Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver.

Normothermic machine perfusion (NMP) has emerged as an innovative organ preservation technique. Developing an understanding for the donor organ immune cell composition and its dynamic changes during NMP is essential. We aimed for a comprehensive characterization of immune cell (sub)populations, cell trafficking and cytokine release during liver NMP. Single-cell transcriptome profiling of human donor livers prior to, during NMP and after transplantation shows an abundance of CXC chemokine receptor 1+/2+ (CXCR1+/CXCR2+) neutrophils, which significantly decreased during NMP. This is paralleled by a large efflux of passenger leukocytes with neutrophil predominance in the perfusate. During NMP, neutrophils shift from a pro-inflammatory state towards an aged/chronically activated/exhausted phenotype, while anti-inflammatory/tolerogenic monocytes/macrophages are increased. We herein describe the dynamics of the immune cell repertoire, phenotypic immune cell shifts and a dominance of neutrophils during liver NMP, which potentially contribute to the inflammatory response. Our findings may serve as resource to initiate future immune-interventional studies.

Investigating self-reported efficacy of lifestyle medicine approaches to tackle erectile dysfunction: a cross-sectional eSurvey based study.

BACKGROUND: Erectile dysfunction (ED) is the most common sexual dysfunction in men. Some types of ED are amenable to treatment using lifestyle medicine approaches with or without pharmacotherapy. AIM: Investigate self-reported efficacy of lifestyle medicine approaches to tackle ED. METHODS: A cross-sectional online survey of 1177 community dwelling adults explored the prevalence and methods used to tackle ED in the community setting. We examined differences between participants with and without ED. Variables associated with ED in univariable analyses were included in a multivariable logistic regression to identify variables independently associated with the condition. OUTCOMES: Self-reported measure: perceived effectiveness of lifestyle medicine interventions to tackle ED. RESULTS: Most respondents (76.5%) had experienced ED, and this was associated with having a long-term condition, taking anti-hypertensive medication, hypercholesterolaemia and obesity. Medication was the most common management strategy overall (65.9%), followed by stress management (43.5%) and weight loss (40.4%). Over half (53.9%) did not use any lifestyle modification strategies to tackle ED. Only 7.0% of ED sufferers received a mental health assessment and 29.2% received other tests (e.g., blood test, medical imaging) by GPs. Cardiovascular training was identified as the best rated strategy by its users (37.8%). Supplements (35.1%) and weight training/physical activity (32.6%) were also positively rated. CLINICAL IMPLICATIONS: Structured education to general practitioners and community dwelling adults about the impact of lifestyle behaviour modification and how this could influence the appearance or trajectory of ED could help improve personal choice when tackling ED. STRENGTHS AND LIMITATIONS: To our knowledge, this is the first study to collect eSurvey responses from community dwelling adults to gauge their reliance and perceived effectiveness of lifestyle medicine approaches to tackle ED. The principal limitation was the lack of follow-up, and not recording other information including lifestyle factors such as nutrition, smoking, and the use of alcohol and recreational drugs, which may have enabled a fuller exploration of the factors that could influence the primary outcome measures examined. CONCLUSION: Despite the high prevalence of ED, there is not enough awareness in the community setting about effective and low-cost lifestyle medicine strategies, including cardiovascular training and the use of supplements and weight training, to help tackle this common condition.

Erectile dysfunction (ED) is the most common sexual dysfunction in men. Some types of ED can be treated using lifestyle medicine approaches with or without the use of medicines. The aim of this study was to investigate self-reported efficacy of lifestyle medicine approaches to tackle ED. We conducted a cross-sectional online survey of 1177 community dwelling adults to explore the prevalence, methods and perceived effectiveness of lifestyle medicine approaches to tackle ED in the community setting. Most respondents (76.5%) had experienced ED, and this was associated with having a long-term condition, taking anti-hypertensive medication, high blood cholesterol and obesity. After medication stress management (43.5%) and weight loss (40.4%) were most frequently cited lifestyle medicine intervention. Cardiovascular training was identified as the best rated strategy by its users (37.8%). To our knowledge, this is the first study to collect eSurvey responses from community dwelling adults to gauge their reliance and perceived effectiveness of lifestyle medicine approaches to tackle ED. Despite the high prevalence of ED, there is not enough awareness in the community setting about effective and low-cost lifestyle medicine strategies, including cardiovascular training and the use of supplements and weight training, to help tackle this common condition.

