Symptomatic rib fracture nonunion: a systematic review of the literature.

INTRODUCTION: Rib fractures commonly occur in trauma patients with varying presentations. Though the literature in recent years has moved toward favoring more early intervention of acute rib fractures, little has been reported on the matter of surgical fixation for symptomatic rib fracture nonunions. MATERIALS AND METHODS: We performed a review of PubMed and Cochrane databases for articles published since 2000. Inclusion criteria were studies with greater than six months of follow-up, while case studies were excluded. A thorough analysis was performed on patient outcomes, complications reported, operative techniques utilized, and fixation systems used, among other parameters reported by the articles. RESULTS: One hundred and thirty-nine studies resulted from our review, and a total of nine studies met our inclusion criteria with a combined total of 182 patients who underwent open reduction and internal fixation for symptomatic rib fracture nonunions. All studies reported a significant reduction of pain with increased satisfaction in the majority of patients. There were a total of 71 postoperative complications, the most common of which included surgical site infections, hardware failure, and hematoma. The most serious complications were insulting injury to the lung parenchyma or pleura; however, these were extremely rare based off the current literature. The use of bone grafting was common with eight of the nine studies mentioning the benefits of grafting. CONCLUSION: Surgical stabilization of rib fracture nonunions appears to be an appropriate treatment alternative, and various techniques and approaches may be used with similar success. Further studies with higher level of evidence are recommended on the subject.

Implementation and outcomes of a pharmacist-led collaborative drug therapy management program for oncology symptom management.

INTRODUCTION: Nausea, vomiting, constipation, and diarrhea are common cancer and cancer therapy adverse effects. Pharmacists are uniquely positioned to optimize patient symptom control and minimize excess use of hospital resources, such as emergency department visits. METHODS: Michigan Medicine oncology clinical pharmacists have been independently providing patient symptom management through a collaborative drug therapy management (CDTM) program which established guidelines for management of gastrointestinal toxicities (nausea, vomiting, diarrhea, and/or constipation) secondary to a patient's cancer diagnosis or treatment of the cancer. Patients were referred to the pharmacist by the treating oncologist or hematologist. RESULTS: From June 2019 to May 2020, there were a total of 62 patient referrals. Ten of the 62 referrals did not meet the CDTM inclusion criteria, resulting in 52 patients who were managed by the pharmacists. The total number of individual pharmacist visits was 136, with a median of 2.2 (range, 0-11) visits per patient referred. A total of 169 categorized pharmacist interventions were captured. Most interventions (100/169, 59.2%) were related to nausea/vomiting. Diarrhea-related and constipation-related interventions accounted for 10 (5.9%) and 13 (7.7%) of the total interventions, respectively. Most patients (36/52, 69.2%) had a reduction in the severity of their referral diagnosis symptom(s) based on Common Terminology Criteria for Adverse Events grading. CONCLUSION: The Michigan Medicine Pharmacist CDTM program allowed pharmacists to independently manage gastrointestinal toxicities of patients with cancer and improved patient symptom severity. The CDTM program has the opportunity to improve quality of care.

Correction to: Targeting and Therapeutic Monitoring of H3K27M-Mutant Glioma.

The original version of this review article unfortunately contained a mistake in the author group section.

Targeting and Therapeutic Monitoring of H3K27M-Mutant Glioma.

PURPOSE OF REVIEW: H3K27M is a frequent histone mutation within diffuse midline gliomas and is associated with a dismal prognosis, so much so that the 2016 CNS WHO classification system created a specific category of "Diffuse Midline Glioma, H3K27M-mutant". Here we outline the latest pre-clinical data and ongoing current clinical trials that target H3K27M, as well as explore diagnosis and treatment monitoring by serial liquid biopsy. RECENT FINDINGS: Multiple epigenetic compounds have demonstrated efficacy and on-target effects in pre-clinical models. The imipridone ONC201 and the IDO1 inhibitor indoximod have demonstrated early clinical activity against H3K27M-mutant gliomas. Liquid biopsy of cerebrospinal fluid has shown promise for clinical use in H3K27M-mutant tumors for diagnosis and monitoring treatment response. While H3K27M has elicited a widespread platform of pre-clinical therapies with promise, much progress still needs to be made to improve outcomes for diffuse midline glioma patients. We present current treatment and monitoring techniques as well as novel approaches in identifying and targeting H3K27M-mutant gliomas.

