In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.

Molecular Testing Results for Indeterminate Thyroid Nodules and Social Habits.

INTRODUCTION: The effects of smoking and alcohol use on the risk of thyroid cancer remain unclear. We sought to investigate the association between these social habits, molecular testing results, and the risk of thyroid cancer. METHODS: We conducted a retrospective chart review of patients with indeterminate thyroid nodules (Bethesda III and IV) who underwent molecular testing. The frequency of abnormal molecular testing results was compared among patients with varying smoking and alcohol consumption habits. RESULTS: Of 460 patients, median age was 51.8 y, 78.3% were female, 60.7% were White, and 79.8% presented with Bethesda III nodules. The rate of malignancy was 42.6% overall; 73.4% of molecular testing was performed with Afirma, 20.1% with ThyroSeq, and 5.0% with ThyGeNEXT. For social habits, 72.2% never smoked and 40.9% never drank alcohol. Never/rare drinkers were less likely to have abnormal results compared to routine drinkers when considering all types of molecular testing together (83.2% versus 91.3%, P = 0.046), as were those who underwent ThyroSeq molecular testing (71.8% versus 94.4%, P = 0.045). Multivariable analysis revealed that being a routine drinker (adjusted OR 2.19, 95% CI 1.08-4.88), having a larger lesion (adjusted OR 0.65, 95% CI 0.54-0.77), being tested by ThyroSeq (adjusted OR 0.41, 95% CI 0.22-0.76), and other commercial panels (adjusted OR 0.12, 95% CI 0.02-0.64) were independent predictors of abnormal molecular testing results. CONCLUSIONS: Our patients' social habits may be associated with the molecular testing results of their indeterminate thyroid nodules but not with their surgical pathology results.

Social Determinants of Health and Quality of Life in Endocrine Surgery Patients.

INTRODUCTION: Quality of life (QoL) of endocrine surgery patients is an important patient outcome but the role of social determinants of health (SDH) on preoperative QoL is understudied. METHODS: This study used preoperative data of 233 endocrine surgery patients participating in a longitudinal QoL study to examine the influence of SDH (patient-level and environmental) on preoperative QoL. Patient-level SDH was assessed with structured survey questions and environmental SDH with the Social Vulnerability Index. Multiple domains of QoL were assessed with the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29). RESULTS: The average age of the sample was 52.9 y and 76.8% were female, 10% were Hispanic, 55.8% were White, 32.6% were Black, 6.9% were Other, and 4.7% were Asian. Patients with patient-level SDH were more likely to have worse preoperative QoL in multiple PROMIS domains. Patients who lived in the most socially vulnerable areas had the same or better QoL scores in the PROMIS-29 domains than those living in less vulnerable areas. Minority race patients were more likely to have patient-level SDH and to live in the most vulnerable areas. CONCLUSIONS: This study is the first to our knowledge to examine the role of patient-level and environmental SDH on preoperative QoL among endocrine surgery patients. The results identified specific patient-level factors that could be used as the basis for interventions aimed to improve patients' QoL. Future studies that evaluate the role of preoperative SDH on long-term QoL and clinical outcomes would further enhance our understanding of the impact of SDH on patient wellbeing.

Pilot Cross-Sectional Quality of Life Study of a Diverse Endocrine Surgery Patient Population.

INTRODUCTION: Quality of life (QOL) studies of endocrine surgery patients have lacked diverse patient representation, long-term follow-up, or the use of validated questionnaires. This cross-sectional pilot study explored the need for prospective QOL studies in diverse endocrine surgery patients who were ≥6 mo postoperative. MATERIALS AND METHODS: In 2019, we mailed anonymous questionnaires to 671 adult patients cared for by an endocrine surgery division between 2018 and 2019. Patients were ≥6 mo postoperative and had undergone thyroidectomy, parathyroidectomy, or adrenalectomy. Patients mailed back responses to two validated questionnaires, the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and the Voice Handicap Index-10 (VHI-10). We compared responses across race. RESULTS: Of 135 respondents (20.1% response rate), 27.4% were 60-69 y and 69.6% were female. Race and ethnicity frequencies include 60.0% White patients, 27.4% Black patients, 4.4% Asian patients, and 5.2% Hispanic/LatinX patients. For surgery, 57.8% underwent thyroidectomy, 28.2% parathyroidectomy, 9.6% both, 4.4% adrenalectomy, and 32.6% surgery for cancer. Regarding PROMIS-29 results for patients who underwent thyroidectomy, significant differences were observed in the domains of physical function, depression, sleep disturbances, social roles, and global pain across race (P < 0.05). However, few differences were seen after completion of post hoc pairwise comparisons. We did not observe differences in PROMIS scores across race among patients who underwent parathyroidectomy and adrenalectomy or in VHI-10 for all surgical groups. CONCLUSIONS: These results suggest long-term QOL differences across race and surgery type and support the need for prospective studies among diverse endocrine surgery patients.

