Recent Publications by CFE Educators

For in-transit melanoma confined to the extremities, regional chemotherapy in the form of hyperthermic isolated limb perfusion and isolated limb infusion are effective treatment modalities carrying superior response rates to current standard systemic therapy. Despite high response rates, most patients will eventually recur, supporting the role for novel research aimed at improving durable responses and minimizing toxicity. Although the standard cytotoxic agent for regional chemotherapy is melphalan, alternative agents such as temozolomide are currently being tested, with promising preliminary results. Current strategies for improving chemosensitivity to regional chemotherapy are aimed at overcoming classic resistance mechanisms such as drug metabolism and DNA repair, increasing drug delivery, inhibiting tumor-specific angiogenesis, and decreasing the apoptotic threshold of melanoma cells. Concurrent with development and testing of these agents, genomic profiling and biomolecular analysis of acquired tumor tissue may define patterns of tumor resistance and sensitivity from which personalized treatment may be tailored to optimize efficacy. In this article rational strategies for treatment of in-transit melanoma are outlined, with special emphasis on current translational and clinical research efforts.

Although lifespan has dramatically improved in the human immunodeficiency virus-positive (HIV+) population, HIV and its treatment continue to be a source of substantial morbidity in many organ systems, including the genitourinary tract. As the number of long-term survivors increases with advances in antiretroviral therapy, age-associated urologic symptoms are also becoming increasingly relevant considerations for people living with HIV. Primary care physicians have a major role to play in maintaining the genitourinary health of their HIV+ patients. This role is of great importance not just for the well-being of the individual patient but for the public health, as the genitourinary tract is a common vector for HIV transmission. In this article the authors review the management of the genitourinary system in patients with HIV infection. Particular consideration is given to urinary tract infections, lower urinary tract symptoms, renal insufficiency, sexual and fertility problems, and cancers of the genitourinary tract. Management algorithms are outlined and indications for referral to a urologist are emphasized.

AIMS

Multiple warfarin pharmacogenetic dosing algorithms have been reported to date. However, there is only limited information available on the performance of the algorithms that can be used with the results of a US FDA-cleared warfarin pharmacogenetic test. We compared the performance of warfarin pharmacogenetic dosing algorithms in a large racially diverse cohort.

MATERIALS & METHODS

Warfarin pharmacogenetic dosing algorithms were identified using the PubMed database. Patient information from the International Warfarin Pharmacogenetics Consortium database was used to predict therapeutic warfarin doses according to each algorithm. By using bootstrapping analysis, the performance of algorithms was tested by comparing the mean absolute error and mean percentage of patients whose predicted dose fell within 20% of actual dose (percentage within 20%) in the entire cohort, and by race and therapeutic dose range.

RESULTS

A total of 13 algorithms and 1940 patients were included in the study. Overall, all the algorithms had similar performances (mean absolute error: 10.3 mg/week and mean percentage within 20%-41.4%). However, algorithms derived from racially mixed populations tended to perform better than those derived from single race populations. Mixed population algorithms had the lowest mean absolute error and the highest percentage within 20% across the racial groups. Most algorithms performed better in the intermediate-dose range (between 21 and 49 mg/week) than in the low (≤21 mg/week) or high-(≥49 mg/week) range.

CONCLUSION

Published warfarin pharmacogenetic algorithms performed similarly, although mixed population algorithms tended to perform better than race-specific algorithms.

OBJECTIVES

Plasma C-reactive protein (CRP) is associated with cardiovascular disease (CVD), but effects may vary by gender and degree of CVD risk. Whether CRP has value as a CVD risk marker in type-2 diabetes (T2DM) is unclear. We examined whether CRP has gender differences in association with coronary artery calcium (CAC) in diabetic and nondiabetic samples without clinical CVD.

METHODS

We performed cross-sectional analyses of gender influence on CRP association with CAC in the Penn Diabetes Heart Study (N = 1299 with T2DM), the Study of Inherited Risk of Coronary Atherosclerosis (N = 860 nondiabetic subjects) and a combined sample.

RESULTS

Female gender was associated with higher plasma CRP in diabetic and nondiabetic samples after adjustment for covariates. There was a strong interaction by gender in the association of CRP with CAC (interaction P 0·001). In diabetic women, CRP was associated with higher CAC even after further adjustment for age, race, medications, metabolic syndrome, Framingham risk score and body mass index [Tobit ratio 1·60, 95% CI (1·03-2·47)]. Although this relationship was attenuated in nondiabetic women, the combined sample maintained this association in fully adjusted models [1·44, 95% CI (1·13-1·83)]. There was no association of CRP with CAC in either diabetic or nondiabetic men.

CONCLUSIONS

CRP may be a useful marker of cardiovascular risk in women, particularly in diabetic women who otherwise have no known CVD. Prospective studies are needed to better assess the gender differences in CRP utility and the use of CRP in T2DM.

