Sentinel lymph node biopsy in patients with T1a cutaneous malignant melanoma: A multicenter cohort study.

BACKGROUND: Sentinel lymph node biopsy is not routinely recommended for T1a cutaneous melanoma due to the overall low risk of positivity. Prognostic factors for positive sentinel lymph node (SLN+) in this population are poorly characterized. OBJECTIVE: To determine factors associated with SLN+ in patients with T1a melanoma. METHODS: Patients with pathologic T1a (<0.80 mm, nonulcerated) cutaneous melanoma from 5 high-volume melanoma centers from 2001 to 2020 who underwent wide local excision with sentinel lymph node biopsy were included in the study. Patient and tumor characteristics associated with SLN+ were analyzed by univariate and multivariable logistic regression analyses. Age was dichotomized into ≤42 (25% quartile cutoff) and >42 years. RESULTS: Of the 965 patients identified, the overall SLN+ was 4.4% (N = 43). Factors associated with SLN+ were age ≤42 years (7.5% vs 3.7%; odds ratio [OR], 2.14; P = .03), head/neck primary tumor location (9.2% vs 4%; OR, 2.75; P = .04), lymphovascular invasion (21.4% vs 4.2%; OR, 5.64; P = .01), and ≥2 mitoses/mm2 (8.2% vs 3.4%; OR, 2.31; P = .03). Patients <42 years with ≥2 mitoses/mm2 (N = 38) had a SLN+ rate of 18.4%. LIMITATIONS: Retrospective study. CONCLUSION: SLN+ is low in patients with T1a melanomas, but younger age, lymphovascular invasion, mitogenicity, and head/neck primary site appear to confer a higher risk of SLN+.

Prognostic Significance of Primary Tumor-Infiltrating Lymphocytes in a Contemporary Melanoma Cohort.

BACKGROUND: The prognostic impact of tumor-infiltrating lymphocytes (TILs) on outcomes and treatment efficacy for patients with melanoma in the contemporary era remains poorly characterized. METHODS: Consecutive patients who underwent wide excision and sentinel lymph node biopsy for cutaneous melanoma 1 mm thick or thicker at a single institution were identified (2006-2019). The patients were stratified based on primary tumor TIL status as brisk (bTILs), non-brisk (nbTILs), or absent (aTILs). Associations between patient factors and outcomes were analyzed using multivariable analysis. RESULTS: Of the 1017 patients evaluated, 846 (83.2 %) had primary TILs [nbTILs (n = 759, 89.7 %) and bTILs (n = 87, 10.3 %)]. In the multivariable analysis, the patients with any type of TILs had higher rates of regression [odds ratio (OR), 1.86; p = 0.016], lower rates of acral lentiginous histology (OR, 0.22; p < 0.001), and lower rates of SLN positivity (OR, 0.64; p = 0.042) than those without TILs. The multivariable analysis found no association between disease-specific survival and bTILs [hazard ratio (HR), 1.04; p = 0.927] or nbTILs (HR, 0.89; p = 0.683). An association was found between bTILs and recurrence-free survival (RFS) advantage [bTILs (HR 0.46; p = 0.047), nbTILs (HR 0.71; p = 0.088)], with 5-year RFS rates of 84 % for bTILs, 71.8 % for nbTILs, and 68.4 % for aTILs (p = 0.044). For the 114 immune checkpoint blockade (ICB)-naïve patients who experienced a recurrence treated with ICB therapy, no association was observed between progression-free survival and bTILs (HR, 0.64; p = 0.482) or nbTILs (HR, 0.58; p = 0.176). CONCLUSIONS: The prognostic significance of primary TILs in the contemporary melanoma era appears complex. Further studies characterizing the phenotype of TILs and their association with regional metastasis and responsiveness to ICB therapy are warranted.

Perturbational phenotyping of human blood cells reveals genetically determined latent traits associated with subsets of common diseases.

Although genome-wide association studies (GWAS) have successfully linked genetic risk loci to various disorders, identifying underlying cellular biological mechanisms remains challenging due to the complex nature of common diseases. We established a framework using human peripheral blood cells, physical, chemical and pharmacological perturbations, and flow cytometry-based functional readouts to reveal latent cellular processes and performed GWAS based on these evoked traits in up to 2,600 individuals. We identified 119 genomic loci implicating 96 genes associated with these cellular responses and discovered associations between evoked blood phenotypes and subsets of common diseases. We found a population of pro-inflammatory anti-apoptotic neutrophils prevalent in individuals with specific subsets of cardiometabolic disease. Multigenic models based on this trait predicted the risk of developing chronic kidney disease in type 2 diabetes patients. By expanding the phenotypic space for human genetic studies, we could identify variants associated with large effect response differences, stratify patients and efficiently characterize the underlying biology.

Fourteen years of pancreatic surgery for malignancy among ACS-NSQIP centers: Trends in major morbidity and mortality.

BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program was established to help participating hospitals track and report surgical complications with the goal of improving surgical care. We sought to determine whether this has led to improvements in surgical outcomes for pancreatic malignancies. METHODS: Patients with pancreatic malignancies who underwent surgical resection were identified from the American College of Surgeons National Surgical Quality Improvement Program database (2006-2019). Thirty-day postoperative major morbidity and mortality were analyzed by year. Major morbidity included organ and deep surgical site infection, venous thromboembolism, cardiac event, pneumonia, acute renal failure, sepsis, and respiratory failure. RESULTS: Of the 28,888 patients identified, 51% were male, the median age was 68, 74.3% underwent a pancreaticoduodenectomy, and 25.7% underwent a distal pancreatectomy. Among patients who underwent a pancreaticoduodenectomy, there was a significant increase in major morbidity (annual percent change 0.77, P = .012) driven by increases in organ space surgical site infection (annual percent change 3.52, P < .001) and venous thromboembolism (annual percent change 4.72, P = .005). However, there was a decrease in postoperative mortality (annual percent change -4.58, P = .001). For distal pancreatectomy patients, there was no change in rates of overall major morbidity (annual percent change -1.35, P = .08) or mortality (annual percent change -3.21, P = .25). CONCLUSION: Although major morbidity and mortality have not significantly changed for distal pancreatectomy patients, mortality has steadily decreased for patients undergoing pancreaticoduodenectomy, despite an increase in major morbidity. Whether this trend reflects a change in patient selection, an increase in detection of postoperative morbidities and/or an improvement in mitigation of these morbidities warrants further study.