Running exercise mitigates the negative consequences of chronic stress on dorsal hippocampal long-term potentiation in male mice.

In the hippocampus, learning and memory are likely mediated by synaptic plasticity, known as long-term potentiation (LTP). While chronic intermittent stress is negatively correlated, and exercise positively correlated to LTP induction, we examined whether exercise could mitigate the negative consequences of stress on LTP when co-occurring with stress. Mice were divided into four groups: sedentary no stress, exercise no stress, exercise with stress, and sedentary with stress. Field electrophysiology performed on brain slices confirmed that stress alone significantly reduced dorsal CA1 hippocampal LTP and exercise alone increased LTP compared to controls. Exercise with stress mice exhibited LTP that was significantly greater than mice undergoing stress alone but were not different from sedentary no stress mice. An ELISA illustrated increased corticosterone in stressed mice compared to no stress mice. In addition, a radial arm maze was used to examine behavioral changes in memory during 6 weeks of stress and/or exercise. Exercised mice groups made fewer errors in week 2. RT-qPCR was used to examine the mRNA expression of components in the stress and exercise pathways in the four groups. Significant changes in the expression of the following targets were detected: BDNF, TrkB, glucocorticoid, mineralocorticoid, and dopamine 5 receptors. Collectively, exercise can mitigate some of the negative impact stress has on hippocampal function when both occur concurrently.

Principles for optimizing anterior cruciate ligament reconstruction outcomes in elite athletes: a review of current techniques.

Anterior cruciate ligament (ACL) tears are one of the most common sport-related injuries and occur in greater than 3% of athletes in a four-year window of sports participation. Non-contact injuries are the most common mechanism for ACL injury in elite-level athletes, especially with increased valgus and external rotation of the knee when loading eccentrically in flexion. Because of the immense toll these injuries and their recovery take on athletes especially, optimal treatment has been a subject of great interest for some time. Many ACL reconstruction (ACLR) and repair techniques have been implemented and improved in the last two decades, leading to many surgical options for this type of injury. The surgical approach to high-level athletes in particular requires additional attention that may not be necessary in the general population. Important considerations for optimizing ACL treatment in high-level athletes include choosing repair vs. reconstruction, surgical techniques, choice of auto- or allograft, and associated concomitant procedures including other injuries or reinforcing techniques as well as attention to rehabilitation. Here, we discuss a range of surgical techniques from repair to reconstruction, and compare and contrast various reconstructive and reinforcing techniques as well as associated surgical pearls and pitfalls. Good outcomes for athletes suffering from ACL injury are attainable with proper treatment including the principles discussed herein.

Supratubercle Anterior Closing Wedge Osteotomy: No Changes in Patellar Height and Significant Decreases in Anterior Tibial Translation at 6 Months Postoperatively.

BACKGROUND: Because of the increased prevalence of revision anterior cruciate ligament (ACL) reconstruction, there has been a desire to understand the role of posterior tibial slope on increased anterior tibial translation and increased ACL graft forces. One potential concern in supratubercle anterior closing wedge proximal tibial osteotomy (ACW-PTO) for decreasing the posterior tibial slope is the risk of altering the patellar height. PURPOSE: To radiographically assess changes in (1) patellar height, (2) anterior tibial translation, and (3) posterior tibial slope after supratubercle ACW-PTO. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients who underwent supratubercle ACW-PTO by a single surgeon between July 2019 and June 2023 were included. Standardized lateral knee weightbearing radiographs to assess patellar height (via the Caton-Deschamps index), anterior tibial translation of the lateral tibial plateau relative to the lateral femoral condyle, and posterior tibial slope were obtained at 4 time points (preoperatively and 1 day, 3 months, and 6 months postoperatively). Paired t test was used to compare differences between preoperative, 1-day, and 3- and 6-month values for patellar height as measured using the Caton-Deschamps index and for posterior tibial slope. Paired t test was also used to compare differences in the preoperative and 6-month postoperative values for anterior tibial translation. RESULTS: In 20 patients after ACW-PTO, the Caton-Deschamps index demonstrated a significant increase in patellar height on postoperative day 1 (P < .001) but no significant differences at 3 (P = .057) and 6 (P = .176) months postoperatively. Anterior tibial translation on standing lateral knee radiographs was significantly decreased by a mean of 8.9 mm from preoperatively to 6 months postoperatively (P < .001). Posterior tibial slope was significantly decreased by a mean of 11.2° from preoperatively to 6 months postoperatively (P < .001). CONCLUSION: Supratubercle ACW-PTO performed for ACL reconstruction failure in the setting of an increased posterior tibial slope did not induce significant changes in patellar height postoperatively. Furthermore, after ACW-PTO, there was a significant decrease in anterior tibial translation and posterior tibial slope.