Endocrine Surgery Patients' and Providers' Perceptions of Telemedicine in the COVID Era.

BACKGROUND: Telemedicine has become a key modality for health care delivery during the COVID-19 pandemic, including for endocrine surgery. Little data exists on patients' and referring endocrinologists' perspectives of its use. The study aimed to assess and compare endocrine surgery patients' attitudes about telemedicine to that of referring endocrinologists. METHOD: Patients from a regional endocrine surgery practice and referring endocrinologists were sent surveys about their perspectives on telemedicine use. RESULTS: Fifty two patients responded: average age was 58.3 years; 78% were female; 33% were Black. Sixteen referring endocrinologists responded: average age was 52.4 years; 62.5% were female. Nearly all patients (92%) and providers (100%) would try telemedicine or use it again. Providers were more likely than patients to use telemedicine because of COVID-19 (100% versus 70.6%, P = 0.03). Patients were more concerned about the lack of personal connection with telemedicine than providers (60.8% versus 25.0%, P = 0.02). Endocrinologists were more interested in using telemedicine to review abnormal results (81.3% versus 35.3%, P <0.01), and more patients were specifically disinterested in reviewing abnormal results via telemedicine (54.9% versus 6.3%, P = 0.04). Patients were more interested in its use for postoperative visits (47.1% versus 0%, P <0.01). More endocrinologists were specifically disinclined to conduct new consultations with telemedicine (87.5% versus 58.8%, P <0.01). CONCLUSION: Telemedicine is a mutually acceptable method for patients and their referring providers for endocrine surgery delivery, although in-person visits continue to have their place. Telemedicine use may continue to expand after the pandemic as an important point of access for endocrine surgery.

Drop Spreading and Confinement in Swelling-Driven Folding of Thin Films.

Surface instabilities are a versatile method for generating three-dimensional (3D) surface microstructure. When an elastomeric film weakly bonded to a substrate is swollen with solvent, buckle delamination and subsequent sliding of the film on the substrate lead to the formation of tall, self-contacting, and permanent folds. This paper explores the mechanics of fold development when such folding is induced by placing a drop on the surface of the film. We show that capillary effects can induce a strong coupling between folding and drop spreading: as folds develop, they wick the solvent toward the periphery of the drop, further propagating radially aligned folds. Accordingly, a solvent drop spreads far more on films that are weakly adhered to the substrate. As drop size reduces and folding becomes increasingly confined, debonding propagates along the perimeter of the wetted region, thus leading to corral-shaped fold patterns. On the other hand, as drop size increases and confinement effects weaken, isotropically oriented folds appear at a spacing that reduces as swelling increases. The spacing between the folds and the size of the corrals are both determined by the extent to which a single fold relieves compressive stress in its vicinity by sliding. We develop a model for folding which explicitly accounts for the fact that folds must initiate with near-zero volume under the buckle. The model shows that folds can appear even at very low swelling if there are large pre-existing debonded regions at the film-substrate interface.

The Evolving Practice Patterns of Academic Endocrine Surgeons: A Cross-sectional Analysis of the Faculty Practice Solutions Center Database 2014 to 2017.

