SARS-CoV-2 mRNA vaccination-induced immunological memory in human nonlymphoid and lymphoid tissues.

Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine-specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, nonlymphoid organs harbored significantly elevated frequencies of spike-specific CD4+ T cells compared with blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived CD4+ T cells further exhibited increased polyfunctionality over those detected in blood. Single-cell RNA-Seq together with T cell receptor repertoire analysis indicated that the clonotype rather than organ origin is a major determinant of transcriptomic state in vaccine-specific CD4+ T cells. In summary, our data demonstrate that SARS-CoV-2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.

First successful treatment of Clostridium perfringens-associated emphysematous hepatitis: a case report.

Emphysematous diseases of the abdomen are rare with an often inconspicuous presentation of symptoms and rapid lethal outcome if untreated. We report the first successfully treated case of Clostridium perfringens-associated emphysematous hepatitis. In the emergency room, a 79-year-old man presented with shortness of breath and deteriorated general condition since the morning of admission. Initial CT scans showed a small but rapidly expanding gas collection in liver segment 6. Emergency surgery with atypical liver resection was performed immediately. With early resection and prolonged administration of antibiotics in the presence of sepsis, the patient recovered successfully and was discharged 37 days after admission. As in our case, prompt diagnosis with early surgical treatment is crucial for the management of emphysematous hepatitis.

Diagnostic Accuracy of Magnetic Resonance Enterography for the Evaluation of Active and Fibrotic Inflammation in Crohn's Disease.

Background: Despite the success of standard magnetic resonance enterography (MRE) in detecting Crohn's disease (CD), characterization of strictures and, thus, therapy guidance is still limited. The aim of the study was to determine diagnostic accuracy of MRE in detecting or ruling out active inflammation and identifying fibrotic lesions in patients with terminal ileal CD with histopathology as reference. Methods: Sixty-seven consecutive patients (median age 32 years, range 19-79 years) with terminal ileal CD were retrospectively enrolled between January 2015 and October 2020. The median interval between MRE and surgery was 9 days (range 0-86 days). Sensitivity, specificity, positive and negative predictive value (PPV and NPV, respectively), and area under the curve (AUC) with 95% confidence intervals (CIs) were calculated for the MRE-based AIS (acute inflammation score) using the histopathology of surgical specimens as the reference standard. Results: Sensitivity, specificity, PPV, and NPV for detecting or ruling out active inflammation were 100% (CI, 0.94-1.00; 0.44-1.00; 0.93-1.00; 0.31-1.00) using an AIS cut-off of >4.1. AUC was 1.00 (CI, 1.00-1.00; p < 0.01). In all patients with fibrotic changes only and no active inflammation, AIS was <4.1. Interobserver agreement was substantial (κ = 0.65, p < 0.01). Conclusion: Our study has shown an excellent diagnostic performance of the MRE-based AIS for determining whether active inflammation is present or lesions are due to chronic changes in ileal CD using the histopathology of surgical specimens as reference. These findings indicate that the MRE-based AIS allows a better determination of the inflammatory stage of terminal ileal CD, which facilitates the decision to perform surgery.

Feasibility of Intestinal MR Elastography in Inflammatory Bowel Disease.

