Gamma entrainment using audiovisual stimuli alleviates chemobrain pathology and cognitive impairment induced by chemotherapy in mice.

Patients with cancer undergoing chemotherapy frequently experience a neurological condition known as chemotherapy-related cognitive impairment, or "chemobrain," which can persist for the remainder of their lives. Despite the growing prevalence of chemobrain, both its underlying mechanisms and treatment strategies remain poorly understood. Recent findings suggest that chemobrain shares several characteristics with neurodegenerative diseases, including chronic neuroinflammation, DNA damage, and synaptic loss. We investigated whether a noninvasive sensory stimulation treatment we term gamma entrainment using sensory stimuli (GENUS), which has been shown to alleviate aberrant immune and synaptic pathologies in mouse models of neurodegeneration, could also mitigate chemobrain phenotypes in mice administered a chemotherapeutic drug. When administered concurrently with the chemotherapeutic agent cisplatin, GENUS alleviated cisplatin-induced brain pathology, promoted oligodendrocyte survival, and improved cognitive function in a mouse model of chemobrain. These effects persisted for up to 105 days after GENUS treatment, suggesting the potential for long-lasting benefits. However, when administered to mice 90 days after chemotherapy, GENUS treatment only provided limited benefits, indicating that it was most effective when used to prevent the progression of chemobrain pathology. Furthermore, we demonstrated that the effects of GENUS in mice were not limited to cisplatin-induced chemobrain but also extended to methotrexate-induced chemobrain. Collectively, these findings suggest that GENUS may represent a versatile approach for treating chemobrain induced by different chemotherapy agents.

Ablation techniques or active surveillance compared to surgical resection in patients with low-risk papillary thyroid cancer: a systematic review and meta-analysis.

BACKGROUND: The global prevalence of thyroid cancer is on the rise. About one-third of newly diagnosed thyroid cancer cases comprise low-risk papillary thyroid cancer (1.5 cm or more minor). While surgical removal remains the prevailing approach for managing low-risk papillary thyroid cancer (LPTC) in patients, other options such as active surveillance (AS), radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) are also being considered as viable alternatives. This study evaluated and compared surgical thyroid resection (TSR) versus non-surgical (NS) methods for treating patients with LPTC. METHODS: The study encompassed an analysis of comparisons between surgical thyroid resection (TSR) and alternative approaches, including active surveillance (AS), radiofrequency ablation (RFA), microwave ablation (MWA), or laser ablation (LA). The focus was on patients with biopsy-confirmed low-risk papillary thyroid cancer (LPTC) of less than 1.5 cm without preoperative indications of local or distant metastasis. The primary outcomes assessed were recurrence rates, disease-specific mortality, and quality of life (QoL). Data were collected from prominent databases, including Cochrane Database, Embase, MEDLINE, and Scopus, from inception to June 3rd, 2020. The CLARITY tool was utilized to evaluate bias risk. The analysis involved odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes, as well as mean differences (MD) and standardized mean differences (SMD) for continuous outcomes. The study is registered on PROSPERO under the identifier CRD42021235657. RESULTS: The study incorporated 13 retrospective cohort studies involving 4034 patients. Surgical thyroid resection (TSR), active surveillance (AS), and minimally invasive techniques like radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) were performed in varying proportions of cases. The analysis indicated that specific disease mortality rates were comparable among AS, MWA, and TSR groups. The risk of recurrence, evaluated over different follow-up periods, showed no significant differences when comparing AS, RFA, MWA, or LA against TSR. Patients undergoing AS demonstrated better physical health-related quality of life (QoL) than those undergoing TSR. However, no substantial differences were observed in the overall mental health domain of QoL when comparing AS or RFA with TSR. The risk of bias was moderate in nine studies and high in four. CONCLUSION: Low-quality evidence indicates comparable recurrence and disease-specific mortality risks among patients with LPTC who underwent ablation techniques or active surveillance (AS) compared to surgery. Nevertheless, individuals who opted for AS exhibited enhanced physical quality of life (QoL). Subsequent investigations are warranted to validate these findings.

Association of patient-practitioner sex concordance with specialist referral in primary hyperparathyroidism.

