Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage.

Plasmodium gene functions in mosquito and liver stages remain poorly characterized due to limitations in the throughput of phenotyping at these stages. To fill this gap, we followed more than 1,300 barcoded P. berghei mutants through the life cycle. We discover 461 genes required for efficient parasite transmission to mosquitoes through the liver stage and back into the bloodstream of mice. We analyze the screen in the context of genomic, transcriptomic, and metabolomic data by building a thermodynamic model of P. berghei liver-stage metabolism, which shows a major reprogramming of parasite metabolism to achieve rapid growth in the liver. We identify seven metabolic subsystems that become essential at the liver stages compared with asexual blood stages: type II fatty acid synthesis and elongation (FAE), tricarboxylic acid, amino sugar, heme, lipoate, and shikimate metabolism. Selected predictions from the model are individually validated in single mutants to provide future targets for drug development.

Moving on: How malaria parasites exit the liver.

An essential step in the life cycle of malaria parasites is their egress from hepatocytes, which enables the transition from the asymptomatic liver stage to the pathogenic blood stage of infection. To exit the liver, Plasmodium parasites first disrupt the parasitophorous vacuole membrane that surrounds them during their intracellular replication. Subsequently, parasite-filled structures called merosomes emerge from the infected cell. Shrouded by host plasma membrane, like in a Trojan horse, parasites enter the vasculature undetected by the host immune system and travel to the lung where merosomes rupture, parasites are released, and the blood infection stage begins. This complex, multi-step process must be carefully orchestrated by the parasite and requires extensive manipulation of the infected host cell. This review aims to outline the known signaling pathways that trigger exit, highlight Plasmodium proteins that contribute to the release of liver-stage merozoites, and summarize the accompanying changes to the hepatic host cell.

Comparative proteomics of vesicles essential for the egress of Plasmodium falciparum gametocytes from red blood cells.

Transmission of malaria parasites to the mosquito is mediated by sexual precursor cells, the gametocytes. Upon entering the mosquito midgut, the gametocytes egress from the enveloping erythrocyte while passing through gametogenesis. Egress follows an inside-out mode during which the membrane of the parasitophorous vacuole (PV) ruptures prior to the erythrocyte membrane. Membrane rupture requires exocytosis of specialized egress vesicles of the parasites; that is, osmiophilic bodies (OBs) involved in rupturing the PV membrane, and vesicles that harbor the perforin-like protein PPLP2 (here termed P-EVs) required for erythrocyte lysis. While some OB proteins have been identified, like G377 and MDV1/Peg3, the majority of egress vesicle-resident proteins is yet unknown. Here, we used high-resolution imaging and BioID methods to study the two egress vesicle types in Plasmodium falciparum gametocytes. We show that OB exocytosis precedes discharge of the P-EVs and that exocytosis of the P-EVs, but not of the OBs, is calcium sensitive. Both vesicle types exhibit distinct proteomes with the majority of proteins located in the OBs. In addition to known egress-related proteins, we identified novel components of OBs and P-EVs, including vesicle-trafficking proteins. Our data provide insight into the immense molecular machinery required for the inside-out egress of P. falciparum gametocytes.

Disruption of a Plasmodium falciparum patatin-like phospholipase delays male gametocyte exflagellation.

An essential process in transmission of the malaria parasite to the Anopheles vector is the conversion of mature gametocytes into gametes within the mosquito gut, where they egress from the red blood cell (RBC). During egress, male gametocytes undergo exflagellation, leading to the formation of eight haploid motile microgametes, while female gametes retain their spherical shape. Gametocyte egress depends on sequential disruption of the parasitophorous vacuole membrane and the host cell membrane. In other life cycle stages of the malaria parasite, phospholipases have been implicated in membrane disruption processes during egress, however their importance for gametocyte egress is relatively unknown. Here, we performed comprehensive functional analyses of six putative phospholipases for their role during development and egress of Plasmodium falciparum gametocytes. We localize two of them, the prodrug activation and resistance esterase (PF3D7_0709700) and the lysophospholipase 1 (PF3D7_1476700), to the parasite plasma membrane. Subsequently, we show that disruption of most of the studied phospholipase genes does neither affect gametocyte development nor egress. The exception is the putative patatin-like phospholipase 3 (PF3D7_0924000), whose gene deletion leads to a delay in male gametocyte exflagellation, indicating an important, albeit not essential, role of this enzyme in male gametogenesis.