BACKGROUND: While MR enterography allows detection of inflammatory bowel disease (IBD), the findings continue to be of limited use in guiding treatment-medication vs. surgery. PURPOSE: To test the feasibility of MR elastography of the gut in healthy volunteers and IBD patients. STUDY TYPE: Prospective pilot. POPULATION: Forty subjects (healthy volunteers: n = 20, 37 ± 14 years, 10 women; IBD patients: n = 20 (ulcerative colitis n = 9, Crohn's disease n = 11), 41 ± 15 years, 11 women). FIELD STRENGTH/SEQUENCE: Multifrequency MR elastography using a single-shot spin-echo echo planar imaging sequence at 1.5 T with drive frequencies of 40, 50, 60, and 70 Hz. ASSESSMENT: Maps of shear-wave speed (SWS, in m/s) and loss angle (φ, in rad), representing stiffness and solid-fluid behavior, respectively, were generated using tomoelastography data processing. Histopathological analysis of surgical specimens was used as reference standard in patients. STATISTICAL TESTS: Unpaired t-test, one-way analysis of variance followed by Tukey post hoc analysis, Pearson's correlation coefficient and area under the receiver operating characteristic curve (AUC) with 95%-confidence interval (CI). Significance level of 5%. RESULTS: MR elastography was feasible in all 40 subjects (100% technical success rate). SWS and φ were significantly increased in IBD by 21% and 20% (IBD: 1.45 ± 0.14 m/s and 0.78 ± 0.12 rad; healthy volunteers: 1.20 ± 0.14 m/s and 0.65 ± 0.06 rad), whereas no significant differences were found between ulcerative colitis and Crohn's disease (P = 0.74 and 0.90, respectively). In a preliminary assessment, a high diagnostic accuracy in detecting IBD was suggested by an AUC of 0.90 (CI: 0.81-0.96) for SWS and 0.84 (CI: 0.71-0.95) for φ. DATA CONCLUSION: In this pilot study, our results demonstrated the feasibility of MR elastography of the gut and showed an excellent diagnostic performance in predicting IBD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Influence of fibrosis progression on the viscous properties of in vivo liver tissue elucidated by shear wave dispersion in multifrequency MR elastography.

PURPOSE: Many elastography studies have shown that liver stiffness increases with fibrosis and thus can be used as a reliable marker for noninvasively staging fibrosis. However, the sensitivity of viscosity-related mechanical parameters, such as shear wave dispersion, to liver fibrosis is less well understood. METHODS: In this proof-of-concept study, 15 healthy volunteers and 37 patients with chronic liver disease and biopsy-proven fibrosis were prospectively investigated by MR elastography at six drive frequencies of 35-60 Hz. Maps of shear wave speed (SWS, in m/s) and loss angle (φ, in rad), as a marker of stiffness and viscous properties, respectively, were generated using tomoelastography data processing. The Child-Pugh score was used to assess cirrhosis severity. RESULTS: While SWS increased with fibrosis (F0: 1.53 ± 0.11 m/s, F1-F3: 1.71 ± 0.17 m/s, F4: 2.50 ± 0.39 m/s; P < 0.001), φ remained unchanged during mild to severe fibrosis (F0: 0.63 ± 0.05 rad, F1-F3: 0.60 ± 0.05 rad, P = 0.21) but increased in cirrhosis (F4: 0.81 ± 0.16 rad; P < 0.001). Correspondingly, the slope of SWS-dispersion within the investigated range of vibration frequencies increased from insignificant (F0-F3: 0.010 ± 0.007 m/s/Hz) to significant (F4: 0.038 ± 0.025 m/s/Hz; P = 0.005). Significant correlation with the Child-Pugh score was found for φ (R = 0.60, P = 0.01) but not for SWS. CONCLUSION: Although cirrhosis is associated with liver stiffening and, intuitively, transition towards more rigid material properties, the observed increases in φ and slope of SWS-dispersion indicate abnormally high mechanical friction in cirrhotic livers. This biophysical signature might provide a prognostic imaging marker for the detection of pathological processes associated with fibrosis independent of stiffness.

Diagnostic performance of tomoelastography of the liver and spleen for staging hepatic fibrosis.

