BRAF V600E Mutation Lacks Association with Poorer Clinical Prognosis in Papillary Thyroid Carcinoma.

BACKGROUND: Previous literatures showed wide range of prevalence of BRAF V600E in papillary thyroid carcinoma (PTC). The correlation of BRAF V600E mutation with aggressive tumor characteristics and poor prognosis is controversial. The present study was designed to evaluate the association between BRAF V600E mutation with clinicopathological factors and tumor recurrence. PATIENTS AND METHODS: We performed a retrospective chart review of 672 patients who underwent thyroid surgery for PTC during 2013 and 2018. The prevalence of the BRAF V600E mutation was studied. Its correlation with clinicopathologic characteristics and aggressive features, including macroscopic extrathyroidal extension, lymph node metastasis, and distant metastasis, were analyzed with Fisher's exact test. RESULTS: A total of 672 patients who underwent surgical treatment for PTC were included in this study with a mean age of 49.7 (± 13.2) years; 76.8% of the patients were detected with BRAF V600E mutation. Mean tumor size was 1.30 (± 1.07) cm. A significant association was demonstrated between negative BRAF V600E and larger primary tumor size, distant metastasis, and advanced staging (p < 0.05), whereas there was no significant association with age, sex, lymph node metastasis, extrathyroidal extension, and multicentricity. Kaplan-Meier curve showed similar disease-free survival rate between the two groups. CONCLUSIONS: Negative BRAF V600E tumors show more aggressive behavior with a higher risk of developing distant metastasis in patients with PTC. The usefulness of BRAF in predicting the prognosis of PTC remains questionable. Further molecular analysis should be conducted for contribution to aggressive tumor phenotype.

Parathyroidectomy for dialysis patients in the era of calcimimetics: The surgeons' point of view.

Calcimimetics is a new drug for lowering serum parathyroid hormone (PTH), calcium and phosphate in patients with hyperparathyroidism (HPT) on long-term dialysis. It became available on market in 2006. The impact of calcimimetics on the treatment by parathyroidectomy (PTx) was reviewed from the surgeons' point of view. Cure of renal HPT by calcimimetics is not feasible, but calcimimetics can improve preoperative cardiac ventricle ejection fractions by lowering serum PTH. Heart failure is not necessarily a contraindication for PTx. PTx should be done before irreversible organ damage occurs. Limb gangrenes is an ominous sign and should be prevented by frequent checkup for peripheral arterial circulation. The impact of renal osteodystrophy on the quality of life and as indirect cause of mortality deserves more attention in patients with renal HPT. Delayed referral to PTx leads to more complicated patients. A consensus between nephrologists and surgeons about propitious timing for PTx is necessary. Future prospect on the surgical treatment of renal HPT is proposed. Supplemental figure; http://links.lww.com/ASAIO/A782.

Goiter disease in traditional Chinese medicine: Modern insight into ancient wisdom.

Goiter is a disease with history perhaps as long as human has been around. Almost all the available references are in Western language works of literature while information concerning the occurrence of goiter disease in ancient China and the comparison between the treatment in traditional Chinese medicine (TCM) with current Western medicine remains lacking. In this article, the description of goiter, the history of surgical intervention for goiter disease, and the general concept of goiter disease treatment in ancient China literature such as seaweed decoction and acupuncture analgesia for surgery were reviewed.

Combination of peroxisome proliferator-activated receptor gamma and retinoid X receptor agonists induces sodium/iodide symporter expression and inhibits cell growth of human thyroid cancer cells.

