What Is the Accuracy of Bimaxillary Orthognathic Surgery Using Occlusally-Based Guides and Patient-Specific Fixation in Both Jaws? A Cohort Study and Discussion of Surgical Techniques.

PURPOSE: The development of advanced digital orthognathic surgical protocols requires investigation to determine the accuracy of surgical outcomes. This report's purpose is to quantify 3-dimensional linear discrepancies between simulated and actual results for double-jaw orthognathic surgery utilizing occlusally-based guides in conjunction with patient-specific fixation in both jaws. METHODS: This retrospective cohort study assessed the accuracy of double-jaw orthognathic surgery, in all cases performed by 1 surgeon between May 2019 and January 2021, utilizing occlusally-based guides and patient-specific fixation plates in both maxillary and mandibular surgeries. The primary outcome was absolute linear discrepancy between virtually-planned and surgically-achieved maxillary and mandibular position in 3 dimensions. Secondary outcomes were relative (directional) discrepancy, to assess if protocols erred in 1 direction of each surgical axis. Sequencing of bimaxillary surgery, age, and sex were covariates. Absolute and relative linear differences at A-point, B-point, and pogonion were evaluated using t tests. Descriptive statistics were amassed, and results were analyzed to determine if discrepancies differed from a null hypothesis of 2-mm error. RESULTS: Forty-nine patients were enrolled, consisting of 25 males and 24 females with a mean age of 24.8 years. Thirty-five single-piece and 14 multipiece LeFort I osteotomies, 49 bilateral sagittal splits, and 35 genioplasties were studied; there were 22 maxilla-first and 27 mandible-first surgeries. Mean A-point absolute discrepancies of 0.57 (95% confidence interval: 0.41-0.73), 0.37 (0.24-0.50), and 0.45 (0.33-0.57) mm were observed in horizontal, transverse, and vertical planes, respectively. B-point discrepancies were 1.15 (0.79-1.52), 0.62 (0.47-0.78), and 1.14 (0.91-1.38) mm. Pogonion discrepancies were 1.29 (0.86-1.73), 0.85 (0.64-1.06), and 1.24 (1.00-1.49) mm. All P values were <.001. Sequencing of bimaxillary surgery did not alter absolute differences (P = .2 to >.9) with A-point discrepancies consistently smaller than B-point and pogonion discrepancies regardless of sequencing. Mandible-first surgery was associated with posterior directional error; both sequences were associated with superior directional error at B-point and pogonion. CONCLUSION: Bimaxillary orthognathic surgery utilizing a patient-specific protocol in both jaws produces results highly reproducible to planned simulated surgery and accurate below a 2-mm hypothesis, with maxillary discrepancies approaching 0.5 mm and mandibular discrepancies approaching 1 mm.

Low-Intensity Pulsed Ultrasound Therapy: A Nonsurgical Treatment Modality for Mandible Fracture Nonunion?

Standard treatment of mandibular nonunion includes debridement and application of maxillomandibular or rigid internal fixation techniques, with adjunctive bone grafting when necessary. Frequently described in the orthopaedic literature, low-intensity pulsed ultrasound therapy (LIPUS) is a noninvasive treatment modality used to accelerate healing of fresh fractures and established nonunions. The purpose of this study was to conduct a systematic review to determine the extent of LIPUS study in the treatment of mandibular nonunions to identify whether LIPUS represents an effective nonsurgical alternative or adjunct for nonunion management. A literature review was conducted to investigate published reports on the utilization of LIPUS in treating mandible fracture nonunions. The search yielded two randomized controlled trials demonstrating favorable healing parameters in fresh human mandible fractures treated with LIPUS, two randomized controlled trials demonstrating osteogenic differentiation in human mandibular fracture cellular components, and one study reporting improved healing at rabbit mandibular osteotomy sites. No articles published reports studying LIPUS in facial fracture nonunion were identified. This report reviews published literature on mandibular nonunions, and the evidence of LIPUS use in long bone nonunions. There are no known studies presenting LIPUS treatment of mandible fracture nonunions. However, on the basis of published orthopaedic data, LIPUS therapy could be considered as an adjunct or alternative to traditional surgical management of select mandible fracture nonunions.

Protecting the tracheal tube cuff: a novel solution.

