Associations of Blood Biomarkers of Bone Turnover with Static Histomorphometry Parameters at the Hip in Patients with Chronic Kidney Disease Undergoing Surgery for Hip Fracture

medRxiv · 2026-03-05

Individuals with chronic kidney disease (CKD) have higher rates of hip fracture and post-fracture mortality. Although they may develop age-related osteoporosis similar to those without CKD, they may also exhibit CKD-related metabolic bone disease (MBD), characterized by low, high, or mixed turnover at similar levels of bone mineral density (BMD). Because BMD does not provide information about turnover status, clinical decision-making is challenging. This study evaluated the associations between circulating bone-turnover biomarkers and static histomorphometry in patients undergoing hip-fracture surgery. In this cross-sectional study, we enrolled adults with and without CKD, defined as estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73m² (CKD-EPI 2021), undergoing hip-fracture surgery. Blood samples, bone specimens from the femoral head or greater trochanter, and demographic and clinical data were collected at the time of surgery. Plasma biomarkers included α-Klotho, bone alkaline phosphatase (BAP), dickkopf-related protein 1 (DKK-1), fibroblast growth factor 23 (FGF23), tartrate-resistant acid phosphatase 5b (TRAP5b), parathyroid hormone (PTH), and sclerostin. Logistic regression models, adjusted for age, gender, eGFR, and osteoporosis, assessed associations with CKD status. Tertiles of osteoblast surface (Ob.S/BS) and eroded surface (ES/BS) were defined in participants without CKD and applied to the full cohort. Multinomial and multivariable linear regression evaluated associations of biomarkers with these histomorphometry parameters. Among 97 enrolled participants (mean age 80 ± 11 years; 67% female), 68% had CKD. Of 75 with complete biomarker and histomorphometry data, 96% demonstrated low bone turnover. CKD was associated with lower trabecular thickness (Tb.Th) and higher osteoid thickness (O.Th), osteoid volume (OV/BV), and osteoid surface (OS/BS), suggesting thinner, largely unmineralized trabeculae. Higher BAP (222.2% difference per doubling; 95% CI 77.2-485.8) and TRAP5b (319.3%; 95% CI 128.3-669.5) were directly associated with Ob.S/BS and ES/BS, whereas sclerostin was inversely associated with ES/BS (-28.9%; 95% CI -44.8 to -7.1). PTH was not associated with bone-turnover measures. These findings suggest that BAP, TRAP5b, and sclerostin may provide useful adjunct information alongside PTH for assessing bone turnover and guiding therapy in patients with and without CKD.

Publisher Correction: On a tractable single-level reformulation of a multilevel model of the European entry-exit gas market with market power

Journal of Global Optimization · 2025-07-07

We propose a framework that allows to quantitatively analyze the interplay of the different agents involved in gas trade and transport in the context of the European entry-exit system. Previous contributions have focused on the case of perfectly competitive buyers and sellers of gas, which allows to replace the respective market equilibrium problem by a single welfare maximization problem. Our novel framework considers the mathematically more challenging case of a monopolistic and thus strategic gas seller. In this framework, the objective functions of the gas sellers and buyers cannot be aggregated into a common objective function, which is why a multilevel formulation is necessary to accurately capture the sequential nature of the decisions taken. For this setup, we derive sufficient conditions that allow for reformulating the challenging four-level model as a computationally tractable single-level reformulation. We prove the correctness of this reformulation and use it for solving several test instances to illustrate the applicability of our approach.

Choosing Nerve Blocks by Hip Fracture Subtype

Anesthesiology · 2025-12-09

Comparison of tibiofibular syndesmosis stability following treatment of proximal, middle, and distal third fibula fractures

European Journal of Orthopaedic Surgery & Traumatology · 2025-01-11 · 1 citations

