composite humeri and human dermal allografts. The pressure distribution in a double-row suture bridge repair construct was analyzed using the following testing matrix: double-loaded suture anchors with the medial row tied (n = 15) versus untied (n = 15) compared with double-loaded suture tape and anchors with the medial row tied (n = 15) versus untied (n = 15). A digital pressure sensor was used to measure pressure over time after tensioning of the repair site. A multivariate analysis of variance was used for statistical analysis with post hoc testing. RESULTS: The total contact force did not significantly differ between constructs. The contact force between double-loaded suture anchors and double-loaded suture tape and anchors was similar when tied (P = .15) and untied (P = .44). An untied medial row resulted in similar contact forces in both the double-loaded suture anchor (P = .16) and double-loaded suture tape and anchor (P = .25) constructs. Qualitative increases in focal contact pressure were seen when the medial row was tied. CONCLUSION: An untied medial row did not significantly affect the total contact force with double-loaded suture anchors and with double-loaded suture tape and anchors. Tying the medial row qualitatively increased crimping at the construct's periphery, which may contribute to tissue strangulation and hinder clinical healing. Qualitative improvements in force distribution were seen with double-loaded suture tape and anchors. CLINICAL RELEVANCE: Both tied and untied medial rows demonstrated similar pressures across the repair construct.

Distal Metaphyseal Osteotomy Allows for Greater Ulnar Shortening Compared to Diaphyseal Osteotomy for Ulnar Impaction Syndrome: A Biomechanical Study.

Purpose To compare the biomechanical characteristics between diaphyseal and metaphyseal ulnar-shortening osteotomy with respect to (1) maximal shortening achieved at each osteotomy site and (2) force required to achieve shortening at each site. Methods Nine fresh frozen cadaveric upper extremities were affixed through the proximal ulna to a wooden surgical board. A metaphyseal 20-mm bone wedge was resected from the distal ulna and sequential shortening was performed. A load cell was attached to a distal post that was clamped to the surgical board and used to measure the force required for each sequential 5-mm of shortening until maximal shortening was achieved. The resected bone was reinserted, and plate fixation was used to restore normal anatomy. A 20-mm diaphyseal osteotomy was performed, and force measurements were recorded in the same manner with (1) interosseous membrane intact, (2) central band released, and (3) extensive interosseous membrane and muscular attachments released. Results Metaphyseal osteotomy allowed greater maximal shortening than diaphyseal osteotomy with the interosseous membrane intact and with central band release but similar shortening when extensive interosseous membrane and muscle release was performed. Force at maximal shortening was similar between metaphyseal and diaphyseal osteotomy. Sequential soft tissue release at the diaphysis allowed for increased shortening with slightly decreased shortening force with sequential release. Conclusion Metaphyseal ulnar osteotomy allows greater maximal shortening but requires similar force compared with diaphyseal osteotomy. Sequential release of the interosseous membrane permits increased shortening at the diaphysis but requires extensive soft tissue release. Clinical Relevance Both sites of osteotomy can achieve sufficient shortening to decompress the ulnocarpal joint for most cases of ulnar impaction syndrome. The greater shortening from metaphyseal ulnar osteotomy may be reserved for severe cases of shortening, especially after distal radius malunion or in the setting of distal radius growth arrest in the pediatric population. Level of Evidence This is a Level V, basic science study.

Biomechanical Evaluation of Interfragmentary Compression of Lag Screw Versus Positional Screw at Different Angles of Fixation.

