Recent Publications by CFE Educators

Although central serotonergic systems are known to influence responses to noxious stimuli, mechanisms underlying serotonergic modulation of pain responses are unclear. We proposed that serotonin 2C receptors (5-HT2CRs), which are expressed within brain regions implicated in sensory and affective responses to pain, contribute to the serotonergic modulation of pain responses. In mice constitutively lacking 5-HT2CRs (2CKO mice) we found normal baseline sensory responses to noxious thermal, mechanical and chemical stimuli. In contrast, 2CKO mice exhibited a selective enhancement of affect-related ultrasonic afterdischarge vocalizations in response to footshock. Enhanced affect-related responses to noxious stimuli were also exhibited by 2CKO mice in a fear-sensitized startle assay. The extent to which a brief series of unconditioned footshocks produced enhancement of acoustic startle responses was markedly increased in 2CKO mice. As mesolimbic dopamine pathways influence affective responses to noxious stimuli, and these pathways are disinhibited in 2CKO mice, we examined the sensitivity of footshock-induced enhancement of startle to dopamine receptor blockade. Systemic administration of the dopamine D2/D3 receptor antagonist raclopride selectively reduced footshock-induced enhancement of startle without influencing baseline acoustic startle responses. We propose that 5-HT2CRs regulate affective behavioral responses to unconditioned aversive stimuli through mechanisms involving the disinhibition of ascending dopaminergic pathways.

BACKGROUND

There are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations.

METHODS

This study included 115 PTCs diagnosed in a Ukrainian-American cohort (n=13,243) during prescreening and four successive thyroid screenings. Of these PTCs, 65 were subjected to somatic mutation profiling. All individuals were 18 years at the time of the Chernobyl accident and had direct thyroid radioactivity measurements. Statistical analyses included multivariate linear and logistic regression.

RESULTS

We identified a borderline significant linear-quadratic association (P=0.063) between iodine-131 dose and overall tumour invasiveness (presence of extrathyroidal extension, lymphatic/vascular invasion, and regional or distant metastases). Irrespective of dose, tumours with chromosomal rearrangements were more likely to have lymphatic/vascular invasion than tumours without chromosomal rearrangements (P=0.020) or tumours with BRAF or RAS point mutations (P=0.008). Controlling for age, there were significant time trends in decreasing tumour size (P0.001), the extent of lymphatic/vascular invasion (P=0.005), and overall invasiveness (P=0.026).

CONCLUSIONS

We determined that the invasive properties of PTCs that develop in iodine-131-exposed children may be associated with radiation dose. In addition, based on a subset of cases, tumours with chromosomal rearrangements appear to have a more invasive phenotype. The increase in small, less invasive PTCs over time is a consequence of repeated screening examinations.

OBJECTIVE

To characterize the prevalence of and factors associated with clinicians' prenatal suspicion of a large baby; and to determine whether communicating fetal size concerns to patients was associated with labor and delivery interventions and outcomes.

METHODS

We examined data from women without a prior cesarean who responded to Listening to Mothers III, a nationally representative survey of women who had given birth between July 2011 and June 2012 (n = 1960). We estimated the effect of having a suspected large baby (SLB) on the odds of six labor and delivery outcomes.

RESULTS

Nearly one-third (31.2%) of women were told by their maternity care providers that their babies might be getting "quite large"; however, only 9.9% delivered a baby weighing ≥4000 g (19.7% among mothers with SLBs, 5.5% without). Women with SLBs had increased adjusted odds of medically-induced labor (AOR 1.9; 95% CI 1.4-2.6), attempted self-induced labor (AOR 1.9; 95% CI 1.4-2.7), and use of epidural analgesics (AOR 2.0; 95% CI 1.4-2.9). No differences were noted for overall cesarean rates, although women with SLBs were more likely to ask for (AOR 4.6; 95% CI 2.8-7.6) and have planned (AOR 1.8; 95% CI 1.0-4.5) cesarean deliveries. These associations were not affected by adjustment for gestational age and birthweight.

