Lowell General Hospital

As the global COVID-19 pandemic escalates there is a need within radiation oncology to work to support our patients in the best way possible. Measures are required to reduce infection spread between patients and within the workforce. Departments need contingency planning to create capacity and continue essential treatments despite a reduced workforce. The #radonc community held an urgent online journal club on Twitter in March 2020 to discuss these issues and create some consensus on crucial next steps. There were 121 global contributors. This document summarises these discussions around themes of infection prevention, rationalisation of workload and working practice in the presence of infection.

Background. Premature infants need to attain both medical stability and maturational milestones (specifically, independent thermoregulation, resolution of apnea of prematurity, and the ability to feed by mouth) before safe discharge to home. Current practice also requires premature infants to be observed in hospital before discharge for several days (margin of safety) after physiologic maturity is recognized. Objective. To compare postmenstrual age (PMA) at discharge in a homogeneous population of premature infants cared for in different neonatal intensive care units (NICUs) and to assess the impact on hospital stay of the recognition and recording of physiologic maturity and the required margin of safety. Methods. We studied premature infants delivered at 30 to 34 6/7 weeks gestational age (GA), free of significant medical or surgical complications. Medical records of 30 eligible infants consecutively discharged from the hospital before July 1997 from each of 15 NICUs in Massachusetts (9 level 2 and 6 level 3) were reviewed. Results. A total of 435 infants were included in the study sample. Mean (± standard deviation) GA and birth weight of the study population were 33.2 ± 1.2 weeks and 2024 ± 389 g, respectively. Infants were discharged at a similar PMA regardless of GA at birth. Considerable variation in the PMA at discharge between hospital sites was observed (range, 35.2 ± 0.5 weeks to 36.5 ± 1.2 weeks). Despite the homogeneous study population, hospitals in which infants had the latest PMA at discharge also recorded mature cardiorespiratory and feeding behavior at an older age. Longer duration of pulse oximetry use was associated with later resolution of apnea. Differences in the duration of the margin of safety between sites did not contribute to variation in hospital stay. Conclusion. NICUs vary widely in length of hospital stay for healthy premature infants. We speculate that this variation results in part from differences in monitoring for and documentation of apnea of prematurity and feeding behavior.

PURPOSE The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2–positive (HER2+) breast cancer (BC). METHODS Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m 2 IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks). The co-primary objectives were to compare the incidence of clinically relevant toxicities (CRTs) in patients treated with T-DM1 versus TH and to evaluate iDFS in patients receiving T-DM1. RESULTS The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH). CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH ( P = .83). The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis ( P < .0001). Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH. CONCLUSION Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS, but was not associated with fewer CRT compared with TH.

OBJECTIVE: To determine whether pulse oximeter (PO) accuracy and signal quality are affected by level of skin pigmentation. METHODS: Observational study in a community hospital ED. Consecutive adult patients undergoing arterial blood gas determination were enrolled into the study. Skin pigmentation was determined by comparison with standardized color swatches under controlled lighting; assigned values were used to stratify patients into 3 groups (light, intermediate, and dark) using predetermined criteria. Simultaneous with arterial blood sampling, staff recorded PO reading of O2 saturation using the Nellcor D-25 oximeter. PO values were compared with criterion standard values measured using a 4-wavelength spectrophotometer or co-oximeter. PO signal quality also was recorded. Bias (the mean difference between PO and co-oximeter-measured values of hemoglobin saturation) and precision (the standard deviation of the bias) were calculated. Groups were compared using one-way ANOVA, Bartlett's test for variances, and chi2 test. RESULTS: O2 saturation data were obtained for 284 patients. Bias values did not differ between the 3 skin pigment groups (p = 0.79). Precision was of borderline significance (p = 0.05), but there was no dose-response relation between skin pigmentation and precision. Study personnel reported suboptimal PO function most often among patients in the dark group (p = 0.003), but this finding was of no clinical significance. PO signal failure was rare (<1% of all patients). CONCLUSIONS: Although several prior studies suggest the contrary, this study found that skin pigmentation does not affect the bias or precision of pulse oximetry. Furthermore, skin pigmentation has no clinically significant effect on PO signal quality.