A malaria parasite phospholipase facilitates efficient asexual blood stage egress.

Malaria parasite release (egress) from host red blood cells involves parasite-mediated membrane poration and rupture, thought to involve membrane-lytic effector molecules such as perforin-like proteins and/or phospholipases. With the aim of identifying these effectors, we disrupted the expression of two Plasmodium falciparum perforin-like proteins simultaneously and showed that they have no essential roles during blood stage egress. Proteomic profiling of parasite proteins discharged into the parasitophorous vacuole (PV) just prior to egress detected the presence in the PV of a lecithin:cholesterol acyltransferase (LCAT; PF3D7_0629300). Conditional ablation of LCAT resulted in abnormal egress and a reduced replication rate. Lipidomic profiles of LCAT-null parasites showed drastic changes in several phosphatidylserine and acylphosphatidylglycerol species during egress. We thus show that, in addition to its previously demonstrated role in liver stage merozoite egress, LCAT is required to facilitate efficient egress in asexual blood stage malaria parasites.

Direct cellular reprogramming techniques for cardiovascular regenerative therapeutics.

Cardiovascular diseases remain a leading cause of hospitalization affecting approximately 38 million people worldwide. While pharmacological and revascularization techniques can improve the patient's survival and quality of life, they cannot help reversing myocardial infarction injury and heart failure. Direct reprogramming of somatic cells to cardiomyocyte and cardiac progenitor cells offers a new approach to cellular reprogramming and paves the way for translational regenerative medicine. Direct reprogramming can bypass the pluripotent stage with the potential advantage of non-immunogenic cell products, reduced carcinogenic risk, and no requirement for embryonic tissue. The process of directly reprogramming cardiac cells was first achieved through the overexpression of transcription factors such as GATA4, MEF2C, and TBX5. However, over the past decade, significant work has been focused on enhancing direct reprogramming using a mixture of transcription factors, microRNAs, and small molecules to achieve cardiac cell fate. This review discusses the evolution of direct reprogramming, recent progress in achieving efficient cardiac cell fate conversion, and describes the reprogramming mechanisms at a molecular level. We also explore various viral and non-viral delivery methods currently being used to aid in the delivery of reprogramming factors to improve efficiency. However, further studies will be needed to overcome molecular and epigenetic barriers to successfully achieve translational cardiac regenerative therapeutics.

Assessing the Effect of Enzymatic Debridement on the Scar Quality in Partial-Thickness Burns to Deep Dermal Burns of the Hand: A Long-Term Evaluation.

Background and Objectives: Burn surgery on the hands is a difficult procedure due to the complex anatomy and fragility of the area. Enzymatic debridement has been shown to effectively remove burn eschar while minimizing damage to the surrounding tissue and has therefore become a standard procedure in many burn centers worldwide over the past decade. However, surprisingly, our recent literature review showed limited valid data on the long-term scarring after the enzymatic debridement of the hands. Therefore, we decided to present our study on this topic to fill this gap. Materials and Methods: This study analyzed partial-thickness to deep dermal burns on the hands that had undergone enzymatic debridement at least 12 months prior. Objective measures, like flexibility, trans-epidermal water loss, erythema, pigmentation, and microcirculation, were recorded and compared intraindividually to the uninjured skin in the same area of the other hand to assess the regenerative potential of the skin after EDNX. The subjective scar quality was evaluated using the patient and observer scar assessment scale (POSAS), the Vancouver Scar Scale (VSS), and the "Disabilities of the Arm, Shoulder, and Hand" (DASH) questionnaire and compared interindividually to a control group of 15 patients who had received traditional surgical debridement for hand burns of the same depth. Results: Between January 2014 and December 2015, 31 hand burns in 28 male and 3 female patients were treated with enzymatic debridement. After 12 months, the treated wounds showed no significant differences compared to the untreated skin in terms of flexibility, trans-epidermal water loss, pigmentation, and skin surface. However, the treated wounds still exhibited significantly increased blood circulation and erythema compared to the untreated areas. In comparison to the control group who received traditional surgical debridement, scarring was rated as significantly superior. Conclusions: In summary, it can be concluded that the objective skin quality following enzymatic debridement is comparable to that of healthy skin after 12 months and subjectively fares better than that after tangential excision. This confirms the superiority of enzymatic debridement in the treatment of deep dermal burns of the hand and solidifies its position as the gold standard.