BACKGROUND: Thyroid tumors are the most frequent neoplasm of the endocrine system. The major treatment is surgical intervention followed by radioiodine therapy. The sodium/iodide symporter (NIS) has positive expression in thyroid carcinomas with good prognoses and plays a critical role in radioiodine therapy response. Low expression of NIS always leads to tumor recurrence or treatment failure. Redifferentiation therapy is more tumor specific than chemotherapy. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and retinoids are two types of redifferentiating agents. In this study, we examined whether the PPARγ agonist rosiglitazone and retinoid X receptor (RXR) agonist bexarotene could increase NIS expression and exhibit anticancer activity in human thyroid cancer cells. METHODS: Using a TCGA data set, we analyzed the expression of NIS (SLC5A5), PPARγ, and RXR in clinical thyroid tumors and assessed their correlations with the relapse-free survival (RFS) of thyroid tumor patients. Moreover, two human thyroid cancer cell lines, differentiated thyroid papillary BCPAP cells and follicular follicular thyroid cancer-131 cells, were treated with different concentrations of the PPARγ agonist rosiglitazone alone or in combination with the RXR agonist bexarotene. Cell growth was analyzed by the MTT assay. NIS protein expression was determined by Western blotting. RESULTS: From analysis of the TCGA data set, we found that thyroid tumors have lower expression of both NIS (SLC5A5) and PPARγ than nontumor controls. Higher expression levels of NIS, PPARγ, and RXR are associated with higher RFS in patients with thyroid tumors. Moreover, rosiglitazone treatment reduced cell growth and increased NIS protein expression in thyroid cancer cells under normoxic or hypoxic conditions. In addition, bexarotene potentiated the effects of rosiglitazone on cell growth and NIS protein expression. CONCLUSION: Our results suggest that the combination of PPARγ and RXR agonists has potential as a chemotherapeutic strategy for thyroid cancer.

Printing a Three-Dimensional Patient-Specific Safety Device for Reducing the Potential Risk of Mental Nerve Injury During Transoral Thyroidectomy.

BACKGROUND: Thyroidectomy transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe and cosmetically appealing alternative for well-selected patients undergoing thyroidectomy. However, during TOETVA, placement of the two lateral trocars and/or manipulation of the surgical instruments through the trocars may potentially injure and/or compress the mental nerve (MN) because the actual location of the nerve foramen may vary among individuals. The MN injury rate was reported to be as high as 75% in the initial period of robotic-assisted TOETVA. To reduce the potential risk of MN injury, we implemented a three-dimensional printing technology to develop a safety device for TOETVA. METHODS: The patient-specific safety device (PSSD) was a brace with an exact fit to the lower teeth and two safety markers on each side to indicate the location of the mental foramen. For patient in whom the brace would not be applicable, a 3D mandibular model was printed as a PSSD instead. We analyzed 66 patients undergoing TOETVA at our institution from March 2017 to March 2019. The preoperative details and complication profiles were also analyzed. RESULTS: With incorporation of the PSSD into our TOETVA procedure, there have been no cases of MN injury. CONCLUSIONS: Our own TOETVA series has demonstrated that the implementation of the PSSD has been successful in preoperatively identifying and preventing the potential risk of MN injury. Although the additional requirements of preoperative CT and time for fabricating the device impose limitations, the influence of the PSSD in TOETVA is positive.

Analysis of the causes of surgery-related medical disputes in Taiwan: Need for acute care surgeons to improve quality of care.

BACKGROUND: This study investigated surgery-related medical disputes and analyzed disease etiologies and the main causes of disputes in order to identify key points for the purpose of improving the quality of surgical patient care in Taiwan. METHODS: Reports on all surgery-related cases appraised by the Taiwan Witness Examiner Committee of the Department of Health between 2004 and 2008 were reviewed retrospectively by three senior physicians from the emergency department who specialize in both trauma and emergency general surgery. The causes of the various medical disputes were categorized under the following descriptions: operation- or procedure-related complication, anesthesia complication, inappropriate management or decision, delayed diagnosis or misdiagnosis, and unsatisfactory result. RESULTS: A total of 154 cases were reviewed, of which 39 were trauma-related and 115 were disease-related. The two leading causes of disputes in this review were found to be operation- or procedure-related complications (35.7%) and unsatisfactory results (31.8%), followed by delayed diagnoses or misdiagnoses, inappropriate management, and anesthesia complications. Among these, 74 cases (48.1%) required the care of an acute care surgeon and 40 cases (26.0%) required emergency general surgery intervention. CONCLUSION: Surgery- or procedure-related complications and unsatisfactory treatment results constituted the major causes of medical disputes in Taiwan. The majority of these cases involved acute care surgery; thus, the establishment of an acute care surgery system should be considered to improve patient care. The management of hemorrhagic shock and incarcerated hernia should be reinforced in future medical training.

Clinical Manifestations and Gene Expression in Patients with Conventional Papillary Thyroid Carcinoma Carrying the BRAF(V600E) Mutation and BRAF Pseudogene.