OBJECTIVES: To determine the diagnostic performance, cut-off values, and optimal drive frequency range for staging hepatic fibrosis using tomoelastography by multifrequency MR elastography of the liver and spleen. METHODS: This prospective study consecutively enrolled a total of 61 subjects between June 2014 and April 2017: 45 patients with chronic liver disease and proven stage of fibrosis and 16 healthy volunteers. Tomoelastography was performed at 1.5 T using six drive frequencies from 35 to 60 Hz. Cut-off values and AUC were calculated. Shear wave speed (in m/s) of the liver and spleen was assessed separately and in combination as a surrogate of stiffness. RESULTS: For compound multifrequency processing of the liver, cut-off and AUC values by fibrosis stage were as follows: F1, 1.52 m/s and 0.89; F2, 1.55 m/s and 0.94; F3, 1.67 m/s and 0.98; and F4, 1.72 m/s and 0.98. Diagnostic performance of the best single drive frequencies (45 Hz, 55 Hz, 60 Hz) was similar (mean AUC = 0.95, respectively). Combined analysis of the liver and spleen slightly improved performance at 60 Hz in F4 patients (mean AUC = 0.97 vs. 0.95, p = 0.03). Full-field-of-view elastograms displayed not only the liver and spleen but also small anatomical structures including the pancreas and major vessels. CONCLUSION: Tomoelastography provides full-field-of-view elastograms with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. Our analysis of single-frequency tomoelastography suggests that scan time can be further reduced in future studies, making tomoelastography easier to implement in clinical routine. KEY POINTS: • Tomoelastography provides full-field-of-view elastograms of the abdomen with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. • Diagnostic performance of single-frequency tomoelastography at higher frequencies (45 Hz, 55 Hz, 60 Hz) and compound multifrequency processing are equivalent for staging hepatic fibrosis. • Combined assessment of hepatic and splenic stiffness slightly improves diagnostic performance for staging hepatic fibrosis.

Association of smoking and physical inactivity with MRI derived changes in cardiac function and structure in cardiovascular healthy subjects.

We aimed to investigate the association of smoking and physical exercise on ventricular function and structure, determined by cardiac magnetic resonance imaging (CMR), in subjects without known cardiovascular diseases. A total of 381 participants (median age 57 years) of the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort underwent CMR. The participants' smoking and sporting habits were measured by a questionnaire. Physical inactivity was associated with a reduction of left ventricular ejection fraction (LV-EF), stroke volume, early diastolic peak filling rate and peak ejection rate of the left ventricle as well as right ventricular stroke volume. LV-EF was reduced in subjects with almost no physical activity compared to subjects with regular physical activity (68.4%, 95%CI 66.8-70.1% vs. 70.8%, 95%CI 69.2-72.3%, p < 0,05). Smokers had lower right ventricular end-diastolic volumes (80.6 ml/m², 95%CI 76.7-84.5 ml/m²; never-smokers: 85.5 ml/m², 95%CI 82.6-88.3 ml/m²; p < 0.05) but higher extracellular volume fractions (ECV) and fibrosis volumes (34.3 ml, 95%CI 32.5-36.0 ml, vs. 31.0 ml, 95%CI 29.6-32.3 ml, p < 0.01). We conclude that asymptomatic individuals without known cardiovascular diseases show differences in cardiac function and structure depending on their physical activity and smoking habits. This underlines the importance of prevention and health education.

Subclinical changes in MRI-determined right ventricular volumes and function in subjects with prediabetes and diabetes.

OBJECTIVES: The aim of this study was to assess subclinical changes in right ventricular volumes and function in subjects with prediabetes and diabetes and controls without a history of cardiovascular disease. METHODS: Data from 400 participants in the KORA FF4 study without self-reported cardiovascular disease who underwent 3-T whole-body MRI were obtained. The right ventricle was evaluated using the short axis and a four-chamber view. Diabetes was defined according to WHO criteria. Associations between glucose tolerance and right ventricular parameters were assessed using multivariable adjusted linear regression models. RESULTS: Data from 337 participants were available for analysis. Of these, 43 (13%) had diabetes, 87 (26%) had prediabetes, and 207 (61%) were normoglycaemic controls. There was a stepwise decrease in right ventricular volumes in men with prediabetes and diabetes in comparison with controls, including right ventricular end-diastolic volume (ß = -20.4 and ß = -25.6, respectively; p ≤ 0.005), right ventricular end-systolic volume (ß = -12.3 and ß = -12.7, respectively; p ≤ 0.037) and right ventricular stroke volume (ß = -8.1 and ß = -13.1, respectively, p ≤ 0.016). We did not observe any association between prediabetes or diabetes and right ventricular volumes in women or between prediabetes or diabetes and right ventricular ejection fraction in men and women. CONCLUSIONS: This study points towards early subclinical changes in right ventricular volumes in men with diabetes and prediabetes. KEY POINTS: • MRI was used to detect subclinical changes in right ventricular parameters. • Diabetes mellitus is associated with right ventricular dysfunction. • Impairment of right ventricular volumes seems to occur predominantly in men.