BACKGROUND: During the COVID-19 pandemic, a number of conspiracy theories have emerged. A popular theory posits that the pandemic is a hoax and suggests that certain hospitals are "empty." Research has shown that accepting conspiracy theories increases the likelihood that an individual may ignore government advice about social distancing and other public health interventions. Due to the possibility of a second wave and future pandemics, it is important to gain an understanding of the drivers of misinformation and strategies to mitigate it. OBJECTIVE: This study set out to evaluate the #FilmYourHospital conspiracy theory on Twitter, attempting to understand the drivers behind it. More specifically, the objectives were to determine which online sources of information were used as evidence to support the theory, the ratio of automated to organic accounts in the network, and what lessons can be learned to mitigate the spread of such a conspiracy theory in the future. METHODS: Twitter data related to the #FilmYourHospital hashtag were retrieved and analyzed using social network analysis across a 7-day period from April 13-20, 2020. The data set consisted of 22,785 tweets and 11,333 Twitter users. The Botometer tool was used to identify accounts with a higher probability of being bots. RESULTS: The most important drivers of the conspiracy theory are ordinary citizens; one of the most influential accounts is a Brexit supporter. We found that YouTube was the information source most linked to by users. The most retweeted post belonged to a verified Twitter user, indicating that the user may have had more influence on the platform. There was a small number of automated accounts (bots) and deleted accounts within the network. CONCLUSIONS: Hashtags using and sharing conspiracy theories can be targeted in an effort to delegitimize content containing misinformation. Social media organizations need to bolster their efforts to label or remove content that contains misinformation. Public health authorities could enlist the assistance of influencers in spreading antinarrative content.

Case 3. In 2012, a young adult man with history of Klinefelter syndrome presented with intermittent chest pain and was found to have a 15-cm primary mediastinal NSGCT. He was treated with 4 cycles of VIP followed by resection of residual mediastinal mass, which revealed teratoma. In 2014, he was found to have leukocytosis (WBC, 44 000/L [44.0 10 9 / L]). Bone marrow examination confirmed chronic-phase CML by morphologic characteristics, and a t(9;22)(q34;q11) was identified by chromosome analysis. The patient started treatment with dasatinib and achieved a hematologic response. To date, his BCR/ABL transcript declined appropriately from 55% to 9%. He continues to be in remission for his GCT.

The management of patients with prolonged viral shedding and coronavirus disease 2019 symptoms remains unclear. Combining antivirals, as practiced in other infections, is theoretically advantageous. We present a case of persistent, symptomatic severe acute respiratory syndrome coronavirus 2 infection and associated organizing pneumonia that was successfully treated with an extended course of combination antiviral therapy.

Severe insulin resistance syndromes are a heterogeneous group of rare disorders characterized by profound insulin resistance, substantial metabolic abnormalities, and a variety of clinical manifestations and complications. The etiology of these syndromes may be hereditary or acquired, due to defects in insulin potency and action, cellular responsiveness to insulin, and/or aberrations in adipose tissue function or development. Over the past decades, advances in medical technology, particularly in genomic technologies and genetic analyses, have provided insights into the underlying pathophysiological pathways and facilitated the more precise identification of several of these conditions. However, the exact cellular and molecular mechanisms of insulin resistance have not yet been fully elucidated for all syndromes. Moreover, in clinical practice, many of the syndromes are often misdiagnosed or underdiagnosed. The majority of these disorders associate with an increased risk of severe complications and mortality; thus, early identification and personalized clinical management are of the essence. This Review aims to categorize severe insulin resistance syndromes by disease process, including insulin receptor defects, signaling defects, and lipodystrophies. We also highlight several complex syndromes and emphasize the need to identify patients, investigate underlying disease mechanisms, and develop specific treatment regimens.

