Citations

Background: Variable terminology is used in the literature to describe facial synkinesis and hypertonicity following incomplete recovery from facial paralysis and its associated medical and surgical treatments. Study Objectives: Establish a nomenclature consensus for this condition among a group of facial nerve experts. Design Type: Consensus study. Methods: Using modified Delphi methodology, an international, multidisciplinary group of facial nerve experts reviewed the terminology for the name of the clinical condition and treatments of interest. Online surveys and a virtual discussion were performed to establish consensus, defined a priori as agreement by 80% of the group. Results: Twenty-five facial nerve experts established consensus after three Delphi rounds. Consensus terminology for the condition is “facial synkinesis” with 84% agreement. Medical treatment is termed “chemodenervation” with 100% agreement. Surgical treatments including “selective facial neurectomy,” “selective facial neurotomy,” “selective facial myectomy,” and “selective facial myotomy,” were defined and reached agreement of 100%. Conclusions: This international group of facial nerve experts has recommended standardized nomenclature for the condition of facial synkinesis and its various treatments. While “facial synkinesis” reached consensus as the preferred term, some experts noted it may insufficiently describe the full clinical spectrum, which includes muscle hypertonicity, weakness, and spontaneous twitching.

Summary Recipients of haploidentical and unrelated haematopoietic cell transplants (HCTs) historically had a higher risk for graft‐versus‐host disease (GvHD). However, with improved GvHD prophylaxis, recent data suggest adult patients undergoing transplantation from unrelated or mismatched donors now experience the rates of GvHD similar to those receiving matched related donor grafts. This finding is not yet explored in paediatric patients. The objectives of this study were to: (1) compare acute and chronic GvHD incidence, mortality and GvHD‐free relapse‐free survival (GRFS) among matched related donor (MRD), matched unrelated donor (MUD) and haploidentical paediatric HCT recipients in the era of enhanced GvHD prophylaxis for high‐risk patients, (2) identify independent risk factors for GvHD and (3) evaluate the efficacy of various GvHD prophylactic regimens in our cohort. We conducted a retrospective, single‐centre medical record abstraction among patients aged 0–25 years who underwent allogeneic HCT for any indication. The results demonstrated that 5‐year cumulative incidence rates of any GvHD, all‐cause mortality and GRFS are similar across the haploidentical, MRD and MUD groups. Tacrolimus‐containing doublet/triplet regimens were associated with decreased GvHD, as compared to ciclosporin. Adding alemtuzumab also decreased risk for GvHD, without increasing relapse rates. Prospective studies with larger cohorts are warranted to further optimize outcomes for paediatric allogeneic HCT patients.

Objectives: Value based decision making regarding nonoperative management vs. early surgical stabilization for first-time anterior shoulder instability (ASI) events remains controversial. Thus, the purpose of this study was to perform 1) a systematic review of the current literature and 2) a Markov model-based cost-effectiveness analysis comparing an initial trial of nonoperative management to arthroscopic Bankart repair (ABR) for first-time ASI. Methods: A Markov Chain Monte Carlo probabilistic model (Figure 1) was developed to evaluate the outcomes and costs of 1,000 simulated patients (average age » 20 years old) with first-time ASI undergoing nonoperative management vs. ABR. Utility values, recurrence rates, and transition probabilities were derived from the published literature. Costs were determined based on the typical patient undergoing each treatment strategy at our institution. Outcome measures included costs, quality-adjust life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). Probabilities of recurrence as well as the utility of each treatment strategy were obtained from the literature search as described above. Probabilities were pooled across studies to obtain a weighted average for both nonoperative treatment and ABR. Similarly, studies reporting scores on the Western Ontario Shoulder Instability Index (WOSI) scale were utilized to approximate shoulder-related quality of life after each treatment strategy and outcome. Costs for each treatment strategy and transition state in the model were considered from the payer perspective (commercial or government) and obtained from institutional data at a large, academic medical center. Results: The Markov model with Monte Carlo microsimulation demonstrated average (± standard deviation) costs for nonoperative management and ABR of $38,649 ± 10,521 and $43,052 ± 9,352, respectively. Total QALYS acquired over the 10-year time horizon were 7.7 ± 0.4 and 8.4 ± 0.5 for nonoperative management and ABR, respectively. The ICER comparing ABR to nonoperative management was found to be just $5,725/QALY, which falls substantially below the $50,000 willingness-to-pay (WTP) threshold (Figure 2). The mean number of recurrences were 2.6 ± 0.3 and 1.2 ± 0.2 for patients initially assigned to the nonoperative and ABR treatment groups, respectively. Out of 1,000 samples run over 1,000 trials, ABR was the optimal strategy in 98.7% of cases, with nonoperative management the optimal strategy in 1.3% of cases (Figure 3). Conclusions: The primary findings of this systematic review and cost-effectiveness analysis were as follows: 1) when compared to nonoperative management, arthroscopic Bankart repair (ABR) substantially reduces the risk of recurrent dislocations, 2) ABR results in greater shoulder function and higher WOSI scores than does nonoperative management, and 3) despite substantially higher upfront costs, ABR proved to be more cost-effective than an initial trial of nonoperative management, which can be attributed to both fewer recurrent dislocations and greater utility over the long-term.

