Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD

In-hospital Enrollment Into an Electronic Patient Portal Results in Improved Follow-up After Orthopedic Surgery: Cluster Randomized Controlled Trial

BackgroundElectronic patient portal (EPP) use is associated with lower no-show rates and increased patient satisfaction. However, there are disparities in enrollment into these communication platforms. ObjectiveWe hypothesized that guided inpatient enrollment into an EPP would improve clinical follow-up and EPP use rates for patients who underwent orthopedic surgery compared to the usual practice of providing information in the discharge summary. MethodsWe performed a randomized controlled trial of 229 adult patients who were admitted to the hospital for an orthopedic condition that required a 3-month follow-up visit. Patients were cluster-randomized by week to either the control or intervention group. The control group received information on how to enroll into and use the EPP in their discharge paperwork, whereas the intervention group was actively enrolled and taught how to use the EPP. At 3 months postdischarge, the patients were followed to see if they attended their follow-up appointment or used the EPP. ResultsOf the 229 patients, 83% (n=190) presented for follow-up at 3 months (control: 93/116, 80.2%; intervention: 97/113, 85.8%; P=.25). The likelihood of EPP use was significantly higher in the intervention group (control: 19/116, 16.4%; intervention: 70/113, 62%; odds ratio [OR] 8.3, 95% CI 4.5-15.5; P<.001). Patients in the intervention group who used the EPP were more likely to present for postsurgical follow-up (OR 3.59, 95% CI 1.28-10.06; P=.02). ConclusionsThe inpatient enrollment of patients who underwent orthopedic surgery into an EPP increased EPP use but did not independently result in enhanced follow-up. Patients who were enrolled as inpatients and subsequently used the portal had the highest likelihood of 3-month follow-up. Trial RegistrationClinicalTrials.gov NCT03431259; https://clinicaltrials.gov/ct2/show/NCT0343125

Carbon Fiber Implants in Orthopaedic Oncology

Carbon fiber offers numerous material benefits including reduced wear, high strength-to-weight ratio, a similar elastic modulus to that of bone, and high biocompatibility. Carbon fiber implants are increasingly used in multiple arenas within orthopaedic surgery, including spine, trauma, arthroplasty, and oncology. In the orthopaedic oncologic population, the radiolucency of carbon fiber facilitates post-operative imaging for tumor surveillance or recurrence, the monitoring of bony healing and union, and radiation mapping and delivery

A pilot study to examine the effect of chronic treatment with immunosuppressive drugs on mucociliary clearance in a vagotomized murine model.

Previously, we have demonstrated that mucociliary clearance (MCC) is diminished within the first months after surgery in lung transplant patients and the explanation for the reduction in MCC is unknown. We hypothesized that chronic treatment with a commonly prescribed regimen of immunosuppressive drugs significantly impairs MCC. We tested this hypothesis in a murine model of lung transplantation.Fifteen C57BL/6 mice underwent vagotomy on the right side to simulate denervation associated with lung transplantation in humans. For 6 days, seven mice (controls) were intraperitoneally injected with three 100 µL doses of phosphate buffered saline and eight mice (immunosuppressed) were injected with three 100 µL injections of tacrolimus (1 mg/kg), mycophenolate mofetil (30 mg/kg), and prednisone (2 mg/kg) once daily. Then, mice inhaled the radioisotope (99m)technetium and underwent gamma camera imaging of their lungs for 6.5 hrs. Counts in the right lung at 1-1.5 hrs and at 6-6.5 hrs were first background-corrected and then decay-corrected to time 0 counts. Decay-corrected counts were then divided by time 0 counts. Retention at each time point was subtracted from 1.00 and multiplied by 100% to obtain percent removed by mucociliary clearance.Although there was a slowing of MCC at 1-1.5 hrs for the immunosuppressed mice, there was no statistical difference in MCC measured at 1-1.5 hrs for the two groups of mice. At 6-6.5 hrs, MCC was significantly slower in the immunosuppressed mice, compared to controls, with 7.78±5.9% cleared versus 23.01±11.7% cleared, respectively (p = 0.006).These preliminary results suggest that chronic treatment with immunosuppressive medications significantly slows MCC in vagotomized C57BL/6 mice. These findings could shed light on why MCC is reduced in lung transplant patients whose lungs are denervated during surgery and who are chronically treated with immunosuppressive drugs post surgery

When observational studies are as helpful as randomized trials: Examples from orthopedic trauma : Examples from orthopedic trauma

Randomized controlled trials (RCTs) are often challenging to design in surgical fields and can be misleading when poorly executed. While the prevailing belief is that observational studies on therapeutic efficacy are credible only in exceptional circumstances due to unrecognized confounding, we identify three types of intervention in orthopaedic trauma and illustrate relevant features that allow observational studies in orthopaedic surgery to be as helpful as RCTs