Association between blood transfusion and outcomes of free flap head and neck cancer surgery.

OBJECTIVE: Investigate the impact of patient risk factors and blood transfusions in Head and Neck free flap surgeries. STUDY DESIGN: Retrospective chart review. SETTING: Single tertiary referral center. METHODS: 400 patients were included undergoing free flap reconstruction from 2014 to 2020. The primary outcome measures were red blood cell transfusion and volume transfused. Race, sex, flap location and tissue type, pathology, dependent functional status, length of stay, and cancer recurrence were evaluated for association with red blood cell transfusion intraoperatively and/or postoperatively. Transfusions were indicated on patients with Hemoglobin <7-8 and/or symptomatic anemia. ANOVA and Chi2 statistical analysis were performed. The significance was set at p ≤0.05. RESULTS: Of the 400 patients included, 58 required red blood cell transfusion. Of these 67.8 % were males, racial demographics included 9.00 % African American, 1.30 % Asian, 1.00 % Hispanic/Latino, 87.8 % White, 1.00 % other. African American patients received a higher volume of transfused red blood cells versus white patients (855.00 mL vs. 437.07 mL, p = 0.005). Length of stay was significantly associated with red blood cell transfusion (5.95 days vs. 7.22 days, p ≤0.001). Dependent functional status and need for red blood cell transfusion were associated (p = 0.002). Type of free flap was associated with need for red blood cell transfusion (p ≤0.001) with anterolateral thigh flaps being the most common resulting in transfusion (34/58). CONCLUSION: Red blood cell transfusion was significantly associated with race, dependent functional status and length of stay. Certain free flaps have a higher risk of blood transfusion.

First-Principles Nonadiabatic Dynamics of Molecules at Metal Surfaces with Vibrationally Coupled Electron Transfer.

Accurate description of nonadiabatic dynamics of molecules at metal surfaces involving electron transfer has been a long-standing challenge for theory. Here, we tackle this problem by first constructing high-dimensional neural network diabatic potentials including state crossings determined by constrained density functional theory, then applying mixed quantum-classical surface hopping simulations to evolve coupled electron-nuclear motion. Our approach accurately describes the nonadiabatic effects in CO scattering from Au(111) without empirical parameters and yields results agreeing well with experiments under various conditions for this benchmark system. We find that both adiabatic and nonadiabatic energy loss channels have important contributions to the vibrational relaxation of highly vibrationally excited CO(v_{i}=17), whereas relaxation of low vibrationally excited states of CO(v_{i}=2) is weak and dominated by nonadiabatic energy loss. The presented approach paves the way for accurate first-principles simulations of electron transfer mediated nonadiabatic dynamics at metal surfaces.

Functional Status Predicts Delay to Radiation in Free Tissue Transfer for Head and Neck Cancer.

OBJECTIVE: Evaluate the effect of functional status and patient factors on delays in treatment with adjuvant therapy. METHODS: Retrospective chart review (2020-2022) was conducted at a single tertiary referral center. Data were collected between January 2020 and October 2022, and 63 patients underwent free flap reconstructive surgery of the head and neck due to the presence of cancer and received adjuvant radiation therapy (RT). The main outcomes measured were Area Deprivation Index (ADI), Beale scores, distance to radiation center, functional status, patient demographics, gender, and length from surgery to initiation of RT. RESULTS: Of the 63 patients who were reviewed, the average age was 65.5 years old and 63.8% were male. The average ADI state score was 5.6 and the national percentile of 77.1. The average Beale score was 3.7. The average distance traveled was 101.1 miles. Thirty-five patients were living independently, 16 were living in assisted living or received home care, and 15 were dependent or lived in a nursing home. Mann-Whitney U analysis revealed a significant association of increasing levels of dependence to delays in treatment compared to on-time treatment (p = 0.002). The odds of treatment delay were increased almost 10-fold for every additional increase in dependency level (OR = 9.87, 95% CI = 1.42-68.83). CONCLUSIONS AND RELEVANCE: Degree of dependent functional status correlates with delays in postoperative adjuvant RT in patients undergoing free tissue transfer for head and neck cancer. Preoperative risk stratification allows for physicians to address barriers to adjuvant therapy prior to delay. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

Functional Outcomes After the Sacrifice of Mandibular Condyle Using Fibula Free Flap for Immediate Surgical Reconstruction.