Seven tesla knee MRI T2*-mapping detects intrasubstance meniscus degeneration in patients with posterior root tears.

Background: Medial meniscus root tears often lead to knee osteoarthritis. The extent of meniscal tissue changes beyond the localized root tear is unknown. Purpose: To evaluate if 7 Tesla 3D T2*-mapping can detect intrasubstance meniscal degeneration in patients with arthroscopically verified medial meniscus posterior root tears (MMPRTs), and assess if tissue changes extend beyond the immediate site of the posterior root tear detected on surface examination by arthroscopy. Methods: In this prospective study we acquired 7 T knee MRIs from patients with MMPRTs and asymptomatic controls. Using a linear mixed model, we compared T2* values between patients and controls, and across different meniscal regions. Patients underwent arthroscopic assessment before MMPRT repair. Changes in pain levels before and after repair were calculated using Knee Injury & Osteoarthritis Outcome Score (KOOS). Pain changes and meniscal extrusion were correlated with T2* using Pearson correlation (r). Results: Twenty patients (mean age 53 ± 8; 16 females) demonstrated significantly higher T2* values across the medial meniscus (anterior horn, posterior body and posterior horn: all P < .001; anterior body: P = .007), and lateral meniscus anterior (P = .024) and posterior (P < .001) horns when compared to the corresponding regions in ten matched controls (mean age 53 ± 12; 8 females). Elevated T2* values were inversely correlated with the change in pain levels before and after repair. All patients had medial meniscal extrusion of ≥2 mm. Arthroscopy did not reveal surface abnormalities in 70% of patients (14 out of 20). Conclusions: Elevated T2* values across both medial and lateral menisci indicate that degenerative changes in patients with MMPRTs extend beyond the immediate vicinity of the posterior root tear. This suggests more widespread meniscal degeneration, often undetected by surface examinations in arthroscopy.

Combined Rip-Stop and Transtibial Pull-out Technique for Lateral Meniscus Radial Repairs.

Radial tears of the meniscus disrupt circumferential fibers that allow for the dispersion of axial tibiofemoral forces. Both nonoperative treatment and meniscectomy carry increased risk of early-onset degeneration of the joint because of decreased contact surface area and increased point-loading of the chondral surfaces. Radial type tears are also notable for the relatively high failure rate associated with repair. The purpose of this technical note is to demonstrate our surgical technique for a radial lateral meniscus repair construct that allows for good apposition and anatomic reduction of the meniscus with less risk of residual postoperative extrusion through use of a combination inside-out rip-stop and transtibial pull-out suturing repair.

Treatment of a Failed Posterior Cruciate Ligament Avulsion Fracture Fixation in a Skeletally Immature Patient: A Case Report.

CASE: A 12-year-old skeletally immature girl presented with 1 year of persistent instability after an open reduction and internal fixation (ORIF) for a posterior cruciate ligament (PCL) avulsion fracture. With a period of nonoperative management, her PCL stress radiographic measurements significantly decreased and her posterior tibial slope increased because the primary ORIF effectively led to growth arrest with an early fusion of the posterior tibial physis. At age 13 years when she was skeletally mature, revision PCL and fibular collateral ligament (FCL) reconstructions were performed. Promising clinical outcomes were observed at age 17 years. CONCLUSION: Pediatric patients with a failed PCL ORIF can successfully be managed with a period of nonoperative bracing and a revision PCL reconstruction once skeletally mature.

Concurrent Repair of Medial Meniscal Ramp Lesions and Lateral Meniscus Root Tears in Patients Undergoing Anterior Cruciate Ligament Reconstruction: The "New Terrible Triad".

