Advanced non-small-cell lung cancer treated with first-line pembrolizumab plus chemotherapy: tumor response dynamics as a marker for survival.

OBJECTIVES: The study investigated tumor burden dynamics on computed tomography (CT) scans in patients with advanced non-small-cell lung cancer (NSCLC) during first-line pembrolizumab plus chemotherapy, to provide imaging markers for overall survival (OS). METHODS: The study included 133 patients treated with first-line pembrolizumab plus platinum-doublet chemotherapy. Serial CT scans during therapy were assessed for tumor burden dynamics during therapy, which were studied for the association with OS. RESULTS: There were 67 responders, with overall response rate of 50%. The tumor burden change at the best overall response ranged from - 100.0% to + 132.1% (median of - 30%). Higher response rates were associated with younger age (p < 0.001) and higher programmed cell death-1 (PD-L1) expression levels (p = 0.01). Eighty-three patients (62%) showed tumor burden below the baseline burden throughout therapy. Using an 8-week landmark analysis, OS was longer in patients with tumor burden below the baseline burden in the first 8 weeks than in those who experienced ≥ 0% increase (median OS: 26.8 vs. 7.6 months, hazard ratio (HR): 0.36, p < 0.001). Tumor burden remained below their baseline throughout therapy was associated with significantly reduced hazards of death (HR: 0.72, p = 0.03) in the extended Cox models, after adjusting for other clinical variables. Pseudoprogression was noted in only one patient (0.8%). CONCLUSIONS: Tumor burden staying below the baseline burden throughout the therapy was predictive of prolonged overall survival in patients with advanced NSCLC treated with first-line pembrolizumab plus chemotherapy, and may be used as a practical marker for therapeutic decisions in this widely used combination regimen. CLINICAL RELEVANCE STATEMENT: The analysis of tumor burden dynamics on serial CT scans in reference to the baseline burden can provide an additional objective guide for treatment decision making in patients treated with first-line pembrolizumab plus chemotherapy for their advanced NSCLC. KEY POINTS: • Tumor burden remaining below baseline burden during therapy predicted longer survival during first-line pembrolizumab plus chemotherapy. • Pseudoprogression was noted in 0.8%, demonstrating the rarity of the phenomenon. • Tumor burden dynamics may serve as an objective marker for treatment benefit to guide treatment decisions during first-line pembrolizumab plus chemotherapy.

Imaging Findings on Head Computed Tomography Scans in Victims of Intimate Partner Violence.

OBJECTIVE: The aim of the study is to analyze the imaging findings and injury patterns seen on head computed tomography (CT) examinations performed on survivors of intimate partner violence (IPV). METHODS: An institutional review board-approved retrospective analysis of 668 patients reporting IPV to our institution's violence intervention and prevention program between January 2013 and June 2018 identified 40 unique patients with radiological findings visible on head CT. All injuries visible on head CT were analyzed based on the anatomic location and injury type. Demographics, IPV screening at the time of injury, concomitant, prior, and subsequent injuries to the index head injury were also recorded. RESULTS: Our study cohort had 36 women and 4 men with a mean age at presentation of 43 ± 13 years (mean ± SD), 91 unique injuries with 57 (62.6%) isolated soft tissue injuries, 4 (3.2%) fractures, 13 (14.3%) intra-axial, and 17 (18.7%) extra-axial injuries. Soft tissue injuries and intra-axial injuries occurred most commonly in the frontal region (45.6% and 38.5%), followed by the parietal region (22.8% and 23.1%), while most extra-axial injuries were subdural hematomas (41.2%). Left-sided injuries accounted for 49% (45/91) with 29/91 right-sided (32%) and 17/91 bilateral (19%) injuries. The IPV screening occurred in 44% of injury visits (22/50). Concomitant injuries were seen in 14/50 injury visits (28%), most commonly being in the lower extremity (6/14, 42.9% [% of visits with concomitant injuries]) followed by the upper extremity (5/14, 35.7%), while 52% of visits (26/50) were preceded by prior injuries and 68% of events (34/50) were followed by subsequent injuries. CONCLUSIONS: Isolated soft tissue swelling is the most common manifestation of IPV on head CT scans with frontoparietal region being the most common site. Synchronous and metachronous injuries are frequent.