Introduction Head and neck cancer with mandibular invasion often necessitates composite resection, leading to defects requiring reconstruction. Microvascular fibula free flap (FFF) surgery is a common approach for this purpose. In this study, we focus on our experience with condyle sacrifice, emphasizing treatment outcomes and functional results. Additionally, we highlight a contemporary perspective by discussing surgical techniques and radiographic outcomes based on a 3D analysis of neo-condyle placement on CT imaging. Methods We studied 23 patients who had undergone segmental mandibulectomy requiring FFF reconstruction between 2009 and 2020. These were all performed by the same surgeon (M.M.) at an academic tertiary care center. Twenty-three reconstructions included condyle sacrifice. Retrospective chart review was performed with a focus on treatment, functional outcomes, and surgical technique. Results A total of 23 patients were included in the study group (13 females and 10 males) with a mean age of 58.1 years. The most common surgical indication was for oncologic purposes (n=9; 39.1%). Twenty (87%) patients required tracheostomy, and all were decannulated. In terms of surgical complications, two (8.7%) patients had a degree of arterial insufficiency and two (8.7%) developed delayed infections. The average inpatient stay was 5.61 days, with a subsequent average clinic follow-up after 16.9 days. CT or MRI imaging was available for 21 (91.3%) patients, showing 14 (66.7%) neo-condyles within the glenoid fossa. Fifteen (71.4%) patients had some element of anterior displacement (average=6.27 mm), and seven (33.3%) patients had a component of lateral displacement (average=2.23 mm). Three (13%) patients died during the follow-up period. Eighteen (90%) of the surviving patients returned to an oral diet within an average of 24.9 days. All patients returned to normal interincisal distance by 12 months. All FFFs, with and without complications, remained viable. Conclusion We achieved favorable oral function outcomes in the majority of our patients. Intriguingly, although radiographic evidence revealed anterior and/or lateral displacement of the neo-condyle, there was no observed correlation with the resumption of oral diet, trismus, or crossbite among these patients.

Temperature-dependent excited states for detecting reversible phase transitions in 2D lead(II) iodide perovskites.

Significant interest exists in water-tolerant 2D lead iodide perovskites owing to their stability and proven potential in photovoltaic and photonic applications. These materials have solid-state phase transitions that are accessible below 100 °C. Here, the study witnesses the multiple phase transitions of the last members of a series of organic-inorganic hybrid materials, [(CnH2n+1NH3)2PbI4], with even n as n = 14, 16, and 18, once again. By employing temperature-dependent steady-state photoluminescence (PL) and temperature-dependent time-resolved photoluminescence (TRPL) spectroscopy in the temperature range of -18 to +90 °C and at -196 °C, we explore the thermal responses of these materials. The investigation reveals reversible phase transitions occurring between room temperature (RT) and elevated temperatures, impacting the optical properties and emitting colors of the perovskite compounds. The longer the alkyl chain, the higher the phase transition temperature, attributed to increased conformational disorder and enhanced perovskite symmetry. The decay constants for all compounds are very close in value, which confirms the underlying excited-state dynamics, pointing to contributions primarily from inorganic components across different phases. We anticipate that our results on the detection of phase transitions in 2D perovskites will not only motivate the use of these techniques for detecting phase transitions but also would help to understand their excited states in more details to selectively use them for solar cell and next-generation display technologies.

A microporous polymer based on nonconjugated hindered biphenyls that emits blue light.

Microporous organic polymers that have three-dimensional connectivity stemming from monomers with tetrahedral or tetrahedron-like geometry can have high surface areas and strong fluorescence. There are however few examples of such polymers based on hindered biaryls, and their fluorescence has not been studied. Hypothesizing that the contortion in a hindered biphenyl moiety would modulate the optical properties of a polymer built from it, we synthesized a meta-enchained polyphenylene from a 2,2',6,6'-tetramethylbiphenyl-based monomer, in which the two phenyl rings are nearly mutually perpendicular. The polymer was microporous with SBET = 495 m2 g-1. The polymer absorbed near-UV light and emitted blue fluorescence despite the meta-enchainment that would have been expected to break the conjugation. A related copolymer, synthesized from 2,2',6,6'-tetramethylbiphenyl-based and unsubstituted biphenyl-based monomers, was microporous but not fluorescent.

