Clinical and Biomechanical Evaluation of Mid-Level Constrained and Posterior-Stabilized Polyethylene Inserts in Primary Total Knee Arthroplasty: An Analysis of 12,674 Cases.

BACKGROUND: Mid-level constraint polyethylene designs provide additional stability in total knee arthroplasty (TKA). The purposes of this study were to (1) compare the survivorship and reason for revision between mid-level inserts and posterior-stabilized (PS) used in primary TKA and (2) evaluate the biomechanical constraint characteristics of mid-level inserts. METHODS: We reviewed all cases of primary TKA performed at our institution from 2016 to 2019 using either PS or mid-level constrained inserts from 1 of 6 manufacturers. Data elements included patient demographics, implants, reasons for revision, and whether a manipulation under anesthesia was performed. We performed finite element analyses to quantify the varus/valgus and axial-rotation constraint of each mid-level constrained insert. A one-to-one propensity score matching was conducted between the patients with mid-level and PS inserts to match for variables, which yielded 2 cohorts of 3,479 patients. RESULTS: For 9,163 PS and 3,511 mid-level TKAs, survivorship free from all-cause revision was estimated up to 5 years and was lower for mid-level than PS inserts (92.7 versus 94.1%, respectively, P = .004). When comparing each company's mid-level insert to the same manufacturer's PS insert, we found no differences in all-cause revision rates (P ≥ .91) or revisions for mechanical problems (P ≥ .97). Using propensity score matching between mid-level and PS groups, no significant differences were found in rates of manipulation under anesthesia (P = .72), all-cause revision (P = .12), revision for aseptic loosening (P = .07), and revision for instability (P = .45). Finite element modeling demonstrated a range in varus/valgus constraint from ±1.1 to >5°, and a range in axial-rotation constraint from ±1.5 to ±11.5° among mid-level inserts. CONCLUSIONS: Despite wide biomechanical variations in varus/valgus and axial-rotation constraint, we found minimal differences in early survivorship rates between PS and mid-level constrained knees.

Firearm-Related Injuries-Wound Management, Stabilization, and Associated Injuries: A Critical Analysis Review.

¼: Gun violence-related and firearm-related injuries are a public health crisis with increasing rates, particularly among younger demographics, in the United States despite a decline in incidence worldwide. ¼: There exists limited high-quality evidence to guide the management of firearm-related orthopaedic injuries. ¼: Associated injuries (i.e., neurological and vascular) are common in ballistic injuries to the extremity. ¼: Where indicated, low-energy orthopaedic injuries can be managed successfully with standard fixation and management strategies with similar complications to closed fractures.

Sickle cell trait and multisystem trauma: an unaddressed urgent knowledge gap.

Sickle cell trait (SCT) has historically been considered a benign condition, but SCT-positive patients have increased baseline risk of venous thromboembolism and chronic kidney disease, as well as increased risk of sickled erythrocytes in settings of hypoxia, acidosis, and hypovolemia. Multisystem traumatic injuries are a common clinical scenario, in which hypoxia, acidosis, and hypovolemia occur; however, little is known about how SCT-positive status impacts outcomes in multisystem trauma. We conducted a scoping literature review to investigate what was known about SCT in the setting of multisystem trauma. In the 110+ years that sickle cell hemoglobinopathies have been known, only three studies have ever examined the relationship between SCT and multisystem traumas. All three articles were case reports. None of the articles intentionally measured the association between SCT and multisystem trauma outcomes; they only incidentally captured information on SCT. Our article then examines historical reasons why so little research has studied the pathophysiology of the multisystem trauma in patients with SCT. Among the reasons is that historical and logistical factors have long prevented patients from knowing their SCT-status: historical discriminations against SCT-positive patients in the 1960s and 1970s delayed federal mandating of SCT newborn screening until 2006, whereas difficulties communicating known SCT-status to afflicted children also contributed to lack of patient knowledge. In light of our findings, we offer specific calls to action for the trauma surgery research community: (1) consider testing for SCT in trauma patients that have unexpected complications, particularly venous thromboembolism, rhabdomyolysis, or renal failure and (2) support research to understand how SCT impacts multisystem trauma outcomes. We also offer specific guidelines about how to 'proceed with caution' in implementation of these goals in light of the troubled history of SCT testing and policy in the USA.

