Outcomes and prognostic factors in parotid gland malignancies: A 10-year single center experience.

Objectives:To describe a 10-year single center experience with parotid gland malignancies and to determine factors affecting outcomes. Study Design:Retrospective review. Methods:The institutional cancer registry was used to identify patients treated surgically for malignancies of the parotid gland between January 2005 and December 2014. Clinical and pathologic data were collected retrospectively from patient charts and analyzed for their association with overall survival (OS) and disease-free survival (DFS). Results:Two hundred patients were identified. Mean age at surgery was 57.8 years, and mean follow-up time was 52 months. One hundred two patients underwent total parotidectomy, while 77 underwent superficial parotidectomy, and 21 underwent deep lobe resection. Seventy patients (35%) required facial nerve (FN) sacrifice. Acinic cell carcinoma was the most common histologic type (22%), followed by mucoepidermoid carcinoma (21.5%) and adenoid cystic carcinoma (12.5%). Twenty-nine patients (14.5%) experienced recurrences, with mean time to recurrence of 23.6 months (range: 1-82 months). Five- and 10-year OS were 81% and 73%, respectively. Five- and 10-year DFS were 80% and 73%, respectively. In univariate analyses, age > 60, histologic type, positive margins, high grade, T-stage, node positivity, perineural invasion, and FN involvement were predictors of OS and DFS. In the multivariate analysis, histology, positive margins, node positivity, and FN involvement were independent predictors of OS and DFS. Conclusions:Our single-center experience of 200 patients suggests that histology, positive margins, node positivity, and FN involvement are independently associated with outcomes in parotid malignancies. Level of Evidence:4

Ossifying Parotid Carcinoma ex Pleomorphic Adenoma

We present a unique case of an extensively ossified carcinoma ex pleomorphic adenoma (CXPA) in a 76-year-old man with a five-year history of a slowly growing parotid mass. Fine-needle aspiration of the mass was nondiagnostic. A computed tomography (CT) scan of the lesion revealed a well-circumscribed mass with peripheral calcification. Initial pathological analysis suggested a benign parotid mass, but rigorous decalcification revealed noninvasive CXPA. The patient underwent complete resection of the mass and remained disease-free nine months later. Extensive ossification of a seemingly benign parotid mass may mask areas of carcinoma that may progress if left untreated

Predicting length of stay in head and neck patients who undergo free flap reconstruction

ObjectiveUnderstanding factors that affect postoperative length of stay (LOS) may improve patient recovery, hasten postoperative discharge, and minimize institutional costs. This study sought to (a) describe LOS among head and neck patients undergoing free flap reconstruction and (b) identify factors that predict increased LOS.MethodsA retrospective cohort was performed of 282 head and neck patients with free flap reconstruction for oncologic resection between 2011 and 2013 at a tertiary academic medical center. Patient demographics, tumor characteristics, and surgical and infectious complications were characterized. Multivariable regression identified predictors of increased LOS.ResultsA total of 282 patients were included. Mean age was 64.7 years (SD = 12.2) and 40% were female. Most tumors were located in the oral cavity (53.9% of patients), and most patients underwent radial forearm free flap (RFFF) reconstruction (RFFF—73.8%, anterolateral thigh flap—11.3%, and fibula free flap—14.9%). Intraoperative complications were rare. The most common postoperative complications included nonwound infection (pneumonia [PNA] or urinary tract infection [UTI]) (15.6%) and wound breakdown/fistula (15.2%). Mean and median LOS were 13 days (SD = 7.7) and 10 days (interquartile range = 7), respectively. Statistically significant predictors of increased LOS included flap take back (Beta coefficient [C] = +4.26, P < .0001), in‐hospital PNA or UTI (C = +2.52, P = .037), wound breakdown or fistula (C = +5.0, P < .0001), surgical site infection (C = +3.54, P = .017), and prior radiation therapy (C = +2.59, P = .004).ConclusionSeveral perioperative factors are associated with increased LOS. These findings may help with perioperative planning, including the need for vigilant wound care, optimization of antibiotics prophylaxis, and institution‐level protocols for postoperative care and disposition of free flap patients.Level of Evidence2b; retrospective cohort.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155916/1/lio2410.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155916/2/lio2410_am.pd

Single-cell RNA sequencing identifies a paracrine interaction that may drive oncogenic notch signaling in human adenoid cystic carcinoma

