Emergence of SARS-CoV-2 B.1.1.7 Lineage at Outpatient Testing Site, Berlin, Germany, January-March 2021.

Within 5 weeks in 2021, B.1.1.7 became the dominant severe acute respiratory syndrome coronavirus 2 lineage at an outpatient testing site in Berlin, Germany. Compared with outpatients with wild-type virus infection, patients with B.1.1.7 had similar cycle threshold values, more frequent sore throat and travel history, and less frequent anosmia/ageusia.

Effect of Indacaterol/Glycopyrronium on Pulmonary Perfusion and Ventilation in Hyperinflated Patients with Chronic Obstructive Pulmonary Disease (CLAIM). A Double-Blind, Randomized, Crossover Trial.

Rationale: In the CLAIM study, dual bronchodilation with indacaterol/glycopyrronium (IND/GLY) significantly reduced hyperinflation, which translated into improved cardiac function, measured by left ventricular end-diastolic volume and cardiac output. Pulmonary microvascular blood flow (PMBF) is reduced in chronic obstructive pulmonary disease (COPD); however, the effect of reduced lung hyperinflation on PMBF remains unknown. Objectives: To determine the effect of lung deflation with IND/GLY on PMBF and regional pulmonary ventilation using magnetic resonance imaging (MRI) in hyperinflated patients with COPD. Methods: In this double-blind, randomized, two-period crossover study, gadolinium-enhanced MRI and phase-resolved functional lung MRI were used to measure PMBF and regional ventilation, respectively, in patients with COPD receiving IND/GLY versus placebo. Measurements and Main Results: Sixty-two patients were randomized to receive once-daily IND/GLY (110/50 µg) for 14 days, followed by 14 days of placebo, or vice versa. Treatment periods were separated by a 14-day washout. Sixty patients were included in the per-protocol analysis. MRI measurements showed significant improvements in total PMBF (P = 0.006) and regional PMBF (P values for individual lobes were between 0.004 and 0.022) in response to IND/GLY versus placebo. Regional ventilation was also significantly improved with IND/GLY, as evidenced by a 12.4% increase versus placebo (P = 0.011), a 14.3% relative decrease in ventilation defect percentage of nonventilated/hypoventilated lung tissue (cutoff was defined as 0.075 regional ventilation; P = 0.0002), and a 15.7% reduction in the coefficient of variation of regional ventilation compared with placebo (P < 0.0001). Conclusions: Pharmacologic intervention with IND/GLY improves pulmonary microvascular blood flow and regional ventilation in patients with COPD with hyperinflation. Clinical trial registered with www.clinicaltrials.gov (NCT02442206).

Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF patients.

PURPOSE: In this feasibility study, a phase-resolved functional lung imaging postprocessing method for extraction of dynamic perfusion (Q) and ventilation (V) parameters using a conventional 1H lung MRI Fourier decomposition acquisition is introduced. METHODS: Time series of coronal gradient-echo MR images with a temporal resolution of 288 to 324 ms of two healthy volunteers, one patient with chronic thromboembolic hypertension, one patient with cystic fibrosis, and one patient with chronic obstructive pulmonary disease were acquired at 1.5 T. Using a sine model to estimate cardiac and respiratory phases of each image, all images were sorted to reconstruct full cardiac and respiratory cycles. Time to peak (TTP), V/Q maps, and fractional ventilation flow-volume loops were calculated. RESULTS: For the volunteers, homogenous ventilation and perfusion TTP maps (V-TTP, Q-TTP) were obtained. The chronic thromboembolic hypertension patient showed increased perfusion TTP in hypoperfused regions in visual agreement with dynamic contrast-enhanced MRI, which improved postpulmonary endaterectomy surgery. Cystic fibrosis and chronic obstructive pulmonary disease patients showed a pattern of increased V-TTP and Q-TTP in regions of hypoventilation and decreased perfusion. Fractional ventilation flow-volume loops of the chronic obstructive pulmonary disease patient were smaller in comparison with the healthy volunteer, and showed regional differences in visual agreement with functional small airways disease and emphysema on CT. CONCLUSIONS: This study shows the feasibility of phase-resolved functional lung imaging to gain quantitative information regarding regional lung perfusion and ventilation without the need for ultrafast imaging, which will be advantageous for future clinical translation. Magn Reson Med 79:2306-2314, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Chronic Lung Allograft Dysfunction: Oxygen-enhanced T1-Mapping MR Imaging of the Lung.