BACKGROUND: The association of BRAF(V600E) with the clinical manifestations of papillary thyroid carcinoma (PTC) remains controversial. Recent studies have shown that the BRAF pseudogene can activate the MAPK pathway and induce tumorigenesis. This study investigated the association of BRAF(V600E), the BRAF pseudogene, and their mRNA levels with clinical features and thyroid-specific gene expression in conventional PTCs. MATERIALS AND METHODS: A total of 78 specimens were collected from patients with conventional PTCs. RNA was isolated, and quantitative polymerase chain reaction was used to measure the mRNA levels of BRAF, the BRAF pseudogene, and thyroid-specific and tumor-related genes. Immunohistochemical (IHC) staining of BRAF, ERK, sodium-iodide symporter (NIS), thyrotropin receptor, glucose transporter 1, and Ki67 was also performed. RESULTS: BRAF(V600E) and the BRAF pseudogene were detected in 73.0% (57/78) and 91.7% (44/48), respectively, of the conventional PTCs. The presence of BRAF(V600E) was not associated with the multiple clinical features assessed or the recurrence rate during 76.9 ± 47.2 months of follow-up. Neither was it associated with IHC staining or tumor-related/thyroid-specific gene expression, except for decreased NIS gene expression. The BRAF pseudogene was not associated with clinical characteristics or thyroid-specific gene expression, except for decreased decoy receptor 3 (DCR3) expression. High BRAF mRNA levels were associated with bilateral and multifocal lesions, and BRAF-pseudogene mRNA levels were positively correlated with BRAF mRNA levels (r = 0.415, p = 0.009). CONCLUSION: These results do not support the use of the BRAF(V600E) mutation as a prognostic marker of conventional PTC. However, the association of high BRAF mRNA levels with more advanced clinical features suggests that BRAF mRNA levels might be a more useful clinical marker of PTCs, independent of the BRAF(V600E) mutation status. The correlation between BRAF-pseudogene mRNA levels and BRAF mRNA levels in PTCs is in agreement with the hypothesis that the BRAF pseudogene regulates BRAF expression during tumorigenesis by acting as competitive noncoding RNA. However, additional studies with larger sample sizes are required to confirm these findings.

Induced pluripotent stem cells alleviate lung injury from mesenteric ischemia-reperfusion.

BACKGROUND: Mesenteric ischemia-reperfusion (I/R) injury is a serious pathophysiologic process that can trigger the development of multiorgan dysfunction. Acute lung injury is a major cause of death among mesenteric I/R patients, as current treatments remain inadequate. Stem cell-based therapies are considered novel strategies for treating several devastating and incurable diseases. This study examined whether induced pluripotent stem cells (iPSCs) lacking c-myc (i.e., induced using only the three genes oct4, sox2, and klf4) can protect against acute lung injury in a mesenteric I/R mouse model. METHODS: C57BL/6 mice were randomly divided into the following groups: sham/no treatment, vehicle treatment with phosphate-buffered saline, treatment with iPSCs, and treatment with iPSC-conditioned medium. The mice were subjected to mesenteric ischemia for 45 minutes followed by reperfusion for 24 hours. After I/R, the lungs and the ileum of the mice were harvested. Lung injury was evaluated by histology, immunohistochemistry, and analyses of the levels of inflammatory cytokines, cleaved caspase 3, and 4-hydroxynonenal. RESULTS: The intravenously delivered iPSCs engrafted to the lungs and the ileum in response to mesenteric I/R injury. Compared with the phosphate-buffered saline-treated group, the iPSC-treated group displayed a decreased intensity of acute lung injury 24 hours after mesenteric I/R. iPSC transplantation significantly reduced the expression of proinflammatory cytokines, oxidative stress markers, and apoptotic factors in injured lung tissue and remarkably enhanced endogenous alveolar cell proliferation. iPSC-conditioned medium treatment exerted a partial effect compared with iPSC treatment. CONCLUSION: When considering the anti-inflammatory, antioxidant, and antiapoptotic properties of iPSCs, the transplantation of iPSCs may represent an effective treatment option for mesenteric I/R-induced acute lung injury.

The preoperative evaluation prevent the postoperative complications of thyroidectomy.

