Charting the Course: Insights into Neuroendocrine Tumor Dynamics in the United States.

OBJECTIVE: To explore changing trends and characteristics in neuroendocrine tumors (NETs) epidemiology, focusing on demographics, clinical aspects, and survival, including the impact of social determinants of health (SDOH) on outcomes. BACKGROUND: The escalating incidence and prevalence of NETs underscore the pressing need for updated epidemiologic data to reveal the evolving landscape of this condition. Access to current information is imperative for informing clinical strategies and public health initiatives targeting NETs. METHODS: A retrospective, population-based study analyzed NET patient data from 1975 to 2020, using the Surveillance, Epidemiology, and End Results (SEER 8, 12, 18) program. We calculated annual age-adjusted incidence, prevalence, and 5-year overall survival (OS) rates. Survival trends from 2000 to 2019 were examined, employing the Fine-Gray model to evaluate cancer-specific mortality. RESULTS: NETs' age-adjusted incidence rate quadrupled from 1.5 per 100,000 in 1975 to 6.0 per 100,000 in 2020. A decline in incidence occurred from 6.8 per 100,000 in 2019 to 6.0 per 100,000 in 2020. All-cause survival multivariable analysis demonstrated high grade (HR: 2.95, 95% CI: 2.63-3.09, P<0.001), single patients (HR: 1.49, 95% CI: 1.45-1.54, P<0.001), and Black patients (HR: 1.17, 95% CI:1.13-1.22, P<0.001) all had worse survival than their controls. CONCLUSION: In conclusion, our study shows a steady increase in NETs incidence until 2019, with a decline in 2020. Understanding the reasons behind this trend is vital for improved management and public health planning. Further research should focus on the factors driving these changes to enhance our understanding of NET epidemiology.

Effect of Delayed Parathyroidectomy on Risk of Future Cardiovascular and Nephrolithiasis Interventions in Adults with Primary Hyperparathyroidism [Original Study].

OBJECTIVE: To determine whether the timing of parathyroid surgery impacts the risk of renal stone retreatment and cardiovascular interventions. SUMMARY BACKGROUND DATA: Long-term, untreated primary hyperparathyroidism is associated with significant morbidity including nephrolithiasis and cardiovascular disease. METHODS: We conducted a Population-based Cohort study of New York and California state-wide data from 2000-2020. Adult patients who underwent renal stone treatment and subsequently diagnosed with primary hyperparathyroidism (pHPT) and underwent parathyroidectomy (PTX) were included. Patients were excluded if PTX was prior to index stone procedure, they underwent second stone treatment within 6 months, with stage V CKD, with secondary or tertiary hyperparathyroidism, with prior kidney transplant or hemodialysis, or with prior cancer diagnosis. Rate of renal stone retreatment and cardiovascular interventions after PTX in pHPT patients with nephrolithiasis who underwent parathyroid surgery at ≤ 2 years and >2 years after index stone procedure was measured. RESULTS: We identified 2,093 patients who underwent first-time stone treatment and subsequent PTX. The median time to PTX was 560 days (IQR 187-1477) and follow-up was 7.4 years (IQR 4.5-13.1). Delaying PTX for more than 2 years increased the risk of renal stone retreatment by 59% (HR 1.59; P<0.001), increased the risk of experiencing coronary disease or associated interventions by 118% (HR=2.18; P=0.01), and increased the risk of experiencing an overall cardiovascular event by 52% (HR 1.52; P<0.01). CONCLUSIONS AND RELEVANCE: In symptomatic pHPT, delaying PTX significantly increases the risk of requiring future stone retreatment and cardiac/vascular surgical interventions. This highlights the importance of early surgical referral and multidisciplinary approaches to optimize outcomes and resource utilization in pHPT.

Risk of neuropsychiatric disorders in primary hyperparathyroidism: Parathyroidectomy versus nonoperative management.