PURPOSE: To evaluate oxygen-enhanced T1-mapping magnetic resonance (MR) imaging of the lungs for detection of chronic lung allograft dysfunction (CLAD) in patients who have undergone double lung transplantation. MATERIALS AND METHODS: The local ethics committee approved this study. Seventy-six recipients of double lung allografts who underwent MR imaging of the lungs during an outpatient visit between 2011 and 2013 were included in this study after they provided written informed consent. Patients were classified as having CLAD on the basis of spirometric results and were divided into three groups: no CLAD (bronchiolitis obliterans syndrome level 0 [BOS 0]), early CLAD (BOS 0p), and late-stage CLAD (BOS 1-3). Coronal T1 maps of the lungs were acquired with the patient breathing room air and 100% oxygen by using an inversion-recovery snapshot fast low-angle shot sequence at 1.5 T. The median and interquartile range of T1 values at room air and at 100% oxygen and the oxygen transfer function were calculated. Statistical analysis was performed with analysis of variance and the Tukey honestly significant difference test or the Kruskal-Wallis test and the Mann-Whitney U test (α = 0.05). Bonferroni correction was applied for multiple comparisons. RESULTS: The oxygen transfer function was significantly lower in patients in the BOS 0p (P = .025) and BOS 1-3 groups (P = .003) than it was in the patients with BOS 0. Absolute T1 values (room air, P = .66; 100% oxygen, P = .67) did not differ significantly among the groups. The heterogeneity of T1 values, measured by using the interquartile range, showed a strong trend toward higher values in patients with BOS (room air, P = .06; 100% oxygen, P = .08). CONCLUSION: Oxygen transfer function may serve as an early marker for detection of CLAD.

Clinical use of oxygen-enhanced T1 mapping MRI of the lung: reproducibility and impact of closed versus loose fit oxygen delivery system.

PURPOSE: To evaluate the reproducibility of oxygen-enhanced magnetic resonance imaging (MRI), and the influence of different gas delivery methods, in a clinical environment. MATERIALS AND METHODS: Twelve healthy volunteers were examined on two visits with an inversion recovery snapshot fast low angle shot sequence on a 1.5 T system. Coronal slices were obtained breathing room air as well as 100% oxygen with a flow rate of 15 L/min. For oxygen delivery a standard nontight face mask and a full closed air-cushion face mask were used. T1 relaxation times and the oxygen transfer function (OTF) were calculated. RESULTS: The mean T1 values did not change significantly between the two visits (P > 0.05). The T1 values breathing 100% oxygen obtained using the full closed mask were significantly lower (1093 ± 38 msec; P < 0.05) compared to the standard mask (1157 ± 52 msec). Accordingly, the OTF was significantly higher for the full closed mask (P < 0.05). The OTF changed significantly on the second visit using the standard mask (P < 0.05). The full closed mask showed lower interindividual variation for both the T1 values (3.5% vs. 4.5%) as well as the OTF (12.4% vs. 22.0%) and no difference of the OTF on the second visit (P > 0.05). CONCLUSION: Oxygen-enhanced T1 mapping MRI produces reproducible data when using a full closed face mask.

Noninvasive quantification of airway inflammation following segmental allergen challenge with functional MR imaging: a proof of concept study.

