Retention of Antibiotic Cement Delivery Implants in Orthopedic Infection Associated With United Fractures Does Not Increase Recurrence Risk.

OBJECTIVES: To evaluate whether retention of antibiotic cement delivery devices after resolution of orthopaedic infection is associated with recurrence. DESIGN: Retrospective cohort. SETTING: Academic medical center. PATIENT SELECTION CRITERIA: Patients with a fracture definitively treated with internal fixation that went on to unite and develop a confirmed fracture-related infection or osteomyelitis after a remote fracture surgery and had implantation of antibiotic-impregnated cement for infection management. OUTCOME MEASURES AND COMPARISONS: Patients were divided into whom the antibiotic implants were retained (Retained Cohort) and whom the antibiotic implants were removed (Removed Cohort). Outcome measures included clinical infection resolution, infection recurrence, time to resolution of infection signs, symptoms and laboratory values, reoperation and readmission rates, and need for soft tissue coverage (local flap vs. free tissue transfer) because of recurrence. RESULTS: Of 98 patients treated for fracture-related infection in united fractures or osteomyelitis after a remote fracture surgery, 39 (39.8%) underwent implantation of antibiotic-impregnated cement delivery devices: 21 (21.4%) beads, 7 (7.1%) rods, and 11 (11.2%) blocks. Twenty patients (51.3%) comprised the Retained Cohort and 19 patients (48.7%) comprised the Removed Cohort. There were few differences in demographics ([American Society of Anesthesiology Score, P = 0.026] and [diabetes, P = 0.047]), infection location, and pathogenic profiles. The cohorts demonstrated no difference in eventual resolution of infection (100% in the Retained Cohort, 95% in the Removed Cohort, P = 0.487) and experienced similar time to clinical infection resolution, based on signs, symptoms, and laboratory values ( P = 0.360). There was no difference in incidence of subsequent infection recurrence after clinical infection resolution (1 recurrence Retained vs. 2 recurrences Removed, P = 0.605) for those considered "cured." Compared with the Retained Cohort, the Removed Cohort underwent more reoperations (0.40 vs. 1.84 reoperations, P < 0.001) and admissions after implantation ( P < 0.001). CONCLUSIONS: Retention of antibiotic-impregnated cement delivery devices in patients with orthopaedic infection after fractured bones that have healed was not associated with infection recurrence. Additional surgical intervention with the sole purpose of removing antibiotic delivery devices may not be warranted. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Current and future therapeutic strategies for high-grade gliomas leveraging the interplay between epigenetic regulators and kinase signaling networks.

Targeted therapies, including small molecule inhibitors directed against aberrant kinase signaling and chromatin regulators, are emerging treatment options for high-grade gliomas (HGG). However, when translating these inhibitors into the clinic, their efficacy is generally limited to partial and transient responses. Recent studies in models of high-grade gliomas reveal a convergence of epigenetic regulators and kinase signaling networks that often cooperate to promote malignant properties and drug resistance. This review examines the interplay between five well-characterized groups of chromatin regulators, including the histone deacetylase (HDAC) family, bromodomain and extraterminal (BET)-containing proteins, protein arginine methyltransferase (PRMT) family, Enhancer of zeste homolog 2 (EZH2), and lysine-specific demethylase 1 (LSD1), and various signaling pathways essential for cancer cell growth and progression. These specific epigenetic regulators were chosen for review due to their targetability via pharmacological intervention and clinical relevance. Several studies have demonstrated improved efficacy from the dual inhibition of the epigenetic regulators and signaling kinases. Overall, the interactions between epigenetic regulators and kinase signaling pathways are likely influenced by several factors, including individual glioma subtypes, preexisting mutations, and overlapping/interdependent functions of the chromatin regulators. The insights gained by understanding how the genome and epigenome cooperate in high-grade gliomas will guide the design of future therapeutic strategies that utilize dual inhibition with improved efficacy and overall survival.

Fracture related infection (FRI) of the upper extremity correlates with poor bone and soft tissue healing.