BACKGROUND: Neuropsychiatric disorders frequently manifest in primary hyperparathyroidism (PHPT), yet evidence of parathyroidectomy's benefit remains mixed. We sought to compare the incidence of neuropsychiatric disorders among patients treated with parathyroidectomy versus nonoperative management. METHODS: We retrospectively reviewed our institutional administrative database for patients with PHPT. Patients with secondary hyperparathyroidism were excluded. The date of biochemical diagnosis of PHPT was designated as day 0 and new-onset neuropsychiatric disorders were defined as conditions diagnosed after this date. The risk of new-onset neuropsychiatric disorders in propensity score-matched surgical and nonsurgical patients was compared using the Cox regression over a median follow-up of 4.2 years. RESULTS: Our cohort included 3728 patients, predominantly female (78%) and white (63.9%), with a mean (± Standard deviation) age of 62 ± 14 years. Of these, 1704 (45.7%) underwent parathyroidectomy. After propensity score matching and adjusting for clinical characteristics, patients who had parathyroidectomy showed a reduced hazard ratio (HR) for new-onset cognitive impairment (HR: 0.65, 95% CI: 0.47-0.91), somnolence (HR: 0.45, 95% CI: 0.23-0.9) and schizophrenia (HR: 0.08, 95% CI: 0.01-0.6), but not for anxiety (HR: 1.07, 95% CI: 0.83-1.37), depression (HR: 1.02, 95% CI: 0.77-1.36) or suicidal ideation (HR: 0.31, 95% CI: 0.04-2.71). Additionally, surgical patients were less likely to require inpatient care (0.3% vs. 1.8%, p < 0.001) for neuropsychiatric disorders. CONCLUSIONS: Parathyroidectomy is associated with lower risks of new-onset cognitive impairment, schizophrenia, or somnolence, indicating potential benefit of operative management in improving neuropsychiatric symptoms in patients with PHPT.

From routine to rescue: Thyroidectomy for life-threatening thyrotoxicosis.

BACKGROUND: Thyroidectomies are routinely same-day elective procedures. The aim of this study was to investigate outcomes in patients who underwent uncommon urgent thyroidectomy. METHODS: We retrospectively reviewed patients diagnosed with thyrotoxicosis at a quaternary medical center between 2011 and 2023. Included patients were admitted nonelectively with thyroidectomies performed during same hospital stay. Patient demographics, comorbidities, hospital course, and operative outcomes were analyzed. RESULTS: Thirty patients met the inclusion criteria. The majority were female (60%) and Black (60%) with a mean age of 41 ± 14 years. At admission, 76.6% had undetectable thyrotropin levels (<0.01 µU/mL) and 26.7% were diagnosed with thyroid storm. Common presenting comorbidities included atrial fibrillation (53.3%), heart failure (40%), and liver failure (16.7%). Graves' disease was diagnosed in 83.3% of patients, while 13.3% had amiodarone-induced thyrotoxicosis. Median hospital stay before surgery was 8 days (interquartile range: 4-16). Indications for surgery were adverse medication events (30%), inadequate therapeutic effect by medication (30%), and worsening heart failure (26.7%). Postoperatively, 6.7% required reoperation for neck hematoma, 13.3% experienced temporary hypoparathyroidism, and 6.7% had hoarseness. Following surgery, 50% of patients with atrial fibrillation experienced resolution and 50% with heart failure with reduced ejection fraction showed ultrasonic improvement. Within 30 days, 20% visited the emergency department, none due to thyroidectomy complications, and 13.3% were readmitted for comorbidities. One patient (3.3%) died from liver failure. CONCLUSIONS: Patients who require an urgent thyroidectomy often have life-threatening comorbidities particularly cardiac disease. Performing thyroidectomy in these patients can potentially create clinical homeostasis for further management of their comorbidities.

The Effects of Parathyroidectomy vs Medical Treatments for Secondary Hyperparathyroidism in Patients Undergoing Dialysis: A Meta-Analysis.