OBJECTIVE: Thyroid surgery is generally a safe surgery but its complications are still common. We wish to identify preoperative factors that predict postoperative complications. METHODS: A nationwide survey was conducted by senior surgeons from 16 medical centers and 5 regional hospitals in Taiwan to thyroid operations performed over 3 years. 3846 cases were retrospectively examined to identify factors influencing complications: indication for surgery, preoperative evaluation, such as ultrasonography, chest X-ray, computed tomography and magnetic resonance imaging, isotope scanning, fine-needle aspiration cytology (FNAC) and thyroid function test, and patient characteristics. RESULTS: Eighty-four percent of patients were female. Seven percent of the patients had immediate postoperative hypocalcemia (mild and severe) and 2.3%, hoarseness (recurrent laryngeal nerve (RLN) injury, temporary/permanent). Logistic regression analysis identified an association between hypocalcemia and RLN injury with age, hospital category, surgical procedure types (total thyroidectomy, unilateral, bilateral subtotal or total resection). A lower incidence of hypocalcemia was related to preoperative neck ultrasound and FNAC analysis (the odds ratio (OR) = 0.5 and 0.65, [95% confidence interval (CI) 0.331-0.768 and 0.459-0.911], P = 0.0014 and 0.0127, respectively), while RLN injury was not associated with any preoperative evaluation. The ORs of hypocalcemia and RLN injury for patients older than 50 years were 0.55 and 2.15, [0.393-0.763 and 1.356-3.4], P < 0.001 and 0.0012, respectively. CONCLUSIONS: The success of thyroid surgery depends on careful preoperative planning, including a preoperative neck ultrasound to determine the proximity of the nodule to the recurrent laryngeal nerve course, and the consideration of the type of anesthesia, adjuvant devices for intra-op monitoring of the RLN, and surgical modalities. Our results suggest that preoperative evaluation implementations are positively associated with strategy of surgery and postoperative hypocalcemia prevention.

Comparing characteristics of adverse drug events between older and younger adults presenting to a Taiwan emergency department.

To compare the proportion, seriousness, preventability of adverse drug events (ADEs) between the older adults (≥ 65 years old) and younger adults (<65 years old) presenting to the emergency department (ED), we conducted a prospective observational cohort study of patients 18 years and older presenting to the ED. For all ED visits between March 1, 2009, and Feb 28, 2010, investigators identified ADEs and assessed cases using the Naranjo adverse drug reaction probability scale. Outcomes (proportion, seriousness, and preventability of ADE, length of ED stay, and hospitalization) and associated variables were measured and compared between younger and older adults. The results showed that of 58,569 ED visits, 295 older adults, and 157 younger adults were diagnosed as having an ADE and included in our analysis. The proportion of ADEs leading to ED visits in the older group, 14.3 per 1000  (295/20,628), was significantly higher than the younger group of 4.1 per 1000  (157/37,941). The older group with ADE had a longer ED stay (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.9-6.4 for stay ≥ 24 hours) and larger proportion of preventable ADEs (OR 2.2, 95% CI 1.4-3.6) than the younger group, but there was no significant difference in terms of serious ADEs (OR 0.6, 95% CI 0.3-1.3 for fatal and life threatening) and hospitalization (OR 1.5, 95% CI 0.9-2.6) between the 2 groups. In addition, patients in the older group were more likely to be male, to have symptoms of fatigue or altered mental status, to involve cardiovascular, renal, and respiratory systems, and to have higher Charlson comorbidity index scores, higher number of prescription medications, and higher proportion of unintentional overdose. In conclusion, the proportion of ADE-related ED visits in older adults was higher than younger adults, and many of these were preventable. The most common drug categories associated with preventable ADEs in the older adults were antithrombotic agents, antidiabetic agents, and cardiovascular agents.

Expression profile of MicroRNAs in gram-negative bacterial sepsis.

Bacterial lipopolysaccharide (LPS) is an effective trigger of the inflammatory response during infection with gram-negative bacilli (GNB), which implicates the pathogenesis of sepsis and septic shock. MicroRNAs (miRNAs) are shown to have a significant role in the fine-tuning of toll-like receptor (TLR)-mediated inflammatory response. We profiled miRNA expression levels in peripheral leukocytes of GNB urosepsis patients and compared them with those of healthy controls. We further explored the regulatory mechanism of endotoxin-responsive miRNAs in TLR and cytokine signaling by using human monocytic cell line (THP-1 cells) treated with LPS antigen stimulation. The expression of two miRNAs, that is, let-7a (P < 0.001) and miR-150 (P < 0.001), were confirmed to be significantly downregulated in GNB urosepsis patients compared with healthy controls. The expression of let-7a is first to be identified as a biomarker of GNB sepsis. By using an in vitro model with the human monocytic cell line, we demonstrated that LPS stimulation downregulated the THP-1 cell expression of let-7a. The downregulation of let-7a is correlated with the induced expression of cytokine-inducible Src homology 2-containing protein without change in cytokine-inducible Src homology 2-containing protein mRNA levels in THP-1 cells via TLR signaling pathway activation. Moreover, gain of function by overexpression of let-7a revealed that let-7a significantly decreased tumor necrosis factor-α and interleukin-1ß production in response to LPS. Reduced let-7a and miR-150 levels in peripheral leukocytes correlate with GNB urosepsis patients. Furthermore, let-7a is relevant to the regulation of TLR-mediated innate immune response.

