Citations

Summary: Facial synkinesis manifests as involuntary muscle movements alongside volitional facial actions and is typically managed with a combination of neuromuscular retraining, botulinum toxin injections, and in some cases, selective neurectomy. Some patients with synkinesis describe persistent neck tightness or pain at the level of the mandibular angle and horizontally towards the midline, similar to the anatomic course of the posterior belly of digastric (PBD) and stylohyoid muscles. There are limited studies exploring the involvement of the PBD and stylohyoid muscles in facial synkinesis and the use of chemodenervation as treatment. Herein, we present 2 patients with facial synkinesis and ipsilateral neck tightness and pain who underwent novel surgical treatment in the form of the standard selective neurectomy procedure along with a myectomy of the PBD and stylohyoid muscles. Following completion of the standard steps of selective neurectomy, the PBD and stylohyoid muscles were carefully dissected and separated from the surrounding structures. Both muscles were divided using bipolar electrocautery. Both patients reported improvement of neck pain and tightness immediately after the intervention and at the 6.5-month follow-up visit. These preliminary results show promise in aiding a subset of patients with synkinesis-related neck pain and tightness.

Background: Static ice storage (SIS) has long been accepted as the conventional lung preservation method, assuming to maintain 4 °C temperature. Although never directly confirmed by temperature measurements, this assumption has been widely accepted. We aimed to measure lung and preservation temperature with SIS in porcine experiments and clinical observations. Methods: Porcine lungs were preserved with SIS for 8 h (group I, n = 3) and 3 h followed by 10 °C storage (group II, n = 3). Tissue (tissueT°), first bag preservation solution (psT°) and second bag saline (salineT°) temperature were monitored. In clinical lungs (n = 4), psT° was monitored during SIS. Surface (surfaceT°) and core (coreT°) temperature were assessed before and after SIS (n = 62). Results: After 4 h in porcine lung group I, average tissueT° was 0.66 °C, psT° was 0.12 °C and salineT° was −0.02 °C. After 3 h in group II, average tissueT° was 1.90 °C, psT° was 0.57 °C and salineT° was 2.33 °C. In clinical observations, psT° was below 4 °C after 9–13 min and 0 °C after 78–267 min. After SIS, median surfaceT° was 1.25 °C (min-max; −3.2–9.2 °C) and coreT° was 1.45 °C (−0.4–4.8 °C). Conclusions: SIS leads to rapid temperature drops below 4 °C, approaching 0 °C within 2–4 h. The post-SIS lung temperature shows considerable variability and does not consistently remain at the commonly assumed 4 °C, posing potential freezing injury to donor lungs.

ABSTRACTAnetumab ravtansine, like other ADC drugs, has high inter‐patient variability in its pharmacokinetic (PK) and pharmacodynamic (PD) outcomes, which raises concerns about whether current dosing regimens are optimal for patients. The objective of this study was to evaluate covariates, especially body habitus and the innate immune system (IIS), which may affect anetumab ravtansine PK and PD as part of two clinical trials in patients with ovarian cancer and mesothelioma. Biomarkers of Fcγ receptors(FcγR) CD64 on IIS cells, total body weight (TBW), body surface area (BSA), and other covariates, such as sex and age, were analyzed for an association with anetumab ravtansine PK. Higher FcγR CD64, TBW, and BSA were associated with higher clearance (CL) of anetumab ravtansine (p < 0.05). However, there was no relationship between TBW or BSA and FcγR CD64. Female patients had a lower anetumab ravtansine CL (0.030 ± 0.007 L/h) compared to male patients (0.042 ± 0.006 L/h) (p < 0.05). In both studies, patients with stable disease (SD) and partial response (PR) had higher anetumab ravtansine AUC0‐inf compared to patients with progressive disease (PD). Individualizing the dose of anetumab ravtansine and potentially other ADCs based only on TBW is not optimal, whereas precision dosing of an ADC based on the inclusion of novel metrics of IIS biomarkers, body habitus, and sex may be more appropriate to reduce variability in PK exposure, reduce toxicity, and improve response.

Abstract Purpose: Monitoring disease progression in patients with high-grade gliomas (HGG) is challenging due to treatment-related changes in imaging and the requirement for neurosurgical intervention to obtain diagnostic tissue. DNA junctions in HGG often amplify oncogenes, making these DNA fragments potentially more abundant in blood than monoallelic mutations. In this study, we piloted a cell-free DNA approach for disease detection in the plasma of patients with HGG by leveraging patient-specific DNA junctions associated with oncogene amplifications. Experimental Design: Whole-genome sequencing of grade 3 or 4 isocitrate dehydrogenase–mutant or wild-type astrocytomas was utilized to identify amplified junctions. Individualized qPCR assays were developed using patient-specific primers designed for the amplified junction. ctDNA levels containing these junctions were measured in patient plasma samples. Results: Unique amplified junctions were evaluated by individualized semi-qPCR assays in presurgical plasma of 18 patients, 15 with tumor-associated focal amplifications and three without tumor-associated focal amplifications. high copy-number junctions were robustly detected in the plasma of 14 of 15 (93.3%) patients with amplified junctions and none of the controls. Changes in junction abundance correlated with disease trajectory in serial plasma samples from five patients, including increased abundance of amplified junctions preceding radiographic disease progression. Conclusions: In patients with grade 3 or 4 astrocytomas who had tumor-associated amplifications, patient-specific amplified junctions were successfully detected in assayed plasma from most patients. Longitudinal analysis of plasma samples correlated with disease trajectory, including cytoreduction and progression.