Appropriate use of antimicrobials in health care continues to be a challenge. Reliable and reproducible antimicrobial susceptibility testing methods are necessary to provide the clinician with valuable information that can be translated into positive clinical outcomes at the bedside. However, there are nuances with these testing methods that, if unrecognized, could lead to misinterpretation of results and inappropriate antibiotic selection. This primer describes the common antimicrobial susceptibility tests used in the clinical microbiology laboratory and reviews how subtle differences in testing methods and technique can influence reported results. Clinicians who have a thorough understanding of qualitative and quantitative methods, automated susceptibility testing systems, and commonly used screening and confirmatory tests for antibiotic-resistant organisms can strengthen institutional antibiotic stewardship programs and improve patient outcomes.

Positron emission tomography (PET) suffers from severe resolution limitations which reduce its quantitative accuracy. In this paper, we present a super-resolution (SR) imaging technique for PET based on convolutional neural networks (CNNs). To facilitate the resolution recovery process, we incorporate high-resolution (HR) anatomical information based on magnetic resonance (MR) imaging. We introduce the spatial location information of the input image patches as additional CNN inputs to accommodate the spatially-variant nature of the blur kernels in PET. We compared the performance of shallow (3-layer) and very deep (20-layer) CNNs with various combinations of the following inputs: low-resolution (LR) PET, radial locations, axial locations, and HR MR. To validate the CNN architectures, we performed both realistic simulation studies using the BrainWeb digital phantom and clinical studies using neuroimaging datasets. For both simulation and clinical studies, the LR PET images were based on the Siemens HR+ scanner. Two different scenarios were examined in simulation: one where the target HR image is the ground-truth phantom image and another where the target HR image is based on the Siemens HRRT scanner - a high-resolution dedicated brain PET scanner. The latter scenario was also examined using clinical neuroimaging datasets. A number of factors affected relative performance of the different CNN designs examined, including network depth, target image quality, and the resemblance between the target and anatomical images. In general, however, all deep CNNs outperformed classical penalized deconvolution and partial volume correction techniques by large margins both qualitatively (e.g., edge and contrast recovery) and quantitatively (as indicated by three metrics: peak signal-to-noise-ratio, structural similarity index, and contrast-to-noise ratio).

