Interim Phase II Results Using Panitumumab-IRDye800CW During Transoral Robotic Surgery in Patients with Oropharyngeal Cancer.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but have the greatest potential impact for improving patient care when the surgeon has limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in OPSCC patients. PATIENTS AND METHODS: 12 consecutive patients with OPSCC were enrolled as part of a non-randomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. RESULTS: Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. CONCLUSIONS: Results from this OPSCC patient cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.

Non-Tobacco Nicotine Dependence and Rates of Postoperative Complications in Total Knee Arthroplasty: A Propensity-Matched Comparison.

INTRODUCTION: Tobacco use elevates the incidence of postoperative complications and remains a key modifiable risk factor of perioperative surgical optimization. It remains unclear whether non-tobacco nicotine dependence confers an increased risk of surgical complications. This study evaluates postoperative complications in patients with non-tobacco nicotine dependence for total knee arthroplasty (TKA). METHODS: We queried the TriNetX health database using Current Procedural Terminology and International Classification of Diseases, 10th Revision (ICD-10) codes and identified two cohorts for evaluation. Cohort A was defined as patients who had a TKA; had a dependence on nicotine; did not have nicotine dependence to cigarettes, chewing tobacco, other tobacco products; and were between the ages of 35 and 90 years. Cohort B was defined as patients who had a TKA but did not have a dependence on nicotine or a personal history of nicotine dependence and were between the ages of 35 and 90 years. RESULTS: This study analyzed a total of 10,594 non-tobacco nicotine-dependent patients and 175,079 non-dependent patients who underwent TKA. In the analysis of propensity-matched cohorts, non-tobacco nicotine-dependent patients demonstrated an increased rate of various postoperative complications within 90 days. Dependent patients saw a significantly increased risk of infection after a procedure (P < 0.001), deep vein thrombosis (P < 0.001), pulmonary embolism (P < 0.001), sepsis (P = 0.0065), and prosthetic joint infection (P = 0.0361) and a higher 3-year revision rate (P = 0.0084). DISCUSSION: Non-tobacco nicotine dependence demonstrated an increased associated risk of postoperative surgical complications for patients undergoing TKA. Orthopaedic surgeons should consider evaluating non-tobacco nicotine dependence within their surgical optimization protocol. LEVEL OF EVIDENCE: Level III, Prognostic.

A petavoxel fragment of human cerebral cortex reconstructed at nanoscale resolution.

To fully understand how the human brain works, knowledge of its structure at high resolution is needed. Presented here is a computationally intensive reconstruction of the ultrastructure of a cubic millimeter of human temporal cortex that was surgically removed to gain access to an underlying epileptic focus. It contains about 57,000 cells, about 230 millimeters of blood vessels, and about 150 million synapses and comprises 1.4 petabytes. Our analysis showed that glia outnumber neurons 2:1, oligodendrocytes were the most common cell, deep layer excitatory neurons could be classified on the basis of dendritic orientation, and among thousands of weak connections to each neuron, there exist rare powerful axonal inputs of up to 50 synapses. Further studies using this resource may bring valuable insights into the mysteries of the human brain.

Panitumumab-IRDye800 Improves Laryngeal Tumor Mapping During Transoral Laser Microsurgery.

Transoral laser microsurgery represents the primary surgical modality for early laryngeal cancers with oncologic outcomes equivalent to radiotherapy. Accurate tumor mapping and margin assessment can be difficult, however, particularly during piecemeal or ablative resections, and for tumors with a wider geographic footprint. Tumor-targeted fluorescence-guided surgery in patients with head and neck cancer has empirically improved tumor and margin identification; this case details, for the first time, a fluorescence-guided surgical resection of a T2N0M0 transglottic tumor using panitumumab-IRDye800, an epidermal growth factor receptor monoclonal antibody covalently linked to near-infrared (NIR) dye. Laryngoscope, 134:1837-1841, 2024.

Breakers and amplifiers in chromatin circuitry: acetylation and ubiquitination control the heterochromatin machinery.

Eukaryotic genomes are segregated into active euchromatic and repressed heterochromatic compartments. Gene regulatory networks, chromosomal structures, and genome integrity rely on the timely and locus-specific establishment of active and silent states to protect the genome and provide the basis for cell division and specification of cellular identity. Here, we focus on the mechanisms and molecular machinery that establish heterochromatin in Schizosaccharomyces pombe and compare it with Saccharomyces cerevisiae and the mammalian polycomb system. We present recent structural and mechanistic evidence, which suggests that histone acetylation protects active transcription by disrupting the positive feedback loops used by the heterochromatin machinery and that H2A and H3 monoubiquitination actively drives heterochromatin, whereas H2B monoubiquitination mobilizes the defenses to quench heterochromatin.

Ambulatory Surgery vs Overnight Observation for Total Thyroidectomy: Cost Analysis and Outcomes.