Dual α-globin and truncated EPO receptor knockin restores hemoglobin production in α-thalassemia-derived red blood cells.

Alpha-thalassemia is an autosomal recessive disease with increasing worldwide prevalence. The molecular basis is due to mutation or deletion of one or more duplicated α-globin genes, and disease severity is directly related to the number of allelic copies compromised. The most severe form, α-thalassemia major (αTM), results from loss of all four copies of α-globin and has historically resulted in fatality in utero. However, in utero transfusions now enable survival to birth. Postnatally, patients face challenges similar to ß-thalassemia, including severe anemia and erythrotoxicity due to imbalance of ß-globin and α-globin chains. While curative, hematopoietic stem cell transplantation (HSCT) is limited by donor availability and potential transplant-related complications. Despite progress in genome editing treatments for ß-thalassemia, there is no analogous curative option for patients suffering from α-thalassemia. To address this, we designed a novel Cas9/AAV6-mediated genome editing strategy that integrates a functional α-globin gene into the ß-globin locus in αTM patient-derived hematopoietic stem and progenitor cells (HSPCs). Incorporation of a truncated erythropoietin receptor transgene into the α-globin integration cassette dramatically increased erythropoietic output from edited HSPCs and led to the most robust production of α-globin, and consequently normal hemoglobin. By directing edited HSPCs toward increased production of clinically relevant RBCs instead of other divergent cell types, this approach has the potential to mitigate the limitations of traditional HSCT for the hemoglobinopathies, including low genome editing and low engraftment rates. These findings support development of a definitive ex vivo autologous genome editing strategy that may be curative for α-thalassemia.

Copper(I) Iodide Thin Films: Deposition Methods and Hole-Transporting Performance.

The pursuit of p-type semiconductors has garnered considerable attention in academia and industry. Among the potential candidates, copper iodide (CuI) stands out as a highly promising p-type material due to its conductivity, cost-effectiveness, and low environmental impact. CuI can be employed to create thin films with >80% transparency within the visible range (400-750 nm) and utilizing various low-temperature, scalable deposition techniques. This review summarizes the deposition techniques for CuI as a hole-transport material and their performance in perovskite solar cells, thin-film transistors, and light-emitting diodes using diverse processing methods. The preparation methods of making thin films are divided into two categories: wet and neat methods. The advancements in CuI as a hole-transporting material and interface engineering techniques hold promising implications for the continued development of such devices.

Reconstruction for Salvage Laryngectomy With Limited Pharyngectomy.

Importance: Closure technique for optimization of postoperative and functional outcomes following salvage laryngectomy remains an area of debate among head and neck surgeons. Objective: To investigate the association of salvage laryngectomy closure technique with early postoperative and functional outcomes. Design, Setting, and Participants: This retrospective cohort study included patients from 17 academic, tertiary care centers who underwent total laryngectomy with no or limited pharyngectomy after completing a course of definitive radiotherapy or chemoradiotherapy with curative intent between January 2011 and December 2016. Patients with defects not amenable to primary closure were excluded. Data were analyzed from February 14, 2021, to January 29, 2024. Exposures: Total laryngectomy with and without limited pharyngectomy, reconstructed by primary mucosal closure (PC), regional closure (RC), or free tissue transfer (FTT). Main Outcomes and Measures: Patients were stratified on the basis of the pharyngeal closure technique. Perioperative and long-term functional outcomes were evaluated with bivariate analyses. A multivariable regression model adjusted for historical risk factors for pharyngocutaneous fistula (PCF) was used to assess risk associated with closure technique. Relative risks (RRs) with 95% CIs were determined. Results: The study included 309 patients (256 [82.8%] male; mean age, 64.7 [range, 58.0-72.0] years). Defects were reconstructed as follows: FTT (161 patients [52.1%]), RC (64 [20.7%]), and PC (84 [27.2%]). A PCF was noted in 36 of 161 patients in the FTT group (22.4%), 25 of 64 in the RC group (39.1%), and 29 of 84 in the PC group (34.5%). On multivariable analysis, patients undergoing PC or RC had a higher risk of PCF compared with those undergoing FTT (PC: RR, 2.2 [95% CI, 1.1-4.4]; RC: RR, 2.5 [95% CI, 1.3-4.8]). Undergoing FTT was associated with a clinically meaningful reduction in risk of PCF (RR, 0.6; 95% CI, 0.4-0.9; number needed to treat, 7). Subgroup analysis comparing inset techniques for the RC group showed a higher risk of PCF associated with PC (RR, 1.8; 95% CI, 1.1-3.0) and predominately pectoralis myofascial flap with onlay technique (RR, 1.9; 95% CI, 1.2-3.2), but there was no association of pectoralis myocutaneous flap with cutaneous paddle interposition with PCF (RR, 1.2; 95% CI, 0.5-2.8) compared with FTT with cutaneous inset. There were no clinically significant differences in functional outcomes between the groups. Conclusion and Relevance: In this study of patients with limited pharyngeal defects, interpositional fasciocutaneous closure technique was associated with reduced risk of PCF in the salvage setting, which is most commonly achieved by FTT in academic practices. Closure technique was not associated with functional outcomes at 1 and 2 years postoperatively.