PURPOSE: The purpose of this study was to evaluate the specific course and complication profile following the development of FRI in the upper extremity. METHODS: An IRB-approved retrospective review was conducted on a consecutive series of operatively managed patients within an academic medical center between 1/2010 and 6/2022. Included patients met the following criteria: (1) upper extremity fracture definitively treated with internal fixation (2) development of criteria for suggestive or confirmatory FRI (as per the FRI Consensus Group) and (3) age ≥ 18 years. Baseline demographics, medical history, injury information, infection characteristics, hospital quality measures, and outcomes were recorded. A 3:1 propensity-matched control cohort of patients without FRI was obtained using the same dataset. Univariable analysis was performed to compare the outcomes (rate of nonunion, time to bone healing, need for soft tissue coverage, patient reported joint stiffness at final follow-up) of the FRI vs Non-FRI cohorts. RESULTS: Of 2827 patients treated operatively for an upper extremity fracture, 43 (1.53%) met criteria for suggestive of confirmatory FRI. The successful propensity match (43 FRI, 129 Non-FRI) revealed no differences in demographics, baseline health status, or fracture location. FRI patients underwent more reoperations (p < 0.001), experienced an increased rate of removal of hardware (p < 0.001), and were admitted more frequently following index operation (p < 0.001). The FRI cohort had higher rates of fracture nonunion (p = 0.003), and a prolonged mean time to bone healing in months (8.37 ± 7.29 FRI vs. 4.14 ± 5.75 Non-FRI, p < 0.001). Additionally, the FRI cohort had a greater need for soft tissue coverage throughout their post-operative fracture treatment (p = 0.014). While there was no difference in eventual bone healing (p = 0.250), FRI patients experienced a higher incidence of affected joint stiffness at final follow-up (p < 0.001). CONCLUSION: Patients who develop an FRI of the upper extremity undergo more procedures and experience increased complications throughout their treatment, specifically increased joint stiffness. Despite this, ultimate outcome profiles are similar between patients who experience FRI and those who do not following operative repair of an upper extremity fracture. LEVEL OF EVIDENCE: III.

Effect of concomitant deformity correction on patient outcomes following femoral (OTA type 32) nonunion repair.

INTRODUCTION: The purpose of this study was to determine what effect, if any, concomitant deformity correction has on outcomes following femoral nonunion repair. METHODS: 605 consecutive patients who presented to our center with a long bone nonunion treated by one of 3 surgeons was queried. Sixty-two patients (10 %) with complete follow up were treated for a fracture nonunion following a Type 32 femur fracture (subtrochanteric, femoral shaft or distal third metaphysis) over an 11-year period. Twenty of these patients underwent a deformity correction (DC)-angular, rotational, or a combination of both-as part of their femoral reconstruction. Patient demographics and initial injury information was reviewed and compared. Outcomes including radiographic healing, time to union, postoperative complications, patient reported pain scores, and functional outcome scores using the Short Musculoskeletal Functional Assessment (SMFA) were recorded. Patients with and without deformity correction were analyzed and compared using independent T-tests and Chi-Square tests. RESULTS: Compared to the non-deformity correction (NDC) cohort, the DC cohort demonstrated a worse complication profile. Notably, the DC cohort had longer time to union (11.6 ± 7.3 months vs 7.6 ± 8.5 months, P = 0.042), reported significantly higher VAS pain scores at 1-year post-op (4.2 ± 2.8 vs 2.3 ± 2.6, P = 0.007), experienced more complications (25 % vs 4.8 %, P = 0.019), and had a higher rate of secondary procedures (30 % vs 4.8 %, P = 0.006). The DC patients reported less improvement in functional capability as displayed by a smaller average improvement in initial and final SMFA scores (P = 0.042) There was no difference in ultimate bone healing (P = 0.585), baseline SMFA (P = 0.294), and latest SMFA (P = 0.066). CONCLUSION: Deformity correction, if needed as part of femoral nonunion repair, is associated with an increased time to heal, greater rate of complications and diminished improvement of functionality. Eventual healing and patient reported outcomes were similar whether a deformity correction is necessary or not. LEVEL OF EVIDENCE: III.

Primary versus conversion reverse total shoulder arthroplasty for complex proximal humeral fractures in elderly patients: a retrospective comparative study.

