Genome-wide signatures of male-mediated migration shaping the Indian gene pool.

Multiple questions relating to contributions of cultural and demographical factors in the process of human geographical dispersal remain largely unanswered. India, a land of early human settlement and the resulting diversity is a good place to look for some of the answers. In this study, we explored the genetic structure of India using a diverse panel of 78 males genotyped using the GenoChip. Their genome-wide single-nucleotide polymorphism (SNP) diversity was examined in the context of various covariates that influence Indian gene pool. Admixture analysis of genome-wide SNP data showed high proportion of the Southwest Asian component in all of the Indian samples. Hierarchical clustering based on admixture proportions revealed seven distinct clusters correlating to geographical and linguistic affiliations. Convex hull overlay of Y-chromosomal haplogroups on the genome-wide SNP principal component analysis brought out distinct non-overlapping polygons of F*-M89, H*-M69, L1-M27, O2a-M95 and O3a3c1-M117, suggesting a male-mediated migration and expansion of the Indian gene pool. Lack of similar correlation with mitochondrial DNA clades indicated a shared genetic ancestry of females. We suggest that ancient male-mediated migratory events and settlement in various regional niches led to the present day scenario and peopling of India.

The Accomplishments and Legacy of Saul Hertz, MD.

The early history of the use of radioactive iodine (RAI) is complicated and interesting, and also difficult to discover, especially since several histories have presented inaccurate content. This article is a comprehensive review of the accomplishments of Saul Hertz. Extensive use of primary-source verification has clarified several issues, including the question of whether Hertz alone conceived and asked the pivotal question: "Could iodine be made radioactive artificially?"; on what date RAI was first used to treat hyperthyroidism; and why 2 articles on the first use of RAI for treatment of hyperthyroidism, from 2 different sets of authors from the same department of the same institution, appeared adjacent to each other in the same issue of the Journal of the American Medical Association in 1946. Our review also chronicles several major challenges that Hertz overcame to produce his pivotal work. Hertz was clearly the originator and a visionary of RAI therapy in benign and malignant thyroid disease. We believe he can be considered one of the fathers of nuclear medicine. Hertz's paradigm-changing work was a pivotal medical discovery of the 20th century. The legacy of Hertz continues while the application of RAI therapy continues to evolve. RAI therapy remains the preferred treatment in most situations for autonomous nodules and toxic multinodular goiter and remains a safe and effective treatment for Graves disease after more than 80 y of global clinical use. RAI treatment of differentiated thyroid cancer remains a first-line treatment for most patients after surgery, especially for those with intermediate- or high-risk disease.

A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, the Society of Nuclear Medicine and Molecular Imaging on Current Diagnostic and Theranostic Approaches in the Management of Thyroid Cancer.

Background: The American Thyroid Association (ATA), the European Association of Nuclear Medicine, the European Thyroid Association, and the Society of Nuclear Medicine and Molecular Imaging have established an intersocietal working group to address the current controversies and evolving concepts in thyroid cancer management and therapy. The working group annually identifies topics that may significantly impact clinical practice and publishes expert opinion articles reflecting intersocietal collaboration, consensus, and suggestions for further research to address these important management issues. Summary: In 2019, the intersocietal working group identified the following topics for review and interdisciplinary discussion: (i) perioperative risk stratification, (ii) the role of diagnostic radioactive iodine (RAI) imaging in initial staging, and (iii) indicators of response to RAI therapy. Conclusions: The intersocietal working group agreed that (i) initial patient management decisions should be guided by perioperative risk stratification that should include the eighth edition American Joint Committee on Cancer staging system to predict disease specific mortality, the modified 2009 ATA risk stratification system to estimate structural disease recurrence, with judicious incorporation of molecular theranostics to further refine management recommendations; (ii) diagnostic RAI scanning in ATA intermediate risk patients should be utilized selectively rather than being considered mandatory or not necessary for all patients in this category; and (iii) a consistent semiquantitative reporting system should be used for response evaluations after RAI therapy until a reproducible and clinically practical quantitative system is validated.

Management of Diabetes Mellitus Before 18F-Fluorodeoxyglucose PET/CT: A Nationwide Patient-Centered Assessment of Approaches to Examination Preparation.