Evaluation of U.S. Army Soldiers wearing a back exosuit during a field training exercise.

Back overuse injuries are a significant problem in the U.S. Army, responsible for nearly a quarter of musculoskeletal injuries. Back exosuits are wearable devices that relieve musculoskeletal strain, make lifting easier, and could potentially reduce Soldier overuse injuries. But published studies have not evaluated exosuits during realistic field operations to assess acceptability to Soldiers. We tested a back exosuit on field artillery Soldiers during a field training exercise. Afterward, Soldiers completed a survey to quantify their satisfaction, intent to use, and performance impact of the exosuit. Feedback was overwhelmingly positive: Approximately 90% of Soldiers reported that exosuits increased their ability to perform their duties, and 100% said that if the exosuit were further developed and made available to them, they would be likely to wear it. These numerical survey results indicated that exosuits can provide a practical and acceptable way to assist lifting and augment physical performance during realistic Army operations without interfering with other duties.

Effect of pressure insole sampling frequency on insole-measured peak force accuracy during running.

Pressure sensing insoles enable us to estimate forces under the feet during activities such as running, which can provide valuable insight into human movement. Pressure insoles also afford the opportunity to collect more data in more representative environments than can be achieved in laboratory studies. One key challenge with real-world use of pressure insoles is limited battery life which restricts the amount of data that can be collected on a single charge. Reducing sampling frequency is one way to prolong battery life, at the cost of decreased measurement accuracy, but this trade-off has not been quantified, which hinders decision-making by researchers and developers. Therefore, we characterized the effect of decreasing sampling frequency on peak force estimates from pressure insoles (Novel Pedar, 100 Hz) across a range of running speeds and slopes. Data were downsampled to 50, 33, 25, 20, 16 and 10 Hz. Force peaks were extracted due to their importance in biomechanical algorithms trained to estimate musculoskeletal forces and were compared with the reference sampling frequency of 100 Hz to compute relative errors. Peak force errors increased exponentially from 0.7% (50 Hz) to 9% (10 Hz). However, peak force errors were < 3% for all sampling frequencies down to 20 Hz. For some pressure insoles, sampling rate is inversely proportional to battery life. Therefore, these findings suggest that battery life could be increased up to 5x at the expense of 3% errors. These results are encouraging for researchers aiming to deploy pressure insoles for remote monitoring or in longitudinal studies.

The liver-resident immune cell repertoire - A boon or a bane during machine perfusion?

The liver has been proposed as an important "immune organ" of the body, as it is critically involved in a variety of specific and unique immune tasks. It contains a huge resident immune cell repertoire, which determines the balance between tolerance and inflammation in the hepatic microenvironment. Liver-resident immune cells, populating the sinusoids and the space of Disse, include professional antigen-presenting cells, myeloid cells, as well as innate and adaptive lymphoid cell populations. Machine perfusion (MP) has emerged as an innovative technology to preserve organs ex vivo while testing for organ quality and function prior to transplantation. As for the liver, hypothermic and normothermic MP techniques have successfully been implemented in clinically routine, especially for the use of marginal donor livers. Although there is evidence that ischemia reperfusion injury-associated inflammation is reduced in machine-perfused livers, little is known whether MP impacts the quantity, activation state and function of the hepatic immune-cell repertoire, and how this affects the inflammatory milieu during MP. At this point, it remains even speculative if liver-resident immune cells primarily exert a pro-inflammatory and hence destructive effect on machine-perfused organs, or in part may be essential to induce liver regeneration and counteract liver damage. This review discusses the role of hepatic immune cell subtypes during inflammatory conditions and ischemia reperfusion injury in the context of liver transplantation. We further highlight the possible impact of MP on the modification of the immune cell repertoire and its potential for future applications and immune modulation of the liver.