Alcohol consumption, but not smoking is associated with higher MR-derived liver fat in an asymptomatic study population.

BACKGROUND: The aim of our study was to determine the relation of alcohol consumption and cigarette smoking on continuous-measured hepatic fat fraction (HFF) in a population free of cardiovascular disease. We suggested a direct correlation of alcohol consumption with HFF and increased HFF in former smokers compared to current smokers. METHODS: Data from 384 subjects (mean age: 56 years, 58% men) of a population-based cohort study (KORA) were included in a cross-sectional design. Liver fat was assessed by 3 Tesla magnetic resonance imaging (MRI) using a multi-echo Dixon sequence and T2-corrected single voxel multi-echo spectroscopy (1H-MRS). Smoking status was classified as never, former or current smoker and alcohol consumption as non-, moderate (0.1-39.9 g/day for men and 0.1-19.9 g/day for women), or heavy drinker (≥ 40 g/day for men and ≥ 20 g/day for women). Fatty liver disease was defined as HFF≥5.56%. RESULTS: Average HFF was 8.8% by 1H-MRS and 8.5% by MRI. Former smokers showed a higher HFF (MRI: ß = 2.64; p = 0.006) and a higher FLD prevalence (MRI: OR = 1.91; p = 0.006) compared to never smokers. Current smokers showed decreased odds for FLD measured by 1H-MRS after multivariable adjustment (OR = 0.37; p = 0.007) with never smoker as reference. Heavy drinking was positively associated with HFF (1H-MRS: ß = 2.99; p = 0.003) and showed highest odds for FLD (1H-MRS: OR = 3.05; p = 0.008) with non-drinker as reference. Moderate drinking showed a positive association with HFF (1H-MRS: ß = 1.54; p = 0.061 and MRI: ß = 1.75; p = 0.050). CONCLUSIONS: Our data revealed lowest odds for FLD in current smokers, moderate drinkers showing higher HFF than non-drinkers and heavy drinkers showing highest HFF and odds for FLD. These findings partly conflict with former literature and underline the importance of further studies to investigate the complex effects on liver metabolism.

Resectable adenocarcinoma developing in the remnant pancreas 7 years after partial pancreatoduodenectomy for invasive ductal adenocarcinoma of the pancreas: a case report.

BACKGROUND: Pancreatic adenocarcinoma still has an excessively high mortality rate and resection is the only potentially curative treatment. The postoperative 5-year survival rate is approximately 20% and recurrence develops generally within 2 years. We report a case of a localized recurrent pancreatic adenocarcinoma in the remnant pancreas, 7 years after initial resection. CASE PRESENTATION: In 2008 an abdominal computed tomography scan showed a mass in the pancreas of a 70-year-old white woman, who presented with occlusive jaundice and abdominal pain in her right upper quadrant. A pancreatoduodenectomy was performed for a clinically suspected pancreatic adenocarcinoma. Histology confirmed a ductal adenocarcinoma. Afterwards, she received adjuvant chemotherapy with gemcitabine. In 2015 a follow-up positron emission tomography-computed tomography scan showed a single lesion in her remnant pancreas. Subsequently, a partial re-resection was performed. Histology confirmed once again a ductal adenocarcinoma. She received adjuvant chemotherapy with gemcitabine again and is still alive almost 9 years after she had first been diagnosed as having pancreatic cancer. CONCLUSIONS: In selected cases re-resection for pancreatic recurrence is feasible and provides a survival benefit. In cases involving late recurrence, it is difficult to distinguish between true recurrence and the development of a new tumor. In order to detect recurrences at an early stage in long-term survivors, follow-up needs to occur on a regular and long-term basis.