Imaging patterns of thoracic injuries in survivors of intimate partner violence (IPV).

PURPOSE: To recognize the imaging patterns of thoracic injuries in survivors of intimate partner violence (IPV). MATERIALS AND METHODS: A retrospective radiological review of 688 patients self-reporting IPV to our institution's violence intervention and prevention program between January 2013 and June 2018 identified 30 patients with 89 thoracic injuries. Imaging and demographic data were collected. RESULTS: Thirty survivors with 89 injuries to the thorax were identified with a median age of 43.5 years (21-65 years). IPV was reported or disclosed as the direct cause of injury in 50% (15/30) of survivors, including all nine patients who sustained penetrating injuries. The most common injury type was fracture (72%, 64/89) with 52 rib, 3 sternal, 2 clavicular, and 7 vertebral fractures. There were 3 acromioclavicular dislocations. Among rib fractures, right lower anterior rib fractures (9-12 ribs) were the most common(30%, 16/52). There were 10 superficial soft tissue injuries. There were 12 deep tissue injuries which included 2 lung contusions, 2 pneumomediastinum, 7 pneumothoraces, 1 hemothorax. One third of patients had concomitant injuries of other organ systems, most commonly to the head and face, followed by extremities and one third of patients had metachronous injuries. CONCLUSION: Acute rib fractures with concomitant injuries to the head, neck, face, and extremities with an unclear mechanism of injury should prompt the radiologist to discuss the possibility of IPV with the ordering physician. ADVANCES IN KNOWLEDGE: Recognizing common injuries to the thorax will prompt the radiologists to suspect IPV and discuss it with the clinicians.

Molecular Characterization and Therapeutic Approaches to Small Cell Lung Cancer: Imaging Implications.

Small cell lung cancer (SCLC) is a highly aggressive malignancy with exceptionally poor prognosis, comprising approximately 15% of lung cancers. Emerging knowledge of the molecular and genomic landscape of SCLC and recent successful clinical applications of new systemic agents have allowed for precision oncology treatment approaches. Imaging is essential for the diagnosis, staging, and treatment monitoring of patients with SCLC. The role of imaging is increasing with the approval of new treatment agents, including immune checkpoint inhibitors, which lead to novel imaging manifestations of response and toxicities. The purpose of this state-of-the-art review is to provide the reader with the latest information about SCLC, focusing on the subtyping of this malignancy (molecular characterization) and the emerging systemic therapeutic approaches and their implications for imaging. The review will also discuss the future directions of SCLC imaging, radiomics and machine learning.

Longitudinal imaging history in early identification of intimate partner violence.

OBJECTIVES: To describe the imaging findings of intimate partner violence (IPV)-related injury and to evaluate the role of longitudinal imaging review in detecting IPV. METHODS: Radiology studies were reviewed in chronological order and IPV-related injuries were recorded among 400 victims of any type of abuse (group 1) and 288 of physical abuse (group 2) from January 2013 to June 2018. The likelihood of IPV was assessed as low/moderate/high based on the review of (1) current and prior anatomically related studies only and (2) longitudinal imaging history consisting of all prior studies. The first radiological study date with moderate/high suspicion was compared to the self-reported date by the victim. RESULTS: A total of 135 victims (33.8%) in group 1 and 144 victims (50%) in group 2 demonstrated IPV-related injuries. Musculoskeletal injury was most common (58.2% and 44.5% in groups 1 and 2, respectively; most commonly lower/upper extremity fractures), followed by neurologic injury (20.9% and 32.9% in groups 1 and 2, respectively; most commonly facial injury). With longitudinal imaging history, radiologists were able to identify IPV in 31% of group 1 and 46.5% of group 2 patients. Amongst these patients, earlier identification by radiologists was provided compared to the self-reported date in 62.3% of group 1 (median, 64 months) and in 52.6% of group 2 (median, 69.3 months). CONCLUSIONS: Musculoskeletal and neurological injuries were the most common IPV-related injuries. Knowledge of common injuries and longitudinal imaging history may help IPV identification when victims are not forthcoming. KEY POINTS: • Musculoskeletal injuries were the most common type of IPV-related injury, followed by neurological injuries. • With longitudinal imaging history, radiologists were able to better raise the suspicion of IPV compared to the selective review of anatomically related studies only. • With longitudinal imaging history, radiologists were able to identify IPV earlier than the self-reported date by a median of 64 months in any type of abuse, and a median of 69.3 months in physical abuse.