Erythropoietin-driven dynamic proteome adaptations during erythropoiesis prevent iron overload in the developing embryo.

Erythropoietin (Epo) ensures survival and proliferation of colony-forming unit erythroid (CFU-E) progenitor cells and their differentiation to hemoglobin-containing mature erythrocytes. A lack of Epo-induced responses causes embryonic lethality, but mechanisms regulating the dynamic communication of cellular alterations to the organismal level remain unresolved. By time-resolved transcriptomics and proteomics, we show that Epo induces in CFU-E cells a gradual transition from proliferation signature proteins to proteins indicative for differentiation, including heme-synthesis enzymes. In the absence of the Epo receptor (EpoR) in embryos, we observe a lack of hemoglobin in CFU-E cells and massive iron overload of the fetal liver pointing to a miscommunication between liver and placenta. A reduction of iron-sulfur cluster-containing proteins involved in oxidative phosphorylation in these embryos leads to a metabolic shift toward glycolysis. This link connecting erythropoiesis with the regulation of iron homeostasis and metabolic reprogramming suggests that balancing these interactions is crucial for protection from iron intoxication and for survival.

Tibial bone forces can be monitored using shoe-worn wearable sensors during running.

Tibial bone stress injury is a common overuse injury experienced by runners, which results from repetitive tissue forces. Wearable sensor systems (wearables) that monitor tibial forces could help understand and reduce injury incidence. However, there are currently no validated wearables that monitor tibial bone forces. Previous work using simulated wearables demonstrated accurate tibial force estimates by combining a shoe-worn inertial measurement unit (IMU) and pressure insole with a trained algorithm. This study aimed assessed how accurately tibial bone forces could be estimated with existing wearables. Nine recreational runners ran at a series of different speeds and slopes, and with various stride patterns. Shoe-worn IMU and insole data were input into a trained algorithm to estimate peak tibial force. We found an average error of 5.7% in peak tibial force estimates compared with lab-based estimates calculated using motion capture and a force instrumented treadmill. Insole calibration procedures were essential to achieving accurate tibial force estimates. We concluded that a shoe-worn, multi-sensor system is a promising approach to monitoring tibial bone forces in running. This study adds to the literature demonstrating the potential of wearables to monitor musculoskeletal forces, which could positively impact injury prevention, and scientific understanding.

Treatment Efficacy Score-continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials.

BACKGROUND: Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on downstaging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments. PATIENTS AND METHODS: The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms. TES is based on a modified Kolmogorov-Smirnov test with added weight function to capture the importance of high RCB values and uses the area under the difference between two distribution functions as a statistical metric. The higher the TES the greater the shift to lower RCB values in the experimental arm. We developed TES from the durvalumab + olaparib arm (n = 72) and corresponding controls (n = 282) of the I-SPY2 trial. The 11 other experimental arms and control cohorts (n = 947) were used as validation sets to assess the performance of TES. We compared TES to Kolmogorov-Smirnov, Mann-Whitney, and Fisher's exact tests to identify trial arms with higher cytotoxic efficacy and assessed associations with trial arm level survival differences. Significance was assessed with a permutation test. RESULTS: In the validation set, TES identified arms with a higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if the pCR rate improved. The correlation between TES and survival was higher than the correlation between the pCR rate difference and survival. CONCLUSIONS: TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone.

Phytochemical Characterization, Antioxidant Activity, and Cytotoxicity of Methanolic Leaf Extract of Chlorophytum Comosum (Green Type) (Thunb.) Jacq.