PURPOSE: To evaluate oxygen-enhanced T1-mapping magnetic resonance (MR) imaging as a noninvasive method for visualization and quantification of regional inflammation after segmental allergen challenge in asthmatic patients compared with control subjects. MATERIALS AND METHODS: After institutional review board approval, nine asthmatic and four healthy individuals gave written informed consent. MR imaging (1.5 T) was performed by using an inversion-recovery snapshot fast low-angle shot sequence before (0 hours) and 6 hours and 24 hours after segmental allergen challenge by using either normal- or low-dose allergen or saline. The volume of lung tissue with increased relaxation times was determined by using a threshold-based method. As a biomarker for oxygen transfer from the lungs into the blood, the oxygen transfer function ( OTF oxygen transfer function ) was calculated. After the third MR imaging examination, eosinophils in bronchoalveolar lavage fluid were counted. Differences between times and segments were analyzed with nonparametric Wilcoxon matched-pairs test and Spearman correlation. RESULTS: In lung segments treated with the standard dose of allergen, the OTF oxygen transfer function was decreased at 6 hours in asthmatic patients, compared with saline-treated segments (P = .0078). In asthmatic patients at 24 hours, the volume over threshold was significantly increased in normal allergen dose-treated segments compared with saline-treated segments (P = .004). In corresponding lung segments, the volume over threshold at 24 hours in the asthmatic group showed a positive correlation (r = 0.65, P = .0001) and the OTF oxygen transfer function at 6 hours showed an inverse correlation (r = -0.67, P = .0001) with the percentage of eosinophils in the bronchoalveolar lavage fluid. CONCLUSION: OTF oxygen transfer function and volume over threshold are noninvasive MR imaging-derived parameters to visualize and quantify the regional allergic reaction after segmental endobronchial allergen challenge.

Performance of perfusion-weighted Fourier decomposition MRI for detection of chronic pulmonary emboli.

PURPOSE: To evaluate the test performance of perfusion-weighted Fourier-decomposition (pw-FD) magnetic resonance imaging (MRI) in comparison to dynamic contrast-enhanced (DCE)-MRI as a reference standard in patients with known or suspected chronic pulmonary embolism (PE). MATERIALS AND METHODS: In 64 patients, chronic PE was ruled out or confirmed by DCE-MRI using a time-resolved angiography with stochastic trajectories (TWIST) sequence in one breath-hold. Pw-FD-MRI was performed using a 2D fast low-angle shot (FLASH) sequence in free-breathing. After a nonrigid image registration, FD was applied to generate pw-images. Lungs were scored by two radiologists (2 and 12 years of lung MRI experience) visually for each lobe and segment for hypoperfused areas. For intra- and interobserver variability, the MR images were analyzed 2 months after the first analysis, blinded to the results of the first reader. RESULTS: PE was diagnosed by DCE-MRI in 39 patients. For the pw-FD MRI sensitivity, specificity, accuracy, and positive and negative predictive value for diagnosis of PE were 100%, 95%, 98%, 98%, and 100% on a per-patient basis, 94%, 94%, 94%, 95%, 94% on a per-lobe basis, and 82%, 92%, 88%, 88%, 88% on a segmental basis, respectively. Detection of subsegmental and segmental hypoperfusion using pw-FD MRI showed a moderate agreement with DCE-MRI (kappa of 0.68; 95% confidence interval: 0.64; 0.72). CONCLUSION: Pw-FD of the lung is a feasible test to diagnose chronic PE on a per-patient level during free-breathing without the use of ionizing radiation or contrast agents.

Phase-contrast MRI for detection of mild systemic hemodynamic response after segmental allergen challenge in asthmatic patients.

