Risk of Revision Shoulder Arthroplasty After Anatomic and Reverse Total Shoulder Arthroplasty.

INTRODUCTION: The objective of this study was to determine the survivorship of anatomic total shoulder arthroplasty (aTSA) and reverse TSA (rTSA) over a medium-term follow-up in a large population-based sample and to identify potential risk factors for revision surgery. METHODS: The State Inpatient Database from the Healthcare Cost and Utilization Project was used to identify patients who underwent aTSA or rTSA from 2011 through 2015 using ICD9 codes. We modeled the primary outcome of time to revision or arthroplasty using the Cox proportional hazards model. The predictors of revision surgery in the model include aTSA versus rTSA, indication for surgery, age, sex, race, urban versus rural residence, hospital length of stay zip code-based income quartile classification, and Elixhauser comorbidity readmission score. RESULTS: Among 43,990 patients in this study, 1,141 (4.0%) underwent revision or implant removal over the 4-year study period. The median age was 71 years, and 57% of patients were female. Indications for the index surgery included primary osteoarthritis (75.2%), cuff tear (8.5%), acute fracture (7.0%), malunion/nonunion (1.4%), and other (7.8%). Among these indications for surgery, the risk of revision or removal was greatest in patients who underwent the primary procedure for malunion/nonunion (hazard ratio [HR] 2.39, 95% confidence interval [CI] 1.69 to 3.39) compared with the reference of primary osteoarthritis. Male patients who underwent aTSA were less likely to need revision surgery than male patients who underwent rTSA (HR: 0.59, 95% CI 0.49 to 0.71), and the opposite relationship was observed in female patients (HR: 1.41, 95% CI 1.18 to 1.69). Age, length of stay, and Elixhauser comorbidity score were predictive of revision surgery (P < 0.0001, P = 0.0005, P < 0.0001, respectively), whereas race, urban versus rural, and zip code-based income quartile were not. DISCUSSION: aTSA and rTSA showed excellent 4-year survivorship of 96.0% in a large population-based sample. aTSA and rTSA survivorships were similar at the 4-year follow-up.

Conversion of Elbow Arthrodesis to Total Elbow Arthroplasty: A Case Report and Literature Review.

Elbow arthrodesis is a salvage operation designed to relieve pain and enable weight bearing in young patients with painful arthritic joints who have failed all other treatment modalities. Unfortunately, elbow arthrodesis is poorly tolerated by many patients because there is no fusion position that accommodates all activities of daily living. As indications for elbow arthroplasty expand and implant design improves, patients living with elbow arthrodesis may seek conversion to arthroplasty to regain a functional range of motion. Only one case of elbow arthrodesis to elbow arthroplasty conversion has been reported in the English literature to date. We present the case of a 58 year old male, five years status post elbow arthrodesis, unable to perform his ADLs adequately, who was successfully converted to a total elbow arthroplasty. Indications, contraindications, and technical pearls are discussed.

Reduced hip bone mineral density is associated with high levels of calciprotein particles in patients with Fabry disease.

Calciprotein particles (CPP) are nanoscale mineralo-protein aggregates that help stabilize excess mineral in the circulation. We examined the relationship between CPP and bone mineral density in Fabry disease patients. We found an inverse correlation with total hip and femoral neck density, but none with lumbar spine. PURPOSE: Calciprotein particles (CPP) are colloidal mineral-protein complexes made up primarily of the circulating glycoprotein fetuin-A, calcium, and phosphate. They form in extracellular fluid and facilitate the stabilization, transport, and clearance of excess minerals from the circulation. While most are monomers, they also exist in larger primary (CPP-I) and secondary (CPP-II) form, both of which are reported to be raised in pathological states. This study sought to investigate CPP levels in the serum of patients with Fabry disease, an X-linked systemic lysosomal storage disorder that is associated with generalized inflammation and low bone mineral density (BMD). METHODS: We compared serum CPP-I and CPP-II levels in 59 patients with Fabry disease (37 female) with levels in an age-matched healthy adult cohort (n=28) and evaluated their association with BMD and biochemical data obtained from routine clinical review. RESULTS: CPP-I and CPP-II levels were higher in male Fabry disease patients than female sufferers as well as their corresponding sex- and age-matched controls. CPP-II levels were inversely correlated with BMD at the total hip and femoral neck, but not the lumbar spine. Regression analyses revealed that these associations were independent of common determinants of BMD, but at the femoral neck, a significant association was only found in female patients. CONCLUSION: Low hip BMD was associated with high CPP-II in patients with Fabry disease, but further work is needed to investigate the relevance of sex-related differences and to establish whether CPP measurement may aid assessment of bone disease in this setting.