The revised AACN grading system includes more recent study designs and minimizes confusion with other grading systems.With the tremendous emphasis on the importance of basing nursing care decisions on the best available evidence to promote the highest quality of care for patients and families, evidenced-based practice has become a common phrase in health care.1 Although evidence is most often supported by research, other forms of evidence such as case studies and expert opinion are considered valuable when research is lacking. Strength of the evidence has also been the focus of attention because not all research studies are equal in quality.2 Levels of evidence or grading systems to rank research studies and other forms of evidence have been developed to offer practitioners a reliable hierarchy to determine the strongest evidence. Evidence is used by practitioners to guide practice related to disease management or skills. As a leader in this area, the American Association of Critical-Care Nurses (AACN) has published numerous resources to help practitioners appraise evidence for integration into clinical practice. Publications such as Practice Alerts, Protocols for Practice, and Procedure Manual3 contain recommendations for clinical practice based on a comprehensive and scientific review of the evidence. To support these recommendations, AACN developed a hierarchy system to grade the level of evidence. AACN’s grading system was originally referred to as a rating scale and was used to rank individual recommendations according to the level of supporting evidence available (Table 1).4AACN was a pioneer of evidence-leveling systems; the association developed its grading system in 1993. The purpose was to create a tool to assist practitioners to determine whether statements about clinical practice were based on research or other reliable evidence. The original rating scale identified higher levels of evidence by the number “VI.” Evidence that was not supported by research was ranked lower on the scale, the lowest level indicated by the number “I.” The original AACN rating scale identified the strength of evidence supporting practice issues, meeting the needs of the association’s members at that time (M. Chulay, oral communication, December 2008).Shortly after the AACN evidence-leveling system was developed, the Centers for Disease Control and the Agency for Healthcare Research and Quality (previously named Agency for Health Care Policy and Research) developed an evidence hierarchy system.5,6 By 1999, the leveling systems used by many organizations to support practice statements or clinical practice guidelines had a reverse order to the system used by AACN. Over time, this created confusion for end-users of AACN resources.In addition to confusion regarding the ordering of evidence, feedback by AACN members and readers included identification of omissions from the evidence-rating system. As evidence-based practice evolved, certain types of evidence such as qualitative research were found to be missing. As a result, AACN’s Board of Directors tasked the 2008–2009 Evidence-Based Practice Resource Work Group (EBPRWG) to perform a review of AACN’s leveling system and to specifically focus on the order of leveling and content.In 2008, AACN’s volunteer EBPRWG conducted a comprehensive review of AACN’s evidence-leveling system, which included a review of 12 existing grading systems from other organizations.6–18 Following lengthy discussions, a decision was made to reverse the order of AACN’s evidence-leveling system to maintain consistency with the hierarchies used by other health organizations. The Gerontological Nursing Intervention Research Center’s leveling system most closely matched the criteria desired by AACN members.7,8 Because this leveling system lacked some of the more recent study designs, the new AACN leveling system was born from an adaptation of the leveling system by the Gerontological Nursing Intervention Research Center.In comparison to the original AACN rating system, recent revisions include clarification of the term “clinical studies” by specifying individual research designs. Research designs identified in the new leveling system include meta-analysis, meta-synthesis (the qualitative counterpart to meta-analysis), randomized and nonrandomized studies, qualitative research, descriptive or correlational studies, systematic reviews, and integrative reviews. Nonresearch evidence includes peer-reviewed professional organizational standards and case reports as well as expert opinion and manufacturers’ recommendations. Meta-analyses and meta-syntheses are placed as the highest levels of evidence.19–21To minimize confusion for readers of previously published older AACN resources, the levels were changed from a numerical to alphabetical scale. The highest levels of evidence are represented by the letter “A” progressing through lower levels of evidence before ending with the letter “M.” The lowest level M, now used to identify manufacturers’ recommendations, is easily separated from traditional standards of evidence. The new evidence leveling system is outlined in Table 2.All new and revised AACN resources will include the new evidence-leveling system. Specifically, practitioners will begin to see the revised evidence-leveling system on AACN’s Web site (www.aacn.org) as Practice Alerts are updated with current references and new Practice Alerts are created. The AACN Procedure Manual, currently undergoing revisions with an expected publication date in late 2009, will also include the new evidence-leveling system.The EBPRWG has completed revisions to the new evidence-leveling system for AACN’s publications to offer consistency with other health organizations and incorporate a more comprehensive list of evidence. It is important for readers to acknowledge that evidence hierarchies vary between organizations. Although evidence hierarchies may appear similar in design, the content may differ slightly. Moreover, in addition to the levels used by an evidence hierarchy, readers must assess the quality of the evidence before making clinical practice decisions. With growth in the evidence-based practice movement, nurses are inundated with a plethora of evidence. Consequently, practitioners require tools to assist with reviewing the best evidence to guide their clinical practice. The new AACN evidence-leveling system furthers AACN’s mission to supply acute and critical care nurses with resources to enhance their knowledge to incorporate evidence-based practice into patient care.AACN and the EBPRWG welcome feedback on the new AACN evidence-leveling system, in addition to suggestions for Practice Alerts or resources required to assist nurses in clinical practice.