PURPOSE: The aim of this study was to perform, from the patient's point of view, a nationwide assessment of nuclear medicine practices regarding diabetic management before 18F-fluorodeoxyglucose (FDG) PET/CT for oncologic indications. METHODS: This prospective observational study was exempt from institutional review board oversight. Sixty-five nuclear medicine scheduling lines (33 academic, 32 private practice, 12-17 in each of the five US regions) were called using a prewritten script under the guise of a nonexpert patient's family member about scheduling a patient with diabetes with "cancer" for FDG PET/CT. Each center was called three times on three different days. The following data were collected: (1) blood glucose threshold for rescheduling an examination, (2) when or if to stop various medications, (3) fasting requirements, and (4) time-of-day scheduling preferences. Withheld information was not specifically requested. Descriptive statistics were calculated. RESULTS: There were 195 phone calls (mean duration, 2.9 min; range, 2-6 min). Relevant information was often withheld; withholding rates were as follows: blood glucose threshold, 71% (138 of 195); short-acting insulin instructions, 30% (59 of 195); long-acting insulin instructions, 99% (193 of 195); metformin instructions, 88% (179 of 195); fasting duration, 37% (72 of 195); and time-of-day scheduling preference, 91% (177 of 195). Mean provided data were as follows: blood glucose threshold, 195 mg/dL (range, 150-210 mg/dL); short-acting insulin withholding, 4.9 hours (range, 4-8 hours); long-acting insulin withholding, 12 hours (range, 12-24 hours); fasting duration, 5 hours (range, 4-8 hours); and preferred examination time, 91% (177 of 195). When specified (n = 18), morning scheduling was preferred (8% [15 of 195] versus 2% [3 of 195]). CONCLUSIONS: Diabetes-specific information is commonly withheld by nuclear medicine call centers throughout the United States when discussing oncologic FDG PET/CT despite local and national policies indicating its importance.

A Critical Assessment of the Linear No-Threshold Hypothesis: Its Validity and Applicability for Use in Risk Assessment and Radiation Protection.

The Society of Nuclear Medicine and Molecular Imaging convened a task group to examine the evidence for the risk of carcinogenesis from low-dose radiation exposure and to assess evidence in the scientific literature related to the overall validity of the linear no-threshold (LNT) hypothesis and its applicability for use in risk assessment and radiation protection. In the low-dose and dose-rate region, the group concluded that the LNT hypothesis is invalid as it is not supported by the available scientific evidence and, instead, is actually refuted by published epidemiology and radiation biology. The task group concluded that the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region.

Controversies, Consensus, and Collaboration in the Use of 131I Therapy in Differentiated Thyroid Cancer: A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association.

BACKGROUND: Publication of the 2015 American Thyroid Association (ATA) management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer was met with disagreement by the extended nuclear medicine community with regard to some of the recommendations related to the diagnostic and therapeutic use of radioiodine (131I). Because of these concerns, the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging declined to endorse the ATA guidelines. As a result of these differences in opinion, patients and clinicians risk receiving conflicting advice with regard to several key thyroid cancer management issues. SUMMARY: To address some of the differences in opinion and controversies associated with the therapeutic uses of 131I in differentiated thyroid cancer constructively, the ATA, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association each sent senior leadership and subject-matter experts to a two-day interactive meeting. The goals of this first meeting were to (i) formalize the dialogue and activities between the four societies; (ii) discuss indications for 131I adjuvant treatment; (iii) define the optimal prescribed activity of 131I for adjuvant treatment; and (iv) clarify the definition and classification of 131I-refractory thyroid cancer. CONCLUSION: By fostering an open, productive, and evidence-based discussion, the Martinique meeting restored trust, confidence, and a sense of collegiality between individuals and organizations that are committed to optimal thyroid disease management. The result of this first meeting is a set of nine principles (The Martinique Principles) that (i) describe a commitment to proactive, purposeful, and inclusive interdisciplinary cooperation; (ii) define the goals of 131I therapy as remnant ablation, adjuvant treatment, or treatment of known disease; (iii) describe the importance of evaluating postoperative disease status and multiple other factors beyond clinicopathologic staging in 131I therapy decision making; (iv) recognize that the optimal administered activity of 131I adjuvant treatment cannot be definitely determined from the published literature; and (v) acknowledge that current definitions of 131I-refractory disease are suboptimal and do not represent definitive criteria to mandate whether 131I therapy should be recommended.

The BEIR VII Estimates of Low-Dose Radiation Health Risks Are Based on Faulty Assumptions and Data Analyses: A Call for Reassessment.

The 2006 National Academy of Sciences Biologic Effects of Ionizing Radiation (BEIR) VII report is a well-recognized and frequently cited source on the legitimacy of the linear no-threshold (LNT) model-a model entailing a linear and causal relationship between ionizing radiation and human cancer risk. Linearity means that all radiation causes cancer and explicitly excludes a threshold below which radiogenic cancer risk disappears. However, the BEIR VII committee has erred in the interpretation of its selected literature; specifically, the in vitro data quoted fail to support LNT. Moreover, in vitro data cannot be considered as definitive proof of cancer development in intact organisms. This review is presented to stimulate a critical reevaluation by a BEIR VIII committee to reassess the validity, and use, of LNT and its derived policies.

ACR Appropriateness Criteria® Shoulder Pain-Traumatic.

Traumatic shoulder pain is pain directly attributed to a traumatic event, either acute or chronic. This pain may be the result of either fracture (the clavicle, scapula, or proximal humerus) or soft-tissue injury (most commonly of the rotator cuff, acromioclavicular ligaments, or labroligamentous complex). Imaging assessment of traumatic shoulder pain begins with conventional radiography and, depending on physical examination findings, will require MRI or MR arthrography for assessment of soft-tissue injuries and CT for delineation of fracture planes. Ultrasound excels in assessment of rotator cuff injuries but has limited usefulness for assessment of the deep soft-tissues. CT angiography and conventional arteriography are helpful for assessment of vascular injury, and bone scintigraphy can be used in assessment of complex regional pain syndrome after traumatic shoulder injury. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Focal hepatic activity during ventilation-perfusion scintigraphy due to systemic-portal shunt due to superior vena cava obstruction from histoplasmosis-induced fibrosing mediastinitis.