OBJECTIVE: The management of secondary hyperparathyroidism in patients undergoing dialysis is debated, with uncontrolled parathyroid hormone (PTH) levels becoming more common despite the expanded use of medical treatments like cinacalcet. This study examines the clinical benefits of parathyroidectomy vs medical treatment in reducing mortality and managing key laboratory parameters in patients undergoing dialysis. METHODS: PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for cohort studies or randomized controlled trials published before August 18, 2023. We included studies with comparative arms, specifically medical treatment vs surgical intervention. Patients with a history of kidney transplant were excluded. Outcomes were analyzed using hazard ratios (HRs) for mortality and weighted mean differences (WMD) for laboratory parameters. RESULTS: Twenty-three studies involving 24 398 patients were analyzed. The pooled meta-analysis has shown a significant reduction in all-cause (HR, 0.47; 95% confidence interval [CI], 0.35-0.61) and cardiovascular mortality (HR, 0.58; 95% CI, 0.40-0.84) for parathyroidectomy vs medical treatments. Subgroup analysis showed that parathyroidectomy was associated with a greater reduction in mortality in patients with a PTH level over 585 pg/mL (HR, 0.37; 95% CI, 0.24-0.58). No mortality difference was found when all patients in the medical group received cinacalcet alongside standard medical treatment (HR, 1.02; 95% CI, 0.49-2.11). Parathyroidectomy also led to a larger decrease in PTH (WMD, 1078 pg/mL; 95% CI, 587-1569), calcium (WMD, 0.86 mg/dL; 95% CI, 0.43-1.28), and phosphate (WMD, 0.74 mg/dL; 95% CI, 0.32-1.16). CONCLUSION: Parathyroidectomy may offer a survival advantage compared to medical management in patients with severe secondary hyperparathyroidism.

Exploring Disparities in Pancreatic Ductal Adenocarcinoma Outcomes among Asian and Pacific Islander Subgroups.

Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy with known disparities in outcomes across ethnicities. Studies specifically investigating PDAC in Asian populations are sparse, overlooking the rich diversity within this group. This research seeks to fill that gap by examining survival differences across the broad spectrum of Asian ethnicities, acknowledging the complexity and varied experiences within these communities. Utilizing the National Cancer Database from 2004 to 2019, we categorized patients into East Asian, Southeast Asian, South Asian, and Pacific Islander groups. Non-Asians or Pacific Islanders were excluded. Overall survival was analyzed using a Cox hazards model. The study consisted of 13,254 patients. Most patients were East Asian (59.4%, n = 7,866). Southeast Asians exhibited the poorest survival in unadjusted analysis (HR, 1.32; 95% confidence interval, 1.23-1.42; P < 0.001) compared with South Asians who exhibited the best survival. Multivariable analysis revealed significantly worse survival for East Asians and Pacific Islanders relative to South Asians, whereas Southeast Asians' results were not significantly different. Asian subgroup differences notably affect PDAC outcomes. Research on genetic and cultural aspects, especially in Southeast Asians, and tackling health disparities are crucial for enhancing survival in this diverse disease. SIGNIFICANCE: This study highlights the significant survival disparities among Asian subgroups with pancreatic cancer, utilizing a large national database. By differentiating among East Asian, Southeast Asian, South Asian, and Pacific Islander groups, it underscores the need for tailored research and healthcare approaches. Addressing these differences is essential for developing culturally sensitive interventions and potentially improving outcomes in a disease that uniquely affects these diverse populations.

Incidental Thyroid Nodules on Computed Tomography: A Systematic Review and Meta-Analysis Examining Prevalence, Follow-Up, and Risk of Malignancy.

