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Biomedical subjects

Julie Ann Sosa

Publications and source records attributed to Julie Ann Sosa.

15 recordsLinked to original sources

Psychiatric and cognitive aspects of primary hyperparathyroidism.

PURPOSE OF REVIEW: Clinical guidelines for the treatment of primary hyperparathyroidism have been established by the 2002 NIH workshop on asymptomatic primary hyperparathyroidism. The panel called for further study of the ill-defined psychiatric and cognitive changes often seen in patients with primary hyperparathyroidism. The present paper provides a rigorous, updated review of the most recent advances and studies that have measured health-related quality of life, neurocognitive and psychiatric changes, as well as neurophysiologic imaging in patients with primary hyperparathyroidism undergoing parathyroidectomy. RECENT FINDINGS: In studies conducted pre and postparathyroidectomy, six recent articles have described improvements in health-related quality of life. Five studies included evaluations with validated psychiatric and cognitive tests in prospective case-control trials, and showed varied improvements in depression, memory and concentration after parathyroidectomy. Two studies evaluated in a preliminary fashion the brains of patients with primary hyperparathyroidism with functional imaging studies, showing regional cerebral blood flow changes and prefrontal cortical activation with sleep improvement in postsurgical patients. SUMMARY: The studies described in this paper underline the benefits of surgical treatment on nontraditional symptoms in patients with primary hyperparathyroidism, and open the door to the continued study of the endocrine effects of primary hyperparathyroidism on brain function.

Cognition Disorders↗

Total thyroidectomy for differentiated thyroid cancer.

There has been a long debate about the optimal surgical management of differentiated thyroid cancer. It has focused on the extent of thyroidectomy, with recommendations ranging from thyroid lobectomy to total thyroidectomy. There is no randomized prospective trial addressing this issue; such a trial would be prohibitive, since differentiated thyroid cancer has a good prognosis and a long natural history. Instead, there is heavy reliance on retrospective analyses, as well as consensus expert opinion and experience. We review this evidence, along with recent recommendations from several professional associations. We believe that total or near-total thyroidectomy followed by (131)I ablation and thyroid hormone suppression are most appropriate for the majority of patients with differentiated thyroid cancer, as retrospective analyses have shown that they reduce the risk of cancer recurrence, address the chance of multifocal intrathyroidal cancer, and facilitate use of surveillance scans and thyroglobulin monitoring for post-operative recurrence. This recommendation comes with the caveat that total thyroidectomy must be performed safely, since there is evidence that surgeon volume is associated with patient outcomes.

Adenocarcinoma, Follicular↗

Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases.

BACKGROUND: Medullary thyroid cancer (MTC) is a rare cancer. There is a relative paucity of data over the last decade with regard to the prognosis of these patients. Therefore, the authors used the population-based Surveillance, Epidemiology, and End Results (SEER) registry to update what to their knowledge is one of the largest series of patients with MTC reported to date. METHODS: All patients with a diagnosis of MTC with active follow-up in the SEER database from 1973 to 2002 were included. Univariate and multivariate regression analyses were used to assess the associations between demographic, clinical, and pathologic characteristics of patients and survival. RESULTS: A total of 1252 patients with MTC were identified over 29 years of follow-up. In all, 87% of patients were white and 60% were female, with a mean age of 50 years. Although many variables were significant on univariate analysis, SEER stage and age at diagnosis were found to be the strongest predictors of survival in the multivariate analysis. Prognosis was poor in patients with advanced disease (hazards ratio [HR], 4.47), or those age >65 years (HR, 6.55). Patients who underwent surgery fared better than those who did not. Overall, 51% of patients had less than the currently recommended treatment guidelines for MTC. Adjuvant radiation therapy was found to be independently associated with a decreased survival (HR, 1.65). CONCLUSIONS: Stage of disease and age at diagnosis were found to be the strongest predictors of survival for patients with MTC. To the authors' knowledge there has been no change in stage at diagnosis or a significant improvement in survival noted over the last 30 years. Many patients underwent surgery that was deemed less than optimal for stage of disease.

Age of Onset↗

Do not roll the videotape: effects of the health insurance portability and accountability act and the law on trauma videotaping practices.