BACKGROUND: The purpose of this study was to compare clinical, implant-related, and patient-reported outcomes of shoulders undergoing conversion to reverse total shoulder arthroplasty (rTSA) following previous open reduction-internal fixation vs. shoulders undergoing rTSA as a primary treatment modality for acute proximal humeral fractures (PHFs) in patients aged ≥65 years. METHODS: We performed a retrospective analysis of a prospectively collected cohort of patients who underwent primary rTSA for PHFs vs. a cohort who underwent conversion arthroplasty with rTSA following fracture repair between 2009 and 2020. Outcomes were assessed preoperatively and at latest follow-up. Demographic characteristics and outcomes were analyzed between cohorts using conventional statistics, as well as stratification by minimal clinically important difference and substantial clinical benefit thresholds where applicable. RESULTS: In total, 406 patients met the study criteria, of whom 322 underwent primary rTSA for PHF and 84 underwent conversion rTSA after failed PHF open reduction-internal fixation. The conversion rTSA cohort was, on average, 7 years younger than the primary rTSA cohort (65 ± 10 years vs. 72 ± 9 years, P < .001). The follow-up periods were similar between the cohorts, with an average of 47.1 months (range, 24-138 months). The percentages of Neer 3-part (41.9% vs. 45.2%) and 4-part (49.1% vs. 46.4%) PHFs were similar (P > .99). The primary rTSA cohort achieved higher forward elevation, external rotation, and patient-reported outcome measurements including Simple Shoulder Test, American Shoulder and Elbow Surgeons, University of California-Los Angeles, Constant, Shoulder Arthroplasty Smart, and Shoulder Pain and Disability Index scores at a minimum of 24 months postoperatively (P < .05 for all). Patient satisfaction was higher in the primary rTSA group than in the conversion rTSA cohort (P = .002). Patient-reported outcome measures uniformly favored the primary rTSA cohort, rising to the level of statistical significance for forward elevation, American Shoulder and Elbow Surgeons score, and Shoulder Pain and Disability Index score (P < .05) relative to substantial clinical benefit. The adverse event rate and revision rate in the conversion rTSA cohort were higher than those in the primary rTSA cohort (26.2% vs. 2.5% [P < .001] and 8.3% vs. 1.6% [P = .001], respectively). At 10 years postoperatively, the revision-free implant survival rate was significantly lower in the conversion cohort compared with the primary cohort (66% vs. 94%, P = .012). Finally, the hazard ratio of revision was 3.69 in the conversion rTSA cohort compared with only 1.0 in the primary rTSA cohort. CONCLUSION: This study demonstrates that elderly patients who undergo rTSA as a conversion procedure following previous osteosynthesis do not fare as well as those treated with rTSA for acute displaced PHFs. Conversion rTSA patients report lower patient satisfaction and have significantly restricted range of shoulder motion, a higher risk of complications, a higher risk of revision, poorer patient-reported outcomes, and a shorter implant survival rate at 10 years compared with patients undergoing acute rTSA.

Impact of COVID-19 pandemic on cross-country runners: changes in training, sleep, diet, and mental health.

Objective: Determine the impact of the COVID-19 pandemic on the changes in training, sleep, diet, and mental health of cross-country runners. Participants: Cross-country runners from NCAA Division II institutes. Methods: Wilcoxon signed-rank test was performed to analyze survey responses to ordinal questions on the survey while Spearman's rank correlation analysis (ρ) was used to calculate correlation between after the start of pandemic questions. Data was marked significant at p < 0.05. Results: Analysis of the survey responses revealed that cross-country runners were more likely to experience feelings of depression (p < 0.001), lack of motivation (p < 0.001), and higher daily stress (p < 0.001) after the start of the pandemic. After the start of the pandemic, runners running less days per week were more likely to report an increased feeling of depression (ρ=-0.315, p = 0.008) and lack of motivation (ρ=-0.458, p < 0.001). Conclusions: The present study underscores the importance of training, sleep, diet, and mental health amongst cross-country runners.

Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis.

High-Dose Rifampicin Regimen for Pulmonary TuberculosisThis randomized, controlled trial tested the efficacy and safety of high-dose rifampicin (1200 or 1800 mg/d) as part of the treatment regimen for pulmonary tuberculosis. Four-month high-dose rifampicin regimens had no dose-limiting side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen.