Investigation of the magnetic ground state of GaV4S8using powder neutron diffraction.

The magnetic ground state of polycrystalline Néel skyrmion hosting material GaV4S8has been investigated usingacsusceptibility and powder neutron diffraction. In the absence of an applied magnetic field GaV4S8undergoes a transition from a paramagnetic to a cycloidal state below 13 K and then to a ferromagnetic-like state below 6 K. With evidence fromacsusceptibility and powder neutron diffraction, we have identified the commensurate magnetic structure at 1.5 K, with ordered magnetic moments of 0.23(2) µBon the V1 sites and 0.22(1) µBon the V2 sites. These moments have ferromagnetic-like alignment but with a 39(8)° canting of the magnetic moments on the V2 sites away from the V4cluster. In the incommensurate magnetic phase that exists between 6 and 13 K, we provide a thorough and careful analysis of the cycloidal magnetic structure exhibited by this material using powder neutron diffraction.

Real-space observation of ferroelectrically induced magnetic spin crystal in SrRuO3.

Unusual features in the Hall Resistivity of thin film systems are frequently associated with whirling spin textures such as Skyrmions. A host of recent investigations of Hall Hysteresis loops in SrRuO3 heterostructures have provided conflicting evidence for different causes for such features. We have constructed an SrRuO3-PbTiO3 (Ferromagnetic - Ferroelectric) bilayer that exhibits features in the Hall Hysteresis previously attributed to a Topological Hall Effect, and Skyrmions. Here we show field dependent Magnetic Force Microscopy measurements throughout the key fields where the 'THE' presents, revealing the emergence to two periodic, chiral spin textures. The zero-field cycloidal phase, which then transforms into a 'double-q' incommensurate spin crystal appears over the appearance of the 'Topological-like' Hall effect region, and develop into a ferromagnetic switching regime as the sample reaches saturation, and the 'Topological-like' response diminishes. Scanning Tunnelling Electron Microscopy and Density Functional Theory is used to observe and analyse surface inversion symmetry breaking and confirm the role of an interfacial Dzyaloshinskii-Moriya interaction at the heart of the system.

Glenohumeral arthrodesis.

Glenohumeral arthrodesis is a salvage procedure indicated for brachial plexus palsy, refractory instability, humeral and/or glenoid bone loss, deltoid and rotator cuff insufficiency, and chronic infections. The aim is to provide a painless, stable shoulder that is positioned to maximize function. Scapulothoracic motion as well as motion of the elbow and hand deliver satisfactory function in most patients. Intra-articular, extra-articular, and more commonly, combined techniques involving glenohumeral and humeroacromial fusion, have been described. More recently, authors have reported arthroscopic assisted techniques for shoulder arthrodesis with promising results as well as less complicated conversion from shoulder arthrodesis to reverse total shoulder arthroplasty. Despite advances in materials and techniques, glenohumeral arthrodesis continues to be associated with complication rates as high as 43%. A thorough understanding of the indications, contraindications, outcomes, and complications is paramount to improving patient results. Glenohumeral arthrodesis is a safe and effective procedure for the appropriate indications. The high frequency of complications mandates a frank preoperative discussion to ensure that each patient understands the magnitude of the procedure, its risks, possible complications, and expected outcome.