OBJECTIVE: To examine the evolution of an academic endocrine surgeon's practice over time. SUMMARY BACKGROUND: Amid growing recognition that surgical volume and specialization are linked to better outcomes, endocrine surgery is one of the youngest fields to develop its own formal fellowship training program. However, 3 decades after the emergence of endocrine surgery as a distinct specialty, the medical community and public still have a limited understanding of endocrine surgeons and what they do. METHODS: We performed a cross-sectional analysis of endocrine surgeons identified in the Faculty Practice Solutions Center Database from 2014 to 2017. Trends in annual number of endocrine surgeries performed, number of all surgeries performed, total work relative value units generated, and patient payer mix stratified by years of practice were evaluated. RESULTS: One hundred thirty-nine endocrine surgeons practicing in 103 institutions over 4 years were analyzed. The proportion of endocrine-specific operations increases over time. A typical academic endocrine surgeon meets the high-volume threshold for thyroidectomies early in their career, but does not reach the thresholds for parathyroidectomies or adrenalectomies until after 4 years. Increased productivity as reflected by adjusted work relative value units does increase over the first 15 years of practice, but also decreases as the proportion of endocrine-specific practice increases. The greatest proportion of endocrine surgeons' patients are insured by commercial plans (46%-50%), and payer mix is stable across all levels of practice. CONCLUSIONS: Although endocrine surgeons perform a high-volume of endocrine-specific operations, practice patterns are heterogeneous and suggest that most surgeons have to grow their endocrine-specific practice over time.

Delayed Calcium Normalization After Presumed Curative Parathyroidectomy is Not Associated with the Development of Persistent or Recurrent Primary Hyperparathyroidism.

BACKGROUND: Following parathyroidectomy for primary hyperparathyroidism (pHPT), serum calcium levels typically normalize relatively quickly. The purpose of this study was to identify potential factors associated with delayed normalization of calcium levels despite meeting intraoperative parathyroid hormone (IOPTH) criteria and to determine whether this phenomenon is associated with higher rates of persistent pHPT. METHODS: This was a retrospective review of 554 patients who underwent parathyroidectomy for sporadic pHPT from January 2009 to July 2013. Patients who underwent presumed curative parathyroidectomy and had elevated POD0 calcium levels (>10.2 mg/dL) were matched 1:2 for age and gender to control patients with normal POD0 calcium levels. RESULTS: Of the 554 patients, 52 (9 %) had an elevated POD0 Ca (median 10.7, range 10.3-12.2). Compared with the control group, these patients had higher preoperative calcium (12 vs. 11.1, p < 0.001) and PTH (144 vs. 110 pg/mL, p = 0.004) levels and lower 25OH vitamin D levels (26 vs. 31 pg/mL; p = 0.024). Calcium normalization occurred in 64, 90, and 96 % of patients by postoperative days (POD) 1, 14, and 30, respectively. There was no difference in rates of single-gland disease or cure rates between the groups. CONCLUSIONS: After presumed curative parathyroidectomy, nearly 10 % of patients had transiently persistent hypercalcemia. Most of these patients had normal serum calcium levels within the first 2 weeks and did not have increased rates of persistent pHPT. Immediate postoperative calcium levels do not predict the presence of persistent pHPT, and these patients may not require more stringent follow-up.

The Effect of Thyroiditis on the Yield of Central Compartment Lymph Nodes in Patients with Papillary Thyroid Cancer.

BACKGROUND: In patients who have undergone thyroidectomy and central compartment neck dissection (CCND) for papillary thyroid cancer (PTC), visualization of enlarged lymph nodes may lead to more extensive CCND. This study sought to determine the effect of patient age and the presence of thyroiditis on the number of malignant and total lymph nodes resected in patients who underwent CCND for PTC. METHODS: This retrospective review examined a prospective database of patients who underwent total thyroidectomy and CCND for PTC between April 2009 and June 2013 and had thyroiditis on the final pathology. The patients were categorized into age groups by decade (18-29, 30-39, 40-49, 50-59, and ≥60 years) and compared with a control group of patients matched by age, gender, and tumor size. RESULTS: Of 74 patients with thyroiditis, 64 (87 %) were women. The median age of the patients was 47.5 years (range 18.2-72.0 years). The patients with thyroiditis had more lymph nodes resected than those without thyroiditis (median 11 vs 7; p < 0.01). However, these patients had fewer malignant lymph nodes (median 0 vs 1.5; p = 0.06), resulting in a lower lymph node ratio (0 vs 0.18; p = 0.02) for the entire cohort, but particularly for the youngest (18-29 years) and oldest (≥60 years) age groups. CONCLUSIONS: Patients with thyroiditis and PTC who underwent CCND had more lymph nodes resected but a had lower proportion of metastatic lymph nodes than those without thyroiditis. Given the relatively low yield of malignant cervical lymphadenopathy, a more judicious approach to CCND might be considered, particularly for the youngest and oldest patients with PTC and thyroiditis.