Ovarian cancer reporting lexicon for computed tomography (CT) and magnetic resonance (MR) imaging developed by the SAR Uterine and Ovarian Cancer Disease-Focused Panel and the ESUR Female Pelvic Imaging Working Group.

OBJECTIVES: Imaging evaluation is an essential part of treatment planning for patients with ovarian cancer. Variation in the terminology used for describing ovarian cancer on computed tomography (CT) and magnetic resonance (MR) imaging can lead to ambiguity and inconsistency in clinical radiology reports. The aim of this collaborative project between Society of Abdominal Radiology (SAR) Uterine and Ovarian Cancer (UOC) Disease-focused Panel (DFP) and the European Society of Uroradiology (ESUR) Female Pelvic Imaging (FPI) Working Group was to develop an ovarian cancer reporting lexicon for CT and MR imaging. METHODS: Twenty-one members of the SAR UOC DFP and ESUR FPI working group, one radiology clinical fellow, and two gynecologic oncology surgeons formed the Ovarian Cancer Reporting Lexicon Committee. Two attending radiologist members of the committee prepared a preliminary list of imaging terms that was sent as an online survey to 173 radiologists and gynecologic oncologic physicians, of whom 67 responded to the survey. The committee reviewed these responses to create a final consensus list of lexicon terms. RESULTS: An ovarian cancer reporting lexicon was created for CT and MR Imaging. This consensus-based lexicon has 6 major categories of terms: general, adnexal lesion-specific, peritoneal carcinomatosis-specific, lymph node-specific, metastatic disease -specific, and fluid-specific. CONCLUSIONS: This lexicon for CT and MR imaging evaluation of ovarian cancer patients has the capacity to improve the clarity and consistency of reporting disease sites seen on imaging. KEY POINTS: • This reporting lexicon for CT and MR imaging provides a list of consensus-based, standardized terms and definitions for reporting sites of ovarian cancer on imaging at initial diagnosis or follow-up. • Use of standardized terms and morphologic imaging descriptors can help improve interdisciplinary communication of disease extent and facilitate optimal patient management. • The radiologists should identify and communicate areas of disease, including difficult to resect or potentially unresectable disease that may limit the ability to achieve optimal resection.

Interstitial Lung Abnormalities in Patients With Locally Advanced Esophageal Cancer: Prevalence, Risk Factors, and Clinical Implications.

PURPOSE: Interstitial lung abnormalities (ILAs) represent nondependent abnormalities on chest computed tomography (CT) indicating lung parenchymal damages due to inflammation and fibrosis. Interstitial lung abnormalities have been studied as a predictor of clinical outcome in lung cancer, but not in other thoracic malignancies. The present study investigated the prevalence of ILA in patients with esophageal cancer and identified risk factors and clinical implications of ILA in these patients. METHODS: The study included 208 patients with locally advanced esophageal cancer (median age, 65.6 years; 166 males, 42 females). Interstitial lung abnormality was scored on baseline CT scans before treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA). Clinical characteristics and overall survival were compared in patients with ILA (score 2) and others. RESULTS: An ILA was present in 14 of 208 patients (7%) with esophageal cancer on pretreatment chest CT. Patients with ILA were significantly older (median age, 69 vs 65, respectively; P = 0.011), had a higher number of pack-years of smoking ( P = 0.02), and more commonly had T4 stage disease ( P = 0.026) than patients with ILA score of 1 or 0. Interstitial lung abnormality on baseline scan was associated with a lack of surgical resection after chemoradiotherapy (7/14, 50% vs 39/194, 20% respectively; P = 0.016). Interstitial lung abnormality was not associated with overall survival (log-rank P = 0.75, Cox P = 0.613). CONCLUSIONS: An ILA was present in 7% of esophageal cancer patients, which is similar to the prevalence in general population and in smokers. Interstitial lung abnormality was strongly associated with a lack of surgical resection after chemoradiotherapy, indicating an implication of ILA in treatment selection in these patients, which can be further studied in larger cohorts.