Salivary adenoid cystic carcinoma (ACC) is a rare, biologically unique biphasic tumor that consists of malignant myoepithelial and luminal cells. MYB and Notch signaling have been implicated in ACC pathophysiology, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilize single-cell RNA sequencing to profile human head and neck ACC, including a comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering diversity in myoepithelial and luminal cell expression. We find differential expression of Notch ligands DLL1, JAG1, and JAG2 in myoepithelial cells, suggesting a paracrine interaction that may support oncogenic Notch signaling. We validate this selective expression in three published cohorts of patients with ACC. Our data provide a potential explanation for the biphasic nature of low- and intermediate-grade ACC and may help direct new therapeutic strategies against these tumors

Light and oxygen induced degradation limits the operational stability of methylammonium lead triiodide perovskite solar cells

Here, we demonstrate that light and oxygen-induced degradation is the main reason for the low operational stability of methylammonium lead triiodide (MeNH3PbI3) perovskite solar cells exposed to ambient conditions. When exposed to both light and dry air, unencapsulated MeNH3PbI3 solar cells rapidly degrade on timescales of minutes to a few hours. This rapid degradation is also observed under electrically bias driven current flow in the dark in the presence of O2. In contrast, significantly slower degradation is observed when the MeNH3PbI3 devices are exposed to moisture alone (e.g. 85% relative humidity in N2). We show that this light and oxygen induced degradation can be slowed down by the use of interlayers that are able to remove electrons from the perovskite film before they can react with oxygen to form O2−. These observations demonstrate that the operational stability of electronic and optoelectronic devices that exploit the electron transporting properties of MeNH3PbI3 will be critically dependent upon the use of suitable barrier layers and device configurations to mitigate the oxygen sensitivity of this remarkable material

A Phase 2, Multicenter, Open-Label Study of Anti-Lag-3 Ieramilimab in Combination With Anti-Pd-1 Spartalizumab in Patients With Advanced Solid Malignancies

Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated). Patients received ieramilimab (400 mg) followed by spartalizumab (300 mg) every 3 weeks. The primary endpoint was objective response rate (ORR), along with safety, pharmacokinetics, and biomarker assessments. Of 235 patients, 142 were naive to anti-PD-1/L1 and 93 were pretreated with anti-PD-1/L1 antibodies. Durable responses (\u3e24 months) were seen across all indications for patients naive to anti-PD-1/L1 and in melanoma and RCC patients pretreated with anti-PD1/L1. The most frequent study drug-related AEs were pruritus (15.5%), fatigue (10.6%), and rash (10.6%) in patients naive to anti-PD-1/L1 and fatigue (18.3%), rash (14.0%), and nausea (10.8%) in anti-PD-1/L1 pretreated patients. Biomarker assessment indicated higher expression of T-cell-inflamed gene signature at baseline among responding patients. Response to treatment was durable (\u3e24 months) in some patients across all enrolled indications, and safety findings were in accordance with previous and current studies exploring LAG-3/PD-1 blockade

Design principles for efficient singlet fission in anthracene-based organic semiconductors

Singlet fission (SF) in two or more electronically coupled organic chromophores converts a high-energy singlet exciton into two low-energy triplet excitons, which can be used to increase solar cell efficiency. Many known SF chromophores are unsuitable for device applications due to chemical instability and low triplet state energies. This work summarizes structurally dependent SF dynamics for 9,10-bis(phenylethynyl)anthracene (BPEA) and its derivatives in the solid-state using time-resolved optical spectroscopies, and electronic structure calculations. By modulating the packing structure in thin films, we can effectively tune electronic energy and coupling. The systematic study in BPEA organic semiconductors shows that maximizing the thermodynamic driving force can achieve the highest SF rate and efficiency

Widespread horse-based mobility arose around 2200 BCE in Eurasia.

Horses revolutionized human history with fast mobility1. However, the timeline between their domestication and their widespread integration as a means of transport remains contentious2-4. Here we assemble a collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged around 2200 BCE, through close-kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than approximately 2700 BCE, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe around 3000 BCE and earlier3,5. Finally, we detect significantly shortened generation times at Botai around 3500 BCE, a settlement from central Asia associated with corrals and a subsistence economy centred on horses6,7. This supports local horse husbandry before the rise of modern domestic bloodlines