Whole brain pattern of iron accumulation in REM sleep behavior disorder.

Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas.

Malignant lymphomas represent the most common type of hematologic malignancies. The first clinically approved TDD modalities in lymphoma patients were anti-CD20 radioimmunoconjugates (RIT) 131I-tositumomab and 90Y-ibritumomab-tiuxetan. The later clinical success of the first approved antibody-drug conjugate (ADC) for the treatment of lymphomas, anti-CD30 brentuximab vedotin, paved the path for the preclinical development and clinical testing of several other ADCs, including polatuzumab vedotin and loncastuximab tesirine. Other modalities of TDD are based on new formulations of "old" cytostatic agents and their passive trapping in the lymphoma tissue by means of the enhanced permeability and retention (EPR) effect. Currently, the diagnostic and restaging procedures in aggressive lymphomas are based on nuclear imaging, namely PET. A theranostic approach that combines diagnostic or restaging lymphoma imaging with targeted treatment represents an appealing innovative strategy in personalized medicine. The future of theranostics will require not only the capability to provide suitable disease-specific molecular probes but also expertise on big data processing and evaluation. Here, we review the concept of targeted drug delivery in malignant lymphomas from RIT and ADC to a wide array of passively and actively targeted nano-sized investigational agents. We also discuss the future of molecular imaging with special focus on monoclonal antibody-based and monoclonal antibody-derived theranostic strategies.

The diagnostic performance of whole-body MRI in the staging of lymphomas in adult patients compared to PET/CT and enhanced reference standard-systematic review and meta-analysis.

BACKGROUND: Morphology highlighted by diffusion weighted imaging (DWI) is the basis of whole-body MRI (wbMRI). The aim of this study was to analyze current knowledge on the diagnostic performance of wbMRI in the pretreatment staging of patients with lymphoma. METHODS: A search for original articles reporting the diagnostic performance (sensitivity, specificity) of pretreatment (first staging or staging in relapsed patients after complete remission) wbMRI in nodal and extranodal involvement by extracranial lymphoma and the agreement of stage by the Cotswolds-modified Ann Arbor classification in adult patients compared to the reference standard (PET/CT or enhanced reference standard) was conducted in PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov. RESULTS: Altogether 15 studies with 519 patients were included in the meta-analysis. The pooled sensitivity and specificity for nodal involvement were 0.93 (95% CI: 0.90 to 0.96) and 0.99 (95% CI: 0.98 to 1.00). For nodal staging, most studies used the size criterion of 10 mm in the short diameter (n=10) and the absence of prominent fatty hilum (n=4). Restricted diffusion on diffusion-weighted imaging as a sign of nodal involvement was either not used (n=5), used for detection (n=4), semi-quantitatively (n=4), or quantitatively (n=1). Only one study (7) relied solely on restricted diffusion as the main criterion for nodal involvement. The pooled sensitivity and specificity for extranodal involvement were 0.89 (95% CI: 0.79 to 0.98) and 0.99 (95% CI: 0.99 to 1.00). Seven studies considered diffuse splenic involvement when its long or vertical axis was greater than 13 cm regardless of the patient's physiognomy. The pooled agreement in staging (Cohen's kappa) was almost perfect (0.90, 95% CI: 0.84 to 0.95). DISCUSSION: The sensitivity and specificity of wbMRI in the assessment of the nodal and extranodal involvement by lymphoma is high. The agreement of wbMRI with the reference standard is almost perfect.

The impact of co-morbidities on a 6-year survival after methanol mass poisoning outbreak: possible role of metabolic formaldehyde.

Context: The influence of co-morbid conditions on the outcome of acute methanol poisoning in mass poisoning outbreaks is not known.Objective: The objective of this is to study the impact of burden of co-morbidities, complications, and methanol-induced brain lesions on hospital, follow-up, and total mortality.Methods: All patients hospitalized with methanol poisoning during a mass poisoning outbreak were followed in a prospective cohort study until death or final follow-up after 6 years. The age-adjusted Charlson co-morbidity index (ACCI) score was calculated for each patient. A multivariate Cox regression model was used to calculate the adjusted hazards ratio (HR) for death. The survival was modeled using the Kaplan-Meier method.Results: Of 108 patients (mean age with SD 50.9 ± 2.6 years), 24 (54.4 ± 5.9 years) died during hospitalization (mean survival with SD 8 ± 4 days) and 84 (49.9 ± 3.0 years; p = .159) were discharged, including 27 with methanol-induced brain lesions. Of the discharged patients, 15 (56.3 ± 6.8 years) died during the follow-up (mean survival 37 ± 11 months) and 69 (48.5 ± 3.3 years; p = .044) survived. The hospital mortality was 22%, the follow-up mortality was 18%; the total mortality was 36%. Cardiac/respiratory arrest, acute respiratory failure, multiorgan failure syndrome, and arterial hypotension increased the HR for hospital and total (but not follow-up) mortality after adjustment for age, sex, and arterial pH (all p < .05). All patients who died in the hospital had at least one complication. A higher ACCI score was associated with greater total mortality (HR 1.22; 1.00-1.48 95% CI; p = .046). Of those who died, 35 (90%) had a moderate-to-high ACCI. The Kaplan-Meier curve demonstrated that patients with a high ACCI had greater follow-up mortality compared to ones with low (p = .027) or moderate (p = .020) scores. For the patients who died during follow-up, cancers of different localizations were responsible for 7/15 (47%) of the deaths.Conclusions: The character and number of complications affected hospital but not follow-up mortality, while the burden of co-morbidities affected follow-up mortality. Methanol-induced brain lesions did not affect follow-up mortality. Relatively high cancer mortality rate may be associated with acute exposure to metabolic formaldehyde produced by methanol oxidation.