Thirty-day readmissions and reoperations after total elbow arthroplasty: a national database study.

BACKGROUND: The purpose of this study was to determine the rate of short-term complications after total elbow arthroplasty (TEA) and identify predictors of readmission and reoperation. We hypothesized that TEA performed for acute elbow trauma would have higher rates of 30-day readmission and reoperation than TEA performed for osteoarthritis (OA). METHODS: Using the National Surgical Quality Improvement Program for the years 2011-2017, we identified patients undergoing TEA for fracture, OA, or inflammatory arthritis. Patient demographic characteristics, comorbidities, reoperations, and readmissions within 30 days of surgery were analyzed. Potential predictors of reoperation and readmission in the model included age, sex, race, body mass index (BMI), diabetes, hypertension, chronic obstructive pulmonary disease, congestive heart failure, smoking, bleeding disorders, American Society of Anesthesiologists classification, wound classification, operative time, and indication for surgery. RESULTS: A total of 414 patients underwent TEA from 2011-2017. Of these patients, 40.6% underwent TEA for fracture; 37.0%, for OA; and 22.7%, for inflammatory arthritis. The overall rate of unplanned readmissions was 5.1% (21 patients). The rate of unplanned reoperations was 2.4% (10 patients). Infection was the most common reason for both unplanned readmissions and reoperations. The rates of reoperations and readmissions were not significantly associated with any of the 3 operative indications: fracture, OA, or inflammatory arthritis. Multiple logistic regression analysis found increased BMI to be associated with lower odds of an unplanned readmission (odds ratio [OR], 0.883; 95% confidence interval [CI], 0.798-0.963; P = .0035) and found wound classification ≥ 3 to be associated with increased odds of an unplanned reoperation (OR, 16.531; 95% CI, 1.300-167.960; P = .0144) and total local complications (OR, 17.587; 95% CI, 2.207-132.019; P = .0057). Patients who were not functionally independent were more likely to experience local complications (OR, 4.181; 95% CI, 0.983-15.664; P = .0309) than were functionally independent patients. CONCLUSIONS: The 30-day unplanned reoperation rate after TEA was 2.4%, and the unplanned readmission rate was 5.1%. Low BMI was predictive of readmission. Wounds classified as contaminated or dirty were predictive of reoperation. Dependent functional status and contaminated wounds were predictive of local complications. The indication for TEA (fracture vs. OA vs. inflammatory arthritis) was not found to be a risk factor for reoperation or readmission after TEA.

Systematic review and network meta-analysis of subscapularis management techniques in anatomic total shoulder arthroplasty.

BACKGROUND: Controversy exists regarding the optimal subscapularis management technique in patients undergoing anatomic total shoulder arthroplasty. The purpose of this study was to compare clinical, radiographic, and functional outcomes between subscapularis tenotomy (ST), lesser tuberosity osteotomy (LTO), and subscapularis peel (SP) techniques. METHODS: We performed a level III systematic review and network meta-analysis comparing ST, LTO, and SP in patients undergoing anatomic total shoulder arthroplasty. Our primary collection endpoints included range of motion, subscapularis function, subscapularis healing, functional patient-reported outcomes, complications, and revision surgery. Data were pooled and network meta-analysis was performed owing to the comparison of 3 groups. RESULTS: Eight studies met our inclusion criteria for meta-analysis. There was no difference in sex or primary diagnosis between the 3 cohorts. No significant difference was found in postoperative external rotation or forward flexion between the groups. Meta-analysis found the SP cohort to have significantly greater internal rotation strength than the ST cohort. The belly-press test results were negative most commonly in the LTO group, and there was a significant difference compared with the ST or SP group (P < .0001). The weighted-mean healing rate for the LTO site was 98.9% on radiographic imaging. There was a significantly higher ultrasound healing rate in the LTO cohort than in the ST and SP cohorts. All groups had good postoperative patient-reported outcome scores (average American Shoulder and Elbow Surgeons score range, 78.6-87) and a relatively low rate of complications (3%). CONCLUSION: This network meta-analysis demonstrates that the LTO group has superior healing and postoperative subscapularis-specific physical examination test results compared with the ST and SP groups. However, no difference in postoperative range of motion was found between the groups, and all techniques demonstrated good functional patient-reported outcomes, with a low rate of postoperative complications. These findings provide evidence-based support that ST, SP, and LTO all demonstrate similar outcomes; therefore, selection should be based on surgeon experience and comfort.

