Impact of Obesity on Risk of Hypocalcemia After Total Thyroidectomy: Targeted National Surgical Quality Improvement Program Analysis of 16,277 Patients.

INTRODUCTION: Hypocalcemia following total thyroidectomy (TT) is common due to postoperative parathyroid dysfunction and vitamin D deficiency. Given the association between obesity and vitamin D deficiency, we sought to correlate body mass index (BMI) with hypocalcemia after TT. METHODS: Patients undergoing TT between 2016 and 2020 were identified from the American College of Surgeons National Surgical Quality Improvement Program thyroidectomy-targeted database. Univariable and multivariable regressions, stratified by BMI category (normal, overweight, obese), identified factors associated with hypocalcemia prior to discharge, within 30 d, and severe hypocalcemic events (emergent evaluation, intravenous calcium supplementation, or readmission). RESULTS: Sixteen thousand two hundred seventy seven TT were performed with available BMI data. Three thousand five hundred thirty one (21.7%) patients had normal BMI, 4823 (29.6%) were overweight, and 7772 (47.7%) were obese. Patients with BMI ≥ 25 had decreased risk of hypocalcemia before discharge (9.8% versus 13%, odds ratio [OR] 0.73, P < 0.001), 30 d (8.1% versus 10.4%, OR 0.76, P < 0.001), and severe hypocalcemic events (5.5% versus 6.4%, OR 0.84, P = 0.029) compared to normal BMI patients. On multivariable analysis for normal BMI patients, age < 45 y was a risk factor for hypocalcemia before discharge, 30 d, and severe hypocalcemic events (P < 0.05 for all). Additional risk factors in this group for 30-d hypocalcemia included parathyroid autotransplant and central neck dissection (P < 0.05) and recurrent laryngeal nerve injury for severe hypocalcemic events (P = 0.01). CONCLUSIONS: Younger patients with BMI < 25 are at an increased risk for hypocalcemia and severe hypocalcemic events after TT. These patients may benefit from preoperative counseling and increased calcium/vitamin D supplementation to reduce prolonged hospitalization and mitigate morbidity.

Patterns of Care for Patients With Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy at Predominately Academic Centers between 2016-2020: An NCDB Analysis.

Total neoadjuvant therapy (TNT) has emerged as the preferred approach for locally advanced rectal cancer (LARC), defined as T3/4 or any T with N+ disease. Our objective was to (1) determine the proportion of patients with LARC receiving TNT over time, (2) determine the most common method in which TNT is being delivered, and (3) determine what factors are associated with a greater likelihood of receiving TNT in the United States. Retrospective data was obtained from the National Cancer Database (NCDB) for patients diagnosed with rectal cancer between 2016 and 2020. Patients were excluded if they had M1 disease, T1-2 N0 disease, incomplete staging information, nonadenocarcinoma histology, received RT to a nonrectum site, or received a nondefinitive RT dose. Data were analyzed using linear regression, χ2 test, and binary logistic regression. Of the 26,375 patients included, most patients were treated at an academic facility (94.6%). Five thousand three (19.0%) patients received TNT, and 21,372 (81.0%) patients did not receive TNT. The proportion of patients receiving TNT increased significantly over time, from 6.1% in 2016 to 34.6% in 2020 (slope = 7.36, 95% CI 4.58-10.15, R2 = 0.96, P = .040). The most common TNT regimen was multiagent chemotherapy followed by long-course chemoradiation (73.2% of cases from 2016-2020). There was a significant increase in utilization of short-course RT as part of TNT from 2.8% in 2016 to 13.7% in 2020 (slope = 2.74, 95% CI 0.37-5.11, R2 = 0.82, P = .035). Factors associated with a lower likelihood of TNT usage included age >65, female gender, Black race, and T3 N0 disease. TNT use in the United States has increased significantly from 2016-2020, with approximately 34.6% of patients with LARC receiving TNT in 2020. The observed trend appears to be in line with the recent National Comprehensive Cancer Network guidelines recommending TNT as the preferred approach.

Radiation oncologist perceptions of therapeutic cannabis use among cancer patients.

INTRODUCTION: Cancer patients are increasingly incorporating medical marijuana into the management of treatment-related side effects. Currently however, data is limited regarding the risks and benefits of therapeutic cannabis for cancer patients. We sought to characterize radiation oncologists' practices and opinions regarding therapeutic cannabis via a nationwide survey. MATERIALS AND METHODS: An anonymous survey was distributed via email to 873 radiation oncologists in the American Society for Radiation Oncology member database. Radiation oncologists were asked their opinions and practices regarding the use of therapeutic cannabis for their patients. Bivariate analyses of potential predictors for responses were conducted using standard statistical techniques. RESULTS: One hundred seven radiation oncologists completed the survey. According to the survey, 36% of respondents would recommend therapeutic cannabis to their patients to mitigate treatment toxicity. Physicians practicing in states where medical marijuana is legal were more likely to recommend it compared to physicians working in states that have not legalized medical marijuana (OR = 3.79, 1.19-12.1, p = 0.01). Seventy-one percent of respondents reported therapeutic cannabis as being effective at least some of the time for managing treatment-related toxicities. Fifty-eight percent of physicians reported lacking sufficient knowledge to advise patients regarding therapeutic cannabis, while 86% of respondents were interested in learning more about therapeutic cannabis for cancer patients. CONCLUSIONS: Although a majority of radiation oncologists believe there are benefits to therapeutic cannabis, many are hesitant to recommend for or against its use. Radiation oncologists appear to be interested in learning more about how therapeutic cannabis may play a role in their patients' care.

Development of a Functional Observational Battery in the Minipig for Regulatory Neurotoxicity Assessments.