BACKGROUND: We hypothesized that trauma video practices would be affected as a result of Health Insurance Portability and Accountabilty Act (HIPAA) enactment. METHODS: A survey was distributed electronically to coordinators and/or directors of level 1 trauma centers. Centers were queried on demographics, trauma video use, and reasons for changes, if any, in their video practice patterns. Descriptive statistics and chi-square analysis were employed. RESULTS: Survey response rate was 75%. Prior to HIPAA, 58% of responding trauma centers used video compared to 18% now. On a Likert scale of 1-5, video analysis rated 3.80. For those using video currently, the most common purposes are education (91%) and quality assurance (83%). HIPAA has affected the way video is used at one third of these centers. Ten percent receive institutional review board approval for videotaping, 35% get patient consent, and more than half report capturing a poor patient outcome on tape. The most commonly cited reasons for stopping video use were HIPAA and legal concerns about patient privacy, consent, and discoverability (79%). Scarce resources were, in part, to blame at 70% of centers, while video technology was found to be ineffective at only 32%. CONCLUSIONS: A minority of level I trauma centers currently use video, although it is effective according to users. HIPAA and medicolegal concerns have affected its use at some centers and contributed to its abandonment at others.

Data Collection↗

Papillary thyroid cancer.

In summary, PTC is common, although it rarely results in disease-specific mortality. It is being diagnosed increasingly in the subclinical phase as a result of enhanced ultrasound imaging and more aggressive surveillance of smaller thyroid nodules. US-guided FNA is the "gold-standard" for diagnosis. Although controversy continues about the appropriate surgical management of PTC, total thyroidectomy is usually indicated given the frequent multicentricity and metastases of the disease, which in turn, necessitates adjuvant RAI and careful surveillance. An enhanced prognostic classification could better guide initial surgical therapy, standardize surveillance, and reduce the risk of recurrent and persistent disease. Research efforts should focus on the genetic and molecular underpinnings of PTC, as these would facilitate the identification of additional prognostic factors and potential targets for novel therapies.

Biopsy, Fine-Needle↗

A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas.

Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1alpha. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1alpha activity in tumors.

Journal Article↗

Parathyroidectomy improves neurocognitive deficits in patients with primary hyperparathyroidism.

BACKGROUND: Clinical guidelines for the treatment of primary hyperparathyroidism (pHPT) often suggest parathyroidectomy, but generally fail to consider neurocognitive and psychiatric symptoms because of the relative paucity of evidence. METHODS: In this prospective study, patients with pHPT (PTX) and benign euthyroid thyroid disease (THY) referred for operation were evaluated pre- and postoperatively with validated psychometric and neurocognitive instruments to determine whether learning, memory, or concentration improved with after parathyroidectomy. Statistical comparisons between groups were performed with univariate analysis and repeated measures of analysis of variance. RESULTS: Fifty-five subjects, mean age of 54 years, were evaluated preoperatively; 41 returned postoperatively. There were no significant differences between groups by age and gender. PTXs reported more depression symptoms preoperatively (P = .04) that improved postoperatively. There were no differences between the 2 groups on verbal memory and trait anxiety. For PTXs, average preoperative serum calcium concentration (11.3 mg/dL) and serum PTH level (100 pg/mL) normalized postoperatively. Preoperatively PTXs showed greater delays in their spatial learning (P = .03). All subjects learned across the 5 trials, but PTXs were more delayed (P = .03). After operation, PTXs improved and functioned at a level equivalent to the THYs. There was an interaction between trial (neurocognitive testing), visit (pre- vs postoperative), status (PTX vs THY), and change in PTH level (P = .06), suggesting that individuals with greater change in PTH were more likely to improve in their learning efficiency postparathyroidectomy. CONCLUSIONS: PHPT may be associated with a spatial learning deficit and processing that improves after parathyroidectomy. While longer-term follow-up is necessary, neurocognitive symptoms perhaps should be considered as criteria for parathyroidectomy.

Adult↗

Current advances in the diagnosis and treatment of pancreatic endocrine tumors.