Operational Definition Identifying Osteoporotic Vertebral Fractures in the Claims Database.

BACKGROUND: We analyzed the International Classification of Diseases, 10th edition (ICD-10) diagnostic codes, procedure codes, and radiographic image codes for vertebral fracture (VF) used in the database of Health Insurance Review and Assessment Service (HIRA) of Korea to establish a validated operational definition for identifying patients with osteoporotic VF in claims data. METHODS: We developed three operational definitions for detecting VFs using 9 diagnostic codes, 5 procedure codes and 4 imaging codes. Medical records and radiographs of 2,819 patients, who had primary and subordinated codes of VF between January 2016 and December 2016 at two institutions, were reviewed to detect true vertebral fractures. We evaluated the sensitivity and positive predictive value (PPV) of the operational definition in detecting true osteoporotic VF and obtained the receiver operating characteristic (ROC) curve. RESULTS: Among the 2,819 patients who had primary or secondary diagnosis codes for VF, 995 patients satisfied at least one of the criteria for the operational definition of osteoporotic VF. Of these patients, 594 were judged as having true fractures based on medical records and radiographic examinations. The sensitivity and PPV were 62.5 (95% confidence interval [CI], 59.4-65.6) and 59.7(95% CI, 56.6-62.8) respectively. In the receiver operating characteristic analysis, area under the curve (AUC) was 0.706 (95% CI, 0.688-0.724). CONCLUSION: Our findings demonstrate the validity of our operational definitions to identify VFs more accurately using claims data. This algorithm to identify VF is likely to be useful in future studies for diagnosing osteoporotic VF.

Facial injury patterns in victims of intimate partner violence.

PURPOSE: To evaluate the imaging findings of facial injuries in patients reporting intimate partner violence (IPV). METHODS: A retrospective review of radiology studies performed for 668 patients reporting IPV to our institution's violence prevention support program identified 96 patients with 152 facial injuries. Demographics, imaging findings, and clinical data obtained from a review of the electronic medical records (EMR) were analyzed to categorize injury patterns. RESULTS: The study cohort consisted of 93 women and 3 men with a mean age of 35 years (range 19-76; median 32). At the time of presentation, 57 (59.3%) patients reported IPV as the mechanism of injury. The most frequent site of injury was the midface, seen in 65 (67.7%) patients. The most common fracture sites were the nasal bones (45/152, 29.6%), followed by the mandible (17/152, 11.1%), and orbits (16/152, 10.5%). Left-sided injuries were more common (90/152; 59.2%). A vast majority of fractures (94.5%) showed minimal or no displacement. Over one-third of injuries (60/152, 39.4%) demonstrated only soft tissue swelling or hematoma without fracture. Associated injuries were seen most frequently in the upper extremity, occurring synchronously in 11 (11.4%) patients, and preceding the index facial injury in 20 (21%) patients. CONCLUSION: /advances in knowledge. The midface was the most frequent location of injury in victims of intimate partner violence, and the nasal bone was the most commonly fractured facial bone. Recognizing these injury patterns can help radiologists suspect IPV and prompt them to discuss the possibility of IPV with the clinical providers.

Exacerbation of Physical Intimate Partner Violence during COVID-19 Pandemic.

