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We propose optimizing dynamic treatment regimes using sequential structural mean models in the treatment of acute myelogenous leukemia (AML) involving multiple stages of chemotherapy. The inverse-probability-of-treatment-weighted (IPTW) or g-computation estimator is used at each stage to estimate what we call the ‘preliminary’ optimal treatment regime, given patient information up to the current stage and prior treatment assignment. Essentially, this tailors the optimal treatment assignment at the current stage and provides an optimal strategy for the remaining stages given the information currently available. We compare this method for optimizing a dynamic treatment regime to Q-learning. Additionally, we use a two-step prescriptive variable selection procedure that supports the tailored optimization of dynamic treatment regimes using structural mean models by eliminating from consideration any suboptimal treatment regimes and sifting out the covariates that prescribe the optimal treatment regimes. The weighting techniques of the g-computation and IPTW estimators allow an appropriate comparison of the treatments at each stage, while avoiding the non-regularity issues associated with backwards induction techniques. This facilitates standard large sample theory and the bootstrap for constructing confidence intervals and performing hypothesis tests. Though applied to a specific two-stage sequential multiple assignment randomized trial (SMART) design, the methods described herein are easily generalized to other SMART designs and applications.

IMPORTANCE: Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized. OBJECTIVE: To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening.Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort). EXPOSURES: Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis. MAIN OUTCOMES AND MEASURES: The ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex. RESULTS: A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002). CONCLUSIONS AND RELEVANCE: In this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.

Background: Peptide receptor radionuclide therapy with 177Lu-dotatate is a novel therapy for metastatic neuroendocrine cancers. It undergoes reabsorption at the proximal tubule; after the breakdown of the peptide fragment, 177Lu is retained and continues its decay process exposing the nephron to continuous low dose radiation. Pivotal NETTER-1 trial did not include patients with eGFR <50 and so its effects in CKD patients is not known.Methods: We performed a retrospective chart review of all consecutive adult patients that received 177Lu-dotatate over 1 year at Mayo Clinic, Rochester. We analyzed renal and hematological laboratory data obtained prior to each of four treatment cycles and at 3- and 6-month post completion of all treatment. We defined CKD as eGFR <60 ml/min and AKI as creatinine increase of ⩾0.3 from baseline by AKIN criteria.Results: Overall 86 patients were included in the study with 39 (45%) with known CKD. About three patients had CKD, four with eGFR of 20–30 ml/min. About 4 (4.6%) patients had AKI and the predominant cause being hypotension. Among the CKD patients the average eGFR improved after the first cycle of PRRT therapy from baseline of 49 (13) to 53.5 (17) ml/min (p= 0.01) with no significant decline of renal function noted at 3- and 6-months post treatment follow up. Rate of thrombocytopenia and leukopenia were significantly more in the CKD patients starting even after single treatment. No drug dose correlation was noted.Conclusion: Patients with CKD are at a higher risk of hematological toxicity especially with thrombocytopenia and require close monitoring and ongoing dose adjustment. Ongoing safety studies to assess the long-term impact of 177Lu-dotatate on the kidney are needed.

An approach to the use of lutetium 177 gallium 68 tetraazacyclododecane tetraacetic acid octreotate peptide receptor radionuclide therapy (PRRT), an effective treatment for advanced gastroenteropancreatic neuroendocrine tumors, is presented. A systematic workflow and engagement of multidisciplinary teams can promote a PRRT program for delivery of efficient treatments and for treatment of patients with complex medical histories.

Pancreatic neoplasms have high morbidity and dismal prognosis. Substantial progress in translational research and advances in scanner technology have resulted in rapid integration of molecular radionuclide imaging of pancreatic neoplasms into mainstream clinical practice. Metabolic imaging with 18F-FDG PET has extensive utility in the staging, assessment of treatment response, and follow-up of pancreatic ductal adenocarcinoma. Integrated PET/MRI has the potential to further expand this utility and lead to innovative applications. Somatostatin receptor PET imaging has had a profound effect on the evaluation and management of pancreatic neuroendocrine tumours. Peptide receptor radionuclide therapy is a new frontier in personalised medicine because it customises treatment to the unique biological features of a patient and the molecular signature of the patient's tumour. Further investigation is needed to optimise use of advanced molecular imaging techniques and novel radiotracers to achieve better outcomes for patients with pancreatic neoplasms.