Functional inactivation of Plasmodium falciparum glycogen synthase kinase GSK3 modulates erythrocyte invasion and blocks gametocyte maturation.

Malaria is responsible for hundreds of thousands of deaths every year. The lack of an effective vaccine and the global spread of multidrug resistant parasites hampers the fight against the disease and underlines the need for new antimalarial drugs. Central to the pathogenesis of malaria is the proliferation of Plasmodium parasites within human erythrocytes. Parasites invade erythrocytes via a coordinated sequence of receptor-ligand interactions between the parasite and the host cell. Posttranslational modifications such as protein phosphorylation are known to be key regulators in this process and are mediated by protein kinases. For several parasite kinases, including the Plasmodium falciparum glycogen synthase kinase 3 (PfGSK3), inhibitors have been shown to block erythrocyte invasion. Here, we provide an assessment of PfGSK3 function by reverse genetics. Using targeted gene disruption, we show the active gene copy, PfGSK3ß, is not essential for asexual blood stage proliferation, although it modulates efficient erythrocyte invasion. We found functional inactivation leads to a 69% decreased growth rate and confirmed this growth defect by rescue experiments with wildtype and catalytically inactive mutants. Functional knockout of PfGSK3ß does not lead to transcriptional upregulation of the second copy of PfGSK3. We further analyze expression, localization, and function of PfGSK3ß during gametocytogenesis using a parasite line allowing conditional induction of sexual commitment. We demonstrate PfGSK3ß-deficient gametocytes show a strikingly malformed morphology leading to the death of parasites in later stages of gametocyte development. Taken together, these findings are important for our understanding and the development of PfGSK3 as an antimalarial target.

Association between vitamin D status and eryptosis-results from the German National Cohort Study.

Vitamin D, besides its classical effect on mineral homeostasis and bone remodeling, can also modulate apoptosis. A special form of apoptosis termed eryptosis appears in erythrocytes. Eryptosis is characterized by cell shrinkage, membrane blebbing, and cell membrane phospholipid disorganization and associated with diseases such as sepsis, malaria or iron deficiency, and impaired microcirculation. To our knowledge, this is the first study that linked vitamin D with eryptosis in humans. This exploratory cross-sectional trial investigated the association between the vitamin D status assessed by the concentration of plasma 25-hydroxyvitamin D (25(OH)D) and eryptosis. Plasma 25(OH)D was analyzed by LC-MS/MS, and eryptosis was estimated from annexin V-FITC-binding erythrocytes by FACS analysis in 2074 blood samples from participants of the German National Cohort Study. We observed a weak but clear correlation between low vitamin D status and increased eryptosis (r = - 0.15; 95% CI [- 0.19, - 0.10]). There were no differences in plasma concentrations of 25(OH)D and eryptosis between male and female subjects. This finding raises questions of the importance of vitamin D status for eryptosis in terms of increased risk for anemia or cardiovascular events.

CRISPR activation of endogenous genes reprograms fibroblasts into cardiovascular progenitor cells for myocardial infarction therapy.