A course to teach students to learn mobile health by serving the elderly.

We designed a special course based on Service Learning theory to train the undergraduate students to teach the elderly people in community college to learn using smartphones for health. A 2-credit course was designed, composed of lecture & discussion and community service. 20 undergrduate stundents from university and 26 seniors from community college registered at this course. The results show very postitive impacts in both groups. The students felt doing something meaningful and learning helping the elder when the elderly felt very appreciated by being served and taught by students about the smartphones. The elderly wished us to go back in the future.

Induced pluripotent stem cells mediate the release of interferon gamma-induced protein 10 and alleviate bleomycin-induced lung inflammation and fibrosis.

Chronic lung diseases cause serious morbidity and mortality, and effective treatments are limited. Induced pluripotent stem cells (iPSCs) lacking the reprogramming factor c-Myc (3-gene iPSCs) can be used as ideal tools for cell-based therapy because of their low level of tumorigenicity. In this study, we investigated whether 3-gene iPSC transplantation could rescue bleomycin-induced pulmonary fibrosis. After the induction of pulmonary inflammation and fibrosis via intratracheal delivery of bleomycin sulfate, mice were i.v. injected with 3-gene iPSCs or conditioned medium (iPSC-CM) at 24 h after bleomycin treatment. Administration of either 3-gene iPSCs or iPSC-CM significantly attenuated collagen content and myeloperoxidase activity, diminished neutrophil accumulation, and rescued pulmonary function and recipient survival after bleomycin treatment. Notably, both treatments reduced the levels of inflammatory cytokines and chemokines, including interleukin 1 (IL-1), IL-2, IL-10, tumor necrosis factor-α, and monocyte chemotactic protein 1 yet increased the production of the antifibrotic chemokine interferon-γ-induced protein 10 (IP-10) in bleomycin-injured lungs. Furthermore, IP-10 neutralization via treatment with IP-10-neutralizing antibodies ameliorated the reparative effect of either 3-gene iPSCs or iPSC-CM on collagen content, neutrophil and monocyte accumulation, pulmonary fibrosis, and recipient survival. Intravenous delivery of 3-gene iPSCs/iPSC-CM alleviated the severity of histopathologic and physiologic impairment in bleomycin-induced lung fibrosis. The protective mechanism was partially mediated by the early moderation of inflammation, reduced levels of cytokines and chemokines that mediate inflammation and fibrosis, and an increased production of antifibrotic IP-10 in the injured lungs.

The influence of neural cell adhesion molecule isoform 140 on the metastasis of thyroid carcinoma.

We previously showed that the preservation of neural adhesion molecule (NCAM) in differentiated thyroid carcinoma is an important indicator for a higher risk of distant metastasis. In the present study, we further demonstrated that forced NCAM-140 isoform expression in human thyroid cancer cells could lead to aggressive growth by enhancing migration and anchorage-independent growth, and exhibiting partial features of epithelial mesenchymal transition. More extensive distant metastasis was also noted in an animal xenograft model when NCAM-expressing thyroid cancer cells were introduced into mice intravascularly. Bioinformatic analysis of NCAM-associated expression profiles predicted a highly interactive protein network, which further implies potential molecular mechanisms underlying the metastatic processes of thyroid cancer.

CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy.

PURPOSE: (131)I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133(+) cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. METHODS: Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. RESULTS: The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133(+) cells and higher radioresistance. After γ-irradiation of the cells, the CD133(+) population was enriched due to the higher apoptotic rate of CD133(-) cells. In vivo (131)I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133(+) cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. CONCLUSION: This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133(+) cells.

Expression of decoy receptor 3 in diffuse sclerosing variant of papillary thyroid carcinoma: correlation with M2 macrophage differentiation and lymphatic invasion.