Gender Disparity in Earliest Phase of Academic Surgical Training: An Area for Intervention.

BACKGROUND: To overcome persistent gender disparities in academic surgery, it is critical to examine the earliest phase of surgical training. This national study sought to assess whether gender disparities also existed among surgical interns, as a proxy for medical school research experience in both quantity and quality. STUDY DESIGN: Using the 2021 to 2022 public information of 1,493 US-graduated categorical general surgery interns, a bibliometric evaluation was conducted to assess medical school research experience. Multivariable linear regressions with response log-transformed were performed to evaluate the impact of intern gender on (1) total number of peer-reviewed publications, (2) total impact factor (TIF), and (3) adjusted TIF based on authorship placement (aTIF). Back-transformed estimates were presented. RESULTS: Of these interns, 52.3% were female. Significant differences were observed in TIF (male 6.4 vs female 5.3, p = 0.029), aTIF (male 10.8 vs female 8.7, p = 0.035), gender concordance with senior authors (male 79.9% vs female 34.1%, p < 0.001), Hirsch index (male 21.0 vs female 18.0, p = 0.026), and the geographic region of their medical schools (p = 0.036). Multivariable linear regressions revealed that female interns were associated with lower TIF (0.858, p = 0.033) and aTIF (0.851, p = 0.044). Due to a significant gender-by-region interaction, adjusted pairwise comparisons showed that male interns in the Northeast had approximately 70% higher TIF (1.708, p = 0.003) and aTIF (1.697, p = 0.013) than female interns in the South. CONCLUSIONS: Gender disparities existed in the quality of research experience in the earliest phase of surgical training. These timely results call for additional interventions by the stakeholders of graduate medical education.

Prognosis of patients with unresectable stage IV Colon cancer undergoing primary tumor resection: A multicenter study of minimally symptomatic or asymptomatic primary tumor.

AIM: To determine the factors affecting survival of patients with unresectable stage IV colon cancer with Primary tumour resection (PTR) as first treatment compared with those with conventional palliative chemotherapy. METHODOLOGY: Patient with minimally or asymptomatic stage IV colon cancer at diagnosis were identified from prospectively managed database in included centers from 2015 to 2020. Patient with and without PTR performed were followed up. Primary end point was overall survival. Risk factors affecting survival will be analysis by Kaplan Meier statistics and Cox regression analysis. Secondary outcome will be stoma formation, complication rate and reoperation. RESULTS: 162 patients were included in analysis. 68 patients treated with systemic therapy PTR and 94 patients with tumour in-situ before systemic therapy. Baseline demographics including sex, age, functional status, tumour location, site of metastasis, RAS status were similar except there was slightly more liver metastasis on non-resection group (63.2% vs 79.8%). Cox regression analysis found PTR (HR 0.485, 0.302-0.778, p = 0.003)), bone metastasis (HR 3.163, 1.146-6.918, p = 0.004) commencement (HR 0.579, 0.345-0.971, p = 0.038) and completion of systemic therapy (HR 0.310, 0.178-0.539, p = 0.000) are independent factors predicting survival. The median overall survival after PTR vs tumour in-situ is 28 (IQR: 16-47) vs 12 (IQR:6-31) months (p<0.001). CONCLUSION: Resection of primary tumour is an independent good prognostic factor in relatively asymptomatic stage IV CA colon patients with unresectable metastasis. Resection should be considered as long as the procedure is straight forward and do not impose significant morbidities with careful patient selection.

Improved sexual function after parathyroidectomy in women with primary hyperparathyroidism.