OBJECTIVES: To compare the compressive force achieved and retained with the lag versus positional screw technique at various angles of screw application. METHODS: Sixty humeral sawbones were stratified into 6 groups based on the technique (lag or positional) and fixation angle (30, 60, or 90 degrees relative to the fracture plane). A sensor was placed between fragments to record compressive force. Absolute screw force is the final screw force. Normalized force is the final screw force minus force generated by reduction forceps. Retained force is the quotient of absolute force relative to reduction forceps force. RESULTS: Lag screws attained higher force than positional at 60 degrees (absolute force 41% higher, P = 0.041; normalized force 1300% higher, P = 0.008; retained force 60% higher, P = 0.008) and 90 degrees (absolute force 86% higher, P = 0.006; normalized force 730% higher, P = 0.005; retained force 70% higher, P = 0.011), but not at 30 degrees. For lag screws, compressive force was similar at 60 and 90 degrees (absolute force P = 0.174, normalized force P = 0.364, and retained force P = 0.496), but not 30 degrees. For positional screws, no difference was found between the 3 angles of fixation for absolute force (P = 0.059). Normalized force and retained force were similar at 60 and 90 degrees (P = 0.944 and P = 0.725, respectively), but not 30 degrees. CONCLUSIONS: Lag screw technique compressive force was superior to positional screw technique at 60 and 90 degrees. Comparison of force at angles of 60 and 90 degrees showed no significant difference for both techniques. Indicating 30 degrees deviation from perfect technique is tolerated without significant decrease in compressive force.

Metastatic sigmoid colon adenocarcinoma and tumour-related sarcoid reaction.

The association between malignancy and tumour-related sarcoid reaction is well documented, characterised by non-caseating granulomatous disease in haematological and solid malignancies. Its occurrence in colon cancer is rare and of unclear clinical significance. Herein, we present a case report of a 32-year-old woman diagnosed with concurrent metastatic sigmoid colon adenocarcinoma and pulmonary granulomatous disease suggestive of a tumour-related sarcoid reaction.

Quantifying the force transmission through the pelvic joints during total hip arthroplasty: A pilot cadaveric study.

BACKGROUND: Total hip arthroplasty is one of the most successful and cost effective procedures in orthopedics. The purpose of this study is to investigate force transmission through the sacroiliac joint as a possible source of post-operative pain after total hip arthroplasty through the following three questions: Does the ipsilateral sacroiliac joint, contralateral sacroiliac joint, or pubic symphysis experience more force during placement? Does the larger mallet used to seat the implant generate a higher force? Does the specimen's bone density or BMI alter force transmission? METHODS: A solid design acetabular component was impacted into five human cadaver pelves with intact soft tissues. The pressure at both sacroiliac joints and the pubic symphysis was measured during cup placement. This same procedure was replicated using an existing pelvis finite element model to use for comparison. FINDINGS: The location of the peak force for each hammer strike was found to be specimen specific. The finite model results indicated the ipsilateral sacroiliac joint had the highest pressure and strain followed by the pubic symphysis over the course of the full simulation. The heft of the mallet and bone mineral density did not predict force values or locations. The largest median force was generated in extremely obese specimens. INTERPRETATION: Contrary to previous ideas, it is highly unlikely that forces experienced at the pelvic joints are large enough to contribute post-operative pain during impaction of an acetabular component. These results indicate more force is conveyed to the pubic symphysis compared to the sacroiliac joints.

Precision grip responses to unexpected rotational perturbations scale with axis of rotation.

It has been established that rapid, pulse-like increases in precision grip forces ("catch-up responses") are elicited by unexpected translational perturbations and that response latency and strength scale according to the direction of linear slip relative to the hand as well as gravity. To determine if catch-up responses are elicited by unexpected rotational perturbations and are strength-, axis-, and/or direction-dependent, we imposed step torque loads about each of two axes which were defined relative to the subject's hand: the distal-proximal axis away from and towards the subject's palm, and the grip axis which connects the two fingertips. Precision grip responses were dominated initially by passive mechanics and then by active, unimodal catch-up responses. First dorsal interosseous activity, marking the start of the catch-up response, began 71-89 ms after the onset of perturbation. The onset latency, shape, and duration (217-231 ms) of the catch-up response were not affected by the axis, direction, or magnitude of the rotational perturbation, while strength was scaled by axis of rotation and slip conditions. Rotations about the grip axis that tilted the object away from the palm and induced rotational slip elicited stronger catch-up responses than rotations about the distal-proximal axis that twisted the object between the digits. To our knowledge, this study is the first to investigate grip responses to unexpected torque loads and to show characteristic, yet axis-dependent, catch-up responses for conditions other than pure linear slip.