ABSTRACT Objectives To characterize practice patterns and outcomes in the management of low‐ and intermediate‐grade salivary gland carcinoma prior to the existence of treatment guidelines. Methods Analysis of a registry of patients who underwent parotid and submandibular gland resections for low‐and intermediate‐grade carcinomas between 2010 and 2019. Results Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial ( n = 384, 53%) or total ( n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was associated with a significant increase in transient facial weakness (72/177 (41%) vs. 82/311 (26%), RR 0.65, 95% CI 0.50–0.84, p < 0.05) and permanent facial nerve weakness (23/176 (13%) vs. 16/301 (5%), RR 0.41, 95% CI 0.22–0.75, p < 0.05) compared to superficial parotidectomy. Adjuvant radiation therapy ( RT ) was delivered to 285 (36%) patients. The proportion of patients receiving adjuvant RT declined significantly over the time period from 2015 to 2019 compared to 2010 to 2014 at 162/504 (32%) and 123/282 (44%), respectively ( RR 0.74, 95% CI 0.61–0.89, p < 0.05). When comparing the time periods from 2015 to 2019 and 2010 to 2014, there was no significant difference in local control rates ( RR 0.52, 95% CI 0.26–1.04, p = 0.06) or regional control rates ( RR 0.75, 95% CI 0.26–2.13, p = 0.58). Conclusions Management of low‐ and intermediate‐grade salivary cancer from 2010 to 2019 was variable, which is expected given the rarity and heterogeneity of the disease and the lack of treatment guidelines prior to 2021. Most patients with parotid malignancies underwent superficial or total parotidectomy. The extent of parotidectomy had an impact on facial nerve function outcomes. Delivery of adjuvant radiation trended down with time. The data presented here will support dissemination of the guidelines and provide data that could inform future trials. Level of Evidence 2b.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

Background: Longitudinal genomic profiling through serial circulating tumor DNA (ctDNA) testing offers a noninvasive method to monitor clonal evolution in advanced prostate cancer. This study evaluated the frequency and nature of newly emergent and potentially actionable genomic alterations detected through serial testing in a real-world setting. Methods: We conducted a retrospective analysis of advanced prostate cancer patients who underwent multiple Guardant360 ctDNA tests between October 2020 and March 2023. The study focused on identifying new genomic alterations absent in the initial test, with particular attention to alterations relevant for on-label therapies, therapies approved in other oncologic indications (i.e., off-label), or a clinical trial. Results: Among 479 patients with at least two ctDNA tests, the median interval between the first and second evaluable tests was 207 days. New and potentially actionable alterations emerged in 57.8% of patients, including potential targets for on-label therapies (16.7%), off-label therapies (16.5%), and clinical trials (55.7%). Tumor mutational burden (TMB) increased from “low” to “high” in 11% of patients, although none had microsatellite instability or mismatch repair deficiency. In a Mayo Clinic subset, ten patients received olaparib based on treatment-emergent alterations, but none achieved a prostate-specific antigen (PSA) response. Two patients who transitioned from low to high TMB received pembrolizumab, both with progressive disease as best response. Conclusions: In a large real-world cohort, serial ctDNA testing frequently identified new alterations that were not detected at baseline and are potentially actionable therapeutic targets, highlighting the value of serial genomic profiling for capturing clonal dynamics. Additional research is needed to better establish a framework for retesting and to clarify how these results should influence subsequent treatment decisions.

Abstract Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have a propensity to transform to an accelerated or blast phase (MPN-AP/BP). The resulting disease has clinically similar manifestations to Acute Myeloid Leukemia (AML) but worse clinical outcomes. Here we present the first comprehensive description of the transcriptomic characteristics of MPN-AP/BP. Our analysis incorporates data from 261 patients of the BeatAML cohort and 56 MPN-AP/BP patients, 11 of whom had paired samples from before and after transformation. We establish that transformed MPN is a transcriptionally distinct entity from de novo AML and chronic phase MPNs. Genomic pathways traditionally associated with MPN pathogenesis, such as IL2/STAT5 signaling and IL6/JAK/STAT3 signaling were enriched in chronic-phase MPNs but are absent in transformed disease, suggesting JAK2 directed therapy may be less effective in this disease phase. We also discovered that gene expression signatures associated with doxorubicin resistance are highly enriched in transformed MPNs, which may explain the lack of efficacy of standard AML therapies. In addition, we identify that lineage composition at the time of transformation may define distinct subsets of MPN-AP/BP patients, which may assist in the future development of novel treatment strategies.