CONCLUSIONS FOR PRACTICE

Only one in five US women who were told that their babies might be getting quite large actually delivered infants weighing ≥4000 g. However, the suspicion of a large baby was associated with an increase in perinatal interventions, regardless of actual fetal size.

BACKGROUND

Little is known about hospitalization-associated disability (HAD) in older adults who receive care in safety-net hospitals.

OBJECTIVES

To describe HAD and to examine its association with age in adults aged 55 and older hospitalized in a safety-net hospital.

DESIGN

Secondary post hoc analysis of a prospective cohort from a discharge intervention trial, the Support from Hospital to Home for Elders.

SETTING

Medicine, cardiology, and neurology inpatient services of San Francisco General Hospital, a safety-net hospital.

PARTICIPANTS

A total of 583 participants 55 and older who spoke English, Spanish, or Chinese. We determined the incidence of HAD 30 days post-hospitalization and ORs for HAD by age group.

MEASUREMENTS

The outcome measure was death or HAD at 30 days after hospital discharge. HAD is defined as a new or additional disability in one or more activities of daily living (ADL) that is present at hospital discharge compared to baseline. Participants' functional status at baseline (2 weeks prior to admission) and 30 days post-discharge was ascertained by self-report of ADL function.

RESULTS

Many participants (75.3 %) were functionally independent at baseline. By age group, HAD occurred as follows: 27.4 % in ages 55-59, 22.2 % in ages 60-64, 17.4 % in ages 65-69, 30.3 % in ages 70-79, and 61.7 % in ages 80 or older. Compared to the youngest group, only the adjusted OR for HAD in adults over 80 was significant, at 2.45 (95 % CI 1.17, 5.15).

CONCLUSIONS

In adults at a safety-net hospital, HAD occurred in similar proportions among adults aged 55-59 and those aged 70-79, and was highest in the oldest adults, aged ≥ 80. In safety-net hospitals, interventions to reduce HAD among patients 70 years and older should consider expanding age criteria to adults as young as 55.

OBJECTIVE

Evaluate the current status of Hepatopancreatobiliary (HPB) Surgery workforce in North America.

BACKGROUND

HPB fellowships have proliferated, with HPB surgeons entering the field through 3 pathways: transplant surgery, surgical oncology, or HPB surgery training. Impact of this growth is unknown.

METHODS

An anonymous survey was distributed to 654 is used as HPB surgeons from October 2012 to January 2013. Questions evaluated satisfaction with job availability after training and description of current practice. Nationwide Inpatient Sample (NIS) data from 2003 to 2010 was queried to describe the growth of HPB cases in the United States; these data were compared to prior HPB workforce projections performed using 2003 NIS data.

RESULTS

A total of 416 HPB surgeons responded (66%). HPB surgeons are concentrated in a small number of states/provinces with a lack of HPB surgeon workforce in central United States. HPB graduates from 2008 to 2012 report increased difficulty in identifying an HPB-focused practice versus prior to 2008. Mature HPB surgery practices report a composition of 25% to 50% non-HPB operative cases. Fifty-one percent of respondents reported an opinion that current HPB Surgeon production was excessive; however, 2010 NIS data demonstrate that major HPB surgery cases have grown significantly more than was previously projected using 2003 NIS data.

CONCLUSIONS AND RELEVANCE

A cohesive strategy for responsibly responding to the HPB surgical workforce requirements of North America is needed. Elevation of training standards, standardization of requirements for certification, and careful modeling that accounts for regionalization of care should be pursued to prevent overtraining and decentralization of HPB surgical care in the future.

OBJECTIVES

To determine the effectiveness of currently available medical and surgical interventions for treating symptoms of Patulous Eustachian Tube (PET).

DATA SOURCES

A comprehensive search of MEDLINE (January 1948 to July 8, 2015), EMBASE (January 1974 to July 8, 2015), gray literature, hand searches, and cross-reference checking.

STUDY SELECTION

Original published reports evaluating an intervention to treat the symptoms of patulous eustachian tube in patients 18 years and older.