A 59-year-old woman with a history of fibrosing mediastinitis secondary to histoplasmosis diagnosed on mediastinoscopy presented with dyspnea. A ventilation-perfusion scan demonstrated decreased perfusion to the entire right lung. In addition, the perfusion images demonstrated focal abnormal activity in part of the liver. On computed tomography of the chest, there was significant soft tissue opacification in the mediastinum occluding the right pulmonary artery, with passage of the injected contrast via collateral vessels to the liver. The main collateral pathway was via the right internal thoracic vein and the umbilical vein. Pulmonary angiography confirmed complete occlusion of the right pulmonary artery.

Role of PET/CT for precision medicine in lung cancer: perspective of the Society of Nuclear Medicine and Molecular Imaging.

This article discusses the role of PET/CT in contributing to precision medicine in lung cancer, and provides the perspective of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) on this process. The mission and vision of SNMMI are listed, along with the guidance provided by SNMMI to promote best practice in precision medicine. Basic principles of PET/CT are presented. An overview of the use of PET/CT imaging in lung cancer is discussed. In lung cancer patients, PET/CT is vitally important for optimal patient management. PET/CT is essential in determining staging and re-staging of disease, detecting recurrent or residual disease, evaluating response to therapy, and providing prognostic information. PET/CT is also critically important in radiation therapy planning by determining the extent of active disease, including an assessment of functional tumor volume. The current approach in tumor imaging is a significant advance over conventional imaging. However, recent advances suggest that therapeutic response criteria in the near future will be based on metabolic characteristics and will include the evaluation of biologic characteristics of tumors to further enhance the effectiveness of precision medicine in lung cancer, producing improved patient outcomes with less morbidity.

ACR Appropriateness Criteria® Osteoporosis and Bone Mineral Density.

Osteoporosis is a considerable public health risk, with 50% of women and 20% of men >50 years of age experiencing fracture, with mortality rates of 20% within the first year. Dual x-ray absorptiometry (DXA) is the primary diagnostic modality by which to screen women >65 years of age and men >70 years of age for osteoporosis. In postmenopausal women <65 years of age with additional risk factors for fracture, DXA is recommended. Some patients with bone mineral density above the threshold for treatment may qualify for treatment on the basis of vertebral body fractures detected through a vertebral fracture assessment scan, a lateral spine equivalent generated from a commercial DXA machine. Quantitative CT is useful in patients with advanced degenerative bony changes in their spines. New technologies such as trabecular bone score represent an emerging role for qualitative assessment of bone in clinical practice. It is critical that both radiologists and referring providers consider osteoporosis in their patients, thereby reducing substantial morbidity, mortality, and cost to the health care system. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Suspected Osteomyelitis, Septic Arthritis, or Soft Tissue Infection (Excluding Spine and Diabetic Foot).

Infection of the musculoskeletal system is a common clinical problem. Differentiating soft tissue from osseous infection often determines the appropriate clinical therapeutic course. Radiographs are the recommend initial imaging examination, and although often not diagnostic in acute osteomyelitis, can provide anatomic evaluation and alternative diagnoses influencing subsequent imaging selection and interpretation. MRI with contrast is the examination of choice for the evaluation of suspected osteomyelitis, and MRI, CT, and ultrasound can all be useful in the diagnosis of soft tissue infection. CT or a labeled leukocyte scan and sulfur colloid marrow scan combination are alternative options if MRI is contraindicated or extensive artifact from metal is present. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Chronic Extremity Joint Pain-Suspected Inflammatory Arthritis.

Evaluation for suspected inflammatory arthritis as a cause for chronic extremity joint pain often relies on imaging. This review first discusses the characteristic osseous and soft tissue abnormalities seen with inflammatory arthritis and how they may be imaged. It is essential that imaging results are interpreted in the context of clinical and serologic results to add specificity as there is significant overlap of imaging findings among the various types of arthritis. This review provides recommendations for imaging evaluation of specific types of inflammatory arthritis, including rheumatoid arthritis, seronegative spondyloarthropathy, gout, calcium pyrophosphate dihydrate disease (or pseudogout), and erosive osteoarthritis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Chronic Back Pain Suspected Sacroiliitis-Spondyloarthropathy.

Inflammatory sacroiliitis or the seronegative axial spondyloarthropathies often presents as back pain or sacroiliac joint pain of more than 3-month duration with inflammatory symptoms and typically in patients younger than 45 years of age. Imaging plays an important role in diagnosis and disease monitoring. This article addresses the appropriate sequence of initial imaging for evaluation of a suspected spondyloarthropathy, the imaging follow-up of treatment response and the special considerations for imaging of trauma in patients with ankylosis of the spine. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.