Achieving the Fundamental Quantum Limit of Linear Waveform Estimation.

Sensing a classical signal using a linear quantum device is a pervasive application of quantum-enhanced measurement. The fundamental precision limits of linear waveform estimation, however, are not fully understood. In certain cases, there is an unexplained gap between the known waveform-estimation quantum Cramér-Rao bound and the optimal sensitivity from quadrature measurement of the outgoing mode from the device. We resolve this gap by establishing the fundamental precision limit, the waveform-estimation Holevo Cramér-Rao bound, and how to achieve it using a nonstationary measurement. We apply our results to detuned gravitational-wave interferometry to accelerate the search for postmerger remnants from binary neutron-star mergers. If we have an unequal weighting between estimating the signal's power and phase, then we propose how to further improve the signal-to-noise ratio by a factor of sqrt[2] using this nonstationary measurement.

Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains.

A key aspect of nutrient absorption is the exquisite division of labour across the length of the small intestine, with individual nutrients taken up at different proximal:distal positions. For millennia, the small intestine was thought to comprise three segments with indefinite borders: the duodenum, jejunum and ileum. By examining the fine-scale longitudinal transcriptional patterns that span the mouse and human small intestine, we instead identified five domains of nutrient absorption that mount distinct responses to dietary changes, and three regional stem cell populations. Molecular domain identity can be detected with machine learning, which provides a systematic method to computationally identify intestinal domains in mice. We generated a predictive model of transcriptional control of domain identity and validated the roles of Ppar-δ and Cdx1 in patterning lipid metabolism-associated genes. These findings represent a foundational framework for the zonation of absorption across the mammalian small intestine.

Stimulant Patterns, Alone or with Other Psychotropic Classes, in Medicaid-Insured Youth Continuously Enrolled for 3-8 Years.

Objective: Little U.S. pharmacoepidemiologic study is based on treatment during continuous enrollment for periods more than a year. This study aims to show pediatric patterns of stimulant use (alone or with other psychotropic classes) from Medicaid administrative claims data for stimulant patterns of 3- to 8-year continuous enrollees. Methods: A retrospective cohort study was derived from Medicaid enrollment, pharmacy, and diagnosis claims data (2007-2014) in a mid-Atlantic state. Youth aged 2-17 years with 3-8 years of continuous enrollment treated with stimulants were compared with a date-matched comparison group treated without stimulants. Major outcomes include prevalence and duration of stimulant use and patterns of stimulant polypharmacy across relatively long enrollments (3-8 years). Results: Among 264,518 unique 2- to 17-year olds with 3-8 years of continuous enrollment, 16.5% had stimulant prescription dispensings, doubling the annual national prevalence of 8.1%. Subgroup analysis showed that the highest prevalence of stimulant use was for 6- to 11-year olds (20.4%), foster care eligible youth (42.3%), and those with 7-8 years of continuous enrollment (20.1%). Externalizing psychiatric disorders were far more common in those treated with stimulants than in those treated without stimulants. The duration of stimulant exposure overall was a median of 487 days, half that of foster care stimulant users. Stimulant polypharmacy with two or more psychotropic classes concomitantly characterized 29.8% of stimulant users. Among those with three or four or more class polypharmacy, 85% and 88%, respectively, had concomitant stimulant and antipsychotic use. The adjusted odds ratio (AOR) of three or more class polypharmacy significantly increased in 12- to 17-year-old age group (AOR = 1.8), foster care eligibility (AOR = 4.5), and among those with the longest enrollment (AOR = 1.7). Conclusions and Relevance: Stimulant prevalence in Medicaid-insured youth with continuous enrollment of 3-8 years was twice as common as in annual data sets. Future research should investigate three to five interclass stimulant polypharmacy effectiveness in reliably diagnosed community populations.