How to recognize stent graft infection after endovascular aortic repair: the utility of 18F-FDG PET/CT in an infrequent but serious clinical setting.

OBJECTIVE: To evaluate the diagnostic performance of 18F-FDG PET/CT in the detection of stent graft infection (SGI). METHODS: In a retrospective study, two nuclear medicine physicians have independently analyzed 17 18F-FDG PET/CT examinations performed for clinical suspicion of SGI. The images were evaluated for the uptake pattern and intensity, and by the maximum standard uptake value (SUVmax), the target-to-background ratio with blood pool (TBRBP) and liver uptake (TBRhep) as a reference. The SGI was defined as the presence of focal hyperactivity with an intensity exceeding hepatic uptake. CT images were independently assessed for signs of SGI. Clinical review of all further patients' data served as the standard of reference. RESULTS: Nine cases were established as SGI by the clinical review. PET/CT correctly diagnosed SGI in eight and yielded a sensitivity of 89% and specificity of 100%. The mean SUVmax, TBRBP, and TBRhep values were 9.8 ± 4.0, 6.9 ± 2.6, and 4.6 ± 1.7 in the group of patients with true SGI, and 4.0 ± 1.1, 2.5 ± 0.4 (p < 0.001) and 1.9 ± 0.2 (p < 0.001) in true negative cases, respectively. CT alone showed a sensitivity of 78% and specificity of 100% and was concordant with PET/CT in 14 cases. The best performing threshold values of SUVmax, TBRBP, and TBRhep were 5.6, 3.5, and 2.2, respectively. CONCLUSION: 18F-FDG PET/CT with expert evaluation, semiquantitative and quantitative image analysis with the proposed threshold values for SUVmax, TBRBP, and TBRhep has good diagnostic accuracy in the detection of SGI. We propose that visual grading scale for SGI should use hepatic uptake as a visual reference.

Assessment of renal function before contrast media injection: right decisions based on inaccurate estimates.

OBJECTIVES: Information on renal function required before specified radiological examinations with contrast agents is usually obtained through prediction equations using serum creatinine and anthropometric data. The aim of our study was to demonstrate discrepancy between poor prediction and good diagnostic accuracy of glomerular filtration rate (GFR) estimated by prediction equations. METHODS: In 50 patients, reference GFR was measured as plasma clearance of 51-chromium labeled ethylene-diamine-tetraacetic-acid (51Cr-EDTA) and compared with GFR assayed by creatinine clearance (CC) and estimated by Cockcroft-Gault prediction equation (CG). For comparisons, CC and CG were considered as continuous, categorical, and binary variables. Accuracy of the reference GFR prediction was expressed in terms of prediction errors and diagnostic accuracy indices. RESULTS: As continuous variable, CG estimated individual values of GFR with large prediction error exceeding that of CC. As categorical variable, it classified the patient stage of chronic kidney disease (CKD) with medium diagnostic accuracy of 74% (CKD 3) and 62% (CKD 4). As binary variable, CG classified individual patient's GFR below 30 and 60 ml/min/1.73 m2 with good diagnostic accuracy of 80 and 94%, respectively. Performance of other prediction equations did not significantly differ from CG. CONCLUSIONS: Despite large variance and poor prediction accuracy of individual GFR estimates, most of them correctly classified individual patient's GFR below specified level. Results of prediction equations thus should be used and reported exclusively as binary variables, while numerical values of GFR, if required, should be measured by more accurate radionuclide or laboratory methods. KEY POINTS: • Radiological guidelines on contrast media require estimation of glomerular filtration rate to assess kidney function before specified contrast examinations. • Estimated glomerular filtration rate is obtained through prediction equations using serum creatinine and anthropometric data as predictors. • While numerical estimates of glomerular filtration rate are inaccurate (their prediction accuracy is poor), diagnostic accuracy of binary estimates (ability to classify patient's glomerular filtration rate below or above a specified level) is very good.

A rare case of regressively changed lipomatous hypertrophy of the interatrial septum presenting with anemia and recurrent fever.

Lipomatous hypertrophy of the interatrial septum (LHIS) is characterized by excessive accumulation of adipose tissue within some segments of the interatrial septum. Only one published case so far describes fever as a presenting feature of LHIS. On the other hand, systemic symptoms including anemia and fever are well-known clinical presentations of cardiac myxomas. We report an unusual case of a 79-year-old woman who was thoroughly but unsuccessfully investigated for recurrent fever and anemia in several specialized departments over the course of 4 years. Computed tomography scan showed a pathological mass localized in the interatrial septum and spreading to ascending aorta. Histological analysis of the biopsy samples from surgery revealed the unexpected diagnosis of regressively changed LHIS. We discuss the clinical and pathologic features of this lesion suggesting that its regressive changes may be associated with inflammation and can cause systemic symptoms such as fever and anemia.

Premalignant and malignant lesions of the heterotopic pancreas in the esophagus: a case report and review of the literature.

Heterotopic pancreas is a congenital pathology of the gastrointestinal tract, particularly rare in the esophagus. Both symptomatology and findings during preoperative examinations are non-specific and therefore do not often lead to an accurate diagnosis, which is usually revealed only by histopathological assessment of a resected specimen. We report an unusual case of a patient suffering from severe dysphagia caused by heterotopic pancreas in the distal esophagus with chronic inflammation and foci of premalignant changes. This article also reviews 14 adult cases of heterotopic pancreas in the esophagus previously reported in the literature, with the aim of determining the clinical features of this disease and possible complications including rare premalignant lesions and malignant transformation. Especially with regard to those complications, we suggest that both symptomatic and incidentally found asymptomatic lesions should be resected.