Impact of a History of COVID-19 Infection on Postoperative Outcomes for Free Flap Patients.

Objectives: This study examines the impact of a history of coronavirus disease 2019 (COVID-19) infection on patients' outcomes after microvascular free flap surgery and to examine the recommendations on when to perform microvascular surgery after a COVID-19 infection. Methods: A retrospective chart review using the TriNetX database was completed on March 5, 2023. Two cohorts were created: (1) patients who had a positive COVID-19 diagnosis within 1 year before microvascular free flap surgery, and (2) patients with no history of COVID-19 who underwent free flap surgery. Current Procedural Terminology codes were used to identify procedures and International Classification of Diseases-10 codes were used to identify outcomes. Results: There was a total of 31,505 patients who underwent microvascular free flap surgery, 500 of whom had a diagnosis of COVID-19 within 1 year of free flap surgery and 31,005 without history of COVID-19. There was increased risk of sepsis, surgical site infection (SSI), generalized infection, gangrene, dehiscence, hematoma, seroma, intensive care unit admission, and death in patients who underwent free flap surgery within a year of COVID-19 infection. After propensity score matching, there were 498 patients in both groups. Increased risk remained for SSI and gangrene in patients with a history of COVID-19 after matching. When comparing surgical timing between 0 to 2 months after COVID-19 infection and 2 to 12 months after COVID-19 infection, there were no significant differences between groups. Conclusions: After propensity score matching, patients with a history of COVID-19 infection were at increased risk for SSI and gangrene. However, many flap surgeries cannot be delayed. This study may help counsel patients regarding the possible complications after surgery and provide a heightened awareness in the surgical team of a possible increase in infectious complications in this population. Additional studies should investigate optimal timing of free flap surgery after COVID-19 infection and ways to mitigate the risk of infectious complications.

Evaluation of Hypocalcemia Following Total Laryngectomy With and Without Thyroidectomy.

OBJECTIVE: Hypoparathyroidism and associated hypocalcemia are well-established complications following laryngectomy. This study further characterizes the rates of hypocalcemia in patients undergoing total laryngectomy (TL) with and without thyroidectomy and hemithyroidectomy. STUDY DESIGN: Retrospective cohort study. SETTING: TriNetX. METHODS: We queried TriNetX, a deidentified patient database, to identify patients who underwent TL with and without thyroidectomy and hemithyroidectomy. Rates of hypocalcemia, low parathyroid hormone (PTH), calcium, and calcitriol supplementation were compared between groups with multivariable repeated measures logistic regression. RESULTS: We identified 870 patients in the TL without thyroidectomy cohort, 158 patients in the hemithyroidectomy cohort, and 123 in the total thyroidectomy cohort. Rates of hypocalcemia differed between patients receiving total thyroidectomy versus TL alone for 0 to 1 month (odds ratio [OR]: 2.88 [1.95-4.26]) 1 to 6 months (OR: 5.08 [2.29-11.3]), and 6 to 12 months (OR: 2.63 [1.003-6.88]) postoperatively, with adjustment for age at laryngectomy, race, ethnicity, and gender. Results were similar among those who received calcium supplementation. The rate of low PTH levels differed in these groups for 0 to 1 month (OR: 5.13 [3.10-8.51]), 1 to 6 months (OR: 3.47 [1.46-8.22]), and 6 to 12 months (OR: 3.63 [1.40-9.38]) following surgery. Rates of postoperative calcium supplementation were increased for patients receiving total thyroidectomy versus TL for 1 to 6 months (OR: 2.44 [1.62-3.68]), and 6 to 12 months following surgery (OR: 1.79 [1.18-2.72]). CONCLUSION: Patients undergoing TL with total thyroidectomy have a higher risk of postoperative hypocalcemia compared to patients receiving TL alone. Risk of parathyroid injury in these patients may warrant further emphasis on PTH measurement after surgery and a multidisciplinary approach to management.

Spontaneous Corneal Clearing after Descemet Membrane Rupture and Near-Total Detachment in Keratoglobus: A Case Report.

Introduction: We present a case of a patient with osteogenesis imperfecta (OI) and keratoglobus (KG) who had a near-total rupture of Descemet's membrane followed by spontaneous corneal clearing. This case is unique in that it demonstrates the potentially excellent outcome of conservative treatment for Descemet's rupture in patients with KG and illustrates the impressive migratory potential of healthy endothelial cells. Case Presentation: An 11-year-old girl with OI and KG who had rupture and near-total detachment of Descemet's membrane presented for evaluation. This was managed conservatively and resulted in the eventual spontaneous clearing of the cornea. A similar process happened in the fellow eye some years later. Given the result of conservative management originally, the patient was once again treated conservatively, with significant improvement in corneal edema and visual acuity. Conclusion: Given the size of the ruptures, this case highlights the dynamic nature of the corneal endothelium and provides an extreme example of the migratory potential of corneal endothelial cells.

