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Background: Limb regeneration in the axolotl is achieved by epimorphosis, thus depending on the blastema formation, a mass of progenitor cells capable of proliferating and differentiating to recover all lost structures functionally. During regeneration, the blastema cells accelerate the cell cycle and duplicate its genome, which is inherently difficult to replicate because of its length and composition, thus being prone to suffer double-strand breaks., Results: We identified and characterized two remarkable components of the homologous recombination repair pathway (Amex.RAD51 and Amex.MRE11), which were heterologously expressed, biochemically characterized, and inhibited by specific chemicals. These same inhibitors were applied at different time points after amputation to study their effects during limb regeneration. We observed an increase in cellular senescent accompanied by a slight delay in regeneration at 28 days postamputation regenerated tissues; moreover, inhibitors caused a rise in the double-strand break signaling as a response to the inhibition of the repair mechanisms., Conclusions: We confirmed the participation and importance of homologous recombination during limb regeneration. The chemical inhibition induces double-strand breaks that lead to DNA damage associated senescence, or in an alternatively way, this damage could be possibly repaired by a different DNA repair pathway, permitting proper regeneration and avoiding senescence., (© 2022 American Association for Anatomy.)

The remarkable regenerative capabilities of the salamander Ambystoma mexicanum have turned it into one of the principal models to study limb regeneration. During this process, a mass of low differentiated and highly proliferative cells, called blastema, propagates to reestablish the lost tissue in an accelerated way. Such a process implies the replication of a huge genome, 10 times larger than humans, with about 65.6% of repetitive sequences. These features make the axolotl genome inherently difficult to replicate and prone to bear mutations. In this context, the role of DNA repair mechanisms acquires great relevance to maintain genomic stability, especially if we consider the necessity of ensuring the correct replication and integrity of such a large genome in the blastema cells, which are key for tissue regeneration. On the contrary, DNA damage accumulation in these cells may result in senescence, apoptosis and premature differentiation, all of them are mechanisms employed to avoid DNA damage perpetuation but with the potential to affect the limb regeneration process. Here we review and discuss the current knowledge on the implications of DNA damage responses during salamander regeneration., (© 2020 American Association of Anatomists.)

Problem Addressed: Floseal is a novel matrix hemostatic sealant composed of collagen-derived particles and topical bovine-derived thrombin. It is applied as a high-viscosity gel for hemostasis and has been clinically proven to control bleeding. This study is a prospective, randomized, controlled clinical trial of Floseal sealant compared to traditional suction cautery hemostasis in children undergoing adenoidectomy., Methods and Measures: Seventy patients (mean age 7.0 yrs, 45.7% male) with obstructive sleep apnea underwent traditional cold steel adenoidectomy with an adenoid curette and were then randomized to receive the hemostatic sealant (Floseal) or cautery to obtain hemostasis. Patients were crossed over to the other hemostatic technique if hemostasis was not achieved after more than 100 mL of blood loss or 15 minutes elapsed time. Objective data collected included time to hemostasis and blood loss during hemostasis. Visual analog scales (VAS) were used to record subjective data by the operating surgeon including bleeding following adenoid pack removal (0 = none, 3 = brisk) and ease of operation (1 = extremely easy, 6 = extremely difficult). Parents recorded diet on a journal and were contacted by phone at postoperative day 7 and questioned with regard to return to regular diet and use of narcotics., Results: Compared to patients in the cautery group (n = 35), Floseal patients (n = 35) had significantly shorter times to hemostasis (0.6 +/- 1.3 minutes vs 9.5 +/- 5.4 minutes [mean +/- SD], P < 0.001), less blood loss (2.5 +/- 9.2 mL vs 29.4 +/- 27.1 mL, P < 0.001), less subjective bleeding (0.0 +/- 0.6 vs 2.0 +/- 0.7, [median 4-point VAS +/- SD], P < 0.001), and subjectively easier operations (2.6 +/- 1.0 vs 5.2 +/- 1.0 [mean 6-point VAS +/- SD], P < 0.001). Furthermore, Floseal patients returned to regular diet earlier (2.7 +/- 0.7 vs 4.1 +/- 0.5 days [mean +/- SD], P < 0.001) and had less use of narcotics at 7 days postoperatively (40% vs 69%, P < 0.05). Lastly, three patients in the cautery group were crossed over to the Floseal group, but no Floseal subjects were crossed over to the cautery group. The retail cost of Floseal is US 85 dollars. Operating room costs are estimated at US 12 dollars/minute. Reducing the operative length by 8.9 minutes on average produces a cost savings of US 106.80 dollars per operation. There were no complications in either experimental group including postoperative hemorrhage, hospitalization, blood transfusion, or aspiration., Conclusions: Floseal matrix hemostatic sealant is a safe, efficacious, easy, and cost-effective technique for obtaining hemostasis in children undergoing adenoidectomy. Limitations of the study include the fact that it is nonblinded, which does allow for some bias in the subjective data recorded. However, utilizing 4 different operating surgeons, 3 of whom were not affiliated with the study, minimized this. CLINICAL SIGNIFICANCE OF STUDY: This study demonstrates the safety and efficacy of a novel hemostatic sealant in children undergoing adenoidectomy. Floseal matrix hemostatic sealant can be used as a first-line hemostatic agent, and it is a good tool in the armamentarium of otolaryngologists who encounter significant bleeding following adenoidectomy.