BACKGROUND: Prior research has demonstrated barriers to the workup and management of primary hyperparathyroidism. As recent data have suggested that patient and practitioner sex concordance is associated with lower surgical complications, we sought to evaluate the effect of sex concordance on referral for primary hyperparathyroidism. METHODS: We queried an institutional database for patients with first-incident hypercalcemia and subsequent biochemical evidence of primary hyperparathyroidism between 2010 and 2018. Primary care practitioner and endocrinologist sex, laboratory values, and complications of primary hyperparathyroidism were collected. Sex concordance (male patient/male practitioner or female patient/female practitioner) was evaluated as a binary predictor of specialist evaluation using logistic regression and Cox proportional hazards modeling. RESULTS: Among 1,100 patients, mean age was 62.5 (standard deviation 13.6), and 74% were female sex. Primary care practitioner sex was 52% female, and 63% of patients had sex concordance with their primary care practitioner. Endocrinologist sex was 59% female, and 45% of patients had sex concordance with their endocrinologist. Patients with sex concordance with their primary care practitioner (70 vs 80%, P = .001) and endocrinologist (71 vs 82%, P < .001) were less likely to be female sex compared to those with discordance. After adjusting for demographics and clinical covariates, those patients with primary care practitioner sex concordance had 32% higher odds of endocrinologist evaluation (odds ratio 1.32, 95% confidence interval 1.003-1.734, P = .047). Similarly, those patients with endocrinologist sex concordance had a 48% higher rate of surgeon evaluation (hazard ratio 1.48, confidence interval 1.1-2.0, P = .009). Stratified analysis revealed that sex discordance reduced the rate of surgeon referral for female patients (hazard ratio 0.63, confidence interval 0.44-0.89, P = .008) but not male patients (hazard ratio 1.06, CI 0.58-1.93, P = .861). CONCLUSION: Sex discordance between patients and their health care professionals may contribute to under-referral in primary hyperparathyroidism. Further evaluation of the effect of patient and practitioner identities on communication and decision-making in surgery are needed.

Social vulnerability and time to surgeon evaluation for primary hyperparathyroidism in a Massachusetts cohort.

BACKGROUND: Identifying patients at risk for under-evaluation of primary hyperparathyroidism is essential to minimizing long-term sequelae, including osteoporosis, nephrolithiasis, and cardiovascular disease. This study assessed the impact of social vulnerability on time-to-surgery evaluation among patients with primary hyperparathyroidism in a Massachusetts cohort. METHODS: This is a retrospective review of patients from an institutional database with the first incident of hypercalcemia between 2010 and 2018 and subsequent biochemical diagnosis of primary hyperparathyroidism. The overall social vulnerability index and social vulnerability index subthemes were merged with the institutional data via patient ZIP code. Patients were stratified into social vulnerability index quartiles, where quartile 4 represented the highest vulnerability. Baseline sociodemographic and clinical characteristics were compared, and Cox regression was used to assess the association between social vulnerability index and time to surgeon evaluation. RESULTS: Of 1,082 patients included, those with a higher social vulnerability index were less likely to be evaluated by a surgeon (quartile 1 social vulnerability index: 31.1% vs. quartile 2 social vulnerability index: 31.41% vs. quartile 3 social vulnerability index: 25.93% vs. quartile 4 social vulnerability index: 21.92%, P = .03). On adjusted analysis, patients with the highest vulnerability had a 33% lower estimated rate of surgeon evaluation and were seen 67 days later compared with patients with the lowest vulnerability (hazard ratio: 0.67, confidence interval 0.47-0.97, P = .032). Differential rates of surgical evaluation by vulnerability persisted for the social vulnerability index subthemes for socioeconomic status, minority status and language, and housing type and transportation. CONCLUSION: Among a Massachusetts cohort, highly vulnerable populations with primary hyperparathyroidism are at greater risk for under-evaluation by a surgeon, which may contribute to the development of long-term sequelae of their disease.

Financial toxicity in thyroid cancer survivors.