Background: The increased utilization of computed tomography (CT) has led to a higher detection rate of thyroid incidentalomas. Currently, there are no widely agreed-upon guidelines for managing these incidentalomas. This study aims to investigate the prevalence, follow-up practices, and malignancy rates of thyroid incidentalomas detected by CT. Methods: We conducted a comprehensive search of PubMed, Embase, and Cochrane databases to identify relevant studies published before April 12, 2024 (PROSPERO #42024535501). Studies reporting on the prevalence, follow-up, and risk of malignancy (ROM) of thyroid incidentalomas detected by CT were included. Combined outcomes were analyzed using pooled proportion with a random-effects model. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Newcastle-Ottawa Scale tool. Subgroup analyses were conducted based on characteristics including size of the incidentaloma, CT area, and age of the study population. Results: Thirty-eight studies involving 195,959 patients were included in the prevalence analysis, revealing a prevalence of thyroid incidentalomas on CT of 8.3% (confidence interval [CI], 7.4-9.3). The prevalence was higher in neck CT (16.5%, CI, 11.0-22.1) compared with chest CT (6.6%, CI, 5.3-7.9). Multiple incidentalomas were found in 27.0% (CI, 12.9-41.1) of patients. Of the nodules, 46.3% (CI, 32.3-60.3) were ≥1 cm, and 28.6% (CI, 19.9-37.3) were ≥1.5 cm. Thyroid ultrasounds, biopsies, and surgeries were performed in 34.9% (CI, 26.1-43.7), 28.4% (CI, 19.9-36.9), and 8.2% (CI, 2.1-14.4) of cases, respectively. Additionally, 25 studies with 6272 patients reported a ROM of 3.9% (CI, 3.0-4.9) for thyroid incidentalomas detected on CT. A higher ROM was observed in incidentalomas ≥1 cm (11.7%, CI, 3.9-19.4) and ≥1.5 cm (24.9%, CI, 0-52.7) compared with those <1 cm (0.1%, CI, 0-0.8) and <1.5 cm (0%, CI, 0-0.2). Conclusions: Most thyroid incidentalomas identified on CT are benign. Implementing a collaborative protocol between radiologists and thyroid specialists to manage high-risk thyroid incidentalomas can ensure appropriate follow-up and optimal patient care.

Incidental but Not Insignificant: Thyroid Cancer in Patients with Graves Disease.

BACKGROUND: Graves disease is the most common cause of hyperthyroidism in the US. Treatment with antithyroid drugs and radioactive iodine is more commonly used than surgical management with total thyroidectomy (TTx). However, incidentally discovered thyroid cancer (TC) has been described on surgical pathology from patients who underwent surgical treatment of Graves disease, which would be missed with these other treatment strategies. We sought to determine the incidence rate of TC among patients with surgically treated Graves disease. STUDY DESIGN: We retrospectively reviewed patients with Graves disease who underwent TTx at a single institution from 2011 to 2023. Pathology reports were reviewed for TC. Patient demographics, preoperative laboratory and radiological evaluations, preoperative medical management, and surgical outcomes were compared between patients with and without incidental TC. RESULTS: There were 934 patients, of whom 60 (6.4%) patients had incidentally discovered TC on pathology. The majority (58.3%) of patients had papillary thyroid carcinoma, followed by 33.3% with papillary microcarcinoma. Preoperative ultrasound (US) was obtained in 564 (60.4%) of patients, with 44.3% with nodules, but only 34 (13.7%) of those with nodules had TC on final pathology. Preoperative fine needle aspiration was obtained in 15 patients with TC, and 8 patients (53.3%) were reported as benign lesions, which ultimately had TC on final pathology. There was no difference in sex, race or ethnicity, preoperative medical management, and postoperative outcomes between the 2 groups. CONCLUSIONS: Incidental TC was found on surgical pathology in 6.4% of patients undergoing TTx for Graves disease. Preoperative imaging with US and fine needle aspiration were often unreliable at predicting TC. The incidence of TC should not be underestimated when counseling patients on definitive management for Graves disease.

Primary Hyperparathyroidism With Undetectable Intact Parathyroid Hormone.