BACKGROUND: The study aimed to evaluate whether women with primary hyperparathyroidism (PHPT) experience improvement in their sexual function after parathyroidectomy. METHODS: Women with PHPT or benign thyroid nodules (controls) undergoing surgery were administered the validated Parathyroidectomy Assessment Score (PAS), Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) and Female Sexual Function Index (FSFI) pre-operatively, at 3 months and 6 months postoperatively. RESULTS: Of the 26 PHPT and 18 control patients, PHPT patients were older (53.1 vs 45.3 years, p â€‹= â€‹0.008). Post-operatively, both PHPT (pre-op 2.4 vs 3-month 3.0 vs 6-month 2.4, p â€‹= â€‹0.022) and control patients (pre-operative 2.4 vs 3-month 3.3 vs 6-month 3.6, p â€‹= â€‹0.032) reported increased desire for sexual activities. In addition, PHPT patients experienced increased arousal (pre-operative 2.7 vs 3-month 3.9 vs 6-month 3.6, p â€‹= â€‹0.047) and satisfaction (pre-operative 3.0 vs 3-month 4.8 vs 6-month 4.0, p â€‹= â€‹0.006). CONCLUSIONS: The current study indicates that women with PHPT may experience improved sexual function after parathyroidectomy.

Endocrine Patients' Views on Transoral Endoscopic Thyroidectomy via Vestibular Approach (TOETVA).

TOETVA's adoption has been slow in the Western hemisphere. Our study aimed to evaluate how endocrine patients in the United States perceive the risks and benefits of TOETVA. This was a cross-sectional study where a de novo survey was sent via email to patients seen from 2018 to 2020. The survey asked how each of TOETVA's risks and benefits affect their choice between traditional thyroidectomy (TT) and TOETVA on a scale from 1 (favors TT) to 10 (favors TOETVA). Statistical significance was determined at p < 0.05. Of 422 patients (3.2% response rate), 76.0% were female, 28.9% were non-Whites, 58.3% possessing graduate/professional degrees, and 34.1% were diagnosed with thyroid cancer. Significant differences were found between groups of age, race, educational attainment, thyroid cancer diagnosis, and history of thyroid or parathyroid surgery with respect to their preference for thyroidectomy between TT and TOETVA. In multivariate analysis, attitudes towards longer operative time (estimate 0.130, 95% CI 0.026-0.235, p = 0.002), limited outcome data (estimate 0.142, 95% CI 0.029-0.254, p = 0.024), having less pain (estimate 0.108, 95% CI 0.004-0.212, p = 0.042), travel to seek care (estimate 0.166, 95% CI 0.042-0.290, p = 0.009), as well as African American race (estimate 0.714, 95% CI 0.093-1.334, p = 0.024), and history of surgery (estimate - 0.843, 95% CI - 1.364- - 0.323, p = 0.002) were independently predictive of overall preferences. TOETVA's risks and benefits may carry varying degrees of significance in patients' decision-making process, which helps tailor the discussion to choose the right procedure for patients.

Efficacy of machine learning to identify clinical factors influencing levothyroxine dosage after total thyroidectomy.

BACKGROUND: We employed Machine Learning (ML) to evaluate potential additional clinical factors influencing replacement dosage requirements of levothyroxine. METHOD: This was a retrospective study of patients who underwent total or completion thyroidectomy with benign pathology. Patients who achieved an euthyroid state were included in three different ML models. RESULTS: Of the 487 patients included, mean age was 54.1 ± 14.1 years, 86.0% were females, 39.0% were White, 53.0% Black, 2.7% Hispanic, 1.4% Asian, and 3.9% Other. The Extreme Gradient Boosting (XGBoost) model achieved the highest accuracy at 61.0% in predicting adequate dosage compared to 47.0% based on 1.6 mcg/kg/day (p < 0.05). The Poisson regression indicated non-Caucasian race (p < 0.05), routine alcohol use (estimate = 0.03, p = 0.02), and osteoarthritis (estimate = -0.10, p < 0.001) in addition to known factors such as age (estimate = -0.003, p < 0.001), sex (female, estimate = -0.06, p < 0.001), and weight (estimate = 0.01, p < 0.001) were associated with the dosing of levothyroxine. CONCLUSIONS: Along with weight, sex, age, and BMI, ML algorithms indicated that race, ethnicity, lifestyle and comorbidity factors also may impact levothyroxine dosing in post-thyroidectomy patients with benign conditions.