A functional observational battery (FOB) is recommended as the first-tier neurotoxicity screening in the preclinical safety pharmacology testing guidelines. Minipigs have increasingly been used in regulatory toxicology studies; however, no current FOB protocol is available for neurotoxicity testing in these species. Hence, a minipig FOB instrument was developed. A complete crossover study with Sinclair minipigs was performed to evaluate physiologic, neurologic, and behavioral effects of amphetamine, ketamine, and diazepam. The treated minipigs were first observed in their home cage, were video-recorded for 10 minutes in an open field, and then went through a complete neurologic examination. Both ketamine and diazepam were shown to reduce the freezing and behavior shifts of treated minipigs, while increasing their exploratory behaviors. Both drugs also caused muscular and gait impairment. The effects of ketamine and diazepam were consistent with their roles as central nervous system (CNS) suppressants. Unique effects were also observed with ketamine and diazepam treatments, which may reflect their unique mechanisms of action. Consistent with its role as a CNS stimulant, amphetamine caused the treated minipigs to be hyperactive and to display increased freezing and behavior shifts and reduced exploring activities. These effects of amphetamine were opposite to those observed with ketamine and diazepam. Amphetamine also increased locomotion in the treated minipigs. The present effects of amphetamine, ketamine, and diazepam are in agreement with observations by others. In conclusion, the minipig is a suitable species for FOB evaluation of pharmaceuticals in preclinical safety pharmacology testing.

The importance of minipigs in dermal safety assessment: an overview.

The use of miniature swine as a non-rodent species in safety assessment has continued to expand for over a decade and their use has become routine, particularly in pharmacology as a model for human integumentary diseases. Translational preclinical swine study data are now favorably compared and contrasted to human data, and miniature swine models provide important information in dermal safety assessment and skin pharmacology. For example, the miniature swine model has been well-accepted for cutaneous absorption and toxicity studies due to swine integument being morphologically and functionally similar to human skin. Subsequently, this model is important to dermal drug development programs, and it is the animal model of choice for assessment of dermal absorption, local tolerance and systemic toxicity following dermal exposures. In conclusion, the miniature swine model has an important role to play in the safety assessment of pharmaceutical products and in multiple aspects of human dermal drug development.

Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses' Health Study.

BACKGROUND: Coffee is an important source of antioxidants, and consumption of this beverage is associated with many health conditions and a lower mortality risk. However, no study, to our knowledge, has examined whether varying coffee or caffeine consumption levels are associated with telomere length, a biomarker of aging whose shortening can be accelerated by oxidative stress. OBJECTIVE: We performed a large comprehensive study on how coffee consumption is associated with telomere length. METHODS: We used data from the Nurses' Health Study (NHS), a prospective cohort study of female nurses that began in 1976. We examined the cross-sectional association between coffee consumption and telomere length in 4780 women from the NHS. Coffee consumption information was obtained from validated food-frequency questionnaires, and relative telomere length was measured in peripheral blood leukocytes by the quantitative real-time polymerase chain reaction. Unconditional logistic regression was used to obtain ORs when the telomere length outcome was dichotomized at the median. Linear regression was used for tests of trend with coffee consumption and telomere length as continuous variables. RESULTS: Higher total coffee consumption was significantly associated with longer telomeres after potential confounding adjustment. Compared with non-coffee drinkers, multivariable ORs for those drinking 2 to <3 and ≥3 cups of coffee/d were, respectively, 1.29 (95% CI: 0.99, 1.68) and 1.36 (95% CI: 1.04, 1.78) (P-trend = 0.02). We found a significant linear association between caffeine consumption from all dietary sources and telomere length (P-trend = 0.02) after adjusting for potential confounders, but not after additionally adjusting for total coffee consumption (P-trend = 0.37). CONCLUSIONS: We found that higher coffee consumption is associated with longer telomeres among female nurses. Future studies are needed to better understand the influence of coffee consumption on telomeres, which may uncover new knowledge of how coffee consumption affects health and longevity.

Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells.

Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.

Miniature swine model of phototoxicity testing.

BACKGROUND/PURPOSE: This study determined the threshold doses for 'solar erythema' and for phototoxic responses to 8-methoxypsoralen (8-MOP) in white skin Hanford and grey skin Yucatan miniature swine. METHODS: For threshold erythema determinations, the UVR exposures included both UVA (315-400 nm) and UVB (290-315 nm) radiation by positioning one fluorescent 'sunlamp' among 10 'PUVA' lamps. With this configuration the UVR exposures ranged from 0.5-2.8 times the 'instrumental MED' (MEDi) for Hanford and from 1.0-5.6 times the MEDi for Yucatan. For phototoxicity determinations (i.e., with and without topically-applied graduated concentrations of 8-MOP), the UVB component was minimized by extinguishing the sunlamp, thus permitting higher UVA exposures. RESULTS: The Hanford had the lower UV erythema dose threshold (1.0-1.4 times the MEDi) and the erythema that developed was readily observable. The exposure doses for the phototoxicity test were 5 J/cm(2) of UVA in 35 minutes or 10 J/cm(2) in 70 minutes. The phototoxic (vascular) response to 8-MOP was observed in the two highest concentrations (0.01% and 0.1%) in Hanford pigs, in a dose-related manner. Microscopic evidence of a dose-related response was also observed as the concentration of 8-MOP increased. CONCLUSION: This verified that the Hanford miniature swine is the preferable strain for phototoxic effects. In contrast, UVR exposure of the Yucatan pig skin produced tanning rather than erythema, confirming that the Yucatan is the more appropriate strain for studying the melanization response. Thus, Hanford and Yucatan miniature swine have cutaneous photobiological responses that reflect their respective strain differences.