Hypercalcemia can result from either hyperparathyroidism or non-parathyroid conditions. When hypercalcemia is accompanied by undetectable parathyroid hormone (PTH) levels, hyperparathyroidism is rarely considered the diagnosis. Herein, we report the case of a 65-year-old Caucasian woman referred to our hospital for further evaluation of hypercalcemia. Her symptoms included fatigue and brain fog, with undetectable PTH levels. A comprehensive workup, including a series of laboratory and imaging tests, excluded common non-parathyroid causes such as malignancy and familial hypocalciuric hypercalcemia. Ultrasound identified a likely enlarged parathyroid gland, which was further confirmed by a sestamibi scan. After 2 weeks of cinacalcet treatment, the patient's calcium levels decreased, indicating the parathyroid gland as the likely source of hypercalcemia. Parathyroidectomy was subsequently performed, revealing a 1927 mg adenoma. Postoperatively, the patient's calcium levels normalized, PTH levels became detectable within the normal range, and her symptoms resolved, with a marked improvement in energy. This case demonstrates that primary hyperparathyroidism can present with hypercalcemia and undetectable PTH. A genetic mutation in the PTH gene within the adenoma may explain the undetectable PTH levels preoperatively.

This case report discusses a 65-year-old woman who was found to have high calcium levels in her blood, a condition known as hypercalcemia. Typically, hypercalcemia can result from either a condition where the parathyroid glands produce too much parathyroid hormone (PTH) or from other non-parathyroid-related issues like cancer. However, when hypercalcemia occurs with undetectable levels of PTH, it is unusual for hyperparathyroidism to be the cause. In this patient's case, she experienced symptoms like fatigue and brain fog, but her initial tests showed undetectable PTH levels. Further tests ruled out other common causes of high calcium, such as cancer or a genetic condition called familial hypocalciuric hypercalcemia. An ultrasound and a special scan called a sestamibi scan revealed an enlarged parathyroid gland, suggesting the presence of a parathyroid adenoma, a non-cancerous tumor. To confirm this, the doctors gave the patient a medication called cinacalcet, which is known to lower calcium levels if the parathyroid glands are involved. After two weeks of treatment, her calcium levels dropped, indicating that the parathyroid gland was indeed the source of the problem. The patient underwent surgery to remove the adenoma, which weighed nearly two grams. Following the surgery, her calcium levels returned to normal, and her PTH levels became detectable again within the normal range. Her symptoms, including fatigue, improved significantly, and she reported feeling more energetic. This case is unusual because it demonstrates that primary hyperparathyroidism can still be the cause of hypercalcemia even when PTH levels are initially undetectable. The doctors suspect that a genetic mutation in the adenoma might explain why PTH levels were undetectable before surgery. This case emphasizes the importance of thorough clinical evaluation, even when initial test results are not typical.

Anticancer Activity of Diosgenin and Its Molecular Mechanism.

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.

B Cell IL-4 Drives Th2 Responses In Vivo, Ameliorates Allograft Rejection, and Promotes Allergic Airway Disease.

B cells can be polarized to express various cytokines. The roles of IFNγ and IL-10, expressed respectively by B effector 1 (Be1) and Bregs, have been established in pathogen clearance, tumor growth, autoimmunity and allograft rejection. However, the in vivo role of B cell IL-4, produced by Be2 cells, remains to be established. We developed B-IL-4/13 iKO mice carrying a tamoxifen-inducible B cell-specific deletion of IL-4 and IL-13. After alloimmunization, B-IL-4/13 iKO mice exhibited decreased IL-4+ Th2 cells and IL-10+ Bregs without impact on Th1, Tregs, or CD8 T cell responses. B-IL-4/13 iKO mice rejected islet allografts more rapidly, even when treated with tolerogenic anti-TIM-1 mAb. In ovalbumin-induced allergic airway disease (AAD), B-IL-4/13 iKO mice had reduced inflammatory cells in BAL, and preserved lung histology with markedly decreased infiltration by IL-4+ and IL-5+ CD4+ T cells. Hence, B cell IL-4 is a major driver of Th2 responses in vivo which promotes allograft survival, and conversely, worsens AAD.