Pancreatic fat content by magnetic resonance imaging in subjects with prediabetes, diabetes, and controls from a general population without cardiovascular disease.

BACKGROUND/OBJECTIVE: Despite the relevance of pancreatic fat content in the development of metabolic diseases, its association with impaired glucose metabolism, diabetes, and other adipose tissue compartments remains unclear. Thus, we determined differences in pancreatic fat content by magnetic resonance imaging (MRI) between subjects with prediabetes, diabetes, and normal controls in a cohort from the general population. METHODS: Subjects without history of cardiovascular disease with established diabetes or prediabetes as well as normal controls were included and underwent whole-body MRI on a 3T scanner. Pancreatic fat content was quantified by measuring the proton-density fat fraction (PDFFpanc) using a 3D multi-echo GRE sequence (increment: 1.23 ms, 6 echoes) by placing ROIs in the pancreatic head, body, and tail by independent readers. In addition, hepatic fat content as well as abdominal subcutaneous and visceral adipose tissue (SAT and VAT) were measured by multi-echo GRE and 3D 2-point volume-interpolated DIXON MRI, respectively. Univariate and multivariate analyses were employed to determine associations. RESULTS: A total of 385 subjects were included in the analysis (median age: 57 years, 58.2% males), of them 53 were classified as subjects with diabetes, 95 as prediabetes, and 237 as controls (13.8%, 24.7%, and 61.6%; respectively). The median PDFFpanc was 5.2% [IQR 3.3-9.4], and significantly higher in subjects with prediabetes and diabetes as compared to controls (PDFFpanc: 6.2% [IQR: 3.5-12] vs. 8.6% [IQR: 4.3-17.5] vs. 4.9% [3.1-7.4], p<0.001, respectively). After adjusting for age, gender and BMI the association was attenuated (all p>0.12). While in univariate analysis BMI, PDFFhepatic, SAT and VAT were associated with PDFFpanc (all p<0.05), only VAT predicted PDFFpanc independently (ß: 0.02, 95%-confidence interval: 0.01-0.04, p<0.001). CONCLUSION: While pancreatic fat content differs significantly between subjects with prediabetes, diabetes and controls, this association may be confounded by age, gender, and the amount of VAT in this cross-sectional study.

Association between MRI-derived hepatic fat fraction and blood pressure in participants without history of cardiovascular disease.

OBJECTIVES: We assessed whether liver fat content, as determined by MRI, correlates with blood pressure (BP), a major vascular risk factor, in individuals from the general population without history of stroke and coronary or peripheral artery disease. METHODS: Cross-sectional data from 384 participants (161 women; aged 39-73 years) of a MRI substudy of the KORA FF4 survey were used. Hepatic fat fraction (HFF) was measured in the left and right lobe of the liver using single voxel multiecho H-spectroscopy and at the level of the portal vein using a multiecho Dixon-sequence. Associations of HFF with SBP and DBP as well as hypertension were assessed by right censored normal regression (accounting for antihypertensive treatment) and by logistic regression, respectively. RESULTS: High levels of HFF measured on the level of the portal vein (90th percentile, 21.8%), compared with low HFF levels (10th percentile, 1.7%), were associated with higher SBP (131 vs. 122 mmHg; overall P = 0.001), higher DBP (82 vs. 76 mmHg, P < 0.001) and with higher odds of hypertension [odds ratio (OR) = 2.16, P = 0.025]. A level of 5.13% (54th percentile) was identified as optimal HFF cut-off for the prediction of hypertension (OR = 2.00, P = 0.015). Alcohol consumption emerged as an effect modifier for the association between HFF and hypertension (nonalcohol drinker: OR = 3.76, P = 0.025; alcohol drinker: OR = 1.59, P = 0.165). CONCLUSION: MRI-derived subclinical HFF is associated with SBP and DBP as well as with hypertension in participants from the general population without history of cardiovascular disease.