RATIONALE AND OBJECTIVES: Detection of a systemic hemodynamic response in patients suffering from allergic asthma after segmental endobronchial allergen challenge using phase-contrast magnetic resonance imaging (MRI). MATERIALS AND METHODS: Nine asthma patients and four healthy volunteers were examined using MRI (1.5T) before (0 hour), 6 hours, and 24 hours after segmental allergen challenge. Two-dimensional phase-contrast MRI measurements were performed in the aorta (AO) and in the pulmonary artery (PA). In addition, short-axis balanced steady state free precession cardiac cine MRI was performed. Maximum systolic flow, maximum flow acceleration, acceleration volume, acceleration time, distensibility, ejection fraction, stroke volume, end-systolic/diastolic volume, cardiac mass, heart rate (HR), and cardiac output (CO) were determined. Spirometry and bronchoalveolar lavage were also performed. RESULTS: In patients with asthma, maximal systolic flow and maximal flow acceleration increased 6 hours after provocation in the AO (112.3% and 118.9%, respectively) and PA (113.9% and 116.0%, respectively) compared to baseline (100%, P < .05). HR and CO increased significantly at 6 hours (115% and 118%, respectively) compared to baseline (100%, P = .003). In healthy subjects, almost all MRI-derived hemodynamic parameters did not significantly change at 6 hours and were significantly lower than baseline values at 24 hours (P < .02). Twenty-four hours after allergen challenge, all MRI-derived flow parameters were significantly lower in the control group compared to the asthma group (P < .05). HR, CO, and cardiac function parameters measured at 24 hours showed no significant difference comparing the two groups (P > .05). CONCLUSIONS: In asthmatic patients, MRI-derived hemodynamic parameters using phase-contrast MRI are slightly altered after segmental allergen provocation compared to normal controls indicating a mild systemic reaction to local allergen challenge.

Quantification of pulmonary inflammation after segmental allergen challenge using turbo-inversion recovery-magnitude magnetic resonance imaging.

RATIONALE: There is a need to develop novel noninvasive imaging biomarkers that help to evaluate antiinflammatory asthma treatments. OBJECTIVES: To investigate whether the extent of the segmental lung edema measured noninvasively using turbo-inversion recovery-magnitude magnetic resonance imaging (TIRM MRI) corresponds to the severity of the regional allergic reaction determined by the percentage of eosinophils in bronchoalveolar lavage fluid (BAL) 24 hours after segmental allergen challenge in patients with asthma compared with normal control subjects. METHODS: Eleven volunteers with allergic asthma and five healthy volunteers underwent segmental challenges with different allergen doses by two bronchoscopies 24 hours apart. They had lung MRI at baseline and 6 and 24 hours after segmental challenge. MRI TIRM scores were correlated with the eosinophilic response at 24 hours. MEASUREMENTS AND MAIN RESULTS: In patients with asthma, there were significant differences of eosinophil percentages in BAL at 24 hours from segments given standard-dose, low-dose, or no allergen (saline) (P < 0.001). Correspondingly significant differences between the TIRM score in allergen standard-dose, low-dose, and saline-treated segments were observed at 24 hours post-challenge (P < 0.001). With increasing TIRM score at 24 hours the percent eosinophils per segment 24 hours post-challenge also increased accordingly (P < 0.001). There was interobserver agreement for TIRM score grading (kappa = 0.72 for 24-h time point). CONCLUSIONS: The MRI-based noninvasive TIRM score is a promising biomarker for the noninvasive detection of the inflammatory response after segmental allergen challenge in patients with asthma and may serve to monitor the therapeutic effectiveness of novel antiinflammatory drugs in future human trials.

Determinants of malaria prophylaxis among German travelers to Kenya, Senegal, and Thailand.