Increased articular exposure of the lateral elbow joint with the anconeus approach compared to the Kocher approach: a cadaver study.

INTRODUCTION: The Kocher approach is the workhorse approach to the lateral elbow. However, the exposure is often limited, particularly for open reduction. The purpose of this study is to quantitatively compare the articular exposure of the anconeus and Kocher approaches to the lateral elbow. METHODS: Eight surgical approaches (four Kocher and four Anconeus) were performed on four fresh cadavers. The right elbows of the first two specimens were dissected via the Kocher approach, and the left elbows via the anconeus approach. For the remaining two specimens, the laterality of the approaches was reversed. Access to key articular landmarks were assessed, including the capitellum, humeral trochlea, radial head, olecranon, coronoid process, and greater and lesser sigmoid notches of the ulna. A calibrated digital image was taken from the optimum surgeon's viewing angle of each approach, and these images were analyzed with ImageJ software (NIH, Bethesda, MD, USA) to calculate the area of exposed articular surfaces. RESULTS: The average surface area exposed was 2.9 times greater with the anconeus approach compared with the standard Kocher approach (8.3 vs 3.1 cm2, p value 0.001). All key anatomic landmarks were directly visualized with the anconeus approach in each specimen. Visualization of the humeral trochlea, olecranon, coronoid process, and greater and lesser sigmoid notches of the ulna was not obtained in any of the Kocher approaches. DISCUSSION: The Anconeus approach provides superior exposure of the lateral elbow joint compared with the Kocher approach. We recommend consideration of the anconeus approach for treatment of select traumatic injuries of the lateral elbow requiring increased access to the ulnohumeral and radiocapitellar joints.

Sources of contamination in the operating room: A fluorescent particle powder study.

This study utilized fluorescent particle powder to investigate 2 potential sources of sterile field contamination in the operating room (OR): forced-air warming blankets and OR light manipulation. In part 1, sterile draping for knee replacement surgery was performed on a mannequin in a sterile OR, comparing field contamination with the forced-air warming on versus off during draping. In part 2, OR lights coated with fluorescent powder were manipulated over a sterile field. Proper operation of these devices may reduce the particle burden on the surgical field.

Factors Affecting Resident Satisfaction in Continuity Clinic-a Systematic Review.

PURPOSE: In recent years, with an increasing emphasis on time spent in ambulatory training, educators have focused attention on improving the residents' experience in continuity clinic. The authors sought to review the factors associated with physician trainee satisfaction with outpatient ambulatory training. METHODS: A systematic literature review was conducted for all English language articles published between January 1980 and December 2016 in relevant databases, including Medline (medicine), CINAHL (nursing), PSYCHinfo (psychology), and the Cochrane Central Register of Controlled Clinical Trials. Search terms included internship and residency, satisfaction, quality of life, continuity of care, ambulatory care, and medical education. We included studies that directly addressed resident satisfaction in the ambulatory setting through interventions that we considered reproducible. RESULTS: Three hundred fifty-seven studies were reviewed; 346 studies were removed based on exclusion criteria with 11 papers included in the final review. Seven studies emphasized aspects of organizational structure such as block schedules, working in teams, and impact on resident-patient continuity (continuity between resident provider and patient as viewed from the provider's perspective). Four studies emphasized the importance of a dedicated faculty for satisfaction. The heterogeneity of the studies precluded aggregate analysis. CONCLUSIONS: Clinic structures that limit inpatient and outpatient conflict and enhance continuity, along with a dedicated outpatient faculty, are associated with greater resident satisfaction. Implications for further research are discussed.