PURPOSE OF REVIEW: Financial burden and distress are high in patients with thyroid cancer. However, little has been done to evaluate potential interventions to mitigate financial toxicity in survivors. This review will cover current data on the impact of financial toxicity on quality of life and clinical outcomes in patients with thyroid cancer and highlight areas for future study. RECENT FINDINGS: Thyroid cancer incidence has nearly tripled in the past decades, and cost of treatment is predicted to rise more than other cancers over the next decade. With mean age of diagnosis at 51 years, most patients begin treatment while still working, do not qualify for Medicare or Social Security, and are susceptible to higher financial burden. Though thyroid cancer has high survival rates, some studies suggest patients have worse quality of life and higher financial burden than more morbid cancers. SUMMARY: Thyroid cancer survivors have high rates of financial toxicity, and there remains need for longitudinal studies to evaluate how financial burden may change during the treatment process while also assessing potential tools to mitigate this burden.

Inequities in Thyroid Cancer Care: Populations Most at Risk for Delays in Diagnosis and Treatment.

Background: Delays in treatment for thyroid cancer (TC) have been associated with higher overall mortality rates. However, few studies have explored the impact of health disparities on delayed presentation and treatment for TC. This study aims to investigate what patient sociodemographic factors contribute to delays in presentation and treatment of TC. Methods: Using the National Cancer Database, we identified patients diagnosed with well-differentiated TC between 2004 and 2016 who underwent thyroidectomy. Multivariable regression analyses were conducted to examine the impact of race, insurance status, income, and distance from treatment facility on time to surgical treatment, stage, the presence of distant metastases, and tumor size. Results: We identified 89,105 patients diagnosed with well-differentiated TC who underwent thyroidectomy. Nonwhite patients who were uninsured or had Medicare or Medicaid insurance were more likely to experience delays in care, present with higher stages at diagnosis, and have distant metastases and larger tumors at presentation. Distance from treatment facility was associated with delays in surgical treatment and higher stage at presentation. Conclusion: Delays in TC presentation and surgical treatment vary by race, insurance status, and patient location. Health care policies should focus on targeting at-risk individuals to reduce health care disparities in this disease.

Urban and Rural Surgical Practice Patterns for Papillary Thyroid Carcinoma.

Background: The 2015 American Thyroid Association (ATA) guidelines shifted recommendations toward less aggressive management of papillary thyroid cancer (PTC). Subsequently, several studies demonstrated a trend in performing thyroid lobectomy (TL) over total thyroidectomy (TT). However, regional variation has persisted without a clear indication of what factors may be influencing practice variation. We aimed to evaluate the surgical management of PTC in patients in rural and urban settings to assess trends of TL compared with TT following the implementation of the 2015 ATA guidelines. Methods: A retrospective cohort analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2019 of patients with localized PTC <4 cm who underwent TT or TL. Patients were classified as living in urban or rural counties based on the 2013 Rural-Urban Continuum Codes. Procedures performed from 2004 to 2015 were categorized as preguidelines, while those performed from 2016 to 2019 were categorized as postguidelines. Chi-square, Student's t-test, logistic regression, and Cochran-Mantel-Haenszel test were used. Results: A total of 89,294 cases were included in the study. Eighty thousand one hundred and fifty (89.8%) were from urban settings and 9144 (9.2%) were from rural settings. Patients from rural settings were older (52 vs. 50 years, p < 0.001) and had smaller nodules (p < 0.001). On adjusted analysis, patients in rural areas were less likely to undergo TT (adjusted odds ratio 0.81, confidence interval [CI] 0.76-0.87). Before the 2015 guidelines, patients in urban settings had a 24% higher odds of undergoing TT compared with those in rural settings (odds ratio 1.24, CI 1.16-1.32, p < 0.001). There was no difference in the proportions of TT and TL based on setting following guideline implementation (p = 0.185). Conclusions: The 2015 ATA guidelines led to a change in overall practice in surgical management of PTC toward increasing TL. While urban and rural practice variation existed before 2015, both settings had an increase in TL following the guideline change, emphasizing the importance of clinical practice guidelines to ensure best practice in both rural and urban settings.

Thyroid Mucosa-associated Lymphoid Tissue Lymphoma Presenting as Intermediate-risk Thyroid Nodule with Positive KRAS Mutation.