PURPOSE: To histologically evaluate biopsy specimens from patients who previously underwent rotator cuff repair augmented with a highly porous collagen implant. METHODS: Biopsies of collagen implant/host-tissue constructs were obtained from 7 patients undergoing a second arthroscopic procedure at various time periods (5 weeks to 6 months) after arthroscopic rotator cuff repair augmented with a collagen implant overlay. The biopsy specimens were examined histologically for host-tissue ingrowth, host-tissue maturation, and host-implant biocompatibility. RESULTS: At the earliest time period (5 weeks), the biopsy revealed the presence of host cells (fibroblasts) within the interstices of the porous collagen implant. Cells were aligned along the linear orientation of the collagen implant structure, and there was evidence of early collagen formation. The 3-month biopsies showed increased collagen formation, maturation, and organization over the surface of the implant and evidence of the collagen implant. At 6 months, the newly generated tissue had the histologic appearance of a tendon, suggesting functional loading of the new generated host tissue. There was no evidence of any remnants of the collagen implant in the 6-month biopsy. There was no evidence of any inflammatory or foreign body reaction within any of the tissue samples. CONCLUSIONS: Biopsies of collagen implants retrieved from human rotator cuff repair subjects revealed cellular incorporation, tissue formation and maturation, implant resorption, and biocompatibility. CLINICAL RELEVANCE: The histologic observations from these clinical biopsies support the biocompatibility of this implant and its ability to promote new connective tissue with the histological appearance of tendon over the surface of the native cuff tendon.

Background: Failure to initiate discussions about patients' values and goals in serious illness remains a common problem. Many clinicians are inadequately trained for these discussions. Objective: Evaluate whether a novel train-the-trainer model results in high-quality training that improves clinicians' self-reported competencies in serious illness communication. Design: Multimethod evaluation of an educational program. Setting/Context: In 2016, three faculty at Ariadne Labs (AL) conducted three train-the-trainer courses to equip faculty trainers at each of the three institutions to teach serious illness communication to clinicians. Measures: As collected by a post-training questionnaire, primary evaluation measure is clinicians' self-reported change in skills after the training compared with before. Secondary measures include a course evaluation and qualitative learnings. Results: From 2016 to 2018, AL trained 22 trainers (19/22 were palliative care specialists) in three systems, who trained 297 clinicians (49% physicians; 35% advanced practice clinicians; 12% registered nurses, social workers, or chaplain; 4.0% Other) spanning subspecialties (48%); primary care (28%); palliative care (17%); and other (7.1%). Clinicians reported statistically significant improvement in all skills for two of the systems, with a third system demonstrating improvement in all skills with two reaching statistical significance ( p &lt; 0.0001). Participants rated the quality of the training highly (95% mostly/extremely effective) and shared a diverse array of takeaways that reflect positive shifts in knowledge, attitudes, and skills. Conclusion: Serious illness communication training, delivered through a train-the-trainer model, was highly acceptable and resulted in significant self-reported improvements in competencies of clinicians. This may be a viable method for health systems seeking to train their clinical workforce.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a mature B-cell neoplasm that typically follows an indolent clinical course. Amyloid deposition associated with MALT lymphoma is uncommon. We describe the clinical and pathologic features of 20 cases of MALT lymphoma and associated amyloid deposition across diverse primary sites. Frozen section immunofluorescence performed on 4 cases suggests that these deposits are a localized form of AL amyloid. Clinical follow-up was available for 15 patients. Amyloid deposits distant from the initial site occurred in 5 cases, always at sites also involved by the underlying lymphoma. No definitive evidence of systemic amyloidosis affecting the heart, kidneys, or liver was present in any patient. Given the generally indolent clinical behavior of MALT lymphomas with associated amyloid, we do not recommend extensive follow-up testing for systemic amyloidosis or more aggressive therapy than would be indicated for other MALT lymphomas of similar clinical stage.

It has been shown that CD1d expression and glycolipid-reactive, CD1d-restricted NKT cells exacerbate the development of obesity and insulin resistance in mice. However, the relevant CD1d-expressing cells that influence the effects of NKT cells on the progression of obesity remain incompletely defined. In this study, we have demonstrated that 3T3-L1 adipocytes can present endogenous ligands to NKT cells, leading to IFN-γ production, which in turn, stimulated 3T3-L1 adipocytes to enhance expression of CD1d and CCL2, and decrease expression of adiponectin. Furthermore, adipocyte-specific CD1d deletion decreased the size of the visceral adipose tissue mass and enhanced insulin sensitivity in mice fed a high-fat diet (HFD). Accordingly, NKT cells were less activated, IFN-γ production was significantly reduced, and levels of adiponectin were increased in these animals as compared with control mice on HFD. Importantly, macrophage recruitment into the adipose tissue of adipocyte-specific CD1d-deficient mice was significantly blunted. These findings indicate that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity.