Chlorophytum genus has been extensively studied due to its diverse biological activities. We evaluated the methanolic extract of leaves of Chlorophytum comosum (Green type) (Thunb.) Jacques, the species that is less studied compared to C. borivilianum. The aim was to identify phytoconstituents of the methanolic extract of leaves of C. comosum and biological properties of its different fractions. Water fraction was analyzed with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Nineteen compounds belonging to different chemical classes were identified in the methanolic extract of leaves of C. comosum (Green type) (Thunb.) Jacques. In addition to several fatty acids, isoprenoid and steroid compounds were found among the most abundant constituents. One of the identified compounds, 4'-methylphenyl-1C-sulfonyl-ß-d-galactoside, was not detected earlier in Chlorophytum extracts. The water fraction was toxic to HeLa cells but not to Vero cells. Our data demonstrate that methanolic extract of leaves of C. comosum can be a valuable source of bioactive constituents. The water fraction of the extract exhibited promising antitumor potential based on a high ratio of HeLa vs. Vero cytotoxicity.

Improvement in colorectal cancer outcomes over time is limited to patients with left-sided disease.

PURPOSE: Incidence and mortality of colorectal cancer (CRC) declined over the last decades. However, survival depends on the primary tumor location. It is unknown if all progress in outcomes vary depending on left-sided (LCRC) versus right-sided (RCC) colorectal cancer. We compare incidence and mortality rates over time according to the primary tumor location. METHODS: Data from the Austrian National Cancer Registry spanning from 1983 to 2018 were used to calculate annual incidence and mortality rates and survival stratified by primary tumor localization and stage. Joinpoint regression with linear regression models were used on different subgroups to identify significant changes of incidence- and mortality slopes. RESULTS: A total of 168,260 (incidence dataset) and 87,355 cases (mortality dataset) were identified. Survival of disseminated RCC was worse compared to LCRC (HR 1.14; CI 1.106-1.169). Total and LCRC incidence and mortality rates declined steadily over time, whereas the rates of RCC did not. Incidence of disseminated RCC declined significantly less (slope - 0.07; CI - 0.086; - 0.055) than in LCRC (slope - 0.159; CI - 0.183; - 0.136); mortality rate of RCC was unchanged over time. Incidence and mortality of localized RCC remained unchanged over time, whereas both rates declined independently of stage in LCRC. CONCLUSION: Colorectal cancer outcomes during the last 35 years have preferentially improved in LCRC but not in RCC, indicating that the progress made is limited to LCRC. It is necessary to define RCC as a distinct form of CRC and to focus on specific strategies for its early detection and treatment.

Serologic response to COVID-19 infection and/or vaccine in cancer patients on active treatment.

BACKGROUND: It was shown that immunocompromised patients have significantly reduced immunologic responses to COVID-19 vaccines. The immunogenicity of COVID-19 vaccine/infection in patients with solid tumors is reduced. We evaluated the immunologic response to COVID-19 and/or the BNT162b2 mRNA COVID-19 vaccine among cancer patients on active treatments and reviewed previous literature to identify subgroups that may require third vaccination. PATIENTS AND METHODS: Anti-SARS-CoV-2 S1/S2 antibodies were measured in a cohort of 202 cancer patients on active treatment with chemotherapy (96), immunologic (52), biologic (46), and hormonal (12) treatments for early (n = 66, 32.7%) or metastatic disease (n = 136, 67.3%). Of those, 172 had received two vaccine doses, and 30 had COVID-19 infection (20/30 also received one dose of vaccine). Specific anti-S receptor-binding domain antibodies were further measured in patients with equivocal anti-S1/S2 results. RESULTS: Among cancer patients, the SARS-CoV-2 antibody response rate was 89.1% (180/202) after COVID-19 vaccination or infection and 87.2% (150/172) in patients after vaccination without a history of COVID-19, compared with 100% positive serologic tests in a control group of 30 health care workers (P < 0.001). Chemotherapy treatment was independently associated with significantly reduced humoral response to infection or vaccination, with an 81.3% response rate, compared with 96.2% in patients on other treatments (P = 0.001). In vaccinated patients on chemotherapy, the positive response rate was 77.5%. In a multiple regression model, a neutralizing antibody titer (>60 AU/ml) was more likely with immunotherapy (odds ratio 2.44) and less likely with chemotherapy (odds ratio 0.39). CONCLUSIONS: Overall, both COVID-19 vaccine and natural infection are highly immunogenic among cancer patients. Our study, however, identifies those under chemotherapy as significantly less responsive, and with lower antibody levels. These findings justify close virological and serological surveillance along with consideration of these patients for booster (third dose) vaccine prioritization, as new highly spreading SARS-CoV-2 variants emerge.