Background Intimate partner violence (IPV) is a global social and public health problem, but published literature regarding the exacerbation of physical IPV during the coronavirus disease 2019 (COVID-19) pandemic is lacking. Purpose To assess the incidence, patterns, and severity of injuries in IPV victims during the COVID-19 pandemic in 2020 compared with the prior 3 years. Materials and Methods The demographics, clinical presentation, injuries, and radiologic findings of patients reporting physical abuse arising from IPV during the statewide COVID-19 pandemic between March 11 and May 3, 2020, were compared with data from the same period for the past 3 years. Pearson χ2 and Fisher exact tests were used for analysis. Results A total of 26 victims of physical IPV from 2020 (mean age, 37 years ± 13 [standard deviation]; 25 women) were evaluated and compared with 42 victims of physical IPV (mean age, 41 years ± 15; 40 women) from 2017 to 2019. Although the overall number of patients who reported IPV decreased during the pandemic, the incidence of physical IPV was 1.8 times greater (95% CI: 1.1, 3.0; P = .01). The total number of deep injuries was 28 during 2020 versus 16 from 2017 to 2019; the number of deep injuries per victim was 1.1 during 2020 compared with 0.4 from 2017 to 2019 (P < .001). The incidence of high-risk abuse defined by mechanism was two times greater in 2020 (95% CI: 1.2, 4.7; P = .01). Patients who experienced IPV during the COVID-19 pandemic were more likely to be White; 17 (65%) victims in 2020 were White compared with 11 (26%) in the prior years (P = .007). Conclusion There was a higher incidence and severity of physical intimate partner violence (IPV) during the coronavirus disease 2019 (COVID-19) pandemic compared with the prior 3 years. These results suggest that victims of IPV delayed reaching out to health care services until the late stages of the abuse cycle during the COVID-19 pandemic. © RSNA, 2020.

Upper extremity injuries in the victims of intimate partner violence.

OBJECTIVES: To recognize most common patterns of upper extremity (UE) injuries in victims of Intimate Partner Violence (IPV). METHODS: Radiological review of 308 patients who reported physical IPV at our institution from January 2013 to June 2018, identified 55 patients with 88 unique UE injuries. Demographic data and injury patterns and associations were collected from the electronic medical records. RESULTS: The cohort included 49 females and 6 males (age 19-63, mean 38). At the time of injury, IPV was reported in 15/88 (17%) and IPV screening was documented for 22/88 (25%) injuries. There were 46 fractures, 8 dislocations or subluxations, and 34 isolated soft tissue injuries, most commonly involving the hand (56/88). Fractures most commonly involved the fingers (21/46, 46%) and the 5th digit (8/27, 30%). Medial UE fractures (5th digit, 4th digit) constituted 44% of hand and finger fractures (12/27) and 26% of all fractures (12/46). Comminuted and displaced fractures were rare (8/46, 17%). Head and face injuries were the most common concomitant injuries (9/22, 41%) and subsequent injuries (21/61, 35%). Of 12 patients with recurrent UE injuries, 6 had recurrent injuries of the same hand. Five of 6 non-acute fractures (83%) were of the hand. CONCLUSIONS: Hand and finger injuries are the most common UE injuries in patients with IPV, with finger being the most common site and medial hand the most common region of fracture. Repeated injuries involving the same site and a combination of medial hand and head or face injuries could indicate IPV. KEY POINTS: • Upper extremity injuries in victims of intimate partner violence are most commonly seen in the hand and fingers. • Fingers are the most common site of fracture and the medial hand is the most common region of fracture in the upper extremity in victims of intimate partner violence. • In intimate partner violence victims with upper extremity injuries, concomitant injuries and subsequent injuries are most commonly seen in the head and neck region.

Imaging patterns of lower extremity injuries in victims of intimate partner violence (IPV).