PURPOSE OF REVIEW: A comprehensive literature review of more than 200 original manuscripts published in the last 18 months was conducted to summarize landmark studies performed on the molecular biology, diagnosis, imaging, and treatment of endocrine tumors of the pancreas. RECENT FINDINGS: Recent achievements occurred on many fronts. Identification of a novel insulin splice variant with increased translation efficiency moved forward the understanding of the molecular biology of insulinomas. Results of a 29-year prospective study from the National Institutes of Health clarified the epidemiology of multiple endocrine neoplasia-1 syndrome. Chromogranin A was identified as a promising marker for pancreatic endocrine tumors. New imaging, including F-dopa positron emission tomography and laparoscopic ultrasound, and the effective combination of existing modalities localized and staged tumors with greater accuracy. Nonoperative treatment strategies show promise; discovery of the antiangiogenic properties of octreotide and the overexpression of tyrosine kinase receptors such as c-kit, epidermal growth factor receptor, and platelet-derived growth factor receptor on malignant endocrine pancreatic tumors may lead to promising pharmacologic treatment. SUMMARY: There have been exciting recent advancements in research surrounding endocrine pancreas that hopefully will pave the way for potential improvement in clinical outcomes for patients with these tumors.

Biomarkers, Tumor↗

Assessment and management of patients with abnormal calcium.

Calcium is essential for homeostasis, and normocalcemia should be maintained strictly during the perioperative period. The biochemistry of calcium equilibrium results from the calcium-sensing receptors on the parathyroid glands, which detect changes in calcium concentrations and initiate the proper response. Asymptomatic hypercalcemia is a common metabolic derangement that is often discovered on routine serum screening. The most common etiologies are primary hyperparathyroidism and cancer. Increasingly, parathyroidectomy is the preferred therapy for primary hyperparathyroidism. Severe hypercalcemia ("hypercalcemic crisis") should be managed aggressively with a combination of intravenous fluids, steroids, bisphosphonates, and calcitonin. Some of these patients may require an urgent parathyroidectomy for calcium control. Hypocalcemia needs to be verified, as many cases of hypocalcemia are the artifact of hypoalbuminemia. Severe hypocalcemia occurs after subtotal or total parathyroidectomy with auto transplantation as well as after massive resuscitation or blood transfusion. Strategies aimed at correcting calcium concentrations depend on the severity of symptomatology. If symptoms are mild, oral calcium supplementation can be given; otherwise, intravenous calcium should be administered.

Algorithms↗

Minimally invasive parathyroidectomy.

Efforts to minimize the incision, extent of exploration, length of hospital stay, and cost associated with parathyroidectomy have resulted in the development of a number of new surgical techniques, including minimally invasive, "concise," radio-guided, and endoscopic parathyroid exploration. With minimally invasive parathyroidectomy, a small incision is used in combination with a cervical block and sedation to perform a unilateral neck exploration. In so doing, risks of bilateral neck exploration are avoided, and the procedure can be done on an outpatient basis. This minimally invasive strategy has been shown to maintain the outstanding success of conventional bilateral neck exploration. All of the new surgical techniques necessitate pre-operative localization, which allows for unilateral neck exploration, and are facilitated by use of the intra-operative parathyroid hormone assay, which provides surgeons with feedback in the operating room regarding whether the patient has undergone adequate resection.

Humans↗

Determinants of willingness to donate living related and cadaveric organs: identifying opportunities for intervention.