Safety and efficacy considerations amongst the elderly population in the updated treatment of heart failure: a review.

INTRODUCTION: Heart failure is one of the cardiovascular diseases that impacts the geriatric population. As new clinical trials investigating heart failure are conducted, groundbreaking information is assessable to further evolve the treatment. To correctly improve the quality of life of elderly patients, it is critical to evaluate the safety and efficacy of new and improved therapy regimens. AREAS COVERED: In reviewal of the 2021 and 2022 updated guidelines, the safety and efficacy of the newly indicated medications will be addressed. The new indications cover sacubitril/valsartan and two SGLT2 inhibitors: dapagliflozin and empagliflozin. An introduction to the medications discussed covers the pharmacology before addressing the efficacy and safety considerations in the elderly population. Furthermore, prime drug-drug interactions associated with the two classes of medications will be considered as well as providing possible solutions to further create the safest drug therapy for geriatric patients with common comorbidities. EXPERT OPINION: The two classes of medications, the ARNI and SGLT2 inhibitors, are well-tolerated amongst the elderly population. With the release of new guidelines, the updated medications will provide safer and better therapy in this disease state for geriatrics. One major limitation includes the high cost of these brand-named medications.

One-year Mortality Outcomes From the Advancing Cryptococcal Meningitis Treatment for Africa Trial of Cryptococcal Meningitis Treatment in Malawi.

In Malawi, 236 participants from the Advancing Cryptococcal Meningitis Treatment for Africa trial were followed for 12 months. The trial outcomes reported at 10 weeks were sustained to 1 year. One-week amphotericin B plus flucytosine was associated with the lowest 1 year mortality (27.5% [95% confidence interval, 16.3 to 44.1]).

Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa.

BACKGROUND: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODS: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. RESULTS: A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P=0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen. CONCLUSIONS: One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in resource-limited settings. (ACTA Current Controlled Trials number, ISRCTN45035509 .).

Influence of mileage accumulation on the particle mass and number emissions of two gasoline direct injection vehicles.

Gasoline direct injection (GDI) is a new engine technology intended to improve fuel economy and greenhouse gas emissions as required by recently enacted legislative and environmental regulations. The development of this technology must also ensure that these vehicles meet new LEV III and Tier 3 emissions standards as they phase in between 2017 and 2021. The aim of the present paper is to examine, at least for a small set, how the PM emissions from GDI vehicles change over their lifetime. The paper reports particle mass and number emissions of two GDI vehicles as a function of mileage up to 150K miles. These vehicles exhibit PM emissions that are near or below the upcoming 3 mg/mi FTP and 10 mg/mi US06 mass standards with little, if any, deterioration over 150K miles. Particle number emissions roughly follow the previously observed 2 × 10(12) particles/mg correlation between solid particle number and PM mass. They remained between the interim and final EU stage 6 solid particle count standard for gasoline vehicles throughout the mileage accumulation study. These examples demonstrate feasibility to meet near-term 3 mg/mi and interim EU solid particle number standards, but continued development is needed to ensure that this continues as further fuel economy improvements are made.

Importance of addressing National Electrical Code violations that result in unusual exposure to 60 Hz magnetic fields.

We evaluated wiring in multifamily developments containing National Electrical Code(R) (NEC(R)) violations as a source of unusual exposure to 60 Hz magnetic fields. Two methods were used in this evaluation: measurement and modeling. We measured the building wiring as a source of magnetic fields in six multifamily developments in Michigan. In this small sample, building wiring proved to be an important source of exposure in four of the six cases. In all four cases with exposure from building wiring, one or more NEC violations were involved. To supplement our measurement efforts, we used computer modeling to compare magnetic field exposure due to building wiring with magnetic field exposure from external power lines. Our calculations showed that where the building wiring has a NEC violation leading to net current loops, the exposure due to wiring is likely to be more important than that from external power lines. Our results support the results obtained in a recent study of the exposure of Californian K-12 students to magnetic fields, where building wiring with one or more NEC violation was found to be the single most important exposure source. If 60 Hz magnetic fields are important to avoid, then improved enforcement of the NEC, as required by law, is perhaps the single most important mitigation policy to adopt. Bioelectromagnetics 25:102-106, 2004.