WHAT IS KNOWN ON THE SUBJECT: Nurses are at a high risk for work-family conflict due to long and irregular work hours and multiple physical and psychosocial stressors in their work environment. Nurses report higher rates of depressive symptoms than the general public, leading to a high rate of burnout, absenteeism, and turnover. Work-family conflict is associated with negative consequences in nurses including physical illnesses and mental disorders. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE: Past research on this topic has not examined the mechanisms for the effect of work family conflict on depression. Studies rarely examine the influence of health behaviors such as sleep in explaining this association. Our study identified significant association of sleep disturbances with both work-family conflict and depressive symptoms in nurses. Our main contribution is reporting the important role of sleep disturbances in translating the effect of work-family conflict on depressive symptoms among nurses. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Nurses need to receive training in best practices for maintaining their own sleep and mental health. Organizations should include sleep health education and training in workplace health programs. Evidence-based interventions to promote healthy sleep practices such as cognitive behavioral therapy and complementary and integrative approaches should be evaluated for their effectiveness in addressing the impact of work-family conflict on the mental health of nurses. Healthcare organizations should incorporate mental health services as part of their Employee Assistance Program for nurses and include psychological and sleep disorders screening, counseling, and follow-up. ABSTRACT: Introduction Depression has been identified as the leading cause of disability worldwide. Nurses report higher rates of depression than the general public. Work-family conflict is challenging for nurses and may lead to depression and poor health. However, the mechanisms for the effect of work-family conflict on depression have not been well understood. Aim The objective is to use a cross-sectional design to examine the role of sleep disturbances in the association between work-family conflict and depressive symptoms in nurses. Methods Questionnaires, measuring working conditions, work-family conflict, sleep disturbances and depressive symptoms were collected from 397 nurses at a not-for-profit community hospital in the north-eastern United States. Results We observed a significant association between work-family conflict and depressive symptoms (β = 2.22, p < .001) among nurses. Sleep disturbances partially mediated this association by 40.54%. Discussion Sleep disturbances play an important role in translating work-family conflict into depressive symptoms. Implications Evidence-based interventions to promote healthy sleep practices should be evaluated for their effectiveness in addressing the impact of work-family conflict on mental health. Organizations should include sleep education and training as a component of workplace health promotion and employee assistance programmes to mitigate the effect of work-family conflict and promote overall health in nurses.

Work-related musculoskeletal disorders (WMSDs) persist as the leading occupational injury, accounting for nearly half of nurses' total occupational injuries. Musculoskeletal pain is a known cause of sleep disruption, and individuals with WMSDs that interfere with sleep often report more pain. Evening chronotype has been associated with poor sleep among nurses. However, the associations among chronotype, sleep, and WMSDs are still unclear, and were explored in the present study. A cross-sectional survey was administered to 397 nurses, with 47.4% reporting WMSDs. Robust Poisson regression modeling suggested that evening type (PR = 1.32, p < .05), prolonged sleep onset latency (PR = 1.37, p < .05), and using sleep-promoting substances (PR = 1.35, p < .01) were associated with increased risk of WMSDs among nurses, after adjusting for shift work, regular exercise, body mass index, and other covariates. This study suggests that well-designed evidence-based nonpharmacological interventions to improve sleep may reduce the risk of WMSDs among nurses.

CONTEXT: Comprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine needle aspiration (FNA) samples has not been reported. OBJECTIVE: To determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules. METHODS: This retrospective analysis of FNA samples, tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier at UPMC Molecular and Genomic Pathology laboratory, analyzed the prevalence of diagnostic, prognostic, and targetable genetic alterations in a total of 50 734 BCIII-VI nodules from 48 225 patients. RESULTS: Among 50 734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alterations. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.9% of cases. CONCLUSION: In this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutations and targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.