PURPOSE: To describe the pattern and distribution of lower extremity injuries in victims of intimate partner violence (IPV). MATERIALS AND METHODS: A retrospective radiological review of 688 patients reporting IPV to our institution's violence intervention and prevention program between January 2013 and June 2018 identified 88 patients with 154 lower extremity injuries. All lower extremity injuries visible on radiological studies were analyzed. Concomitant, recurrent, and associated injuries were also collected, in addition to the demographic data. RESULTS: The injuries consisted of 103 fractures, 46 soft tissue injuries, and 5 dislocations. The foot was the most common site of injury representing 39% (60/154) of total injuries, 48% (49/103) of fractures, 17% (8/46) of soft tissue injuries, and 3 dislocations. The ankle was the second most common site of injury representing 30% (47/154) of total injuries, 20% (21/103) of fractures, and 57% (26/46) of soft tissue injuries. Recurrent injuries of the lower extremity were seen in 30% (26/88) of victims who had 74 recurrent injuries. The most common sites of recurrent injury were the foot and ankle, representing 72% (53/74) of recurrent injuries. CONCLUSION: Recurrent injuries of the foot and ankle, synchronous craniofacial injuries, and upper extremity injuries in young women (<35 years) should prompt radiologists to consider IPV.

Incidence and characteristics of spinal injuries in the victims of intimate partner violence (IPV).

PURPOSE: To describe the incidence and patterns of the spinal injuries in the victims of physical IPV. MATERIALS AND METHODS: With institutional review board (IRB) approval, we retrospectively reviewed patients referred to our institution's domestic violence intervention and prevention program with a diagnosis directly related to physical abuse between January 2013 and June 2018. Electronic health records and radiology reports were reviewed for all patients. RESULTS: A total of 21/688 (3%) IPV patients with 41 vertebral injuries were identified. The study population comprised of 19/21 (90%) females. Median age of the included patients was 43 years with a range of 21-72 years. All vertebral injuries were AO type A spinal injuries. Upper lumbar spine (L1 and L2) was the most common level of injury followed by upper to mid-thoracic spine. The reported mechanism of the injury was IPV in 8/21 (38.0%), fall in 8/21(38.0%), and incidental in 5/21 (24.0%). Ten out of 21 (48%) patients had concomitant injuries, most commonly to the craniofacial region 5/21 (23%). Psychiatry history was positive in 17/21 (81%), and substance abuse was positive in 15/21 (71%) of the patients. CONCLUSION: Incidence of spinal injuries is relatively low in IPV with morphologic AO type A injury being the most common type of injury and the upper lumbar spine being the most common level of injury.

Identification of meat quality-related differentially methylated regions in the DNA of the longissimus dorsi muscle in pig.

The objective of this study was to investigate the association of DNA methylation with postmortem energy metabolism and the pH of the porcine longissimus dorsi muscle (LDM). Analysis of the DNA methylome of eight LDM samples (four pairs of the highest and lowest pH among littermates) identified a total of 3468 differentially methylated regions (DMRs) between high and low pH samples (p ≤ 0.001). Of DMRs, 45.3% co-mapped with quantitative trait loci known to be associated with meat pH and postmortem metabolism. Among the DMRs, 203 hyper-methylated regions (HR) and 190 hypo-methylated regions (HO) were identified for the high pH group compared to the low pH. Furthermore, 44 and 21 protein-coding genes contained HR and HO in their gene body, respectively. It was revealed that ENO1, GYS2, SDHC and DERA, which encode core enzymes in postmortem energy metabolism, contained HR or HO in their gene body.

M1b Disease in the 8th Edition of TNM Staging of Lung Cancer: Pattern of Single Extrathoracic Metastasis and Clinical Outcome.

BACKGROUND: The 8th edition of TNM staging of non-small cell lung cancer (NSCLC) has revised M classification and defined M1b disease with single extrathoracic metastasis, which is distinguished from M1c with multiple extrathoracic metastases. We investigated the prevalence, characteristics, and overall survival (OS) of M1b disease in patients with stage IV NSCLC. METHODS: The study reviewed the medical records and imaging studies of 567 patients with stage IV NSCLC to determine M stage using the 8th edition of TNM staging. Clinical characteristics and OS were compared according to M stages. RESULTS: Among 567 patients, 57 patients (10%) had M1b disease, whereas 119 patients (21%) had M1a disease and 391 patients (69%) had M1c disease. Squamous histology was more common in M1b (16%) than in M1a (6%) and M1c (6%; p = .03). The median OS of patients with M1b disease was 14.8 months, compared with 22.6 months for patients with M1a and 13.4 months for those with M1c disease (p < .0001). Significant OS differences of M1b compared with single-organ M1c and multiorgan M1c groups were noted (single-organ M1c vs. M1b: hazard ratio [HR], 1.49; p = .02; multiorgan M1c vs. M1b: HR, 1.57; p = .01) in multivariable analyses adjusting for smoking and systemic therapy types. Among patients with M1b disease, the brain was the most common site of single metastasis (28/57; 49%), followed by bone (16/57; 28%). Single brain metastasis was more frequently treated with local treatment (p < .0001). CONCLUSION: M1b disease was noted in 10% of patients with stage IV NSCLC. Squamous histology was more common in M1b group than others. The brain was the most common site of single metastasis and was often treated locally. IMPLICATIONS FOR PRACTICE: The newly defined group of M stage consists of a unique subset among patients with stage IV non-small cell lung cancer that can be studied further to optimize treatment approaches.