Prediction of nitrogen oxide emission concentration in cement production process: a method of deep belief network with clustering and time series.

The concentration of nitrogen oxide (NOx) emissions is an important environmental index in the cement production process. The purpose of predicting NOx emission concentration during cement production is to optimize the denitration process to reduce NOx emission. However, due to the problems of time delay, nonlinearity, uncertainty, and data continuity in the cement production process, it is difficult to establish an accurate NOx concentration prediction model. In order to solve the above problems, a NOx emission concentration prediction model using a deep belief network with clustering and time series features (CT-DBN) is proposed in this paper. Particularly, to improve data sparsity and enhance data characteristics, a clustering algorithm is introduced into the model to process the original data of each variable; the time series containing delay information are introduced into the input layer, which combines previous and current variable data into time series data to eliminate the influence of the time delay on the prediction of NOx emission concentration. In addition, restricted Boltzmann machine (RBM) is used to extract data features, and a gradient descent algorithm is used to reversely adjust network parameters to establish a deep belief network model (DBN). Experiments prove that the method in this paper has higher accuracy, stronger stability, and better generalization ability in predicting NOx emission concentration in cement production. The CT-DBN model realizes the accurate prediction of NOx emission concentration, provides guidance for denitration control, and reduces NOx emissions.

[Correlation between hepatic immunological markers and virus genotype in patients with chronic hepatitis C].

OBJECTIVE: To investigate the hepatic expression of immunological markers relevant to a cytotoxic response in relation to viral genotype. METHODS: The frozen liver biopsies were obtained from 28 HF genotyped patients and made the sections stained. The morphometry was used to analyze the major histocompatibility complex class I (MHC-I), CD8, beta(2)-microglobulin (beta(2) -mG), HFE and CD68 in the stained sections. Biopsy data of response to therapy with interferon were available in 18 cases. RESULTS: CD8+ was usually clustered together and localized in portal tracts and sinusoids, and seen to interact with MHC I positive lining cells. MHC-I and beta(2) -mG were expressed mainly in endothelial and Kupffer cells. HFE was expressed in most round and dendritic CD68+ cells. Patients with virus genotype 3a had higher hepatic MHC-I and HFE expression, and a better sustained response to interferon (IFN) therapy than patients without. CONCLUSION: The MHC-I expression in the liver of patient with chronic hepatitis C virus infection seems to relate to viral-genotype. The hepatic MHC-I and HFE expression are higher in patients with virus genotype 3a than that in patients with non-3a genotype.

Up-regulation of NKG2A inhibitory receptor on circulating NK cells contributes to transfusion-induced immunodepression in patients with ß-thalassemia major.

Accumulating evidence has shown that allogeneic blood transfusions can induce significant immunosuppression in recipients, and thereby increase the risk of postoperative infection and/or tumor relapse. Although it is well known that natural killer (NK) cells are responsible for the immunodepression effects of transfusion, the underlying mechanisms remain obscure. In this study, we investigated the role of NK cells in transfusion-induced immunodepression in ß-thalassemia major. The proportion of circulating NK cells and the expression of NK receptors (NKG2A, CD158a, NKP30, NKP46 and NKG2D) as well as CD107a were detected by multicolor flow cytometry. IFN-γ production by circulating NK cells was detected by intracellular cytokine staining. Our results showed that the proportion and cytotoxicity (CD107a expression) of circulating NK cells in transfusion-dependent ß-thalassemia major patients were remarkably lower than those of ß-thalassemia minor patients or healthy volunteers. Expression of NKG2A inhibitory receptor on circulating NK cells in patients with ß-thalassemia major was remarkably up-regulated, but there were no significant differences in the expression levels of NKP30, NKP46, NKG2D, CD158a and IFN-γ. These results indicate NKG2A inhibitory receptor may play a key role in transfusion-induced immunodepression of NK cells in patients with ß-thalassemia major.