Fibroblasts can be reprogrammed into cardiovascular progenitor cells (CPCs) using transgenic approaches, although the underlying mechanism remains unclear. We determined whether activation of endogenous genes such as Gata4, Nkx2.5, and Tbx5 can rapidly establish autoregulatory loops and initiate CPC generation in adult extracardiac fibroblasts using a CRISPR activation system. The induced fibroblasts (>80%) showed phenotypic changes as indicated by an Nkx2.5 cardiac enhancer reporter. The progenitor characteristics were confirmed by colony formation and expression of cardiovascular genes. Cardiac sphere induction segregated the early and late reprogrammed cells that can generate functional cardiomyocytes and vascular cells in vitro. Therefore, they were termed CRISPR-induced CPCs (ciCPCs). Transcriptomic analysis showed that cell cycle and heart development pathways were important to accelerate CPC formation during the early reprogramming stage. The CRISPR system opened the silenced chromatin locus, thereby allowing transcriptional factors to access their own promoters and eventually forming a positive feedback loop. The regenerative potential of ciCPCs was assessed after implantation in mouse myocardial infarction models. The engrafted ciCPCs differentiated into cardiovascular cells in vivo but also significantly improved contractile function and scar formation. In conclusion, multiplex gene activation was sufficient to drive CPC reprogramming, providing a new cell source for regenerative therapeutics.

[Acute heart failure and cardiogenic shock : An update]. / Akute Herzinsuffizienz und kardiogener Schock : Ein Update.

Acute heart failure is a clinical syndrome resulting from elevated intracardiac filling pressures and a systemic venous congestion. In general, patients can present acutely without a history of structural cardiac disease (de novo heart failure) or with acute worsening of a pre-existing dysfunction of the right or left ventricle. The patient population is overall very inhomogeneous and as a result there is also a distinct heterogeneity with respect to the underlying cardiac pathology that leads to the acute presentation. Ultimately, ventricular dysfunction leads to increased preload and afterload resulting in decreased perfusion and retrograde congestion. The forward failure (hypoperfusion) and backwards failure (systemic congestion) can lead to impaired end organ function or even organ failure resulting in cardiogenic shock, in which sufficient organ and tissue perfusion is no longer possible. Consequently, therapeutic strategies currently focus on rectification of the underlying cardiac dysfunction, reduction of volume overload (decongestion) and hemodynamic stabilization with drugs supporting the circulation in the case of a hypoperfusion syndrome. Despite numerous new therapeutic strategies within the last two decades, the empirical data based on randomized trials is considerably less solid than in chronic heart failure, which is expressed in the almost unchanged 1­year mortality of approximately 20-30%.

Whole-body diffusion magnetic resonance imaging with simultaneous multi-slice excitation in children and adolescents.

BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) is an increasingly used guideline-based imaging modality for oncological and non-oncological pathologies during childhood and adolescence. While diffusion-weighted imaging (DWI), a part of WB-MRI, enhances image interpretation and improves sensitivity, it also requires the longest acquisition time during a typical WB-MRI scan protocol. Interleaved short tau inversion recovery (STIR) DWI with simultaneous multi-slice (SMS) acquisition is an effective way to speed up examinations. OBJECTIVE: In this study of children and adolescents, we compared the acquisition time, image quality, signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) values of an interleaved STIR SMS-DWI sequence with a standard non-accelerated DWI sequence for WB-MRI. MATERIALS AND METHODS: Twenty children and adolescents (mean age: 13.9 years) who received two WB-MRI scans at a maximum interval of 18 months, consisting of either standard DWI or SMS-DWI MRI, respectively, were included. For quantitative evaluation, the signal-to-noise ratio (SNR) was determined for b800 images and ADC maps of seven anatomical regions. Image quality evaluation was independently performed by two experienced paediatric radiologists using a 5-point Likert scale. The measurement time per slice stack, pause between measurements including shim and total measurement time of DWI for standard DWI and SMS-DWI were extracted directly from the scan data. RESULTS: When including the shim duration, the acquisition time for SMS-DWI was 43% faster than for standard DWI. Qualitatively, the scores of SMS-DWI were higher in six locations in the b800 images and four locations in the ADC maps. There was substantial agreement between both readers, with a Cohen's kappa of 0.75. Quantitatively, the SNR in the b800 images and the ADC maps did not differ significantly from one another. CONCLUSION: Whole body-MRI with SMS-DWI provided equivalent image quality and reduced the acquisition time almost by half compared to the standard WB-DWI protocol.