Thyroid Cancer With Cutaneous Metastases.

Objectives: Thyroid carcinoma with cutaneous metastases is a rare clinical finding. Cutaneous metastases from thyroid carcinoma have been associated with a poor prognosis, but these data are limited to case reports. The exact mechanism of cutaneous metastases from thyroid carcinoma is not clear. Our study aims to report the demographic, clinical, and histologic findings of patients with cutaneous metastases from thyroid carcinoma. Methods: A review was conducted using the Medline/PubMed, Cochrane, and Scopus databases to review literature from inception to May 2023. Data extracted included patient age at diagnosis of cutaneous metastases, patient sex, thyroid carcinoma histotype, location of metastases, the time interval between diagnoses of thyroid carcinoma and cutaneous metastases, and overall survival (OS) from the time of cutaneous metastases. Results: One hundred thirty-six patients were identified and 75 were female. The most common types of thyroid carcinoma with cutaneous metastases were papillary (47.79%), followed by follicular (30.15%), and medullary (11.03%). In addition, 11 cases of anaplastic carcinoma, 2 cases of oncocytic carcinoma, and 2 cases of poorly differentiated thyroid carcinoma were reported. The average age at diagnosis of cutaneous metastases was 63.13 years, and the average time interval between the diagnoses of primary thyroid carcinoma and cutaneous metastases was 48.27 months. The most common location of metastases was the scalp (n = 48). Other common locations included the neck, chest, and face. The OS after diagnosis of metastases was only available in 34 patients with an average of 13.07 months. Of these 34 cases, 10 were medullary, 10 were papillary, 9 were anaplastic, and 5 had follicular carcinoma. Conclusions: This study represents an up-to-date review of the cases of thyroid carcinoma with cutaneous metastases. While cutaneous metastasis remains a rare finding, one needs a high index of suspicion, and their presence portends a poor prognosis.

Current and Emerging Diagnostic, Prognostic, and Predictive Biomarkers in Head and Neck Cancer.

Head and neck cancers (HNC) are a biologically diverse set of cancers that are responsible for over 660,000 new diagnoses each year. Current therapies for HNC require a comprehensive, multimodal approach encompassing resection, radiation therapy, and systemic therapy. With an increased understanding of the mechanisms behind HNC, there has been growing interest in more accurate prognostic indicators of disease, effective post-treatment surveillance, and individualized treatments. This chapter will highlight the commonly used and studied biomarkers in head and neck squamous cell carcinoma.

History of Bariatric Surgery Before Thyroid Surgery: Recommendations for Prevention and Management of Postoperative Hypocalcemia.

Hypocalcemia following thyroidectomy is a common and potentially life-threatening complication. It is caused by intraoperative injury to the parathyroid glands or their blood supply. Although several studies have shown that patients with a prior history of bariatric surgery may be at an increased risk for hypocalcemia after thyroidectomy, no clear recommendations exist for preventing and managing this condition in this population. This paper highlights the significance of understanding this risk and of obtaining a history of prior bariatric surgery before thyroidectomy. We propose concise recommendations for preventing and managing hypocalcemia following thyroidectomy in patients with a history of bariatric surgery.

Testing the relationship between inhibitory control and soda consumption: An event-related potential (ERP) study.

The intake of sugar-sweetened beverages (SSB) may detrimentally influence health outcomes. Drinking less soda may help manage SSB consumption, as soft drinks are a top contributor to SSB intake. One cognitive factor that may influence soda consumption is inhibitory control, or the ability to withhold a dominant response in order to correctly respond to one's environment. Increased inhibitory control plays a role in decreasing consumption of high-calorie foods and strengthening inhibitory control may help individuals manage their food intake. However, neural response to soda beverages versus traditional non-sweetened beverages, such as water, and how it relates to soda consumption is unknown. In a sample of 116 healthy individuals (M = 20.56; SD = 2.08; 47.4% female), we measured soda consumption and tested event-related potential (ERP) measures of inhibitory control, including the N2 and P3 components, during soda-specific and neutral comparison go/no-go tasks. Female participants consumed less soda on average than males, and as participants got older, they consumed less soda. Participants showed faster response times and higher accuracy on the soda-specific go/no-go task compared to the neutral go/no-go task. ERP results indicated inhibitory control was greater when individuals withheld dominant responses to soda stimuli rather than neutral stimuli. Neither N2 no-go amplitude on the soda-specific go/no-go task nor P3 no-go amplitude on the soda-specific task predicted measures of soda intake. Results suggest greater inhibitory control resources are required when withholding responses to soda beverages compared to neutral stimuli, but inhibitory control ERPs did not predict day-to-day soda intake.

