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.

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.

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.

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.