Recent studies have suggested that up to 8% of patients with anterior cruciate ligament (ACL) tears can present with a combined medial meniscal ramp lesion (MMRL) and lateral meniscus root tear (LMRT). MMRLs and LMRTs often are missed preoperatively and can increase the risk of ACL graft failure if left untreated. Given the potential synergistic biomechanical consequences and challenging repair techniques used for treatment, our group commonly refers to this presentation (MMRL-LMRT-ACL) as the "new terrible triad" of ACL pathology. This Technical Note aims to describe a systematic approach for arthroscopic assessment and our preferred inside-out and transtibial pull-out repair techniques to efficiently diagnose and treat a combined MMRL and LMRT at the time of ACL reconstruction surgery.

Combined Repair of Medial Meniscal Ramp Lesions and Posterior Root Tears of the Lateral Meniscus During Anterior Cruciate Ligament Reconstruction: A Case Report.

CASE: This case report describes the clinical outcomes for 2 patients who underwent a primary or revision anterior cruciate ligament (ACL) reconstruction with a combined inside-out and transtibial pullout repair for a medial meniscal ramp lesion (MMRL) and a lateral meniscus root tear (LMRT), respectively. Promising short-term outcomes were seen at the one-year follow-up for both patients. CONCLUSIONS: Utilization of these repair techniques can successfully treat a combined MMRL and LMRT injury at the time of primary or revision ACL reconstruction.

Treatment related toxicities with combination BRAF and MEK inhibitor therapy in resected stage III melanoma.

Combination dabrafenib (D) and trametinib (T) is an FDA approved adjuvant therapy for patients with resected stage III BRAF-mutant melanoma. We describe treatment-related toxicities with adjuvant D+T in a real-world population through a retrospective case series. The primary endpoint was development of toxicities. Results: Eighteen of the 20 patients (90%) required at least one treatment interruption due to adverse events (AEs), 11 patients (55%) required a dose reduction and 13 (65%) permanently discontinued therapy due to an AE. The nine patients who did not require dose reduction had been initiated on a lower starting dose of dabrafenib. The most common treatment-limiting AEs were recurrent pyrexia and chills (85%) and liver laboratory abnormalities (50%). The median total time on therapy was 148.5 days (range 19-383), 40.7% (range 5.2-100%) of the intended one-year duration. Conclusion: Adjuvant treatment of melanoma with combination D+T is associated with treatment-limiting toxicities in the majority of this patient group. Patients should be carefully monitored throughout therapy.

Panobinostat penetrates the blood-brain barrier and achieves effective brain concentrations in a murine model.

PURPOSE: Panobinostat, an orally bioavailable pan-HDAC inhibitor, has demonstrated potent activity in multiple malignancies, including pediatric brain tumors such as DIPG, with increased activity against H3K27M mutant cell lines. Given limited evidence regarding the CNS penetration of panobinostat, we sought to characterize its BBB penetration in a murine model. METHODS: Panobinostat 15 mg/kg was administered IV to 12 CD-1 female mice. At specified time points, mice were euthanized, blood samples were collected, and brains were removed. LC-MS was performed to quantify panobinostat concentrations. Cmax and AUC were estimated and correlated with previously published pharmacokinetic analyses and reports of IC-50 values in DIPG cell lines. RESULTS: Mean panobinostat plasma concentrations (ng/mL) were 27.3 ± 2.5 at 1 h, 7.56 ± 1.8 at 2 h, 1.48 ± 0.56 at 4 h, and 2.33 ± 1.18 at 7 h. Mean panobinostat brain concentrations (ng/g) were 60.5 ± 6.1 at 1 h, 42.9 ± 5.4 at 2 h, 33.2 ± 6.1 at 4 h, and 28.1 ± 4.3 at 7 h. Brain-to-plasma ratio at 1 h was 2.22 and the brain to plasma AUC ratio was 2.63. Based on the published human pharmacokinetic data, the anticipated Cmax in humans is expected to be significantly higher than the IC-50 identified in DIPG models. CONCLUSION: It is expected that panobinostat would be effective in CNS tumors where the IC-50 is in the low nanomolar range. Thus, our data demonstrate panobinostat crosses the BBB and achieves concentrations above the IC-50 for DIPG and other brain tumors and should be explored further for clinical efficacy.