Ovarian follicular function is not altered by SARS-CoV-2 infection or BNT162b2 mRNA COVID-19 vaccination.

STUDY QUESTION: Does the immune response to coronavirus disease 2019 (COVID-19) infection or the BNT162b2 mRNA vaccine involve the ovarian follicle, and does it affect its function? SUMMARY ANSWER: We were able to demonstrate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG in follicular fluid (FF) from both infected and vaccinated IVF patients, with no evidence for compromised follicular function. WHAT IS KNOWN ALREADY: No research data are available yet. STUDY DESIGN, SIZE, DURATION: This is a cohort study, composed of 32 consecutive IVF patients, either infected with COVID-19, vaccinated or non-exposed, conducted between 1 February and 10 March 2021 in a single university hospital-based IVF clinic. PARTICIPANTS/MATERIALS, SETTING, METHODS: A consecutive sample of female consenting patients undergoing oocyte retrieval was recruited and assigned to one of the three study groups: recovering from confirmed COVID-19 (n = 9); vaccinated (n = 9); and uninfected, non-vaccinated controls (n = 14). Serum and FF samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and heparan sulfate proteoglycan 2 concentration, as well as the number and maturity of aspirated oocytes and day of trigger estrogen and progesterone measurements. Main outcome measures were follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers. MAIN RESULTS AND THE ROLE OF CHANCE: Both COVID-19 and the vaccine elicited anti-COVID IgG antibodies that were detected in the FF at levels proportional to the IgG serum concentration. No differences between the three groups were detected in any of the surrogate parameters for ovarian follicle quality. LIMITATIONS, REASONS FOR CAUTION: This is a small study, comprising a mixed fertile and infertile population, and its conclusions should be supported and validated by larger studies. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function and these early findings suggest no measurable detrimental effect on function of the ovarian follicle. STUDY FUNDING/COMPETING INTEREST(S): The study was funded out of an internal budget. There are no conflicts of interest for any of the authors. TRIAL REGISTRATION NUMBER: CinicalTrials.gov registry number NCT04822012.

Pro- and anti-inflammatory macrophages express a sub-type specific purinergic receptor profile.

Extracellular nucleotides act as danger signals that orchestrate inflammation by purinergic receptor activation. The expression pattern of different purinergic receptors may correlate with a pro- or anti-inflammatory phenotype. Macrophages function as pro-inflammatory M1 macrophages (M1) or anti-inflammatory M2 macrophages (M2). The present study found that murine bone marrow-derived macrophages express a unique purinergic receptor profile during in vitro polarization. As assessed by real-time polymerase chain reaction (PCR), Gαs-coupled P1 receptors A2A and A2B are upregulated in M1 and M2 compared to M0, but A2A 15 times higher in M1. The ionotropic P2 receptor P2X5 is selectively upregulated in M1- and M2-polarized macrophages. P2X7 is temporarily expressed in M1 macrophages. Metabotropic P2Y receptors showed a distinct expression profile in M1 and M2-polarized macrophages: Gαq coupled P2Y1 and P2Y6 are exclusively upregulated in M2, whereas Gαi P2Y13 and P2Y14 are overexpressed in M1. This consequently leads to functional differences between M1 and M2 in response to adenosine di-phosphate stimulation (ADP): In contrast to M1, M2 showed increased cytoplasmatic calcium after ADP stimulation. In the present study we show that bone marrow-derived macrophages express a unique repertoire of purinergic receptors. We show for the first time that the repertoire of purinergic receptors is highly flexible and quickly adapts upon pro- and anti-inflammatory macrophage differentiation with functional consequences to nucleotide stimulation.