We describe the successful insertion of a nasotracheal tube following repeated cuff rupture. The patient was a 55-year-old woman with a history of nasal trauma and multiple rhinoplasties, who underwent elective Lefort I osteotomy and bilateral sagittal split osteotomy for correction of skeletal facial deformity. During fiberoptic bronchoscope-guided nasal intubation after the induction of general anesthesia, the tracheal tube repeatedly ruptured in both nares, despite extensive preparation of the nasal airways. We covered the cuff with a one-inch tape, intubated to the level of the oropharynx, pulled the tracheal tube out through the mouth, and removed the tape. The tracheal tube was then backed out to the level of the uvula, and was successfully advanced.

A Phase II Trial of Prexasertib (LY2606368) in Patients With Extensive-Stage Small-Cell Lung Cancer.

BACKGROUND: This study assessed the checkpoint kinase 1 inhibitor prexasertib in patients with extensive-stage small-cell lung cancer (ED-SCLC). PATIENTS AND METHODS: This was a parallel-cohort phase II study of 105 mg/m2 prexasertib once every 14 days for patients who progressed after no more than two prior therapies and had platinum-sensitive (Cohort 1) or platinum-resistant/platinum-refractory (Cohort 2) disease. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Exploratory endpoints included biomarker identification and assessment of an alternative regimen (Cohort 3: 40 mg/m2 days 1-3, 14-day cycle). RESULTS: In Cohort 1 (n = 58), ORR was 5.2%; DCR, 31%; median PFS, 1.41 months (95% confidence interval [CI], 1.31-1.64); and median OS, 5.42 months (95% CI, 3.75-8.51). In Cohort 2 (n = 60), ORR was 0%; DCR, 20%; median PFS, 1.36 months (95% CI, 1.25-1.45); and median OS, 3.15 months (95% CI, 2.27-5.52). The most frequent all-grade, related, treatment-emergent adverse events were decreased neutrophil count (Cohort 1, 69.6%; Cohort 2, 73.3%), decreased platelet count (Cohort 1, 51.8%; Cohort 2, 50.0%), decreased white blood cell count (Cohort 1, 28.6%; Cohort 2, 40.0%), and anemia (Cohort 1, 39.3%; Cohort 2, 28.3%). Eleven patients (19.6%) in Cohort 1 and one patient (1.7%) in Cohort 2 experienced grade ≥3 febrile neutropenia. Prexasertib pharmacokinetics were consistent with prior studies. Cohort 3 outcomes were similar to those of Cohorts 1 and 2. No actionable biomarkers were identified. CONCLUSION: Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC.

Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2- Breast Cancer.

PURPOSE: neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting. PATIENTS AND METHODS: Postmenopausal women with stage I-IIIB HR+/HER2- breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response. RESULTS: Abemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell-cycle arrest after 2 weeks of treatment compared with anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell-cycle arrest (58%/68% vs. 14%, P < 0.001). At the end of treatment, following 2 weeks lead-in and 14 weeks of combination therapy, 46% of intent-to-treat patients achieved a radiologic response, with pathologic complete response observed in 4%. The most common all-grade adverse events were diarrhea (62%), constipation (44%), and nausea (42%). Abemaciclib, anastrozole, and the combination inhibited cell-cycle processes and estrogen signaling; however, combination therapy resulted in increased cytokine signaling and adaptive immune response indicative of enhanced antigen presentation and activated T-cell phenotypes. CONCLUSIONS: Abemaciclib plus anastrozole demonstrated biological and clinical activity with generally manageable toxicities in patients with HR+/HER2- early breast cancer. Abemaciclib led to potent cell-cycle arrest, and in combination with anastrozole, enhanced immune activation.

Modulation of the unfolded protein response during hepatocyte and cardiomyocyte apoptosis in trauma/hemorrhagic shock.

Trauma with hemorrhagic shock (T/HS), has been shown to result in liver injury marked by hepatocyte apoptosis and heart failure marked by cardiomyocyte apoptosis, both of which we have shown to be prevented by IL-6 administration at resuscitation, and Stat3 largely mediated this. As specific mediators have not been delineated, we investigated the unfolded protein response (UPR), which, with marked activation, can lead to apoptosis. Prior studies of hepatic and cardiac injury examined limited repertoires of UPR elements, making it difficult to assess the role of the UPR in T/HS. This study describes the first global examination of the UPR transcriptome in the liver and heart following T/HS, demonstrating organ-specific UPR transcriptome changes. The non-canonical UPR chaperone, Hsp70, was most dysregulated following T/HS and may contribute to hepatocyte protection via an IL-6-mediated pathway, identifying a potential new therapeutic strategy to prevent hepatocyte death and organ dysfunction in T/HS.