Subclinical Disease Burden as Assessed by Whole-Body MRI in Subjects With Prediabetes, Subjects With Diabetes, and Normal Control Subjects From the General Population: The KORA-MRI Study.

Detailed pathophysiological manifestations of early disease in the context of prediabetes are poorly understood. This study aimed to evaluate the extent of early signs of metabolic and cardio-cerebrovascular complications affecting multiple organs in individuals with prediabetes. Subjects without a history of stroke, coronary artery disease, or peripheral artery disease were enrolled in a case-control study nested within the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and underwent comprehensive MRI assessment to characterize cerebral parameters (white matter lesions, microbleeds), cardiovascular parameters (carotid plaque, left ventricular function, and myocardial late gadolinium enhancement [LGE]), and metabolic parameters (hepatic proton-density fat fraction [PDFF] and subcutaneous and visceral abdominal fat). Among 400 subjects who underwent MRI, 103 subjects had prediabetes and 54 had established diabetes. Subjects with prediabetes had an increased risk for carotid plaque and adverse functional cardiac parameters, including reduced early diastolic filling rates as well as a higher prevalence of LGE compared with healthy control subjects. In addition, people with prediabetes had significantly elevated levels of PDFF and total and visceral fat. Thus, subjects with prediabetes show early signs of subclinical disease that include vascular, cardiac, and metabolic changes, as measured by whole-body MRI after adjusting for cardiometabolic risk factors.

Feasibility of a three-step magnetic resonance imaging approach for the assessment of hepatic steatosis in an asymptomatic study population.

OBJECTIVES: To determine the feasibility of a multi-step magnetic resonance imaging (MRI) approach for comprehensive assessment of hepatic steatosis defined as liver fat content of ≥5 % in an asymptomatic population. METHODS: The study was approved by the institutional review board and written informed consent of all participants was obtained. Participants of a population-based study cohort underwent a three-step 3-T MRI-based assessment of liver fat. A dual-echo Dixon sequence was performed to identify subjects with hepatic steatosis, followed by a multi-echo Dixon sequence with proton density fat fraction estimation. Finally, single-voxel T2-corrected multi-echo spectroscopy was performed. RESULTS: A total of 215 participants completed the MRI protocol (56.3 % male, average age 57.2 ± 9.4 years). The prevalence of hepatic steatosis was 55 %. Mean liver proton density fat fraction was 9.2 ± 8.5 % by multi-echo Dixon and 9.3 ± 8.6 % by multi-echo spectroscopy (p = 0.51). Dual-echo Dixon overestimated liver fat fraction by 1.4 ± 2.0 % (p < 0.0001). All measurements showed excellent correlations (r ≥ 0.9, p < 0.001). Dual-echo Dixon was highly sensitive for the detection of hepatic steatosis (sensitivity 0.97, NPV 0.96) with good specificity and PPV (0.75 and 0.81, respectively). CONCLUSIONS: A multi-step MRI approach may enable rapid and accurate identification of subjects with hepatic steatosis in an asymptomatic population. KEY POINTS: • Dual-echo Dixon can rapidly and reliably exclude hepatic steatosis without complex post-processing. • Multi-echo Dixon and multi-echo spectroscopy yield similar results regarding hepatic fat quantification. • Each sequence can be performed in one breath-hold. • These sequences can be implemented in routine abdominal MRI protocols. • Thus hepatic fat can be evaluated without relevant increase in scan time.

Mucinous cystadenoma arising in a completely isolated infected ileal duplication cyst.

Gastrointestinal duplications are uncommon congenital lesions that can occur anywhere along the alimentary tract, and the symptoms of which generally develop during infancy or childhood. Completely isolated duplication cysts are an extremely rare variant of duplication, where no communication between the cyst and the adjacent bowel segment is present. We report the unique case of an adult who presented with right lower abdominal pain and systemic signs of inflammation caused by infection of a completely isolated ileal duplication cyst. Histological examination of the cyst additionally revealed a low-grade mucinous cystadenoma. We discuss the clinical presentations, diagnosis and treatment of this rare entity.