Molecular Characterization of German Acinetobacter baumannii Isolates and Multilocus Sequence Typing (MLST) Analysis Based on WGS Reveals Novel STs.

Acinetobacter baumannii (A. baumannii) is a major cause of severe nosocomial infections worldwide. The emergence of infections associated with A. baumannii poses a significant health risk in Germany. A. baumannii is part of the ACB complex and is difficult to distinguish from other species phenotypically, necessitating its reliable identification. The current study analyzed 89 A. baumannii strains from human and non-human origins by matrix-assisted laser desorption/ionization (MALDI-TOF) and PCR detection of intrinsic blaOXA-51-like carbapenemase, blaOXA-23-like, blaOXA-24-like, blaOXA-58-like, and ISAba 1 genes. Whole-genome sequencing (WGS) was applied for species confirmation and strain type determination. Combining the molecular detection of the intrinsic blaOXA-51-like carbapenemase gene together with MALDI-TOF with a score value of >2.300 proved to be a suitable tool for A. baumannii identification. WGS data for all of the sequenced strains confirmed the identity of all A. baumannii strains. The Pasteur scheme successfully assigned 79.7% of the strains into distinct STs, while the Oxford scheme succeeded in allocating only 42.7% of isolates. Multilocus sequence typing (MLST) analysis based on the Pasteur scheme identified 16 STs. ST/241 was the most prevalent in samples from non-human origin, whereas ST/2 was predominant in human samples. Furthermore, eight isolates of non-human origin were allocated to seven new STs (ST/1410, ST/1414, ST/1416, ST/1417, ST/1418, ST/1419, and ST/1421). Ten isolates from non-human origin could not be typed since new alleles were observed in the loci Pas_cpn60, Pas_rpoB, and Pas_gltA. MLST analysis based on the Pasteur scheme was more appropriate than the Oxford scheme for the current group of A. baumannii.

Layered van der Waals Topological Metals of TaTMTe4 (TM = Ir, Rh, Ru) Family.

Layered van der Waals materials of the family TaTMTe4 (TM = Ir, Rh, Ru) are showing interesting electronic properties. We report the growth and characterization of TaIrTe4, TaRhTe4, TaIr1-xRhxTe4 (x = 0.06, 0.14, 0.78, 0.92), Ta1+xRu1-xTe4 single crystals. X-ray powder diffraction confirms that TaRhTe4 is isostructural to TaIrTe4. All these compounds are metallic with diamagnetic behavior. Below T ≈ 4 K we observed signatures of the superconductivity in the TaIr1-xRhxTe4 compounds for x = 0.92. All samples show weak quadratic-in-field magnetoresistance (MR). However, for TaIr1-xRhxTe4 with x ≈ 0.78, the MR has a linear term dominating in low fields that indicates the presence of Dirac cones in the vicinity of the Fermi energy. For TaRhTe4 series the MR is almost isotropic. Electronic structure calculations for TaIrTe4 and TaRhTe4 reveal appearance of the Rh band close to the Fermi level.

Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.

Early autologous and allogeneic peripheral blood stem cell transplantation for adult patients with acute B and T cell precursor neoplasms: a 12-year single center experience.