Background: /Objective: Little is known about the epidemiology, clinical presentation, and diagnosis of thyroid mucosa-associated lymphoid tissue (MALT) lymphoma. Case Report: We report the case of a 67-year-old woman who presented with an intermediate-risk thyroid nodule 8 years after diagnosis of hypothyroidism due to Hashimoto's. She was found to have a well-circumscribed hypoechoic 2.6-cm right-sided thyroid nodule lobe, which was biopsied and returned atypia of undetermined significance with positive KRAS mutation on the Thyroseq V3 Genomic Classifier. She subsequently underwent right thyroid lobectomy and was found to have thyroid MALT lymphoma on histopathological sections. After the surgery, she was referred to oncology for further management of the thyroid MALT lymphoma. A positron emission tomography/computed tomography scan was performed for complete staging and revealed diffuse fluorodeoxyglucose uptake in the residual left thyroid lobe without evidence of extrathyroidal involvement. Her case was discussed in a multidisciplinary fashion among oncology, endocrine surgery, and endocrinology. Given the positron emission tomography scan findings, she ultimately underwent completion thyroidectomy 4 months after the initial surgery to rule out residual disease. The patient tolerated the operation well without complication. Discussion: Our report adds to the literature that Hashimoto's thyroiditis may be a risk factor of thyroid MALT lymphoma. Localized thyroid MALT lymphoma may be managed with total thyroidectomy. Conclusion: We report a patient with localized thyroid MALT lymphoma who presented with an intermediate-risk nodule with positive KRAS mutation and was treated with total thyroidectomy.

Delay in Surgery and Papillary Thyroid Cancer Survival in the United States: A SEER-Medicare Analysis.

INTRODUCTION: Delays in surgery and their impact on survival in papillary thyroid cancer (PTC) is unclear. We sought to investigate the association between time to surgery and survival in patients with PTC. METHODS: A total of 8170 Medicare beneficiaries with PTC who underwent thyroidectomy were identified within the Surveillance, Epidemiology, and End Results-Medicare linked data files between 1999 and 2018. Disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meir analysis, and Cox proportional hazards models were specified to estimate the association between time to surgery and survival. RESULTS: Among 8170 patients with PTC, mean age 69.3 (SD+/- 11.4), 89.8% had surgery within the first 90 days, 7.8% had surgery 91 to 180 days from diagnosis, and 2.4% had surgery after 180 days. Increasing time to surgery was associated with increased mortality for OS in the >180-day group [adjusted hazard ratio (aHR) 1.24; 95% CI, 1.01-1.53]. Moreover, on stratification by summary stage, those with localized disease in the 91- to 180-day group increased risk by 25% (aHR 1.25; 95%CI, 1.05-1.51), and delaying over 180 days increased risk by 61% (aHR 1.61; 95%CI, 1.19-2.18) in OS. Those with localized disease in the >180-day group had almost 4 times the estimated rate of DSS mortality (aHR3.51; 95%CI, 1.68-7.32). When stratified by T stage, those with T2 disease in the >180 days group had double the estimated rate of all-cause mortality (aHR 2.0; 95% CI, 1.1-3.3) and almost triple the estimated rate of disease-specific mortality (aHR 2.7; 95% CI, 1.05-6.8). CONCLUSIONS: Delays in surgery for PTC may impact OS and DSS in localized disease, prior to nodal metastasis.

Scarless Surgery: Clinical Indications for Transoral Endocrine Surgery and Implications for Pathologists.

Transoral endocrine surgery (TES) is a scarless approach to thyroidectomy and parathyroidectomy for well-selected patients. Criteria for the TES approach to thyroidectomy include thyroid diameter less than or equal to 10 cm, benign nodule less than or equal to 6 cm, or confirmed or suspected malignant nodule less than or equal to 2 cm. Although fragmentation of surgical specimens has been reported in TES, additional studies are needed to evaluate the implications of TES on pathologic examination.

Thyroid nodules: Global, economic, and personal burdens.