Imaging of Precision Therapy for Lung Cancer: Current State of the Art.

Advances in characterization of molecular and genomic abnormalities specific to lung cancer have made precision therapy the current standard of care for lung cancer treatment. This article will provide a cutting-edge review of imaging of lung cancer in the current era of precision medicine. The focus of the article includes (a) an update on the recent advances in precision therapy for non-small cell lung cancer and their implications on imaging; (b) molecular and genomic biomarkers and pitfalls of image interpretations for lung cancer precision therapy; and (c) review of the current approaches and future directions of precision imaging for lung cancer, emphasizing emerging observations in longitudinal tumor kinetics, radiomics, and molecular and functional imaging. The article is designed to help radiologists to remain up to date in the rapidly evolving world of lung cancer therapy and serve as key members of multidisciplinary teams caring for these patients.

Imaging of Histiocytosis in the Era of Genomic Medicine.

Histiocytosis describes a group of diseases that have long been considered enigmatic in the history of medicine. Recently, novel genomic analyses have identified somatic oncogenic driver mutations responsible for the pathogenesis of these entities. These discoveries have led to the recharacterization of histiocytoses as neoplastic diseases and have opened a new era of precision medicine approaches for treatment. The histiocytic disorders demonstrate a variety of imaging manifestations involving multiple organ systems, and radiologists play a major role in diagnosis and monitoring. An up-to-date knowledge of the novel genomic discoveries and their implications is essential for radiologists to understand the new approaches to treating histiocytic disorders and to contribute as key members of the multidisciplinary treatment team. This article provides a cutting-edge review of the novel concepts in histiocytosis, with a focus on recent genomic discoveries and precision medicine approaches to treating the disease, and describes imaging manifestations with correlative histologic and genomic findings, with an emphasis on adult-onset cases and uncommon subtypes. ©RSNA, 2018.

Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice.

Free cholesterol (FC) accumulation in the liver is an important pathogenic mechanism of nonalcoholic steatohepatitis (NASH). Plasmalogens, key structural components of the cell membrane, act as endogenous antioxidants and are primarily synthesized in the liver. However, the role of hepatic plasmalogens in metabolic liver disease is unclear. In this study, we found that hepatic levels of docosahexaenoic acid (DHA)-containing plasmalogens, expression of glyceronephosphate O-acyltransferase (Gnpat; the rate-limiting enzyme in plasmalogen biosynthesis), and expression of Pparα were lower in mice with NASH caused by accumulation of FC in the liver. Cyclodextrin-induced depletion of FC transactivated Δ-6 desaturase by increasing sterol regulatory element-binding protein 2 expression in cultured hepatocytes. DHA, the major product of Δ-6 desaturase activation, activated GNPAT, thereby explaining the association between high hepatic FC and decreased Gnpat expression. Gnpat small interfering RNA treatment significantly decreased peroxisome proliferator-activated receptor α (Pparα) expression in cultured hepatocytes. In addition to GNPAT, DHA activated PPARα and increased expression of Pparα and its target genes, suggesting that DHA in the DHA-containing plasmalogens contributed to activation of PPARα. Accordingly, administration of the plasmalogen precursor, alkyl glycerol (AG), prevented hepatic steatosis and NASH through a PPARα-dependent increase in fatty acid oxidation. Gnpat+/- mice were more susceptible to hepatic lipid accumulation and less responsive to the preventive effect of fluvastatin on NASH development, suggesting that endogenous plasmalogens prevent hepatic steatosis and NASH. CONCLUSION: Increased hepatic FC in animals with NASH decreased plasmalogens, thereby sensitizing animals to hepatocyte injury and NASH. Our findings uncover a novel link between hepatic FC and plasmalogen homeostasis through GNPAT regulation. Further study of AG or other agents that increase hepatic plasmalogen levels may identify novel therapeutic strategies against NASH. (Hepatology 2017;66:416-431).