BACKGROUND: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a unique variant of PTC that is characterized by extensive lymphovascular invasion of tumor cells in a background of lymphocytic thyroiditis. The lymphatic emboli contain tumor cells as well as macrophages, but the recruitment of these macrophages is not well understood. The aim of this study was to determine the relationship between the expression of Decoy receptor 3 (DcR3), the recruitment of tumor-associated macrophages (TAMs), and lymphatic invasion in DSV-PTC. METHODS: We retrospectively examined 14 cases of DSV-PTC using immunohistochemistry studies. The density of TAMs, lymphatic vessel density, lymphatic invasion, tumor emboli area, and DcR3 expression were assessed. Statistical analyses were performed using Fisher's exact test, unpaired t-test, and linear regression. RESULTS: The lymphatic tumor emboli contained a relatively higher density of TAMs than stroma and classical PTC (CPTC) areas. In addition, the number of lymphatic invasions and the size of the tumor emboli area were positively correlated with the number of M2 TAMs. A higher density of M2 TAMs was associated with older patients and larger tumor size. Moreover, DcR3 was expressed only in lymphatic tumor cells and squamous metaplastic tumor cells, but not in macrophages and CPTC. In addition, the preferential expression of DcR3 in tumors was associated with higher levels of M2 TAMs and lymphatic invasion. CONCLUSION: Despite the fact that the exact relationship between DcR3, M2 macrophages, and lymphatic invasion in DSV-PTC remains to be elucidated, our findings suggest that DcR3 expression in DSV-PTC tumor cells may promote the polarized macrophage differentiation toward the M2 phenotype. This phenomenon may further promote lymphatic invasion of DSV-PTC tumor cells.

Diffuse sclerosing variant of papillary thyroid carcinoma with multiple metastases and elevated serum carcinoembryonic antigen level.

BACKGROUND: Diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) is a rare variant of papillary thyroid carcinoma (PTC). We report a 61-year-old female of DSPC whose course was complicated by multiple metastases and an elevated serum carcinoembryonic antigen (CEA) level. SUMMARY: The patient presented with upper back pain. X-ray showed an osteolytic lesion of the sixth cervical spinous process. She had a hard, nonmovable mass with fixed enlarged lymph nodes (LNs) over right neck. Fine-needle aspiration cytology revealed PTC with LNs metastasis. Positron emission tomography demonstrated multiple brain, bone, liver, and lung metastases. However, the patient had an elevated serum CEA level. She underwent a total thyroidectomy and 200 mCi radioactive (131)I therapy. The pathological findings were diffuse sclerosing variant of PTC with capsular and lymph vessel invasion. A double staining of tumor specimen appeared concomitantly positive for CEA and thyroglobulin. CONCLUSIONS: To our knowledge, DSPC with an elevated CEA level is extremely rare.

Reducing the burden of morbidity and medical utilization of older patients by outpatient geriatric services: implications to primary health-care settings.

AIM: That geriatric evaluation and management (GEM) is associated with better quality of care for elderly patients has been reported by previous studies, but evidence supporting that GEM can reduce the burden of morbidity (BOM) was lacking. The aim of this study was to evaluate the benefits of outpatient GEM on reducing BOM and medical utilization in Taiwan. METHODS: Data of this retrospective case-control study were obtained from the 2004-2006 Taiwan National Health Insurance Research Database (NHIRD). Patients who attended the outpatient GEM program for over 6 months in a tertiary medical center in 2005 were enrolled as the case group, and a 1:5 age and gender-matched control group was formed by randomly-selected patients from the same medical center for comparisons. BOM was obtained by applying the Adjusted Clinical Group (ACG) program, and medical utilization variables were totalled for each patient from the NHIRD. Patients were further reassigned to two morbidity categories, the low (resource utilization bands ≤ 3) and high (resource utilization bands > 3) morbidity category, according to their degree of morbidity before statistical analyses. RESULTS: Data of 4254 elderly patients (709 cases, 3545 controls) were included in the study. BOM and medical utilization were increased in both groups in both morbidity categories during the study period. However, the growth of BOM, total medical expenditure, number of emergency department visit, and days and expenditure of hospitalization were significantly reduced in the case than the control group in the low morbidity category, not the high morbidity category. CONCLUSION: Outpatient GEM could effectively reduce growth of BOM and medical utilization for relatively healthy elderly patients in Taiwan where elderly patients have relatively free access to general and specialty care. The results of this study implied the potential benefits of systematically implementing GEM in primary health-care settings to improve the quality of care and slow down the growth of BOM for elderly patients.