Two hot spot mutant p53 mouse models display differential gain of function in tumorigenesis.

Mutant p53 proteins not only lose their tumor-suppressor function but some acquire oncogenic gain of function (GOF). The published mutp53 knock-in (KI) alleles (R172H, R270H, R248W) manifest GOF by broader tumor spectrum and more metastasis compared with the p53-null allele, but do not shorten survival. However, whether GOF also occurs with other mutations and whether they are all biologically equal is unknown. To answer this, we created novel humanized mutp53 KI mice harboring the hot spot alleles R248Q and G245S. Intriguingly, their impact was very different. Compared with p53-null mice, R248Q/- mice had accelerated onset of all tumor types and shorter survival, thus unprecedented strong GOF. In contrast, G245S/- mice were similar to null mice in tumor latency and survival. This was associated with a twofold higher T-lymphoma proliferation in R248Q/- mice compared with G245S/- and null mice. Moreover, R248Q/- hematopoietic and mesenchymal stem cells were expanded relative to G245S/- and null mice, the first indication that GOF also acts by perturbing pretumorous progenitor pools. Importantly, these models closely mirror Li-Fraumeni patients who show higher tumor numbers, accelerated onset and shorter tumor-free survival by 10.5 years when harboring codon R248Q mutations as compared with Li-Fraumeni patients with codon G245S mutations or p53 deletions/loss. Conversely, both KI alleles caused a modest broadening of tumor spectrum with enhanced Akt signaling compared with null mice. These models are the first in vivo proof for differential oncogenic strength among p53 GOF alleles, with genotype-phenotype correlations borne out in humans.

Stress-mediated nuclear stabilization of p53 is regulated by ubiquitination and importin-alpha3 binding.

The activity of p53 as an inducible transcription factor depends on its rapid nuclear stabilization after stress. However, surprisingly, mechanism(s) that regulate nuclear p53 accumulation are not well understood. The current model of stress-induced nuclear accumulation holds that a decrease in p53 nuclear export leads to its nuclear stabilization. We show here that regulated nuclear import of p53 also has a critical function. p53 import is mediated by binding to the importin-alpha3 adapter and is negatively regulated by ubiquitination. p53 harbors several nuclear localization signals (NLS), with the major NLS I located at amino-acids 305-322. We find that direct binding of p53 to importin-alpha3 depends on the positive charge contributed by lysine residues 319-321 within NLS I. The same lysines are also targets of MDM2-mediated ubiquitination. p53 ubiquitination occurs primarily in unstressed cells, but decreases dramatically after stress. Importin-alpha3 preferentially interacts with non-ubiquitinated p53. Thus, under normal growth conditions, ubiquitination of Lys 319-321 negatively regulates p53-importin-alpha3 binding, thereby restraining p53 import. Conversely, stress-induced accumulation of non-ubiquitinated p53 in the cytoplasm promotes interaction with importin-alpha3 and rapid import. In later phases of the stress response, blocked nuclear export also takes effect. We propose that p53 nuclear import defines an important novel level of regulation in the p53-mediated stress response.

Training-induced changes in serum lipids, fat tolerance, and adipose tissue metabolism in patients with hypertriglyceridemia.

Ten males (mean age 44 years) with primary hypertriglyceridemia were trained for 4 months 3 times/week for 1-h sessions. Eleven patients with similar physical characteristics and hypertriglyceridemia served as controls. Serum was assayed for TG and cholesterol (CH) and the various lipoprotein fractions, apoprotein A-I, glucose, insulin, and C-peptide. The removal of TG from the circulation was estimated by the Intralipid test. An open fat biopsy was taken and the incorporation and esterification of [14C]palmitate and glycerol release were measured in vitro. Following endurance physical training, serum TG and VLDL-TG decreased by 25 and 27%, respectively. No changes were observed in total CH and CH in the lipoprotein fractions or in apoprotein A-I. Fat tolerance increased slightly (+8%) whereas the incorporation of labelled palmitate into adipose tissue was reduced by 16%. The diminished incorporation was concomitant with a reduction in the esterification of fatty acids to TG (-29%). Enhanced removal of TG may contribute to the lowering of serum TG. The skeletal muscle is probably responsible for this adaptation, whereas the uptake of TG into adipose tissue is diminished.