Objectives: To investigate the prevalence of human papillomavirus (HPV), and HPV type 16 (HPV16) infection in cervical ectopy, and the presence of anti-HPV16 secretory IgA (sIgA) antibodies., Methods: DNA from patients with cervical ectopy (n=218), HPV-associated lesions (n=111), and controls without evidence of cervical ectopy or HPV infection (n=93) were analyzed by PCR for the presence of HPV and HPV16. The presence of mucosal sIgA antibodies against HPV16 capsid antigens (VLP) was assayed in cervical mucus by ELISA., Results: Prevalence of HPV DNA was higher in cervical ectopy than in controls (P=0.04; OR=2.06; 95% CI 0.99-4.33). HPV16 was 6.3 times more prevalent in cervical ectopy than in controls. Anti-HPV16 sIgA were detected more frequently in cervical ectopy patients than in controls (P=0.0004)., Conclusions: Cervical ectopy correlates with HPV infection. HPV16 is highly prevalent in cervical ectopy. sIgA antibodies against HPV16 capsids are generated in patients with cervical ectopy.

Objectives: Diagnostic accuracy of the ThinPrep process (Cytyc, Boxborough, MA) was compared with that of conventional (smear) cytopreparation for fine-needle aspiration (FNA) of head and neck masses., Methods: In a prospective, randomized, single-blinded study, 209 patients served as their own controls and underwent 236 FNAs using ThinPrep and conventional (smear) cytopreparatory techniques., Results: ThinPrep produced less air-drying artifact and less mechanical distortion than the conventional method. The conventional technique was diagnostic in 63% of samples; the ThinPrep technique was diagnostic in 55% of samples. When all results were combined, pathologists subjectively preferred the conventional technique but accepted use of ThinPrep as the only cytopreparatory technique for most head and neck masses., Conclusions: For adequately experienced cytopathologists, ThinPrep is acceptable for FNA of salivary masses, neck cysts, metastatic lymph nodes, and thyroid lesions. Conventional smear technique should be used for FNA of nonmetastatic lymphoid lesions. Use of ThinPrep can complement use of the conventional (smear) cytopreparatory technique when aspirate is nondiagnostic or bloody, when the patient has a blood-borne infectious disease, when the clinician is inexperienced, or when aspirate has entered the syringe.

A eutectic mixture of local anesthetics (EMLA), prepared as a cream, is an oil-in-water emulsion of 2 anesthetic agents lidocaine and prilocaine. Several clinical applications of EMLA cream, its effectiveness as a topical anesthetic, and its safety profile have been previously reported. We report our experience with EMLA cream in 17 adult and 24 pediatric patients. We find EMLA to be the preferred anesthetic for performing minor outpatient otologic procedures in adults. We also find EMLA to be a safe, well-tolerated alternative to general anesthesia in some pediatric patients. Potential cost savings of EMLA cream during pediatric myringotomies in the clinic are also discussed.

Recent reports have described an increase in squamous cell carcinoma of the upper aerodigestive tract in young adults. As the preponderance of epidemiologic data exists for the population between 50 and 70 years of age, controversy has developed regarding the clinical course of head and neck cancer in youth. Some authors advocate more aggressive management, calling attention to the lack of "classic" predisposing factors and suggesting genetic disorders or immunodeficiency. Basic science researchers have reported greater DNA fragility, sensitivity to carcinogens, and altered immune responses in young patients with carcinoma. To further elucidate the clinical aspects of this controversy, we performed a retrospective review using multivariate analysis to determine factors that affect recurrence. After screening 820 charts, 155 patients were found who met strict entrance criteria to the study. The patients were separated into five age groups, and 16 clinical variables were collected on each patient. Cox proportional hazards modeling revealed no significantly higher likelihood of recurrence in the 15- to 39-year-old age group. The model did find that metastatic adenopathy was predictive of recurrence (p = 0.034). The overall model further suggested a trend toward higher relative risk of recurrence in the middle-aged groups (p = 0.0541). In our review of the English biomedical literature, this is the first study to directly compare the outcome of young head and neck cancer patients with that of old patients using multivariate analysis. Future research is indicated in developing precise outcome predictions according to TNM staging, aneuploidy status, and DNA fragility in young patients. Efforts at limiting carcinogen exposure should continue.

The detrimental effects of transfusion have been documented--particularly by surgical oncologists, who believe transfusion-induced immunosuppression increases the incidence of recurrence and infectious complications. We examined this relation in surgical oncology of the head and neck. After meeting strict inclusion criteria, 104 patients were entered into the study, in which 31 variables of a clinical, surgical, pathologic, laboratory, and treatment nature were studied. Multivariate analysis showed transfusion did not significantly affect recurrence or infectious complications. However, by univariate analysis, infectious complications were related to transfusion (p = 0.029). The variables age (p = 0.024), postoperative hemoglobin level (p = 0.049), and spread to regional lymph node (p = 0.0015) were found to significantly affect the incidence of recurrence. In the three previous otolaryngologic studies, transfusions had been shown to affect recurrence; however, two studies used univariate analysis only. Since this is one of the first otolaryngologic studies to examine the relation of transfusion with infectious complications, prospective studies using multivariate analysis are warranted. Meanwhile, the decision to transfuse should continue to depend on the clinical status of the patient.