Quality of Life Analysis of HPV-Positive Oropharyngeal Cancer Patients in a Randomized Trial of Reduced-Dose Versus Standard Chemoradiotherapy: 5-Year Follow-Up.

Background: Human papillomavirus-positive oropharyngeal carcinoma (HPVOPC) portends a more favorable prognosis compared to environmentally related oropharynx cancer (EROPC). Patients with HPVOPC may be overtreated and endure unnecessary long-term toxicities. Methods: Patients with untreated locally advanced HPVOPC received induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) and were randomized to standard chemoradiotherapy (sdCRT) (70 Gy) or reduced-dose chemoradiotherapy (rdCRT) (56 Gy) with weekly carboplatin. Patients were followed for changes in five validated quality of life (QoL) surveys: MD Anderson Dysphagia Inventory and Symptom Inventory for head and neck cancer (MDADI, MDASI-HN), Xerostomia Questionnaire (XQ), and European Organization for Research and Treatment of Cancer Questionnaire (EORTC) with head and neck module (EORTC HN). The secondary endpoints of this study were 5-year progression-free survival (PFS) and overall survival (OS). Results: Twenty patients were enrolled and randomized to rdCRT (n = 12) or sdCRT (n = 8). Median follow-up was 88 months. At 5 years, difference in QoL changes all favored the rdCRT arm and two QoL scales reached statistical significance (EORTC global health score: 11.49 vs. -23.94, P = 0.014; EORTC symptom scale: -7.76 vs. 15.19, P = 0.015). The 5-year PFS and OS were 87.5% and 83.3% for sdCRT and rdCRT, respectively. Conclusions: Therefore, rdCRT after TPF in HPVOPC is feasible in accordance with the earlier results of the Quarterback Trial and long-term follow-up. These limited results are more favorable in specific QoL domains compared to those of sdCRT and demonstrate equivalent long-term survival. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01706939, The Quarterback Trial [NCT01706939].

A Drosophila platform identifies a novel, personalized therapy for a patient with adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a rare cancer type that originates in the salivary glands. Tumors commonly invade along nerve tracks in the head and neck, making surgery challenging. Follow-up treatments for recurrence or metastasis including chemotherapy and targeted therapies have shown limited efficacy, emphasizing the need for new therapies. Here, we report a Drosophila-based therapeutic approach for a patient with advanced ACC disease. A patient-specific Drosophila transgenic line was developed to model the five major variants associated with the patient's disease. Robotics-based screening identified a three-drug cocktail-vorinostat, pindolol, tofacitinib-that rescued transgene-mediated lethality in the Drosophila patient-specific line. Patient treatment led to a sustained stabilization and a partial metabolic response of 12 months. Subsequent resistance was associated with new genomic amplifications and deletions. Given the lack of options for patients with ACC, our data suggest that this approach may prove useful for identifying novel therapeutic candidates.

A personalized platform identifies trametinib plus zoledronate for a patient with KRAS-mutant metastatic colorectal cancer.

Colorectal cancer remains a leading source of cancer mortality worldwide. Initial response is often followed by emergent resistance that is poorly responsive to targeted therapies, reflecting currently undruggable cancer drivers such as KRAS and overall genomic complexity. Here, we report a novel approach to developing a personalized therapy for a patient with treatment-resistant metastatic KRAS-mutant colorectal cancer. An extensive genomic analysis of the tumor's genomic landscape identified nine key drivers. A transgenic model that altered orthologs of these nine genes in the Drosophila hindgut was developed; a robotics-based screen using this platform identified trametinib plus zoledronate as a candidate treatment combination. Treating the patient led to a significant response: Target and nontarget lesions displayed a strong partial response and remained stable for 11 months. By addressing a disease's genomic complexity, this personalized approach may provide an alternative treatment option for recalcitrant disease such as KRAS-mutant colorectal cancer.