Neoadjuvant treatment might increase resectability of thymic epithelial tumors (TETs). No standardized pathologic grading scheme for tumor response is available. Also, it is unclear whether radiologic treatment response can predict pathologic response.

Evaluate the quantitative, subjective (Deauville score [DS]) and reader agreement differences between standard ordered subset expectation maximization (OSEM) and Bayesian penalized likelihood (BPL) positron emission tomography (PET) reconstruction methods. A retrospective review of 104 F-18 fluorodeoxyglucose PET/computed tomography (CT) exams among 52 patients with diffuse large B-cell lymphoma. An unblinded radiologist moderator reviewed both BPL and OSEM PET/CT exams. Four blinded radiologists then reviewed the annotated cases to provide a visual DS for each annotated lesion. Significant (P < .001) differences in BPL and OSEM PET methods were identified with greater standard uptake value (SUV) maximum and SUV mean for BPL. The DS was altered in 25% of cases when BPL and OSEM were reviewed by the same radiologist. Interobserver DS agreement was higher for OSEM (>1 cm lesion = 0.89 and ≤1 cm lesion = 0.84) compared to BPL (>1 cm lesion = 0.85 and ≤1 cm lesion = 0.81). Among the 4 readers, average intraobserver visual DS agreement between OSEM and BPL was 0.67 for lesions >1cm and 0.4 for lesions ≤1 cm. F-18 Fluorodeoxyglucose PET/CT of diffuse large B-cell lymphoma reconstructed with BPL has higher SUV values, altered DSs and reader agreement when compared to OSEM. This report finds volumetric PET measurements such as metabolic tumor volume to be similar between BPL and OSEM PET reconstructions. Efforts such as adoption of European Association Research Ltd accreditation should be made to harmonize PET data with an aim at balancing the need for harmonization and sensitivity for lesion detection.

IMPORTANCE: Transthyretin cardiac amyloidosis (also known as ATTR cardiac amyloidosis) is an increasingly recognized cause of heart failure with preserved ejection fraction. In single-center studies, technetium 99m pyrophosphate (Tc 99m PYP) cardiac imaging noninvasively detects ATTR cardiac amyloidosis, but the accuracy of this technique in a multicenter study and the association of Tc 99m PYP myocardial uptake with survival are unknown. OBJECTIVE: To assess Tc 99m PYP cardiac imaging as a diagnostic tool for ATTR cardiac amyloidosis and its association with survival in a multicenter study. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study performed at 3 academic specialty centers for cardiac amyloidosis in the United States in which 229 participants were evaluated for cardiac amyloidosis and also underwent Tc 99m PYP cardiac imaging. The date of analysis and final confirmation from the statistician was May 4, 2016. EXPOSURE: Tc 99m PYP cardiac imaging for detection of ATTR cardiac amyloidosis. MAIN OUTCOMES AND MEASURES: Retention of Tc 99m PYP in the heart was assessed using both a semiquantitative visual score (range, 0 [no uptake] to 3 [uptake greater than bone]) and a quantitative heart to contralateral (H/CL) ratio. The H/CL ratio was calculated as total counts in a region of interest over the heart divided by background counts in an identical size region of interest over the contralateral chest. The outcome measured was time to death after Tc 99m PYP imaging. RESULTS: Tc 99m PYP imaging of 171 participants (121 with ATTR cardiac amyloidosis and 50 with non-ATTR cardiac amyloidosis [34 with AL amyloidosis and 16 with nonamyloid heart failure with preserved ejection fraction]; 86% male; median [IQR] age, 73 years [65-79 years]) demonstrated 91% sensitivity and 92% specificity for detecting ATTR cardiac amyloidosis with an area under the curve of 0.960 (95% CI, 0.930-0.981). Univariable and multivariable Cox proportional hazards regression analyses among participants with ATTR cardiac amyloidosis showed that an H/CL ratio of 1.6 or greater predicted worse survival (hazard ratio, 3.911 [95% CI, 1.155-13.247]; P = .03 for univariable analysis and 7.913 [95% CI, 1.679-37.296]; P = .01 for multivariable analysis). In Kaplan-Meier analysis over a 5-year follow-up period, survival was significantly worse if the H/CL ratio was 1.6 or greater rather than less than 1.6 (log-rank P = .02). CONCLUSIONS AND RELEVANCE: In this multicenter study, Tc 99m PYP cardiac imaging conferred a high level of sensitivity and specificity for differentiation of patients with ATTR cardiac amyloidosis (irrespective of genotype) from patients with AL cardiac amyloidosis and patients with nonamyloid heart failure with preserved ejection fraction. An H/CL ratio of 1.6 or greater was associated with worse survival among patients with ATTR cardiac amyloidosis. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, Tc 99m PYP may be of diagnostic and prognostic importance.

