Molecular Testing of Atypical Thyroid Nodules with Corresponding Surgical Correlation: Five-Year Retrospective Review in Veterans Population.

Objective We report the results of a retrospective five-year study within a veteran population aimed at correlating abnormal thyroid fine-needle aspiration (FNA) diagnosis with associated molecular testing to the histology of the surgical resection. Methods A retrospective analysis of abnormal thyroid FNAs with associated molecular testing and surgical outcome was conducted from January 1, 2015 to December 31, 2020. Aspirates were classified using the Bethesda system for reporting thyroid cytopathology, including atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy (SM), and malignant. Pertinent data, including patient demographics, imaging, and ancillary testing were reviewed. A thyroid cancer mutation panel assessing the most common mutations and rearrangements associated with neoplasia was utilized. The results of molecular testing were directly compared and correlated with final cytological and histological diagnosis. Results A total of 1850 thyroid aspirates were performed, 200 of which were given an abnormal cytologic diagnosis. Thirty-six samples were submitted for molecular testing and subsequent surgical follow-up. Four were called malignant on cytology. 32 were placed in an indeterminate category (89%). Within indeterminate cases: 53% exhibited positive molecular mutations (n=17), 34% no mutation detected (n=11), and 13% insufficient quantity for testing (n=4). Upon surgical resection in the mutation-positive group: 18% had no malignancy (n=3), and the remaining 82% were positive for malignancy (n=14). Mutations in the histologically malignant group included: 57% BRAF (n=8), 21% NRAS (n=3), 7% HRAS (n=1), 7% KRAS (n=1), and 7% PAX8/PPAR gamma (n=1). In indeterminate cases with no mutation detected, 10 cases were found to be benign, and one case of malignancy was diagnosed. The probability of indeterminate diagnosis in combination with no mutation yielded a 91% chance of benign entity and 9% chance of malignancy. We demonstrated 93% sensitivity and 91% negative predictive value (NPV) for the risk of malignancy in indeterminate cytology specimens with ancillary molecular testing. There was 77% specificity and 82% positive predictive value (PPV) for our data set. Conclusions In indeterminate samples, the detection of a mutation was highly predictive of malignancy and a strong indicating factor for surgery with a high sensitivity and NPV. Molecular testing refined or established the diagnosis in 89% of the cases. Our results indicate that molecular testing of thyroid nodules enhances the accuracy of FNA cytology and the subsequent surgical outcome.

Strengthening community involvement in grant review: insights from the Community-University Research Partnership (CURES) pilot review process.

In 2007, the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan received a Clinical and Translational Science Award (CTSA). Within MICHR, the Community Engagement (CE) program supports partnership efforts between researchers, practitioners, and community-based organizations in specific focal communities throughout Michigan. A key component of the CE program is the Community Engagement Coordinating Council, a group that provides input and guidance on program priorities, strategic planning, and reviews pilot funding proposals for community-academic partnerships. This paper will describe a unique MICHR pilot funding mechanism for Community-University Research Partnerships (CURES) with an emphasis on the ways that community partners are involved in the review process, as well as the benefits, challenges, and insights gained over 5 years of pilot review. There is a growing need for community involvement and expertise in review of funding proposals for community-engaged research at both institutional and federal levels. The CURES pilot review process is one example of an institutional effort to engage community partners in university funding decisions and has demonstrated clear benefit toward accomplishing the aims of the CTSA.

Barriers to accessing health care for hematopoietic cell transplantation recipients living in rural areas: perspectives from healthcare providers.

Hematopoietic cell transplantation (HCT) is a curative therapy for patients with malignant and nonmalignant bone marrow disorders. Life after transplantation can vary significantly among HCT recipients, who deal with a variety of physical and emotional issues. This presents numerous challenges, particularly for rural recipients who are required to travel long distances to access specialized HCT care. The objective of this study was to better understand barriers to providing care for HCT recipients living in rural areas. This study uses a cross-sectional design to collect primary data via an Internet survey of HCT healthcare providers. The authors analyzed factors restricting post-HCT care and whether having standard post-transplantation care instructions influenced the resources provided to distant-to-care recipients. Respondents reported limited transportation, coordination of care, and distance to facility as major barriers to post-HCT care, regardless of the number of distant-to-care recipients treated annually. HCT centers with standard post-transplantation care instructions were more likely to provide visits from social workers and medical leave resources to distant-to-care recipients. These instructions may improve recipient and local provider ability to make informed decisions regarding post-HCT care. The findings will help guide the development of programs and resources targeted to recipients of HCT who are distant to care.

Use of upper limb exercise to assess breathlessness in patients with cancer: tolerability, repeatability, and sensitivity.

We report the development of an arm exercise test to assess breathlessness in patients with lung cancer who are breathless at low levels of exertion. Exercise consisted of raising the arm over 40 cm, either the dominant arm only (n=10) or both arms alternating at minute intervals (n=12). Subjects breathed through a mouthpiece, and ventilation (VE) and oxygen uptake (VO(2)) were measured. Following familiarization, three tests were performed over one week to explore repeatability, and sensitivity was assessed in a fourth test. Arm exercise was generally well tolerated and increased breathlessness, VE, and VO(2). The commonest factor limiting exercise was arm fatigue, although four patients in the two-arm test also reported breathlessness. Repeatability for breathlessness score and VE was best in the two-arm test. The added resistance used to assess sensitivity could not be detected. The two-arm test offers a potential means of assessing the effects of an intervention on breathlessness and E in patients for whom a cycle or treadmill exercise test is unsuitable.

Does aromatherapy massage benefit patients with cancer attending a specialist palliative care day centre?

A randomised controlled pilot study was carried out to examine the effects of adjunctive aromatherapy massage on mood, quality of life and physical symptoms in patients with cancer attending a specialist unit. Participants were randomised to conventional day care alone or day care plus weekly aromatherapy massage using a standardised blend of oils for four weeks. At baseline and at weekly intervals, patients rated their mood, quality of life and the intensity and bother of two symptoms most important to them. Forty-six patients were recruited to the study. Due to a large number of withdrawals, only 11 of 23 (48%) patients in the aromatherapy group and 18 of 23 (78%) in the control group completed all four weeks. Mood, physical symptoms and quality of life improved in both groups. There was no statistically significant difference between groups in any of the outcome measures. Despite a lack of measurable benefit, all patients were satisfied with the aromatherapy and wished to continue. Whilst this pilot study has shown that a randomised controlled trial of complementary therapy is feasible, it has also identified several areas that would require further consideration when designing future studies, e.g., the recruitment and retention of appropriate numbers of patients and the outcome measures used.

Pilot study of nasal morphine-chitosan for the relief of breakthrough pain in patients with cancer.

Breakthrough pain in patients with cancer is common, often unpredictable, and can rapidly become severe. Treatment using the oral administration of opioids is not optimal due to the slow onset of pain relief. Nasal administration of analgesics potentially offers more rapid pain relief. This study investigates the tolerability and efficacy of a novel morphine-chitosan formulation. Twenty episodes of breakthrough pain were observed in 14 patients with cancer who received 5-80 mg of nasal morphine-chitosan. Nasal symptoms, sedation, giddiness, nausea, and other volunteered symptoms, along with pain scores (pain intensity and pain relief), were recorded at baseline and at regular intervals up to 4 hours after administration, together with an overall satisfaction rating. The formulation was acceptable to patients, generally well tolerated, and had an onset of pain relief 5 minutes after dosing. This formulation warrants further study.