Clinical Factors Predictive of Lymph Node Metastasis in Thyroid Cancer Patients: A Multivariate Analysis.

BACKGROUND: Early-stage thyroid cancers have excellent survival. However, lymph node metastases (LNM) confer a worse prognosis and are not always known preoperatively. Therefore, investigation on the clinical and histological factors predictive of LNM in thyroid cancers was conducted to tailor the extent of surgery and radioactive iodine therapy. STUDY DESIGN: Multivariate logistic regressions were performed based on retrospective data from thyroid cancer patients seen between 2013 and 2020 at a single institution. RESULTS: Among 913 patients, mean age was 49.4 years, 76.5% were female, 58.3% were White, 21.2% were Black, and 27.9% had LNM. In the multivariate analyses in which the outcome was LNM, White (odds ratio [OR] 1.74, 95% CI 0.98 to 3.15, p = 0.064) and Hispanic patients (OR 2.36, 95% CI 0.97 to 5.77, p = 0.059) trended toward higher risk of LNM compared to Black patients, whereas age (OR 0.98, 95% CI 0.97 to 1.00, p = 0.008) showed protective effect. Tumor size (OR 1.04, 95% CI 1.01 to 1.07, p = 0.007), extrathyroidal extension (OR 2.46, 95% CI 1.53 to 3.97, p < 0.001), lymphovascular invasion (OR 6.30, 95% CI 3.68 to 11.14, p < 0.001), and multifocality (OR 1.47, 95% CI 1.01 to 2.12, p = 0.042) were associated with higher risk of LNM. In another model with outcome as >5 LNM, tumor size (OR 1.07, 95% CI 1.03 to 1.11, p = 0.001), age (OR 0.95, 95% CI 0.93 to 0.97, p < 0.001), extrathyroidal extension (OR 3.20, 95% CI 1.83 to 5.61, p < 0.001), and lymphovascular invasion (OR 6.82, 95% CI 3.87 to 12.17, p < 0.001) remained significant predictors. CONCLUSION: Our analyses demonstrated and confirmed that age, tumor size, extrathyroidal extension, and lymphovascular invasion are independent predictors of significant LNM, thereby conferring higher risk of recurrence. Risk of LNM based on these patient characteristics should be considered when planning an operative approach.

Comparing the rate and extent of malignancy in surgically excised thyroid nodules across race and ethnicity.

BACKGROUND: Few studies have compared the features of thyroid cancer among races and ethnicities. We hypothesized that race and ethnicity may influence the frequency and features of thyroid malignancy in thyroid nodules. METHOD: This was a retrospective chart review of patients between 2013 and 2020 who underwent thyroidectomy. RESULTS: In the analysis of 2737 patients, thyroid cancer was less prevalent among Blacks (24.0% vs Whites 52.1%, Hispanics 58.7%, Asians 71.7%, and Others 57.9%, p < 0.001). Thyroid cancer in Blacks was less likely to have extrathyroidal extension (9.7% vs Whites 18.6%, Hispanics 25.8%, Asians 18.2%, and Others 17.8%, p = 0.01), overall nodal involvement (12.4% vs Whites 31.1%, Hispanics 37.5%, Asians 36.3%, and Others 30.1%, p < 0.01), and lateral neck metastasis (4.4% vs Whites 10.8%, Hispanics 6.3%, Asians 13.2%, and Others 9.6%, p = 0.02). CONCLUSIONS: Race and ethnicity may play important roles in the risk of malignancy as well as in the extent of thyroid cancer.

Comparing surgical thoroughness and recurrence in thyroid cancer patients across race/ethnicity.