Thyroid nodules have garnered attention due to changes in population surveillance systems and rising concerns about the associated financial burden on healthcare systems, payers, and patients. In this review, we find that prevalence rates vary widely based on method of detection and may particularly pronounced in asymptomatic patients undergoing routine screening. Incidence rates may be particularly rising in lower-income and middle-income countries and may be declining in higher-income countries. Despite high incidence rates, survival rates continue to be as high as 97% for papillary thyroid cancer. Over the last few decades, thyroid nodule workup and management has grown more sophisticated with the advent of fine-needle aspiration biopsy, specialized biomarkers, and molecular testing. However, gaps remain in risk stratification that can lead to substantial costs of care. Certain molecular tests, such as the Afirma Gene Sequencing Classifier can lead to a cost per diagnosis of $17,873 while achieving only mild decreases in diagnostic lobectomies for patients (11.6% to 9.7% in one study). Out-of-pocket costs associated with thyroid nodule management continue to drive significant financial toxicity for patients, especially for individuals with thyroid cancer. Financial toxicity has been defined as a term that describes how direct and indirect medical costs of cancer care strain patients and households via decreased income, assets, and spending on basic necessities. Recent studies suggest that such toxicity can lead to adverse financial outcomes, such as foreclosure and bankruptcy. Additional cost-effectiveness analyses are needed to improve existing thyroid nodule management systems and new clinical tools are needed to avoid unnecessary workup and management.

Are patients with limited English proficiency less likely to undergo parathyroidectomy for primary hyperparathyoidism?

BACKGROUND: Despite meeting operative indications for primary hyperparathyroidism (PHPT), many patients never undergo parathyroidectomy. We hypothesized that patients with limited English proficiency (LEP) would be less likely to undergo parathyroidectomy than English-proficient (EP) patients. STUDY DESIGN: We retrospectively analyzed patients with PHPT from an institution-wide registry who met operative criteria between 2010 and 2018. The cohort was stratified by English proficiency. Univariate associations between sociodemographic and clinical factors with parathyroidectomy were assessed. A multivariable logistic regression model was created to assess independent predictors of parathyroidectomy. RESULTS: Among a cohort of 1,104 patients, 262 (24%) underwent parathyroidectomy. LEP patients (n = 135, 12%) were significantly younger (mean age 62 vs. 69, p < 0.001), more likely non-white race and ethnicity (p < 0.001), and less likely to have private insurance (p < 0.001). After adjusting for covariates, non-English and non-Spanish preferred language was an independent negative predictor of undergoing parathyroidectomy (OR 0.46, 95% CI 0.21-0.95, p = 0.037). CONCLUSIONS: Limited English proficiency may be an independent barrier to appropriate surgical management of PHPT. Systems-level and disease-specific interventions are needed to address this disparity faced by patients with LEP.

Limited disease progression in endocrine surgery patients with treatment delays due to COVID-19.

BACKGROUND: The COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans. METHODS: American Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon. RESULTS: Twelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ2 = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66). CONCLUSION: Although some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease.

Surgical Adaptation of the Situation Awareness Rating Technique (S-SART): Assessing Situational Awareness Among Medical Students.

OBJECTIVE: Situational awareness (SA) impacts team dynamics and patient care. However, few formal curricula and tools exist to teach and assess longitudinal SA in surgical environments. We sought to evaluate medical students' SA in the operating room (OR) during surgical clerkships over time. DESIGN: We prospectively administered pre- and post-rotation surveys using a surgical adaptation of the previously validated Situation Awareness Rating Technique (SART). Surgical SART (S-SART) scores were calculated as: Situational Awareness = Understanding - (Attentional Demand - Attentional Supply) + 14. Each of 10 questions was scored from 1 to 7, with a maximum possible score of 60. Two-tailed two-sample and paired t-tests were conducted to determine differences in S-SART scores. PARTICIPANTS/SETTING: Sixty-nine of 75 second- and third-year medical students rotating in Surgery and Obstetrics/Gynecology clerkships at a tertiary academic medical center from September 2018 to September 2019 completed the surveys for a response rate of 92.0%. RESULTS: The mean baseline pre-rotation baseline S-SART score was 29.5 (SD=8.3), which increased by 20.9% to 35.9 (SD=6.9) post-rotation (p<0.001). Significant predictors of higher baseline S-SART scores included age ≥25 (p=0.02), surgical career interest (p=0.01), completion of prior surgical rotations (p<0.001), confidence about pre-procedural OR steps (p<0.001), and knowledge of OR item locations (p<0.001). There were increases in each of the subdomains of Understanding-including OR familiarity (3.2 to 4.3, p<0.001), knowledge of the medical student OR role (3.5 to 5.7, p<0.001), and knowledge of others' OR roles (4.1 to 5.9, p<0.001)-along with increases in alertness within Attentional Supply (5.1 to 5.5, p=0.001). CONCLUSIONS: SA is a learnable skill with increases in S-SART scores from pre- to post-rotation, with the greatest gains in the domain of Understanding. More advanced aspects of SA such as Attentional Demand may require further surgical training or curricular innovations to address these needs.