OBJECTIVE

This study had 2 aims: (1) to assess the timing and magnitude of psychological and neurocognitive changes before and after parathyroidectomy and (2) to examine correlations between changes in serum biomarkers and psychological symptoms and neurocognitive performance.

BACKGROUND

Psychological and neurocognitive changes are common in patients with primary hyperparathyroidism (pHPT), but the associations of serum biomarkers and these changes have not been established.

METHODS

This prospective cohort study carried out at a large tertiary care referral center from 2004 to 2008 screened all adult patients with the biochemical diagnosis of pHPT who underwent first-time parathyroidectomy. Laboratory results, psychological symptom reports, and results of neurocognitive testing using validated instruments were obtained preoperatively and at 1, 3, and 6 months postoperatively. Outcomes measures included serum calcium, intact parathyroid hormone (iPTH), and thyroid stimulating hormone; psychological symptom inventories (Beck Depression Inventory-II, Brief Symptom Inventory-18, and Spielberger State-Trait Anxiety Inventory); and neurocognitive test scores (Rey Auditory Verbal Learning Test and Groton Maze Learning Test).

RESULTS

Two hundred twelve patients were enrolled; mean age was 60 years; 78% were female and had low comorbidity; 78% had parathyroidectomy under ambulatory, minimally invasive techniques; cure rate was 99%. Improvements in psychological and neurocognitive measures were observed at all postoperative follow-up visits. The most pronounced improvements were noted in depressive and anxiety symptoms, and visuospatial and verbal memory. Examination of change scores revealed that postoperative reduction in iPTH was associated with a decrease in state anxiety, which was also associated with improvement in visuospatial working memory.

CONCLUSIONS

Reduction in mood and anxiety symptoms is associated with reductions in both iPTH and spatial working memory in patients with pHPT who undergo successful parathyroidectomy.

PURPOSE OF REVIEW

Medullary thyroid cancer (MTC) is an uncommon malignancy. Its low incidence has limited both widespread clinical expertise and definitive large randomized clinical trials. Variation in practice patterns exist in the United States with regard to diagnosis, treatment, and long-term management. We review the most recent guidelines on management of this challenging neuroendocrine malignancy.

RECENT FINDINGS

Newly identified re-arranged during transfection point mutations have added to clinicians' disease prognostic accuracy, which have been incorporated in the new MTC treatment guidelines. The study of tumor marker doubling times has guided the extent of surgery and lymphadenectomy for MTC. Although data are limited, standard chemotherapy and radiation therapy have not been shown to be effective in the treatment of MTC. Newer targeted drug therapies are promising and are being examined in therapeutic clinical trials.

SUMMARY

There have been several recent advances in the molecular biology, diagnosis, imaging, and treatment options for MTC. Downstaging and treating metastatic disease more effectively may improve overall survival of MTC patients. Dissemination of standardized guidelines is important for optimal treatment with less variation in quality of care.

PURPOSE OF REVIEW

The incidence of differentiated thyroid cancer (DTC) is increasing. There remains controversy regarding several aspects of its management, including the need for prophylactic central compartment neck dissection and use of recombinant human thyroid stimulating hormone (rhTSH) for ¹³¹I radioactive iodine remnant ablation in patients with low-risk disease.

RECENT FINDINGS

Central compartment neck dissection entails removal of the prelaryngeal, pretracheal, and paratracheal lymph nodes. Description of the dissection should include the indication (prophylactic vs. therapeutic) and extent of dissection (unilateral vs. bilateral). After 3.7 years, patients who underwent rhTSH-assisted ablation appeared to have similar rates of ablation as patients who underwent thyroid hormone withdrawal using criteria of negative whole body scans (84% of euthyroid and 94% of hypothyroid patients) and stimulated thyroglobulin less than 2 ng/ml (95%, euthyroid; 96%, hypothyroid). In the United States, rhTSH would cost $15,994 per patient, with an incremental societal cost of $1365 per patient and incremental cost-effectiveness ratio of $52,554/quality-adjusted-life-year.

SUMMARY

The use of rhTSH in patients with low-risk DTC undergoing thyroid remnant ablation appears to have similar efficacy in remnant ablation and tumoricidal effects and is associated with improved patient quality of life. Cost-effectiveness appears to be above the conventional threshold for cost-effectiveness, but is dependent on cost of rhTSH, patient utility, days off work, and rates of remnant ablation.

Two sets of contributory factors to depression among patients with rheumatoid arthritis (RA) are generally examined - the social context of the individual and the biologic disease state of that person's RA. This article will review the evidence for both. RA affects patients both physically and psychologically. Comorbid depression is common with RA and leads to worse health outcomes. Low socioeconomic status, gender, age, race/ethnicity, functional limitation, pain and poor clinical status have all been linked to depression among persons with RA. Systemic inflammation may also be associated with, cause, or contribute to depression in RA. Understanding the socioeconomic factors, individual patient characteristics and biologic causes of depression in RA can lead to a more comprehensive paradigm for targeting interventions to eliminate depression in RA.