Comparing the Incidence of Index Level Fusion Following Minimally Invasive Versus Open Lumbar Microdiscectomy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To determine the incidence of index level fusion following open or minimally invasive lumbar microdiscectomy. METHODS: We conducted a retrospective review of 174 patients with a symptomatic single-level lumbar herniated nucleus pulposus who underwent microdiscectomy via a mini-open approach (MIS; 39) or through a minimally invasive dilator tube (135). Outcomes of interest included revision microdiscectomy and the ultimate need for index level fusion. Continuous variables were analyzed with independent sample t test, and χ2 analysis was used for categorical data. A multivariate regression analysis was performed to identify predictive factors for patients that required index level fusion after lumbar microdiscectomy. RESULTS: There was no difference in patient demographics in the open and MIS groups aside from length of follow-up (60.4 vs 40.03 months, P < .0001) and body mass index (24.72 vs 27.21, P = .03). The rate of revision microdiscectomy was not statistically significant between open and MIS approaches (10.3% vs 10.4%, P = .90). The rate of patients who ultimately required index level fusion approached significance, but was not statistically different between open and MIS approaches (10.3% vs 4.4%, P = .17). Multivariate regression analysis indicated that the need for eventual index level fusion after lumbar microdiscectomy was statistically predicted in smokers and those patients who underwent revision microdiscectomy (P < .05) in both open and MIS groups. CONCLUSIONS: Our results suggest a low likelihood of patients ultimately requiring fusion following microdiscectomy with predictors including smoking status and a history of revision microdiscectomy.

Short-Term Complications of Anterior Fixation of Odontoid Fractures.

STUDY DESIGN: Retrospective study. OBJECTIVE: Anterior fixation of odontoid fracture has been associated with high morbidity and mortality in small, single institution series. Identifying risk factors may improve risk stratification and highlight factors that could be optimized preoperatively. The objective of this study was to determine the 30-day complication rate following anterior fixation of odontoid fractures and to identify associated risk factors among patients in a large national database. METHODS: Patients who underwent anterior fixation were identified in the American College of Surgeons National Quality Improvement Program database (ACS NSQIP) from 2007 to 2012. Patient demographics, medical comorbidities, perioperative complications, and postoperative complications up to 30 days were analyzed by univariate and multivariate analysis. RESULTS: Overall, 103 patients met criteria for the study. The average age was 73.9 years and patients were predominantly white (85.4%). Cardiac comorbidity was common (66.0%), as were dependent functional status (14.6%) and bleeding disorders (13.6%). Complications occurred in 37.9% of patients, and mortality was high (6.8%). Age, white race, and history of bleeding disorders were independently predictive of complications in the multivariate analysis. The postoperative hospital stay was >5 days for 45.6% of patients. CONCLUSION: In a large, multicenter database study, anterior fixation of odontoid fracture was associated with high morbidity and mortality. Although advanced age was associated with increased risk of complications, patients undergoing anterior fixation were older, on average, than in prior studies. Bleeding disorder was a potentially modifiable risk factor for complications that could be optimized prior to surgery.

Trifurcate Origin of Long Head of Biceps Brachii: A Case Report and Literature Review.

INTRODUCTION: Variant anatomy of the intra-articular portion of the long head of the biceps tendon (LHBT) is rare, and its clinical significance is poorly understood. However, these variants are encountered with increasing frequency due to increasing use of shoulder arthroscopy. CASE REPORT: We report a case of a trifurcate intra-articular LHBT, a variation which, to our knowledge, has not been previously described. The patient was an adult male presenting with chronic atraumatic shoulder pain that worsened with overhead activity. On arthroscopy, the LHBT was found to have three origins from the (1) supraspinatus tendon, (2) superior labrum, and (3) rotator interval that joined together distally within the biceps tunnel. We believe the split tendon may have caused impingement the biceps tunnel; therefore, the patient was treated with subpectoral tenodesis. He also underwent subacromial decompression and rotator cuff debridement. CONCLUSION: This case highlights the importance of surgeon and radiologist awareness of split LHBT variant anatomy, such that misdiagnosis and unnecessary treatment may be avoided.