OBJECTIVE: To compare financial impact between patients undergoing ambulatory (same-day discharge) vs overnight admission after total thyroidectomy while showing associated surgical outcomes. STUDY DESIGN: Retrospective review. SETTING: University of Alabama at Birmingham Medical Center from October 2011 and July 2017. METHODS: Patients undergoing total thyroidectomy without concurrent procedures were selected for review. Demographics, comorbidities, admission status, postoperative outcomes including minor and major complications, charges, and costs were collected. Admission status was categorized as inpatient (admission to hospital ≥1 night) or outpatient (discharged from the postoperative recovery unit). Costs were obtained from all related hospital, clinic, and emergency department visits at the University of Alabama at Birmingham within 30 days of the original surgery. After statistical analysis, outcomes and costs were compared between inpatient and outpatient total thyroidectomy patients. RESULTS: Of 870 total thyroidectomy patients included for analysis, 367 (42.2%) met outpatient criteria. A total of 169 patients (19.4%) had a complication, and only hypocalcemia occurred significantly more in the inpatient group (14.3% vs 9.26%; P < .05). No complications occurred more frequently in the outpatient population. There were no mortalities. There was a statistically significant difference between the total cost of inpatient and outpatient thyroidectomies, with outpatient surgery costing on average $2367.27 less per patient (P < .0001). CONCLUSION: Outpatient total thyroidectomy can lead to cost reduction in highly selected patients who have few comorbidities while remaining safe for the patient.

Chronic rhinosinusitis: phenotypes and endotypes.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a broad classification of airway inflammation that affects a significant portion of the population. The current model of delineating patients suffering from CRS is dated and is no longer as simple as the presence of polyps or no polyps. Continued advances in the endotype descriptions of CRS have allowed for new phenotypic descriptions that aid in driving management and research efforts. RECENT FINDINGS: Geographic differences exist between patient presentations, which require a molecular evaluation of the driving forces. Increased understanding of these differences allows for patient-specific treatment decisions. SUMMARY: New descriptions of CRS phenotypes allow for more targeted therapy for patients, particularly to those with difficult to control disease. The previously broad classification of CRS with or without nasal polyps is no longer sufficient at driving these treatment decisions.

Flat sticker as a mobile airway foreign body: A case report and review of the literature.

Diagnosis of an airway foreign body in the setting of an unwitnessed aspiration event remains a challenge for physicians in the emergency setting. We describe a case of a 2-year-old male who presented to the emergency department with atypical symptoms resulting from ingestion and aspiration of a large, flat sticker. The airway foreign body remained in place for over 24 hours despite obtaining appropriate airway imaging, and the object was later removed without complication via rigid bronchoscopy in the operating room. Further review of this case and the current literature highlighted multiple lessons. Initial evaluations should combine a rigorous history and physical with strict guidelines on usage of multiple imaging modalities (eg, plain radiographs and CT). Imaging should be obtained with the patient devoid of all obstructive materials in multiple positions (eg, upright, supine, lateral) in order to maximize the physician's ability to positively diagnose airway foreign bodies prior to definitive treatment with rigid bronchoscopy.

Association of Urine Albumin Excretion With Incident Heart Failure Hospitalization in Community-Dwelling Adults.

OBJECTIVES: This study examined the association between urinary albumin excretion and incident heart failure (HF) hospitalization. BACKGROUND: Excess urinary albumin excretion is more strongly associated with incident stroke and coronary heart disease risk in black than in white individuals. Whether similar associations extend to HF is unclear. METHODS: This study examined the associations between the urinary albumin-to-creatinine ratio (ACR) and incident hospitalization for HF overall in 24,433 REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants free of suspected HF at baseline; findings were stratified by race and HF subtype (preserved vs. reduced ejection fraction). Models were adjusted for sociodemographic, clinical, and laboratory variables including estimated glomerular filtration rate, and multiple imputation was used to account for missing covariate data. RESULTS: After a median follow-up of 9.2 years, 881 incident HF events (332 preserved ejection fraction, 447 reduced ejection fraction, 102 unspecified) were observed. Compared to the lowest ACR category (<10 mg/g), the risk of incident HF increased with increasing ACR categories (10 to 29 mg/g hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.26 to 1.78; 30 to 300 mg/g HR: 2.32; 95% CI: 1.93 to 2.78; >300 mg/g HR: 4.42; 95% CI: 3.36 to 5.83) in the fully adjusted model. Results did not differ by race. The magnitude of the association between ACR and HF with preserved ejection fraction was greater than with HF with reduced ejection fraction (HR comparing highest vs. lowest ACR category: 6.20; 95% CI: 4.15 to 9.26 vs. HR: 4.37; 95% CI: 3.00 to 6.25, respectively; p = 0.05). CONCLUSIONS: Higher ACR was associated with greater risk of incident HF hospitalization in community-dwelling black and white adults.

Crystallization of truncated hemolysin A from Proteus mirabilis.

Proteus species are second only to Escherichia coli as the most common causative agent of Gram-negative bacteria-based urinary-tract infections and many harbor several virulence factors that provide inherent uropathogenicity. One virulence factor stems from a two-partner secretion pathway comprised of hemolysin A and hemolysin B; upon hemolysin B-dependent secretion, hemolysin A becomes activated. This system is distinct from the classic type I secretion pathway exemplified by the hemolysin system within Escherichia coli. In order to describe the mechanism by which hemolysin A is activated for pore formation, an amino-terminal truncated form capable of complementing the non-secreted full-length hemolysin A and thereby restoring hemolytic activity has been constructed, expressed and purified. A room-temperature data set has been collected to 2.5 A resolution. The crystal belongs to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 34.47, b = 58.40, c = 119.74 A. The asymmetric unit is expected to contain a single monomer, which equates to a Matthews coefficient of 1.72 A3 Da(-1) and a solvent content of 28.3%.