Adult acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a rare and heterogeneous malignancy characterized by uncontrolled proliferation of B or T cell precursor cells. Here, we retrospectively analyzed the outcome of early autologous stem cell transplantation in standard-risk patients in first complete remission (n=24) and of allogeneic transplantation in high and highest risk, and relapsed/refractory patients (n=35). The 10-year overall survival after autologous transplantation was 45%. The 10-year overall survival after allogeneic transplantation was 58%. The cumulative incidence of relapse was 29% after allogeneic and 67% after autologous transplantation. The cumulative incidence of non-relapse mortality was 0% after autologous and 12% after allogeneic transplantation. This retrospective single center analysis in a limited number of standard-risk patients clearly demonstrates that early autologous transplantation in first complete remission leads to an acceptable long-term outcome with a short overall treatment duration of less than 6 months compared with more than 2 years with conventional chemotherapy. More sensitive and standardized methods to detect minimal residual disease (MRD) will further help to identify those patients more accurately who are most likely to benefit from such a short and intensive treatment strategy (i.e., MRD negative standard-risk patients) or those who require early targeted therapy (e.g., blinatumomab) in case of MRD positivity. Early allogeneic transplantation results in long-term survival/cure in nearly two-thirds of all high and highest risk, and relapsed/refractory patients.

Infective endocarditis in patients after percutaneous pulmonary valve implantation with the stent-mounted bovine jugular vein valve: Clinical experience and evaluation of the modified Duke criteria.

AIMS: Percutaneous pulmonary valve implantation (PPVI) has proven good hemodynamic results. As infective endocarditis (IE) remains a potential complication with limited available clinical data, we reviewed our patient records to improve future strategies of IE prevention, diagnosis and treatment. METHODS: Medical records of all patients diagnosed with Melody® valve IE according to the modified Duke criteria were retrospectively analyzed in three Belgian tertiary centers. RESULTS: 23 IE episodes in 22 out of 240 patients were identified (incidence 2.4% / patient year) with a clear male predominance (86%). Median age at IE was 17.9 years (range 8.2-45.9 years) and median time from PPVI to IE was 2.4 years (range 0.7-8 years). Streptococcal species caused 10 infections (43%), followed by Staphylococcus aureus (n = 5, 22%). In 13/23 IE episodes a possible entry-point was identified (57%). IE was classified as definite in 15 (65%) and as possible in 8 (35%) cases due to limitations of imaging. Echocardiography visualized vegetations in only 10 patients. PET-CT showed positive FDG signals in 5/7 patients (71%) and intracardiac echocardiography a vegetation in 1/1 patient (100%). Eleven cases (48%) had a hemodynamically relevant pulmonary stenosis at IE presentation. Nine early and 6 late percutaneous or surgical re-interventions were performed. No IE related deaths occurred. CONCLUSIONS: IE after Melody® valve PPVI is associated with a relevant need of re-interventions. Communication to patients and physicians about risk factors is essential in prevention. The modified Duke criteria underperformed in diagnosing definite IE, but inclusion of new imaging modalities might improve diagnostic performance.

Percutaneous closure of a secundum atrial septum defect performed under hypnosis: a case report.

Atrial septal defects (ASDs) are the third most common type of congenital heart diseases with ostium secundum defects (ASDsII) being responsible for approximately 75% of these defects. The treatment consists of either a transcatheter closure or a surgical intervention. The transcatheter approach offers a less invasive alternative for patients who fulfill anatomical and size criteria and is therefore increasingly used as the preferred primary intervention. As general anaesthesia is sometimes contra-indicated for some patients needing ASD or PFO closure and intracardiac echocardiography (ICE) is not always readily available, alternative "supportive" techniques as hypnosis could be of interest. In our case, a relative contra-indication for general anaesthesia was pronounced due to the severely impaired pulmonary function caused by severe deformative torsional scoliosis. Over the years several reviews have been published on hypnotic analgesia used together with usual care suggesting that hypnotic analgesia is a promising non-pharmacologic adjunct treatment for ameliorating pain and surgical distress. Also, various cardiological procedures under hypnosis have already been described in literature, but this is the first time that percutaneous ASD closure under virtual reality (VR) hypnosis is mentioned in literature.