The performance of clinical risk scores in the diagnosis of necrotising fasciitis.

OBJECTIVE: Necrotising fasciitis (NF) is a quickly progressing and potentially life-threatening infection, involving the fascia and subcutaneous tissues. The diagnosis of this disease is challenging, especially due to a lack of specific clinical signs. In order to ensure a better and quicker identification of NF patients, a laboratory risk indicator score has been developed for NF (LRINEC). A variant has widened this score by adding clinical parameters (modified LRINEC). This study shows current outcomes of NF and compares the two scoring systems. METHODS: This study was conducted between 2011 and 2018, and included patient demographics, clinical presentations, sites of infection, comorbidities, microbiological and laboratory findings, antibiotic therapies and LRINEC as well as modified LRINEC scores. The primary outcome was in-hospital mortality. RESULTS: A cohort of 36 patients, diagnosed with NF, were included in this study. The mean hospital stay was 56 days (±38.2 days). The mortality rate in the cohort was 25%. The sensitivity of the LRINEC score was 86%. Calculation of the modified LRINEC score showed an improvement of the sensitivity to 97%. The average LRINEC score and modified LRINEC score for patients who died and who survived were equal (7.4 versus 7.9 and 10.4 versus 10.0, respectively). CONCLUSION: The mortality rate of NF remains high. The modified LRINEC score increased the sensitivity in our cohort to 97%, and this scoring system could be supportive in the diagnosis of NF for early surgical debridement.

[Academic Careers in Medicine: a Sex-Related Analysis of Career Goals]. / Akademische Karriere in der Medizin: eine geschlechterbezogene Analyse zu beruflichen Zielen.

AIM OF THE STUDY: For female and male physicians of the clinical-academic mid-level staff, working conditions as well as the attitude towards profession and career play a decisive role. For years, there has been an increasing proportion of women in medicine. Despite this increase, a significant sex incongruence is still evident, especially in academic medicine. The aim of this work was to analyze current opinions of female and male physicians on sex-related aspects for career. METHODS: By means of an online survey, medical mid-level staff from university and peripheral hospitals were asked about professional biographical as well as career-related topics and the data analyzed in terms of the sexes. RESULTS: Compared to their male counterparts, female physicians had lower career goals and mainly aimed to qualify as senior physicians. Women planned to have families and raise children earlier in their careers. Men were more likely to have their professional careers in mind during the same time period. Although only just under 47% of respondents considered an academic career to be worthwhile, 65% continued to rate the acquisition of an academic title highly. When evaluating equal treatment by superiors, female physicians tended to feel disadvantaged in their professional careers compared to male physicians. Thus, physicians rated the treatment by their respective superiors as characterized by the quality of the work (44% for both genders of superiors) or dependent on sympathy (female superiors 30%; male superiors 24%). Female physicians, however, saw a preference for male colleagues in 37% of male superiors. CONCLUSION: Despite a significantly larger proportion of women in medicine for decades, there is still an incongruence in sexes in favor of men in management positions. The professional and private goals of women and men differ significantly depending on their age decade. The academic career per se is increasingly losing importance, although the acquisition of academic degrees still seems to be desirable. Therefore, to improve the future of academic medicine, significant structural changes are needed to enable projectable career paths (e. g., tenure track, assistant professorship, young medical professionals model) for mid-level academic staff.

The effectiveness of cognitive behavioural therapy for social anxiety disorder in routine clinical practice.