PURPOSE: While treatment modalities for Maisonneuve fractures involving the proximal third of the fibula are established, no studies to date have reported outcomes associated with syndesmotic-only fixation of middle third fibular shaft fractures. The purpose of this study was to evaluate outcomes associated with syndesmotic-only fixation in the treatment of Maisonneuve fractures involving the middle third of the fibula. METHODS: A retrospective review was conducted on 257 cases of syndesmotic ankle instability with associated fibular fractures at a level 1 trauma center between 2013 and 2023. Patients were divided into cohorts based on fibular fracture location in the proximal, middle, or distal third of the fibula. The Chi-square test of independence, two-sample t-test, and analysis of variance were used to compare outcome measures between cohorts. RESULTS: Sixty-six patients were identified including 48% (n = 32) with proximal third fibular fractures, 20% (n = 13) with middle third fibular fractures, and 32% (n = 21) with distal third fibular fractures. Rates of infection, loss of reduction, wound healing complications, and reoperation did not vary significantly between cohorts. Functional outcome measures including range of motion, time to weight-bearing, and tibiofibular/medial clear space measurements at final follow-up were similar across cohorts. CONCLUSION: Patients with Maisonneuve fractures involving the middle third of the fibula demonstrated positive outcomes with syndesmotic fixation alone, with no documented cases of infection, loss of reduction, or wound healing issues. By demonstrating maintenance of anatomic reduction and low rates of complications, our results support the use of syndesmotic-only fixation in the treatment of middle third Maisonneuve fractures.

On a tractable single-level reformulation of a multilevel model of the European entry-exit gas market with market power

Journal of Global Optimization · 2025-03-22

Abstract We propose a framework that allows to quantitatively analyze the interplay of the different agents involved in gas trade and transport in the context of the European entry-exit system. Previous contributions have focused on the case of perfectly competitive buyers and sellers of gas, which allows to replace the respective market equilibrium problem by a single welfare maximization problem. Our novel framework considers the mathematically more challenging case of a monopolistic and thus strategic gas seller. In this framework, the objective functions of the gas sellers and buyers cannot be aggregated into a common objective function, which is why a multilevel formulation is necessary to accurately capture the sequential nature of the decisions taken. For this setup, we derive sufficient conditions that allow for reformulating the challenging four-level model as a computationally tractable single-level reformulation. We prove the correctness of this reformulation and use it for solving several test instances to illustrate the applicability of our approach.

Percutaneous analgesic device enabling both local anesthetic delivery and electrical stimulation (neuromodulation) of peripheral nerves: a pilot feasibility study (case series)

Regional Anesthesia & Pain Medicine · 2025-09-25 · 1 citations

Background A novel device integrating both local anesthetic delivery and peripheral nerve stimulation (PNS) to treat postoperative pain is under development. The device uses a catheter-over-needle design that permits ultrasound-guided percutaneous insertion. An integrated electrode and pulse generator enable PNS for up to 28 days. Such an approach may represent a paradigm shift in postoperative pain management by enabling the delivery of (1) a single-injection peripheral nerve block, (2) a continuous peripheral nerve block, and (3) neuromodulation—all through a single system that can be placed in a timeframe comparable with that of a traditional single-injection nerve block. The current prospective pilot study was executed under a US Food and Drug Investigational Device Exemption to develop insertion and management protocols, as well as assess the feasibility and safety of using the device to treat postoperative pain. Methods Preoperatively, adults (n=20) undergoing moderate-to-severely painful ambulatory shoulder or foot/ankle surgery had a device (RELAY, Gate Science, Moultonborough, NH) inserted under ultrasound guidance adjacent to the brachial plexus or sciatic nerve, respectively. Accurate insertion was confirmed with a 10 mL bolus of lidocaine via the catheter followed by bupivacaine (10 mL). If a continuous infusion was indicated, a portable pump was used to infuse ropivacaine (6–8 mL/h, 500 mL reservoir). Electric current was delivered using the integrated pulse generator for 7 days, followed by removal at home. Participants were contacted for data collection on postoperative days 1–5, 7, 8, and 14. Results During the first seven postoperative days, the median (IQR) “average” daily pain intensity as measured with the numeric rating scale (NRS) was 2 [0, 3]. Following postoperative day 1, daily average and maximum/worst NRS was less than 2 and 5, respectively. Regarding the “worst” (maximum) pain level over the entire study period of Days 0–14, 7 (35%) experienced mild pain (NRS<4), 10 (50%) moderate pain (NRS 4–7), and 3 (15%) severe pain (NRS>7). Cumulative oxycodone consumption the first week was a median of 43 (18, 73) mg. Conclusions This novel device successfully delivered a single-injection local anesthetic bolus, a continuous perineural infusion, and concurrent/subsequent electrical current. A randomized, sham-controlled clinical trial appears warranted. Clinicaltrials.gov NCT06818708