Disparities in Time to Surgeon Evaluation Among Patients with Primary Hyperparathyroidism.

BACKGROUND: A majority of patients with primary hyperparathyroidism are not referred for surgical evaluation. We hypothesized that disparities in the rate of surgeon evaluation by language, race and ethnicity, and insurance contribute to this deficit. METHODS: We queried our institutional electronic health record registry for patients with first-incident hypercalcemia between 2010 and 2018 and subsequent biochemical diagnosis of primary hyperparathyroidism. We used the Kaplan-Meier method and Cox proportional hazards modeling to investigate estimated time to surgeon evaluation by language, race and ethnicity, and insurance status. RESULTS: Of 1,333 patients with a diagnosis of primary hyperparathyroidism, 74% were female, 67% were White, 44% were privately insured, and 88% preferred English. Fewer than one third (n = 377; 28%) were evaluated by a surgeon. After adjusting for demographic and clinical factors, Asian (hazard ratio = 0.38; 95% confidence interval, 0.18-0.84; P = .016) and Black or African American patients (hazard ratio = 0.59; 95% confidence interval, 0.39-0.90; P = .014) had a lower rate of surgeon evaluation compared to White patients. Although patients with Medicaid had a lower rate of surgeon evaluation compared to privately insured patients (hazard ratio = 0.52; 95% confidence interval, 0.35-0.77; P = .001), there was no difference in rate for those with Medicare or who were uninsured. Patients with non-English and non-Spanish language had a lower rate of evaluation compared to those who preferred English (hazard ratio = 0.47; 95% confidence interval, 0.23-0.98; P = .043). CONCLUSION: Rates of surgeon evaluation vary by race and ethnicity, insurance status, and preferred language. Evaluation of factors contributing to these disparities is needed to improve access to surgeon referral.

Optimized cell growth and poly(3-hydroxybutyrate) synthesis from saponified spent coffee grounds oil.

Spent coffee ground (SCG) oil is an ideal substrate for the biosynthesis of polyhydroxyalkanoates (PHAs) by Cupriavidus necator. The immiscibility of lipids with water limits their bioavailability, but this can be resolved by saponifying the oil with potassium hydroxide to form water-soluble fatty acid potassium salts and glycerol. Total saponification was achieved with 0.5 mol/L of KOH at 50 °C for 90 min. The relationship between the initial carbon substrate concentration (C0) and the specific growth rate (µ) of C. necator DSM 545 was evaluated in shake flask cultivations; crude and saponified SCG oils were supplied at matching initial carbon concentrations (C0 = 2.9-23.0 g/L). The Han-Levenspiel model provided the closest fit to the experimental data and accurately described complete growth inhibition at 32.9 g/L (C0 = 19.1 g/L) saponified SCG oil. Peak µ-values of 0.139 h-1 and 0.145 h-1 were obtained with 11.99 g/L crude and 17.40 g/L saponified SCG oil, respectively. Further improvement to biomass production was achieved by mixing the crude and saponified substrates together in a carbon ratio of 75:25% (w/w), respectively. In bioreactors, C. necator initially grew faster on the mixed substrates (µ = 0.35 h-1) than on the crude SCG oil (µ = 0.23 h-1). After harvesting, cells grown on crude SCG oil obtained a total biomass concentration of 7.8 g/L and contained 77.8% (w/w) PHA, whereas cells grown on the mixed substrates produced 8.5 g/L of total biomass and accumulated 84.4% (w/w) of PHA. KEY POINTS: • The bioavailability of plant oil substrates can be improved via saponification. • Cell growth and inhibition were accurately described by the Han-Levenpsiel model. • Mixing crude and saponified oils enable variation of free fatty acid content.

