Serial Magnetic Resonance Imaging for Aortic Dilation in Tetralogy of Fallot With Pulmonary Stenosis.

Aortic dilation occurs in patients with repaired tetralogy of Fallot (TOF), but the rate of growth is incompletely characterized. The aim of this study was to assess the rates of growth of the aortic root and ascending aorta in a cohort of pediatric and adult patients with sequential magnetic resonance angiography Magnetic Resonance Imaging (MRI) data. Using serial MRI data from pediatric and adult patients with repaired TOF, we performed a retrospective analysis of the rates of growth and associations with growth of the aortic root and ascending aorta. Patients with pulmonary atresia or absent pulmonary valve were excluded. Between years 2005 to 2021, a total of 99 patients were enrolled. A follow-up MRI was performed an average of 5.9 ± 3.7 years from the initial study. For the cohort aged ≥16 years, the mean rate of change in diameter was 0.2 ± 0.5 mm/year at the ascending aorta and 0.2 ± 0.6 mm/year at the sinus of Valsalva. For the entire cohort, the mean change in cross-sectional area indexed to height at the ascending aorta was 7 ± 12 mm2/m/year and at the sinus of Valsalva was 10 ± 16 mm2/m/year. Younger age was associated with higher rates of growth of the sinus of Valsalva while the use of ß blockers or angiotensin-converting enzyme inhibitors was associated with a slower rate of growth. There were no cases of aortic dissection in this cohort. We conclude that serial MRI demonstrates a slow rate of growth of the aorta in the TOF.

Posterolateral Corner Reconstruction: Surgical Technique and Postoperative Rehabilitation.

Anatomic posterolateral corner (PLC) reconstruction is utilized for ligamentous knee instability associated with PLC injury in patients who desire a return to active lifestyles1,2. The fibular collateral ligament (FCL) and popliteal tendon (PLT) are reconstructed in anatomic fashion according to techniques described by LaPrade et al.3-7. Description: Various PLC reconstruction techniques have been described; however, the preferred reconstruction technique of the senior author is the method developed by LaPrade et al. that restores the anatomy of the 3 primary stabilizers of the PLC, including the FCL, PLT, and popliteofibular ligament3,5,6. Alternatives: Alternative nonoperative treatments include knee immobilization for 4 weeks and physical therapy. Surgical alternatives include PLC repair, which involves repair of the lateral collateral ligament, PLT, and/or popliteofibular ligament if structures can be anatomically reduced to their attachment site. However, repair of acute grade-III PLC injuries with staged treatment of concurrent cruciate injuries is associated with a substantially higher postoperative PLC failure rate8-10. Rationale: Clinical outcomes have demonstrated that primary repairs have significantly higher rates of reoperation compared with reconstruction; therefore, reconstruction is recommended. Treatment of grade-III PLC injuries with reconstruction of midsubstance tears and any associated cruciate ligament tears results in significantly improved objective stability11. In addition, anatomic PLC reconstruction has demonstrated improved subjective and objective patient outcomes compared with nonsurgical treatment or repair5,11,12. Expected Outcomes: Reconstruction of the PLC offers excellent outcomes after surgery. Studies have shown that the fibular-based technique for treatment of a chronic isolated PLC injury showed good results in terms of clinical outcome, restoring knee varus and rotational stability13. Important Tips: Patients with associated proximal tibiofibular joint instability will benefit from this reconstruction because this technique will add stability to the joint.This surgical approach is technically demanding, requiring proficiency with surgical dissection.Damage to the common peroneal nerve can potentially occur. Careful dissection and placement of retractors should be observed.Risks include surgical failure due to unrecognized malalignment; especially in chronic cases, the patient should have a complete evaluation of the standing alignment and tibial slope12. Acronyms and Abbreviations: FCL = fibular collateral ligamentPFL = popliteofibular ligamentPLC = posterolateral cornerIT = iliotibialIKDC = International Knee Documentation CommitteeACL = anterior cruciate ligamentPCL = posterior cruciate ligamentPEEK = polyetheretherketonePROM = passive range of motion.

Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways.

The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n = 11) and patients with PDAC (n = 24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.

Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform.

Patients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~1300 plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of >5% cancer weight loss (FC ≥ |1.5|, p ≤ 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r ≥ |0.50|, p ≤ 0.05), including some known cachexia mediators/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia.

A Rotated and Laterally Displaced Patellar Dislocation.

BACKGROUND: Patellar dislocations are a common orthopedic emergency with several variants. The rarer variants include rotational dislocations. These often require open reduction in the operating room. CASE REPORT: We report on a case of a combined rotational and lateral patellar dislocation in a young female. We suspected and made the diagnosis of a rotational dislocation after initial unsuccessful attempts at reduction under sedation. With the assistance of our orthopedic colleagues, we were able to perform a reduction of this patient's patella under sedation in the emergency department. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Awareness of uncommon patellar dislocations is an important area of knowledge for the emergency physician. A thorough understanding of indications and contraindications to closed reduction is important for efficient and safe management and disposition. Collaboration with orthopedic surgery colleagues is another important step in the evaluation of these patients.