Familiarity with the spectrum of FDG-avid benign articular and periarticular processes increases diagnostic accuracy and confidence, ensures appropriate follow-up imaging, and guides appropriate therapy.

11C-choline PET/CT is a powerful tool for detecting locally recurrent or metastatic prostate cancer, but it is important to be aware that not all 11C-choline-avid lesions are due to prostate cancer, as detection of secondary lesions or malignancies can significantly alter patient management; therefore, it is essential for interpreting radiologists to be familiar with such findings so that the proper follow-up can be recommended.

The respiratory system is often affected by complications of immunodeficiency, typically manifesting clinically as acute respiratory illness. Ongoing literature reviews regarding the appropriateness of imaging in these patients are critical, as advanced medical therapies including stem cell transplantation, chemotherapy, and immunosuppressive therapies for autoimmune disease continue to keep the population of immunosuppressed patients in our health care system high. This ACR Appropriateness Criteria®topic describes clinical scenarios of acute respiratory illness in immunocompromised patients with cough, dyspnea, chest pain, and fever, in those with negative, equivocal, or nonspecific findings on chest radiography, in those with multiple, diffuse, or confluent opacities on chest radiography, and in those in whom noninfectious disease is suspected. The use of chest radiography, chest computed tomography, transthoracic needle biopsy, and nuclear medicine imaging is discussed in the context of these clinical scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or is not definitive, expert opinion may be used to recommend imaging or treatment.

Pulmonary nodules are commonly detected in computed tomography (CT) chest screening of a high-risk population. The specific visual or quantitative features on CT or other modalities can be used to characterize the likelihood that a nodule is benign or malignant. Visual features on CT such as size, attenuation, location, morphology, edge characteristics, and other distinctive “signs” can be highly suggestive of a specific diagnosis and, in general, be used to determine the probability that a specific nodule is benign or malignant. Change in size, attenuation, and morphology on serial follow-up CT, or features on other modalities such as nuclear medicine studies or MRI, can also contribute to the characterization of lung nodules. Imaging analytics can objectively and reproducibly quantify nodule features on CT, nuclear medicine, and magnetic resonance imaging. Some quantitative techniques show great promise in helping to differentiate benign from malignant lesions or to stratify the risk of aggressive versus indolent neoplasm. In this article, we (1) summarize the visual characteristics, descriptors, and signs that may be helpful in management of nodules identified on screening CT, (2) discuss current quantitative and multimodality techniques that aid in the differentiation of nodules, and (3) highlight the power, pitfalls, and limitations of these various techniques.

The advances in PET scanning for thoracic diseases that are deemed most likely to have clinical impact in the near-term future are highlighted in this article. We predict that the current practice of medicine will continue to embrace the power of molecular imaging and specifically PET scanning. 18F-fluorodeoxyglucose-PET scanning will continue to evolve and will expand into imaging of inflammatory disorders. New clinically available PET scan radiotracers, such as PET scan versions of octreotide and amyloid imaging agents, will expand PET imaging into different disease processes. Major improvements in thoracic PET/CT imaging technology will become available, including fully digital silicone photomultipliers and Bayesian penalized likelihood image reconstruction. These will result in significant improvements in image quality, improving the evaluation of smaller lung nodules and metastases and allowing better prediction of prognosis. The birth of clinical PET/MRI scan will add new imaging opportunities, such as better PET imaging of pleural diseases currently obscured by complex patient motion.

We present a case of both 18F-FDG and 18F-florbetapir uptake in a biopsy-confirmed immunoglobulin light chain (AL) amyloidosis involving the peripheral nerves. AL amyloidosis is the most common cause of acquired amyloid polyneuropathy, manifesting with both sensorimotor and autonomic neuronal dysfunction. Given the overlapping MRI and FDG PET/CT appearances of several different causes of peripheral neuropathy, 18F-florbetapir PET/CT provides another potential tool in the imaging algorithm of these patients and may guide targeted fascicular biopsy for pathologic confirmation.