Emergency department neurologic deterioration in patients with spontaneous intracerebral hemorrhage: incidence, predictors, and prognostic significance.

OBJECTIVES: The objective was to explore the incidence, predictors, and prognostic significance of emergency department (ED) neurologic deterioration in patients with spontaneous intracerebral hemorrhage (SICH). METHODS: This was a retrospective cohort study conducted at the ED, neurocritical care unit, and general intensive care unit of a university-affiliated medical center. Consecutive adult SICH patients treated in our ED from January 2002 through December 2009 were included, identified from the registered stroke data bank. These were cross-checked for coding with International Classification of Diseases, Ninth Revision, Clinical Modification 431 and 432.9. Enrolled patients had SICH with elapsed times of <12 hours and Glasgow Coma Scale (GCS) scores ≥ 13 on arrival. ED neurologic deterioration was defined as having a two-or-more-point decrease in consciousness noted in any GCS score assessment between ED presentation and admission. Comparisons of numerical data were performed using an unpaired t-test (parametric data) or Mann-Whitney U-test (nonparametric data). Comparisons of categorical data were done by chi-square tests. Variables with p < 0.1 in univariate analysis were further analyzed using multiple logistic regression. No variable automated or manual selection methods were used. RESULTS: Among the 619 patients with SICH included in the study, 22.6% had ED neurologic deterioration. Independent predictors for ED neurologic deterioration included regular antiplatelet use, ictus to ED arrival time under 3 hours, initial body temperature ≥ 37.5°C, intraparenchymal hemorrhage associated with intraventricular hemorrhage (IVH), and presence of a midline shift of greater than 2 mm on computed tomography (CT). ED neurologic deterioration was associated with 1-week mortality, 30-day mortality, and poor neurologic outcome on discharge. CONCLUSIONS: Nearly one-quarter of SICH patients with an initial GCS of 13 to 15 had a two points or more deterioration of their GCS while in the ED. ED neurologic deterioration was associated with death and poor neurologic outcomes on discharge. Several risk factors that are available early in the patients' courses appear to be associated with ED neurologic deterioration. By identifying patients at risk for early neurologic decline and intervening early, physicians may be able to improve patient outcomes.

Targeting signal transducer and activator of transcription 3 pathway by cucurbitacin I diminishes self-renewing and radiochemoresistant abilities in thyroid cancer-derived CD133+ cells.

Anaplastic thyroid cancer (ATC) is a lethal solid tumor with poor prognosis because of its invasiveness and its resistance to current therapies. Recently, ATC-CD133+ cells were found to have cancer stem cell (CSC) properties and were suggested to be important contributors to tumorigenicity and cancer metastasis. However, the molecular pathways and therapeutic targets in thyroid cancer-related CSCs remain undetermined. In this study, ATC-CD133+ cells were isolated and found to have increased tumorigenicity, radioresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared with ATC-CD133 cells. Microarray bioinformatics analysis suggested that the signal transducer and activator of transcription 3 (STAT3) pathway could be important in regulating the stemness signature in ATC-CD133+ cells; therefore, the effect of the potent STAT3 inhibitor cucurbitacin I in ATC-CD133+ cells was evaluated in this study. Treatment of ATC-CD133+ cells with cucurbitacin I diminished their CSC-like abilities, inhibited their stemness gene signature, and facilitated their differentiation into ATC-CD133⁻ cells. Of note, treatment of ATC-CD133+ cells with cucurbitacin I up-regulated the expression of thyroid-specific genes and significantly enhanced radioiodine uptake. Furthermore, cucurbitacin I treatment increased the sensitivity of ATC-CD133+ cells to radiation and chemotherapeutic drugs through apoptosis. Finally, xenotransplantation experiments revealed that cucurbitacin I plus radiochemotherapy significantly suppressed tumorigenesis and improved survival in immunocompromised mice into which ATC-CD133+ cells were transplanted. In summary, these results show that the STAT3 pathway plays a key role in mediating CSC properties in ATC-CD133+ cells. Targeting STAT3 with cucurbitacin I in ATC may provide a new approach for therapeutic treatment in the future.