Numerous randomized controlled trials have shown cognitive behaviour therapy (CBT) to be effective in treating social anxiety disorder (SAD). Yet, less is known about the effectiveness of CBT for SAD conducted by psychotherapists in training in routine clinical practice. In this study, 231 patients with SAD were treated with CBT under routine conditions and were examined at pre- and post-treatment as well as at 6 and 12 months follow-up. We applied self-reports to assess symptoms of SAD (defined as primary outcome), depression and psychological distress (defined as secondary outcome). We conducted both completer and intent-to-treat analyses and also assessed the reliability of change with the reliable change index. Results revealed significant reductions in symptoms of SAD between pre- and post-assessments, with effect sizes ranging from d = 0.9 to 1.2. Depending on the SAD specific questionnaire applied, 47.8% to 73.5% of the sample showed a reliable positive change, whereas 1.9% to 3.8% showed a reliable negative change. Depressive symptoms and psychological distress also decreased significantly from pre- to post-assessment, with large effect sizes. Significant treatment gains regarding both primary and secondary outcomes were further observed at 6 and 12 months follow-up. The current findings based on a large sample of patients suggest that psychotherapists in CBT training working under routine conditions can effectively treat symptoms of SAD, depression and psychological distress.

[Changes in the routine work and moral distress in psychiatric care during the COVID-19 pandemic : A survey among physicians active in inpatient care in Germany]. / Änderungen des Arbeitsalltags und Moral Distress in der psychiatrischen Versorgung während der COVID-19-Pandemie : Eine Umfrage unter stationär tätigen Ärzt*innen in Deutschland.

BACKGROUND: During the COVID-19 pandemic a number of ethical challenges have arisen in the healthcare system. A psychological response to moral challenges is termed moral distress (MD). OBJECTIVE: Identification of causes of MD in inpatient psychiatric care in the context of the COVID-19 pandemic in Germany. MATERIAL AND METHODS: A survey was conducted using a self-administered non-validated online questionnaire as part of a cross-sectional study, in which 26 items about the experience of MD were examined and open questions about the handling of the pandemic and its effects on everyday work were posed. Physicians who worked in inpatient psychiatric care during the COVID-19 pandemic in Germany were surveyed anonymously with a convenience sample. The data acquisition took place between 17 November 2020 and 6 May 2021. RESULTS: A total of 141 participants were included. They indicated multiple pandemic-related changes in their daily work partly resulting in MD. CONCLUSION: MD is a neglected potential burden of inpatient psychiatric care under pandemic conditions (and beyond), which requires further research and an adequate handling. These results include implications for decision makers in crisis teams as well as a need for support services such as clinical ethics consultation services.

Atlas of type 2 dopamine receptors in the human brain: Age and sex dependent variability in a large PET cohort.

BACKGROUND: The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. METHODS: In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. RESULTS: Striatal D2R availability decreased through age for both sexes (2-5 % in striatal ROIs per 10 years) and was higher in females versus males throughout age (7-8% in putamen). BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). CONCLUSIONS: D2R availability is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.

Identification of novel inner membrane complex and apical annuli proteins of the malaria parasite Plasmodium falciparum.

The inner membrane complex (IMC) is a defining feature of apicomplexan parasites, which confers stability and shape to the cell, functions as a scaffolding compartment during the formation of daughter cells and plays an important role in motility and invasion during different life cycle stages of these single-celled organisms. To explore the IMC proteome of the malaria parasite Plasmodium falciparum we applied a proximity-dependent biotin identification (BioID)-based proteomics approach, using the established IMC marker protein Photosensitized INA-Labelled protein 1 (PhIL1) as bait in asexual blood-stage parasites. Subsequent mass spectrometry-based peptide identification revealed enrichment of 12 known IMC proteins and several uncharacterized candidate proteins. We validated nine of these previously uncharacterized proteins by endogenous GFP-tagging. Six of these represent new IMC proteins, while three proteins have a distinct apical localization that most likely represents structures described as apical annuli in Toxoplasma gondii. Additionally, various Kelch13 interacting candidates were identified, suggesting an association of the Kelch13 compartment and the IMC in schizont and merozoite stages. This work extends the number of validated IMC proteins in the malaria parasite and reveals for the first time the existence of apical annuli proteins in P. falciparum. Additionally, it provides evidence for a spatial association between the Kelch13 compartment and the IMC in late blood-stage parasites.