Occupational lung disease is a category of disease entities characterized by a reaction of the lung parenchyma to inhaled aerosolized particles found in the environment. This document summarizes the imaging appropriateness data for silicosis, coal worker pneumoconiosis, and asbestosis. The main points of the document are that computed tomography is more sensitive than radiography, computed tomography without contrast generally suffices for evaluation, and fluorodeoxyglucose-positron emission tomography may have utility in patients with mesothelioma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

An aluminogermanate, Na₂Al₂Ge₃O₁₀·2H₂O (NaAlGe-NAT), possessing the natrolite topology has been synthesized under hydrothermal conditions at 423 K from sodium- and tetramethylammonium-containing gels. Room temperature single crystal X-ray diffraction data indicate a tetragonal unit cell with a = 13.314(2) and c = 6.819(2) Å, and space group I4¯2d. NaAlGe-NAT displays complete disorder of aluminium and germanium in the framework, with Ge/Al = 1.5. The substitution of germanium for silicon in the framework leads to a larger unit cell volume for NaAlGe-NAT compared with Na₈Al₈Si₁₂O₄₀·8H₂O (NaAlSi-NAT) and Na₈Ga₈Si₁₂O₄₀·8H₂O (NaGaSi-NAT) framework structures. The mean rotation angle Ψ of the chains (composed of 4=1 secondary building units) relative to the a and b cell axes is 20.4°, compared with 21.7 and 22.9° calculated for NaGaSi-NAT and NaAlSi-NAT, respectively. Elliptical channels along the c-axis host well-ordered water molecules and sodium cations in fully occupied sites.

Correlations derived from the structural parameters of a wide range of gallium and germanium containing sodalites have been examined. This has allowed the effect of introducing gallium and germanium onto the framework sites to be studied. The framework expansion associated with gallium and germanium incorporation is principally accommodated by co-operative rotations about the 4&cmb.macr;axis and an increase in framework T–O–T bond angle. Correlations involving structural parameters such as framework T–O–T bond angle, T–O bond lengths and tetrahedral tilt angle have been examined and have been shown to be analogous to those found for their aluminosilicate counterparts.

The effect of sodium taurocholate (NaTC) (5 mM) and ethanol (5%) on H+ absorption by the esophagus was studied duringin vivo perfusion of rabbit esophagus with solutions of graded concentration of H+ containing either one of these agents. Net ion and volume fluxes, changes in osmolality and PD, histological change, absorption of NaTC or ethanol, were correlated with concentration of acid in the perfusate. There was linear correlation between H+ efflux and luminal H+ concentration except for experiments with NaTC at H+ concentrations higher than 100 mM. Both NaTC and ethanol caused greatly increased rate of removal of H+ from the lumen (accompanied by fall in PD), increased transport of other ions in the direction of their chemical gradients, and much structural disintegration. These changes were more severe with NaTC than with ethanol. In neutral solutions NaTC did not cause changes in PD or net ion fluxes, while ethanol depressed PD and increased net ion fluxes to a lesser extent than when acid was present. NaTC was not absorbed in a neutral solution but absorption increased with acidity. Acidity did not affect ethanol absorption. These data suggest that increased permeability of the esophageal mucosa is the basic mechanism underlying esophagitis. Increased permeability is related to absorption of NaTC or ethanol. The synergistic action of bile or alcohol and acid on the esophageal mucosa is compared to that of aspirin/acid on the gastric mucosa.

N-Bromosuccinimide cleavage of in vivo 32P-labelled lysine-rich histone isolated from rapidly dividing cells has been studied. N-Bromosuccinimide cleaves F1-histone into two fragments, a small N-terminal piece and a larger C-terminal portion. The phosphate-induced microheterogeneity and associated radioactivity which has been linked to cell replication, is found in the carboxyterminal fragment. No phosphorous is found associated with the amino-terminal fragment when histone phosphorylation is associated with cell division. The specific tryptic phosphopeptides obtained from in vivo labelled F1are clearly different from those obtained from in vitro incubations of free F1-histone and cytoplasmic protein kinase.