Characterization and functional inferences of a genome-wide DNA methylation profile in the loin (longissimus dorsi) muscle of swine.

OBJECTIVE: DNA methylation plays a major role in regulating the expression of genes related to traits of economic interest (e.g., weight gain) in livestock animals. This study characterized and investigated the functional inferences of genome-wide DNA methylome in the loin (longissimus dorsi) muscle (LDM) of swine. METHODS: A total of 8.99 Gb methylated DNA immunoprecipitation sequence data were obtained from LDM samples of eight Duroc pigs (four pairs of littermates). The reference pig genome was annotated with 78.5% of the raw reads. A total of 33,506 putative methylated regions (PMR) were identified from methylated regions that overlapped at least two samples. RESULTS: Of these, only 3.1% were commonly observed in all eight samples. DNA methylation patterns between two littermates were as diverse as between unrelated individuals (p = 0.47), indicating that maternal genetic effects have little influence on the variation in DNA methylation of porcine LDM. The highest density of PMR was observed on chromosome 10. A major proportion (47.7%) of PMR was present in the repeat regions, followed by introns (21.5%). The highest conservation of PMR was found in CpG islands (12.1%). These results show an important role for DNA methylation in species- and tissue-specific regulation of gene expression. PMR were also significantly related to muscular cell development, cell-cell communication, cellular integrity and transport, and nutrient metabolism. CONCLUSION: This study indicated the biased distribution and functional role of DNA methylation in gene expression of porcine LDM. DNA methylation was related to cell development, cell-cell communication, cellular integrity and transport, and nutrient metabolism (e.g., insulin signaling pathways). Nutritional and environmental management may have a significant impact on the variation in DNA methylation of porcine LDM.

Analytical Evaluation of Portable and Simple FREND Fluorescent Immunoassay for Rapid Quantification of Thyroid-Stimulating Hormone and Free Thyroxine.

BACKGROUND: The FREND™ thyroid stimulating hormone (TSH) and free thyroxine (FT4) assays are newly developed rapid quantitative immunoassays utilizing antibody-conjugated fluorescent nanoparticles in a microfluidic flow system. The FREND system is a simple and portable fluorescence reader with rapid turnaround time (4 - 10 minutes). METHODS: The analytical sensitivity, precision, and linearity were evaluated. For the method comparison, FREND TSH and FT4 levels were compared with those from ADVIA Centaur XP and Abbott ARCHITECT i2000. RESULTS: The limit of detection was 0.047 mIU/L and 5.031 pmol/L in FREND TSH and FT4 assays. FREND system had acceptable linearity and precision of  10% across the assay range (0.05 - 25.0 mIU/L for TSH and 1.4 - 96.8 pmol/L for FT4). The functional sensitivity was 0.057 mIU/L for the TSH assay and 4.644 pmol/L for the FT4 assay. Passing-Bablok regression analysis of TSH data showed good correlation among the three assays. For the FT4 assay, FREND FT4 displayed good correlation with the ARCHITECT FT4 assay, but the intercepts and slopes significantly differed between FREND and Centaur results: [FREND FT4] = 4.799 + 0.600 [Centaur FT4]. CONCLUSIONS: The analytical performance of FREND TSH and FT4 assays was satisfactory for use in the clinical laboratory. The FREND FT4 assay was in concordance with ARCHITECT FT4, but it needs further investigation and harmonization.