BACKGROUND: Although low rates of cadaveric organ donation have been attributed to potential cadaveric donors' concerns regarding their religious beliefs and mistrust of the health care system, it is unclear whether similar concerns are important to potential living related donors. It is also not known which factors might be most responsible for low rates of cadaveric and living related donation among the general public. METHODS: We conducted a cross-sectional study of households in Maryland, using a standardized telephone questionnaire, to assess factors associated with willingness to donate cadaveric and living related organs. We compared factors (demographic, cultural, attitudinal, and clinical) related to willingness to donate cadaveric organs with factors related to willingness to donate living related organs. In multivariate analyses, we assessed the independent relation of factors to willingness to donate cadaveric and living related organs, and we assessed the relative importance of these factors in explaining variation in the general public's willingness to donate. RESULTS: Of 385 participants (84% of randomized homes), 254 (66%) were extremely willing to donate to a sibling but only 179 (47%) had designated themselves a cadaveric donor on their drivers' licenses. In bivariate analysis, older age, comorbid conditions, mistrust in hospitals, and concerns about discrimination in hospitals were statistically significantly associated with less willingness to donate living related organs, although African-Americans, older age, lower education, lack of insurance, unemployment, comorbid conditions, and religion/spirituality were associated with less willingness to donate cadaveric organs. After adjusting for potential confounders, only mistrust in hospitals and concerns about discrimination remained strongly and independently associated with 50 to 60% less odds of willingness to donate living related organs [[relative odds [95% confidence intervals (CI)]: 0.4 (0.2-0.7) to 0.5 (0.3-1.0) and 0.4 (0.2-0.9), respectively]] although presence of dependents was associated with 70% higher odds of willingness to donate living related organs [relative odds (95% CI): 1.7 (1.0-3.0)]. In contrast, older age, employment status, religion/spirituality, and mistrust in hospitals were associated with 50 to 90% less odds of willingness to donate living related organs cadaveric organs [relative odds (95% CI): 0.3 (0.1-0.8), 0.4(0.2-0.8), 0.1 (0.1- 0.5) to 0.5 (0.2-0.9), and 0.3 (0.2-0.6), respectively]. Mistrust in hospitals and concerns about the surgical donation procedure contributed most to the variation in willingness to be a living related donor, although race contributed most to the variation in willingness to be a cadaveric donor. CONCLUSIONS: Many factors affect the general public's willingness to donate organs, but their relative contribution is different for living related versus cadaveric donation. Efforts to improve organ donation rates should be directed toward factors that are most important in explaining the existing variation in willingness to donate.

Adult↗

The general public's concerns about clinical risk in live kidney donation.

Difficulty in attracting live kidney donors may be related to fears regarding both the surgical procedure for kidney harvesting and future failure of the remaining kidney. We conducted a cross-sectional study of households in Maryland to identify public disincentives to living related kidney donation. In multivariate analyses, we assessed the independent effects of several factors on willingness to donate a kidney to a sibling. We also assessed thresholds for factors above which persons would not donate a kidney. Of 385 participants, 66% were extremely willing to donate to a sibling. After adjustment, those who considered the length of a hospital stay, out-of-pocket expenses, size and appearance of a scar, the time it takes to get to the transplant center, and the donor risk of developing kidney failure very important had 50-60% less odds of being extremely willing to donate. Median acceptable levels for risk of complications, hospital stay, compensated and uncompensated time from work, time requiring pain medications, and out-of-pocket expenses were greater than levels from clinical evidence regarding both laparoscopic and open nephrectomy. Unrealistic concerns among the general public regarding live donation may serve as potential disincentives to donation. Efforts to educate the public regarding live donation might help assuage fears and attract those who may not otherwise donate.

Adult↗

Understanding disparities in donor behavior: race and gender differences in willingness to donate blood and cadaveric organs.

BACKGROUND: Recent efforts to recruit blood and organ donors have only marginally improved demographic disparities in willingness to donate. Few studies have examined which factors are most important in explaining race and gender disparities in willingness to donate. OBJECTIVES: To assess race and gender differences in willingness to donate blood and cadaveric organs, and to determine the extent to which several factors (including sociodemographic characteristics and attitudes about religion and mistrust of hospitals) might explain differences in willingness to donate. RESEARCH DESIGN: Cross-sectional telephone survey of Maryland households contacted via random-digit dialing. MEASURES: Past blood donation, organ-donor status on driver's license, and measures of medical mistrust and religious and spiritual salience. SUBJECTS: Persons age 18 to 75 living in the Baltimore, Maryland metropolitan area. RESULTS: Of 385 respondents (84% of randomized households), 114 were black females, 46 were black males, 110 were white females, and 69 were white males. Before adjustment, black females were least willing to donate blood (41%), and black males were least willing to become cadaveric donors (19%) among all race-gender groups. Adjustment for respondent concerns about mistrust of hospitals and discrimination in hospitals explained most differences in willingness to donate blood, whereas adjustment for respondents' beliefs regarding the importance of spirituality and religion explained most differences in willingness to donate cadaveric organs. CONCLUSIONS: Both race and gender are important identifiers of those less willing to donate. To maximize efficiency, donor recruitment efforts should focus on race-gender groups with lowest levels of willingness. Potential donor concerns regarding mistrust in hospitals and religion/spirituality may serve as important issues to address when developing programs to improve donation rates.