Association Between Size of Dominant Candidate Lesion on Four-Dimensional CT and Four-Gland Hyperplasia among Patients with Primary Hyperparathyroidism.

BACKGROUND: Four-dimensional (4D) CT localization allows minimally invasive parathyroidectomy as treatment for primary hyperparathyroidism (PHPT), but false positive localization is frequent. We sought to characterize the ability of 4D CT to predict four-gland hyperplasia (HP) based on the size of candidate lesions. STUDY DESIGN: We retrospectively analyzed patients with PHPT who underwent 4D CT imaging and parathyroidectomy between 2014 and 2020 from a prospectively collected institutional database. The cohort was stratified into two groups, HP vs single adenoma (SA) and double adenoma (DA), based on operative findings and pathology. Logistic regression models assessed the association between the greatest diameter of the dominant candidate lesion on 4D CT and the outcomes of four-gland hyperplasia vs SA and DA. RESULTS: Among a cohort of 240 patients, 41 were found to have HP, and 199 had adenomas (SA = 155, DA = 44). Patients with HP were less likely to have a preoperative calcium level greater than 1 mg/dL above the upper limit of normal compared with patients with adenomas (63% vs 81%, p = 0.02) and more likely to report symptoms (61% vs 43%, p = 0.04). After adjusting for BMI, we found an estimated 13% reduction in odds of HP for every 1-mm increase in the greatest diameter of dominant candidate lesions identified on 4D CT scan (odds ratio 0.87, 95% CI 0.78 to 0.96, p = 0.009). CONCLUSIONS: A smaller size of the dominant lesion on 4D CT scan is associated with an increased risk of HP in PHPT. Use of 4D CT imaging localization may provide evidence for differentiating HP from adenomas.

The Cost and Financial Burden of Thyroid Cancer on Patients in the US: A Review and Directions for Future Research.

Importance: In the US, thyroid cancer has been identified as a cancer type with a high degree of associated financial burden on patients, and survivors of thyroid cancer report higher rates of bankruptcy than those of other cancer types. However, the available literature on the financial burden of thyroid cancer has not yet been described. Observations: Estimates of the out-of-pocket costs of initial thyroid cancer diagnosis and treatment range widely ($1425-$17 000) and are influenced by age, surgical treatment type, and health insurance coverage. The rates of patient-reported financial burden are heterogeneous (16%-50%) and are rarely compared with those of other cancer types. Independent risk factors of financial burden have included younger age, lack of health insurance, and annual household income of less than $49 000. Two studies measured medical debt associated with thyroid cancer diagnosis and treatment at notably different rates (2.1% vs 18.7%). The bankruptcy incidence at 1 year after cancer diagnosis is highest for thyroid cancer (9.3 per 1000 person-years) than other studied cancer types (ie, lung, uterine, leukemia/lymphoma, colorectal, melanoma, breast, prostate) and 4.39-fold higher than control individuals among those aged 35 to 49 years. Conclusions and Relevance: Current estimates of the financial burden of thyroid cancer are methodologically limited and are based on cross-sectional analyses of patient-reported data. We propose novel frameworks for new research by improvements in (1) data sourcing and utilization, (2) study design, and (3) pilot interventions. To understand how out-of-pocket thyroid cancer-related expenditures transition to various forms of debt, how households finance ongoing costs of care, and rates at which debts are sent to collection agencies, future research should focus on integrating underutilized sources of primary data, including credit reports, public records, and mortgage-backed securities loan-level data. Improvements in study design, such as the development of prospective cohorts, can allow for more objectively measured estimates of out-of-pocket costs, and robust covariate analysis can further reveal the influence of demographic factors, including age, sex, race, income, and health insurance coverage. Finally, new pilot interventions on cost controls can both enable further study and alleviate financial burden.