BACKGROUND: For patients with differentiated thyroid cancer who will receive postoperative radioactive iodine, thyroid remnant uptake can be calculated and may point to the thoroughness of the surgical resection. In the United States, outcome disparities exist among ethnic/racial minorities with differentiated thyroid cancer. Data about surgical thoroughness and recurrence rates across races/ethnicities do not exist. This study compared the amount of thyroid remnant uptake and cancer recurrence rates across race/ethnicity. METHODS: This was a retrospective analysis of adult patients with differentiated thyroid cancer who had postoperative radioactive iodine in 2017 and 2018 and were followed to 2020. We collected thyroid bed remnant uptake from postoperative radioactive iodine scans and analyzed it as a ratio of percent of uptake to dose of radioactive iodine received to control for varying radioactive iodine doses. Thyroid remnant, uptake to dose of radioactive iodine received, and recurrence were evaluated across race/ethnicity. RESULTS: Of 218 patients: 61% were White, 21% Black, 11% Asian, and 7% Hispanic; 72% were female. Seventy-one percent of patients had their surgery done by a high-volume surgeon, although volume data were not available for all. In White, Black, Asian, and Hispanic patients, median uptake was 0.68%, 0.44%, 1.5%, and 0.8%, respectively (P = .13). We did not observe differences in median uptake to dose of radioactive iodine received across groups (P = .41). Recurrence rate was 17.0% among White patients, 16.7% among Black patients, 17.6% among Asian patients, and 16.7% among Hispanic patients (P = 1.00). CONCLUSION: We did not observe differences across race/ethnicity in surgical thoroughness or rate of recurrence. These findings suggest that disparities may be mitigated when ethnic/racial minorities have similar access to quality surgical care.

Drug delivery strategies in maximizing anti-angiogenesis and anti-tumor immunity.

Metronomic chemotherapy has been shown to elicit anti-tumor immune response and block tumor angiogenesis distinct from that observed with maximal tolerated dose (MTD) therapy. This review delves into the mechanisms behind anti-tumor immunity and seeks to identify the differential effect of dosing regimens, including daily low-dose and medium-dose intermittent chemotherapy (MEDIC), on both innate and adaptive immune populations involved in observed anti-tumor immune response. Given reports of VEGF/VEGFR blockade antagonizing anti-tumor immunity, drug choice, dose, and selective delivery determined by advanced formulations/vehicles are highlighted as potential sources of innovation for identifying anti-angiogenic modalities that may be combined with metronomic regimens without interrupting key immune players in the anti-tumor response. Engineered drug delivery mechanisms that exhibit extended and local release of anti-angiogenic agents both alone and in combination with chemotherapeutic treatments have also been demonstrated to elicit a potent and potentially systemic anti-tumor immune response, favoring tumor regression and stasis over progression. This review examines this interplay between various cancer models, the host immune response, and select anti-cancer agents depending on drug dosing, scheduling/regimen, and delivery modality.

Crystallization of the Multi-Receptor Tyrosine Kinase Inhibitor Sorafenib for Controlled Long-Term Drug Delivery Following a Single Injection.

INTRODUCTION: A major challenge in cancer medicine is the safe and effective delivery of drugs to the right tissue at the right time. Despite being designed for greater target specificity, many drugs still result in side effects and lack of safety in patients following global dissemination. Therefore, to develop new, more effective formulations capable of improving specificity and reducing off-target effects, here we describe formulation of drug crystals, from even a very hydrophobic and otherwise difficult to solubilize small molecule chemical compound, capable of providing constant drug release for weeks following a single injection. METHODS: We chose to utilize the multi-tyrosine kinase inhibitor and multi-modal (anti-angiogenic and tumor cell cytotoxic) agent sorafenib, to combat aberrant angiogenesis and tumor growth which contribute to metastasis, ultimately responsible for poor patient outcomes. We tuned crystal size (surface area:volume ratios), imaged by SEM, to display controllability of drug delivery kinetics in in vitro drug release assays. RESULTS: Single and powder crystal X-ray diffraction (XRD) established that all crystals were the same polymorph and drug form. When utilized against an orthotopic triple negative breast cancer (TNBC) mouse model (4T1 in syngeneic BALB/c mice), we established anti-tumor activity from a single local, subcutaneous injection of crystalline sorafenib. CONCLUSION: From our findings, we support that engineering crystalline drug delivery systems has implications in the treatment of cancer or other diseases where high enough constitutive drug levels are needed to maintain target saturation and inhibition while also preventing emergence of drug resistance, which is a consequence often seen with suboptimal dosing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00708-6.

The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates.

SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro , while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo , increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.