Risk Factors for Readmission Following Elderly Low Energy Pelvis Fractures

Geriatric Orthopaedic Surgery & Rehabilitation · 2025-05-01

Introduction Fragility fractures of the pelvis (FFP) are associated with loss of mobility and significant mortality in elderly patients. The purpose of this study was to assess the 60-day readmission rates following FFP and to identify what factors may predict readmission. Methods Six hundred thirty-one patients over 65 years of age presenting for FFP to a level 1 trauma center between 2010 and 2022 were reviewed. The chi-square test of independence and logistic regression were performed to identify factors associated with readmission. Results One hundred and thirty-six patients met inclusion criteria. Of these, 31 (23%) returned to the Emergency Department (ED) within 60 days of discharge and 16 (12%) were readmitted. Chronic obstructive pulmonary disease (COPD) (OR = 3.30, P = .01), discharge home instead of to a skilled nursing facility (SNF) (OR = 2.75, P = .01), discharge home from the ED instead of admission to the hospital (OR = 2.95, P = .009), and an American Society of Anesthesiologists (ASA) score ≥4 (OR = 5.14, P = .03) were all associated with return to the ED. Patients who were able to ambulate in the ED were less likely to be admitted to the hospital (OR = 0.05, P < .001) and more likely to return to the ED within 60 days (OR = 4.52, P = .03). Conclusion Return to the ED and readmission following FFP is common, with an incidence of 23% and 12% in our cohort. Patients who were not admitted as an inpatient after their initial presentation, and patients who were discharged home instead of to a SNF, both had a higher risk of repeat presentation within 60 days of discharge. Additionally, ambulation by patients in the ED may provide false reassurance, as these patients were less likely to be admitted as an inpatient, but more likely to subsequently return within 60 days.

Ultrasound-Guided Percutaneous Cryoneurolysis for Perioperative Analgesia Following Major Lower Extremity Amputation: A Randomized, Participant- and Observer-Masked, Sham-Controlled Pilot Study

Cureus · 2024-02-04 · 3 citations

BACKGROUND: Extremity amputations are associated with pain in both the residual limb and the phantom limb. This pain, which is often debilitating, may be prevented by excellent perioperative pain control. Ultrasound-guided percutaneous cryoneurolysis is an analgesic modality offering pain control for weeks or months following surgery. This treatment has not been compared to the sham procedure for large nerves (e.g., femoral and sciatic) to provide preoperative analgesia. We therefore conducted a randomized, controlled pilot study to evaluate the use of this modality for the treatment of pain following amputation to (1) determine the feasibility of and optimize the study protocol for a subsequent definitive clinical trial; and (2) estimate analgesia and opioid reduction within the first postoperative weeks. METHODS: A convenience sample of seven patients undergoing lower extremity amputation were randomized to receive either active cryoneurolysis or a sham procedure targeting the sciatic and femoral nerves in a participant-masked fashion. This was a pilot study with a relatively small number of participants, and therefore the resulting data were not analyzed statistically. RESULTS: Compared to the participants who received sham treatment (n=3), those who underwent active cryoneurolysis (n=4) reported lower pain scores and decreased opioid consumption at nearly all time points between days one and 21 following amputation. CONCLUSIONS: Ultrasound-guided percutaneous cryoneurolysis of the femoral and sciatic nerves prior to lower extremity amputation appears feasible and potentially effective. The data from this pilot study may be used to power a definitive randomized clinical trial.

Do all patients with history of pelvic ring injuries need a cesarean section? – A survey of orthopaedic and obstetric providers

Journal of Gynecology Obstetrics and Human Reproduction · 2024-03-27 · 1 citations

The sparse(st) optimization problem: reformulations, optimality, stationarity, and numerical results

Computational Optimization and Applications · 2024-11-28 · 2 citations

Abstract We consider the sparse optimization problem with nonlinear constraints and an objective function, which is given by the sum of a general smooth mapping and an additional term defined by the $$ \ell _0 $$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mi>ℓ</mml:mi> <mml:mn>0</mml:mn> </mml:msub> </mml:math> -quasi-norm. This term is used to obtain sparse solutions, but difficult to handle due to its nonconvexity and nonsmoothness (the sparsity-improving term is even discontinuous). The aim of this paper is to present two reformulations of this program as a smooth nonlinear program with complementarity-type constraints. We show that these programs are equivalent in terms of local and global minima and introduce a problem-tailored stationarity concept, which turns out to coincide with the standard KKT conditions of the two reformulated problems. In addition, a suitable constraint qualification as well as second-order conditions for the sparse optimization problem are investigated. These are then used to show that three Lagrange–Newton-type methods are locally fast convergent. Numerical results on different classes of test problems indicate that these methods can be used to drastically improve sparse solutions obtained by some other (globally convergent) methods for sparse optimization problems.