DATA EXTRACTION

Quality-of-case reviews were assessed with the National Institute of Health (NIH) Quality Assessment Tool for Case Series Studies.

DATA SYNTHESIS

The search strategy identified 1,104 unique titles; 39 articles with 533 patients are included. The available evidence consists of small case series and case reports. The most common medical treatment was nasal instillation of normal saline. Surgical treatments were categorized as mass loading of the tympanic membrane, eustachian tube plugging, and manipulation of eustachian tube musculature.

CONCLUSIONS

The available evidence for management of patients with PET is poor in quality and consists predominantly of small case series. Further research is needed to determine the comparative efficacy of the current treatments.

CONTEXT

Abnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population.

OBJECTIVE

To determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis.

DESIGN

Cross-sectional study nested within the Multicenter AIDS Cohort Study.

SETTING

Four US academic medical centers.

PARTICIPANTS

There were 578 HIV-infected and 344 HIV-uninfected men.

MAIN OUTCOME MEASURES

Coronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors.

RESULTS

OPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque.

CONCLUSIONS

OPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.

BACKGROUND

Follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FV-PTC) are difficult entities to distinguish based on cytology prior to pathologic evaluation of surgical specimens but may have different treatment algorithms. The current study describes trends in rates of FTC versus FV-PTC in the U.S. and develops a risk assessment tool to aid clinicians in predicting final diagnosis and shaping treatment plans.

METHODS

Relative rates of FTC and FV-PTC in the surveillance, epidemiology, and end results (SEER) database were evaluated for temporal trends from 1988 to 2011. Using multivariable logistic regression, a simplified scoring system was developed to estimate the risk of FTC versus FV-PTC using patient and tumor characteristics. The National Cancer Data Base was used for model validation.

RESULTS AND DISCUSSION

Of 115,091 thyroid cancer cases in the SEER database from 1988 to 2011, 23,980 involved FTC (n = 5056; 21 %) or FV-PTC (n = 18,924; 79 %). In 1988, half of follicular cases were FV-PTC; however, FV-PTC accounted for over 85 % of these lesions by 2010. Increasing age >45 years, male gender, black race, increasing tumor size, and distant metastases were strongly associated with increased risk of FTC, while lymph node disease and extrathyroidal extension were associated with FV-PTC. A bedside risk assessment nomogram using these preoperative variables classified patient risk of FTC from 2 to 70 %. FV-PTC has become the dominant malignancy with follicular cytology, accounting for >85 % of these cases. A simple bedside risk assessment tool can risk stratify patients with follicular lesions and inform patient and clinician discussions and decision making.

BACKGROUND

Incomplete surgical resection with gross positive tumor margin increases the risk of recurrence in patients with well-differentiated thyroid cancer (WDTC); however, it is not clear whether a microscopic positive margin found only on final pathology has similar implications on patient outcomes.

METHODS

We conducted a single-institution retrospective review of all patients undergoing total thyroidectomy for T1-T2 WDTC (January 2000-January 2010). Factors that may influence the risk of locoregional recurrence or distant metastasis were evaluated by univariate and multivariate analysis.

RESULTS

Of 1000 consecutive patients undergoing surgical resection for WDTC, 684 T1-T2 cancers were included. Mean age was 46 years and 81 % were women. Of this total cohort, 78 (11 %) patients had microscopic positive margins. Radioactive iodine (RAI) was administered in 47/78 (60 %) patients with positive margins versus 312/606 (51 %) patients without positive margins. After a mean follow-up of 46 months, 53 (8 %) patients developed recurrent disease (1 local and 52 nodal). On multivariate analysis, nodal metastases (N1, odds ratio [OR] 7.7) and contralateral multifocality (OR 3.7) were independent risk factors for recurrent disease. A microscopic positive margin was not a risk factor for recurrence.

CONCLUSIONS

A microscopic positive margin found only on final pathological analysis does not increase the risk of recurrence in T1-T2 WDTC. Clinicians should interpret such pathology findings accordingly when considering further surveillance and treatment decisions such as the use of RAI ablation.