PURPOSE: Numerous publications during the COVID-19 pandemic recommended the use of hypofractionated radiation therapy. This project assessed aggregate changes in the quality of the evidence supporting these schedules to establish a comprehensive evidence base for future reference and highlight aspects for future study. METHODS AND MATERIALS: Based on a systematic review of published recommendations related to dose fractionation during the COVID-19 pandemic, 20 expert panelists assigned to 14 disease groups named and graded the highest quality of evidence schedule(s) used routinely for each condition and also graded all COVID-era recommended schedules. The American Society for Radiation Oncology quality of evidence criteria were used to rank the schedules. Process-related statistics and changes in distributions of quality ratings of the highest-rated versus recommended COVID-19 era schedules were described by disease groups and for specific clinical scenarios. RESULTS: From January to May 2020 there were 54 relevant publications, including 233 recommended COVID-19-adapted dose fractionations. For site-specific curative and site-specific palliative schedules, there was a significant shift from established higher-quality evidence to lower-quality evidence and expert opinions for the recommended schedules (P = .022 and P < .001, respectively). For curative-intent schedules, the distribution of quality scores was essentially reversed (highest levels of evidence "pre-COVID" vs "in-COVID": high quality, 51.4% vs 4.8%; expert opinion, 5.6% vs 49.3%), although there was variation in the magnitude of shifts between disease sites and among specific indications. CONCLUSIONS: A large number of publications recommended hypofractionated radiation therapy schedules across numerous major disease sites during the COVID-19 pandemic, which were supported by a lower quality of evidence than the highest-quality routinely used dose fractionation schedules. This work provides an evidence-based assessment of these potentially practice-changing recommendations and informs individualized decision-making and counseling of patients. These data could also be used to support radiation therapy practices in the event of second waves or surges of the pandemic in new regions of the world.

BACKGROUND: Noninvasive quantitative measurement of fibrosis in chronic kidney disease (CKD) would be desirable diagnostically and therapeutically but standard radiologic imaging is too variable for clinical usage. By applying a vibratory force, tissue shear wave stiffness can be measured by magnetic resonance elastography (MRE) that may correlate with progression of kidney fibrosis. Since decreased kidney perfusion decreases tissue turgor and stiffness, we combined newly available three-dimensional MRE shear stiffness measurements with MR arterial spin labeling (ASL) kidney blood flow rates to evaluate fibrosis in diabetic nephropathy. METHODS: Thirty individuals with diabetes and Stage 0-5 CKD and 13 control individuals without CKD underwent noncontrast MRE with concurrent ASL blood flow measurements. RESULTS: MRE cortical shear stiffness at 90 Hz was decreased significantly below controls in all CKD stages of diabetic nephropathy. Likewise, ASL blood flow decreased progressively from 480 ± 136 mL/min/100 g of cortical tissue in controls to 302 ± 95, 229 ± 7 and 152 ± 32 mL/min/100 g in Stages 3, 4 and 5 CKD, respectively. A magnetic resonance imaging (MRI) surrogate for the measured glomerular filtration fraction [surrogate filtration fraction = estimated glomerular filtration rate (eGFR)/ASL] decreased progressively from 0.21 ± 0.07 in controls to 0.16 ± 0.04 in Stage 3 and 0.10 ± 0.02 in Stage 4-5 CKD. CONCLUSIONS: In this pilot study, MRI with ASL blood flow rates can noninvasively measure decreasing kidney cortical tissue perfusion and, with eGFR, a decreasing surrogate filtration fraction in worsening diabetic nephropathy that appears to correlate with increasing fibrosis. Differing from the liver, MRE shear stiffness surprisingly decreases with worsening CKD, likely related to decreased tissue turgor from lower blood flow rates.