Rigidity of commonly used dental trauma splints.

BACKGROUND/AIMS: The stability of immobilization devices varies from flexible to rigid, depending on the trauma. We evaluated the rigidity of various commonly used splints in vitro MATERIAL AND METHODS: An acrylic resin model was used. The central incisors simulated injured teeth, with increased vertical and horizontal mobility. The lateral incisors and canines stimulated uninjured teeth. Tooth mobility was measured with the Periotest device. Vertical and horizontal measurements were made before and after splinting, and the difference between values was defined as the splint effect. We evaluated 4 composite splints, 3 wire-composite splints, a titanium trauma splint, a titanium ring splint, a bracket splint, and 2 Schuchardt splints RESULTS: For all injured teeth and all splints, there was a significant splint effect for the vertical and horizontal dimensions (P < 0.05). For injured teeth, the composite splints produced the largest changes in vertical tooth mobility; wire-composite splints 1 and 2, using orthodontic wires, produced the smallest vertical splint effects. For uninjured teeth, the Schuchardt 1 splint and the bracket splint produced the largest splint effects; wire-composite splints 1 and 2 produced only a slight change in tooth mobility. Composite splints 2 and 3 produced the largest horizontal splint effects for injured teeth, and the 4 composite splints produced the largest horizontal splint effects for uninjured teeth. The most horizontally flexible splints were the titanium trauma splint and wire-composite splints 1 and 2. CONCLUSIONS: According to the current guidelines and within the limits of an in vitro study, it can be stated that flexible or semirigid splints such as the titanium trauma splint and wire-composite splints 1 and 2 are appropriate for splinting teeth with dislocation injuries and root fractures, whereas rigid splints such as wire-composite splint 3 and the titanium ring splint can be used to treat alveolar process fractures.

Metagenomic discovery of novel enzymes and biosurfactants in a slaughterhouse biofilm microbial community.

DNA derived from environmental samples is a rich source of novel bioactive molecules. The choice of the habitat to be sampled predefines the properties of the biomolecules to be discovered due to the physiological adaptation of the microbial community to the prevailing environmental conditions. We have constructed a metagenomic library in Escherichia coli DH10b with environmental DNA (eDNA) isolated from the microbial community of a slaughterhouse drain biofilm consisting mainly of species from the family Flavobacteriaceae. By functional screening of this library we have identified several lipases, proteases and two clones (SA343 and SA354) with biosurfactant and hemolytic activities. Sequence analysis of the respective eDNA fragments and subsequent structure homology modelling identified genes encoding putative N-acyl amino acid synthases with a unique two-domain organisation. The produced biosurfactants were identified by NMR spectroscopy as N-acyltyrosines with N-myristoyltyrosine as the predominant species. Critical micelle concentration and reduction of surface tension were similar to those of chemically synthesised N-myristoyltyrosine. Furthermore, we showed that the newly isolated N-acyltyrosines exhibit antibiotic activity against various bacteria. This is the first report describing the successful application of functional high-throughput screening assays for the identification of biosurfactant producing clones within a metagenomic library.

Systematic study on STR profiling on blood and saliva traces after visualization of fingerprint marks.

This paper describes a systematic study of the influence of optical, physical, and chemical methods used for fingerprint enhancement on subsequent DNA analysis of biological stains. Latent fingerprints as well as fingerprints in contact with blood and saliva on different surfaces were treated with dactyloscopic methods. As a general finding, subsequent STR profiling of the blood/saliva traces led to good results after all the enhancement methods included in this study. Concerning blood enhancement procedures, the airbrush technique showed deleterious effects on subsequent STR analysis in some cases. We therefore recommend the implementation of the layer technique, as it brings advantages for fingerprint enhancement as well. It could also be shown that, as can be necessary in practical casework, two enhancement methods can be performed on a single stain without having influence on STR profiling. In terms of methodological variety, this paper reflects a comprehensive study performed on STR profiling after fingerprint enhancement methods, including rare methods and variations of techniques, which can be a useful alternative in certain case scenarios.

Massive macronodular juvenile xanthogranuloma of the eyelid in a newborn.

A newborn baby with a lump on his right upper eyelid that was unresponsive to warm compresses and oral antibiotics presented at 3 weeks of age with a yellow mass measuring 20 mm in diameter at the base. Preliminary diagnosis was benign choristomatous mass; and warm compresses were continued. The mass continued to enlarge and 5 weeks later was 35 mm, with a tight, atrophic overlying epidermis and greater pupillary occlusion. Concern for possible malignancy prompted surgical resection and reconstruction with a supraclavicular graft. Histopathology disclosed that the eyelid tissue was nearly completely replaced by a highly cellular histiocytic neoplasm with prominent eosinophilic, often foamy cytoplasm, and nuclear pleomorphism. Poorly formed Touton giant cells were found. The mass showed positive immunoreactivity, with histiocytic markers CD163 and factor XIII, and was negative for cytokeratin markers, smooth muscle actin, and desmin. These features were compatible with JXG.