Ultrashort echo time MRI of the lung in children and adolescents: comparison with non-enhanced computed tomography and standard post-contrast T1w MRI sequences.

OBJECTIVES: To compare the diagnostic value of ultrashort echo time (UTE) magnetic resonance imaging (MRI) for the lung versus the gold standard computed tomography (CT) and two T1-weighted MRI sequences in children. METHODS: Twenty-three patients with proven oncologic disease (14 male, 9 female; mean age 9.0 + / - 5.4 years) received 35 low-dose CT and MRI examinations of the lung. The MRI protocol (1.5-T) included the following post-contrast sequences: two-dimensional (2D) incoherent gradient echo (GRE; acquisition with breath-hold), 3D volume interpolated GRE (breath-hold), and 3D high-resolution radial UTE sequences (performed during free-breathing). Images were evaluated by considering image quality as well as distinct diagnosis of pulmonary nodules and parenchymal areal opacities with consideration of sizes and characterisations. RESULTS: The UTE technique showed significantly higher overall image quality, better sharpness, and fewer artefacts than both other sequences. On CT, 110 pulmonary nodules with a mean diameter of 4.9 + / - 2.9 mm were detected. UTE imaging resulted in a significantly higher detection rate compared to both other sequences (p < 0.01): 76.4% (84 of 110 nodules) for UTE versus 60.9% (67 of 110) for incoherent GRE and 62.7% (69 of 110) for volume interpolated GRE sequences. The detection of parenchymal areal opacities by the UTE technique was also significantly higher with a rate of 93.3% (42 of 45 opacities) versus 77.8% (35 of 45) for 2D GRE and 80.0% (36 of 45) for 3D GRE sequences (p < 0.05). CONCLUSION: The UTE technique for lung MRI is favourable in children with generally high diagnostic performance compared to standard T1-weighted sequences as well as CT. Key Points • Due to the possible acquisition during free-breathing of the patients, the UTE MRI sequence for the lung is favourable in children. • The UTE technique reaches higher overall image quality, better sharpness, and lower artefacts, but not higher contrast compared to standard post-contrast T1-weighted sequences. • In comparison to the gold standard chest CT, the detection rate of small pulmonary nodules small nodules ≤ 4 mm and subtle parenchymal areal opacities is higher with the UTE imaging than standard T1-weighted sequences.

Surgical treatment of mechanical bowel obstruction: characteristics and outcomes of geriatric patients compared to a younger cohort.

PURPOSE: Mechanical bowel obstruction (MBO) is one of the most common indications for emergency surgery. Recent research justifies the method of attempting 3-5 days of nonoperative treatment before surgery. However, little is known about specific characteristics of geriatric patients undergoing surgery compared to a younger cohort. We aimed to analyze patients with MBO that required surgery, depending on their age, to identify potential targets for use in the reduction in complications and mortality in the elderly. METHODS: Thirty-day and in-hospital mortality were determined as primary outcome. We retrospectively identified all patients who underwent surgery for MBO at the University Hospital of Bonn between 2009 and 2019 and divided them into non-geriatric (40-74 years, n = 224) and geriatric (≥ 75 years, n = 88) patients, using the chi-squared-test and Mann-Whitney U test for statistical analysis. RESULTS: We found that geriatric patients had higher 30-day and in-hospital mortality rates than non-geriatric patients. As secondary outcome, we found that they experienced a longer length of stay (LOS) and higher complication rates than non-geriatric patients. Geriatric patients who suffered from large bowel obstruction (LBO) had a higher rate of bowel resection, stoma creation, and a higher 30-day mortality rate. The time from admission to surgery was not shown to be crucial for the outcome of (geriatric) patients. CONCLUSION: Geriatric patients suffering from mechanical bowel obstruction that had to undergo surgery had higher mortality and morbidity than non-geriatric patients. Especially in regard to geriatric patients, clinicians should treat patients in a risk-adapted rather than time-adapted manner, and conditions should be optimized before surgery.