Aire in Autoimmunity.

The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype-phenotype correlations and the spectrum of Aire-associated autoimmunity-including insights from patients with Aire mutations with broad and diverse implications for human health. We then highlight emerging trends in Aire biology, focusing on three topic areas. First, we discuss medullary thymic epithelial diversity and the role of Aire in thymic epithelial development. Second, we highlight recent developments regarding the molecular mechanisms of Aire and its binding partners. Finally, we describe the rapidly evolving biology of the identity and function of extrathymic Aire-expressing cells (eTACs), and a novel eTAC subset called Janus cells, as well as their potential roles in immune homeostasis.

Association of Age and Sex at Onset With Glenohumeral Osteoarthritis: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the present systematic review is to synthesize existing evidence (qualitative and quantitative) regarding age- and sex-specific differences with glenohumeral osteoarthritis. DESIGN: The electronic databases PubMed, MEDLINE, and Web of Science were searched up to March 15, 2023. Articles reporting on the association of risk factors (age and sex) with glenohumeral osteoarthritis were considered. We used Newcastle-Ottawa Scale to assess study quality. Meta-analysis was conducted to quantitatively summarize the association of age and sex with glenohumeral osteoarthritis. RESULTS: A total of 24 articles were retrieved for full-text review. Of 24 articles, 8 reporting age-specific and 5 articles reporting sex-specific associations with glenohumeral osteoarthritis were included. The odds ratio for the age (odds ratio = 3.18; 95% confidence interval = 1.10-15.92) and female sex (odds ratio = 1.78; 95% confidence interval = 0.95-3.42) were increased and observed statistically significant. CONCLUSIONS: The present systematic review and meta-analysis suggests the role of increasing age as one of the significant contributors to glenohumeral osteoarthritis. However, association of female sex with glenohumeral osteoarthritis is least convincing. Future studies are required to understand the molecular mechanisms behind the contributory role of increasing age and female sex in the establishment of glenohumeral osteoarthritis.

Routine Contrasted Chest CT Accurately Identifies Anatomic Variations of the Proximal Subscapular System.

OBJECTIVE: The vascular anatomy of the proximal subscapular artery has been previously classified into 2 major types depending on the presence of a common subscapular trunk. The purpose of this study was to determine the utility, reliability, and cost of routine chest imaging to identify these anatomical variations. METHODS: Data were collected retrospectively at a tertiary medical center for patients who were undergoing CT chest for various indications between October 2019 and October 2020. Two independent and blinded readers interpreted CT chest with contrast of 52 patients for a total 104 sides. RESULTS: The proximal branching pattern of the subscapular system was identified to have a common trunk in 99 (95%) sides. The remaining five sides (5%) demonstrated two arterial pedicles; with one patient exhibiting the variant anatomy bilaterally. CONCLUSION: Preoperative CT chest with contrast can accurately identify anatomic variation of the subscapular vascular system. For complex reconstruction requiring a single anastomosis in the vessel depleted neck, preoperative imaging can assure selection of a type I vascular anatomy of the proximal subscapular system. Preoperative imaging with contrasted CT has value in assessing this anatomy when planning for chimeric flaps involving circumflex scapular and thoracodorsal arteries. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:684-687, 2024.