Incidence and Risk Factors for 30-Day Unplanned Readmissions After Elective Posterior Lumbar Fusion.

STUDY DESIGN: Retrospective study of prospectively collected data. OBJECTIVE: To perform a multiinstitutional assessment on the incidence and risk factors for unplanned readmissions following elective posterior lumbar fusion (PLF) surgery. SUMMARY OF BACKGROUND DATA: Understanding what may drive rehospitalizations is a necessary step toward higher quality care. Identifying risk factors for unplanned readmission is especially important for elective PLF, which is a common procedure that is known to be associated with significant adverse events. METHODS: Adult patients undergoing PLF were identified using current procedure terminology (CPT) from the American College of Surgeons National Surgical Quality Improvement Program. Both descriptive and comparative statistics were performed for patient characteristics, clinical factors, and postoperative complications. Subsequently, a step-wise multivariate logistic regression was employed. RESULTS: Of the 2301 patients who met inclusion criteria for this study, 117 were unplanned readmissions (5.1%). These occurred at a mean of 15.9 days (range: 3-30 days) after surgery. The risk-adjusted analysis revealed that bleeding disorder (odds ratio, OR = 2.8, confidence intervals, CI = 1.0-7.6, P = 0.043), insulin dependent diabetes (OR = 2.5, CI = 1.4-4.4, P = 0.004), and total length of stay > 5 days (OR = 1.8, CI = 1.2-2.8, P = 0.009) were independent predictors for unplanned readmission. Significant postoperative complications included wound complications (OR = 27.6, CI = 13.9-54.8, P < 0.0001), pulmonary embolism and/or deep vein thrombosis/thrombophlebitis (OR = 11.9, CI = 5.0-28.5, P < 0.0001), sepsis (OR = 8.5, CI = 2.3-32.1, P = 0.002), and urinary tract infections (OR = 2.4, CI = 0.9-6.9, P = 0.094). CONCLUSION: The unplanned readmission rate for patients undergoing PLF was low, but this study's findings of potentially modifiable risk factors suggest that substantial improvement with this quality metric is possible. LEVEL OF EVIDENCE: N/A.

Primary squamous cell carcinoma of the breast in association with Zuska's disease.

Breast cancer is the most common malignancy in women in the UK with well-defined algorithms of management in place in the western world. Squamous cell carcinoma of the breast is a rare entity and as such knowledge about the pathophysiology, treatment and prognosis are still uncertain. The report describes an unusual case of squamous cell carcinoma arising in an area of Zuska's disease of the breast. It illustrates the heterogeneity of the imaging findings with review of the literature. Decisions on management should be taken on an individual basis with full discussion in the multidisciplinary team meetings where all facets of the case are considered.

Epidemiology of infections and antimicrobial use in Australian haemodialysis outpatients: findings from a Victorian surveillance network, 2008-2015.

BACKGROUND: Patients with chronic renal failure who require haemodialysis are at high risk for infections. AIM: To determine the burden of bloodstream and local access-related infections and the prescribing patterns for intravenous antibiotics in Australian haemodialysis outpatients. METHODS: A surveillance network was established following stakeholder consultation, with voluntary participation by haemodialysis centres and data collation by the Victorian Healthcare Associated Infection Surveillance System Coordinating Centre. Definitions for infection and intravenous antimicrobial starts were based upon methods employed by the Centers for Disease Control and Prevention. Longitudinal mixed-effects Poisson regression was used to model time-trends for the period 2008-2015. FINDINGS: Forty-eight of 78 Victorian dialysis centres participated in the network, with 3449 events reported over 78,826 patient-months. Rates of bloodstream infection, local infection and intravenous antimicrobial starts were much higher for patients with tunnelled central lines (2.60, 1.41, and 3.37 per 100 patient-months, respectively), compared to those with arteriovenous fistulae (0.27, 0.23, and 0.73 per 100 patient-months, respectively) and arteriovenous grafts (0.76, 1.08, 1.50 per 100 patient-months, respectively). Staphylococcus aureus was the most frequent pathogen, with meticillin-resistant isolates (MRSA) responsible for 14.0%. Access-related infections diminished significantly across all vascular-access modalities over time. Vancomycin contributed nearly half of all antimicrobial starts consistently throughout the study period. CONCLUSION: Risk for bloodstream and local access-related infections is highest in Australian haemodialysis patients with tunnelled central lines. S. aureus is the most frequent cause of infection, with a low incidence of MRSA. Future programmes should evaluate infection prevention practices and appropriateness of antibiotic prescribing in this population.