Adult↗

Fine needle aspiration of poorly differentiated oxyphilic (Hürthle cell) thyroid carcinoma: a case report.

BACKGROUND: Poorly differentiated oxyphilic (Hürthle cell) carcinomas are a more recently described variant of poorly differentiated thyroid carcinoma and are characterized by a prominent Hürthle cell component in a solid or trabecular arrangement. Clinically, poorly differentiated oxyphilic carcinomas behave more aggressively as compared to classic Hürthle cell carcinomas, which have a predominantly follicular pattern. Although the histology of these rare thyroid tumors has been reported in the literature, the cytologic features on fine needle aspiration biopsy have not been described before. CASE: A 73-year-old man with a long history of radioactive iodine and levothyroxine therapy for multinodular goiter presented with a painful, rapidly expanding, 6-cm, left thyroid mass with aggressive radiologic features. Fine needle aspiration biopsy of the mass yielded extremely cellular smears with a dual population of medium-sized follicular cells and numerous Hürthle cells. Subsequent thyroidectomy confirmed the malignant nature of this Hürthle cell-rich tumor, warranting a diagnosis of poorly differentiated oxyphilic (Hürthle cell) thyroid carcinoma. CONCLUSION: Poorly differentiated oxyphilic thyroid carcinoma is an aggressive variant of Hürthle cell carcinomas and must enter the differential diagnosis when fine needle aspiration biopsy of a radiologically aggressive thyroid mass yields extremely hypercellular smears with a prominent Hürthle cell component.

Adenocarcinoma↗

Clinical management of primary hyperparathyroidism and thresholds for surgical referral: a national study examining concordance between practice patterns and consensus panel recommendations.

OBJECTIVE: To determine whether 1990 guidelines established by the National Institutes of Health (NIH) for the optimal management (surgical versus nonsurgical) of patients with asymptomatic primary hyperparathyroidism (PHPT) are known and followed by endocrinologists. METHODS: We surveyed endocrinologists in the United States who were randomly selected in 1998 from two endocrine societies. Endocrinologists were asked about management of asymptomatic patients with PHPT, awareness of NIH recommendations, practice demographics, and annual PHPT case volume. We classified endocrinologists into either low-volume (<12 cases of PHPT per year) or high-volume (> or = 12 cases per year) physicians. RESULTS: Of 374 eligible physicians, 146 (39%) responded to our survey. In comparison with nonrespondents, respondents were of similar age, sex, years in practice, and geographic location profiles; this finding suggested minimal nonresponse bias. More high-volume physicians than low-volume physicians were aware of the NIH guidelines (75% versus 50%; P<0.01). Management of asymptomatic patients was similar between volume groups; overall, 39% of patients were referred for surgical treatment. Nevertheless, considerable variation in management existed; 7% of all physicians referred > or = 90% of their asymptomatic patients for surgical treatment, whereas 31% referred < or = 10%. Adherence to monitoring guidelines for nonsurgically managed patients ranged widely, depending on the specific recommendation (from 6% of physicians obtaining creatinine clearance assessments every 6 months to 78% of physicians ordering serum calcium measurements every 6 months). Surgical referral practices also varied substantially, with 25% of all physicians referring a 40-year-old patient with PHPT when hypercalcemia was mild (< or = 1 mg/dL above normal), 39% when hypercalcemia was moderate, and 31% when hypercalcemia was severe (>1.5 mg/dL above normal). Of the responding physicians, 4% reported that hypercalcemia alone was not sufficient justification to refer a patient for surgical intervention. Higher PHPT case volume was not associated with differences in surgical referral. CONCLUSION: Suboptimal awareness of the 1990 NIH panel recommendations and the substantial variation in clinical management of PHPT indicate that newer NIH guidelines developed in 2002 must be more widely disseminated and strongly recommended if practice patterns are to be influenced and clinical outcomes improved.

Adult↗