BACKGROUND: Malaria chemoprophylaxis is a mainstay of malaria prevention in travelers. Adequate pretravel advice forms the basis for efficient malaria prophylaxis. This study assessed the determinants for seeking pretravel advice and evaluated the quality of advice from each source and its influence on the patterns and outcome of malaria prophylaxis intake. METHODS: In March and April 2004, a self-administered questionnaire was distributed by cabin crews to passengers flying back to Germany from three popular tourist destinations: Kenya, Senegal, and Thailand. To evaluate the quality of advice and actual intake, figures were assessed against the official recommendations of the German Society of Travel Medicine and International Health (DTG). RESULTS: A total of 1,001 passengers were included in the study (Kenya, 492; Senegal, 131; and Thailand, 378), of which 81% had sought any kind of pretravel health advice. Travelers' age and time of pretravel consultation were associated with the source of information consulted. Seventy-five percent of travelers from Senegal and Kenya received DTG compliant advice compared to only 17% of travelers from areas with low malaria risk in Thailand. Travelers returning from Kenya and Senegal had used correct chemoprophylaxis in only 65 and 47% of trips, respectively. In multivariate analysis, the factors determining correct intake among Senegal and Kenya travelers were receiving pretravel advice (from nonmedical professionals: OR 4.4, 95% CI 1.9-10.0 and from medical professionals: OR 15.4, 95% CI 7.3-32.4), a correct risk perception (OR 2.9, 95% CI 1.9-4.5), 2 to 3 weeks of travel abroad (vs a duration >3 wk: OR 2.2, 95% CI 1.3-3.8), and travel to Kenya (OR 1.9, 95% CI 1.1-3.1). CONCLUSIONS: Malaria prevention among a large proportion of German travelers to tropical destinations is inadequate. Public health efforts should be made to raise awareness among travelers, travel agencies, and medical institutions in Germany.

Response to tick-borne encephalitis (TBE) booster vaccination after prolonged time intervals to primary immunization with the rapid schedule.

Tick-borne encephalitis can be prevented by active immunization, for which different schedules and booster recommendations exist. However, recommended booster intervals are often exceeded. In the present study, 178 adults aged 18-81 years received the first booster dose 2-11 years after primary immunization (instead of 12-18 months as recommended) according to the rapid schedule (vaccination on days 0, 7, and 21). The booster dose was well tolerated. All subjects showed a typical anamnestic response with an 11-fold increase in the geometric mean titre as measured both by neutralization test and ELISA.

Risk and spectrum of diseases in travelers to popular tourist destinations.

BACKGROUND: Traveling to tropical regions is related to increased health risks. Travelers' diarrhea is the most frequent health problem, but the range of travel-related diseases also includes potential life-threatening diseases such as malaria. The actual risk of European travelers acquiring specific infectious diseases and other hazards in the tropics is to a large extent unknown and is therefore often adopted from that of the indigenous population. The objective of this study was to elucidate the risk for travel-related diseases, symptoms, and accidents in a population of Europeans who travel to popular tourist destinations. METHODS: From July 2003 to June 2004, 794 travelers consulting the travel clinic of the Berlin Institute of Tropical Medicine were recruited for a questionnaire-based observational study before traveling to Kenya, Tanzania, Senegal, the Gambia, India, Nepal, Thailand, or Brazil. RESULTS: Overall, illness was reported by 42.9% of travelers, with 10.2% reporting more than one adverse health event. Most frequently gastrointestinal symptoms were noted (34.6%), followed by respiratory symptoms (13.7%). More than 5% experienced an accident. Travel to the Indian subcontinent nearly doubled the risk of becoming ill; travel to Thailand significantly decreased the risk. Additional risk factors were a long duration of staying abroad, young age, and traveling under basic conditions. Of all travelers, 80% did not follow the traditionally recommended dietary restrictions. Among travelers visiting malaria-endemic areas, 20% did not carry any antimalarial drugs with them, not continuous chemoprophylaxis or standby medication. CONCLUSIONS: Because of the rising travel activity, especially to tropical countries, the importance of qualified pretravel advice consultation is increasing. To improve the travelers' health, attention needs to be paid to individual risk factors, the prevention and therapy of travelers' diarrhea, malaria prophylaxis, management of respiratory illness, and personal safety.

Immunisations in solid-organ transplant recipients.

Solid-organ transplant recipients are at increased risk of various infectious diseases, some of which are vaccine preventable mmunisations are among the most efficient interventions available. Solid-organ tranplant recipients would greatly benefit from effective immunisations, provided the recommendations are based on a careful risk-benefit analysis in which the effectiveness of the vaccine is weighed against possible adverse reactions, including graft rejection. In this review, we summarise the data from studies on relevant immunisations in solid-organ transplant recipients. The major issues are the immunogenicity and safety of immunisations, the factors associated with poor immune response, and recommendations for immunisation schemes.