On-chip magnetic cooling of a nanoelectronic device.

We demonstrate significant cooling of electrons in a nanostructure below 10 mK by demagnetisation of thin-film copper on a silicon chip. Our approach overcomes the typical bottleneck of weak electron-phonon scattering by coupling the electrons directly to a bath of refrigerated nuclei, rather than cooling via phonons in the host lattice. Consequently, weak electron-phonon scattering becomes an advant- age. It allows the electrons to be cooled for an experimentally useful period of time to temperatures colder than the dilution refrigerator platform, the incoming electrical connections, and the host lattice. There are efforts worldwide to reach sub-millikelvin electron temperatures in nanostructures to study coherent electronic phenomena and improve the operation of nanoelectronic devices. On-chip magnetic cooling is a promising approach to meet this challenge. The method can be used to reach low, local electron temperatures in other nanostructures, obviating the need to adapt traditional, large demagnetisation stages. We demonstrate the technique by applying it to a nanoelectronic primary thermometer that measures its internal electron temperature. Using an optimised demagnetisation process, we demonstrate cooling of the on-chip electrons from 9 mK to below 5 mK for over 1000 seconds.

Parenteral iron polymaltose changes i:c-terminal FGF23 ratios in iron deficiency, but not in dialysis patients.

BACKGROUND/OBJECTIVES: Iron and phosphate are both vital to many biological cellular processes with central roles in energy metabolism, cellular proliferation and nucleic acid synthesis. Regulatory pathways in some of these metabolic pathways may intersect at fibroblast growth factor 23 (FGF23), a major phosphate regulatory hormone. Iron is reported to induce hypophosphataemia in rare cases, and recent reports suggest that iron deficiency may upregulate FGF23 synthesis by mechanisms involving hypoxia-inducible factor 1α (HIF1α). Our objective was to evaluate the effect of administration of intravenous iron polymaltose on intact and c-terminal FGF23 (i:cFGF23) ratios in two independent cohorts of patients, iron-deficient but non-inflamed patients and haemodialysis (HD)-dependent patients, and to examine the balance of synthesis and degradation. SUBJECTS/METHODS: We studied biochemical effects of intravenous iron polymaltose on both iFGF23 and cFGF23 fragments and their ratios in two patient groups: iron-deficient patients with normal renal function (ID-norm) and HD patients receiving iron supplementation (HD-ESKD) at a single institution. Patients were tested at baseline, day 4 and day 12 post iron administration. RESULTS: Parenteral iron polymaltose resulted in increased i:cFGF23 ratios in ID-norm patients where circulating cFGF23 levels decreased with no appreciable effect on iFGF23, whereas no significant changes in i:cFGF23 ratios were observed in HD-ESKD patients following intravenous administration of 100mg iron polymaltose. CONCLUSIONS: Dysregulation of intracellular FGF23-processing mechanisms may be related to iron deficiency per se rather than iron repletion with iron polymaltose. In ID-norm, i:cFGF23 ratios altered with iron administration without significant clinical alterations in mineral parameters, implying that other regulatory mechanisms may be important. Finally, iron supplementation in HD-ESKD patients does not appear to significantly affect i:cFGF23 ratios already disturbed by a chronic inflammatory or functionally iron-deficient state.