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The COVID-19 pandemic had an unprecedented impact on the well-being of individuals working in the healthcare sector. Though many studies exist that focus on physician and nurse well-being, few have specifically identified stressors that affect professionals working within the end-of-life interdisciplinary team. The primary objective of this study was to expand research on moral distress and clinician well-being to include healthcare professionals working with patients with chronic and life-limiting illnesses during the COVID-19 pandemic. A survey approach was used with 110 professionals working within one hospital network's palliative and hospice team to identify key indicators of moral distress (using the MMD-HP scale) and professional well-being during the pandemic. Quantitative and qualitative analysis was completed to determine themes related to moral distress and professional well-being. Numerous themes were identified, including the importance of caseload, general support, team support, management, and professional flexibility. Additional end-of-life themes were identified, including the impact of death, lack of personal protective equipment, fear of transmitting the virus, COVID disbelief, and the inability of clinicians and/or family to be with patients in person. From the experience participants had during COVID-19, four areas of change were identified: professional resilience, management/ethics support, professional development, and physical and emotional safety.

Background: Surviving sepsis can lead to chronic physical, psychological and cognitive impairments, which affect millions of patients worldwide, including survivors after COVID-19 viral sepsis. We aimed to characterize the magnitude and trajectory of functional dependence and new impairments post-sepsis., Methods: We conducted a prospective cohort study including sepsis survivors who had been discharged from five German intensive care units (ICUs), until 36 months post-discharge. Primary outcome was functional dependence, defined as ≥1 impaired activity of daily living (ADL; 10-item ADL score <100), self-reported nursing care dependence or nursing care level. Secondary outcome was post-sepsis morbidity in the physical, psychological or cognitive domain. We used a multistate, competing risk model to address competing events in the course of dependence, and conducted multiple linear regression analyses to identify predictors associated with the ADL score., Findings: Of 3210 sepsis patients screened, 1968 survived the ICU treatment (61.3%). A total of 753 were included in the follow-up assessments of the Mid-German Sepsis cohort. Patients had a median age of 65 (Q1-Q3 56-74) years, 64.8% (488/753) were male and 76.1% (573/753) had a septic shock. Considering competing risk modelling, the probability of still being functional dependent was about 25%, while about 30% regained functional independence and 45% died within the three years post-sepsis. Patients reported a high burden of new and often overlapping impairments until three years post-sepsis. In the subgroup of three-year survivors (n = 330), new physical impairments affected 91.2% (n = 301) while new cognitive and psychological impairments were reported by 57.9% (n = 191) and 40.9% (n = 135), respectively. Patients with pre-existing functional limitations and higher age were at risk for low ADL scores three years after sepsis., Interpretation: Sepsis survivorship was associated with a broad range of new impairments and led to functional dependence in around one quarter of patients. Targeted measures are needed to mitigate the burden of this Post-Sepsis-Syndrome and increase the proportion of patients that achieve functional improvements., Funding: This work was supported by the Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC) at the Jena University Hospital funded by the German Ministry of Education and Research and by the Rudolf Presl GmbH & Co, Kreischa, Germany., Competing Interests: Over the past 5 years, Sven Bercker was investigator in studies sponsored by BioMeriéux, Boehringer Ingelheim, AM-Pharma B.V., Roche, Takeda, Dompé, and he is member of a DSMB for a study sponsored by hemotune AG. He has not received any personal fees for lectures or as a consultant or any reimbursement of travel expenses outside the sponsored studies. Konrad Reinhart holds shares from InflaRx NV, which is based in Jena, Germany and listed at NASDQ. This company recently received emergency use authorization by the FDA for an antibody against C5a—Gohibic (vilobelimab)—to treat critically ill COVID-19 patients, which fulfill the criteria for viral sepsis. E. Wesley Ely received NIH/VA Grant support. Over the last 36 months, the institution of Heinrich Groesdonk has received fees for his lectures, for his consultant activities, for his work in an advisory board or reimbursement for personal travel expenses by Edwards Lifescience, Amomed, and he personally holds shares from Fresenius SE. All other authors declare no conflict of interest., (© 2024 The Author(s).)

Background: The passive leg raising (PLR) test is a simple test to detect preload responsiveness. However, variable fluid doses and infusion times were used in studies evaluating the effect of PLR. Studies showed that the effect of fluid challenge on hemodynamics dissipates in 10 min. This prospective study aimed to compare PLR and a rapid fluid challenge (RFC) with a 300-ml bolus infused within 5 min in adult patients with a hemodynamic compromise., Materials and Methods: Critically ill medical patients with signs of systemic hypoperfusion were included if volume expansion was considered. Hemodynamic status was assessed with continuous measurements of cardiac output (CO), when possible, and mean arterial pressure (MAP) at baseline, during PLR, and after RFC., Results: A total of 124 patients with a median age of 65.0 years were included. Their acute physiology and chronic health evaluation (APACHE) II score was 19.7 ± 6.0, with a sequential organ failure assessment (SOFA) score of 9.0 ± 4.4. Sepsis was diagnosed in 73.3%, and 79.8% of the patients were already receiving a norepinephrine infusion. Invasive MAP monitoring was established in all patients, while continuous CO recording was possible in 42 patients (33.9%). Based on CO changes, compared with those with RFC, the false positive and false negative rates with PLR were 21.7 and 36.8%, respectively, with positive and negative predictive values of 70.6 and 72.0%, respectively. Based on MAP changes, compared with those with RFC, the false positive and false negative rates with PLR compared to RFC were 38.2% and 43.3%, respectively, with positive and negative predictive values of 64.4 and 54.0%, respectively., Conclusion: This study demonstrated a moderate agreement between PLR and RFC in hemodynamically compromised medical patients, which should be considered when testing preload responsiveness., (© 2024. The Author(s).)

The high value of fiber-type Cannabis sativa L. (hemp) due to its phytochemicals has yet to be fully recognized and leveraged. Besides cannabidiol (CBD), which is the most prevalent non-psychoactive cannabinoid, hemp contains numerous other cannabinoids with unexplored bioactivities, in addition to various compound classes. Previous works have aimed to correlate chemical profiles of C. sativa inflorescences with important parameters, mostly based on experiments under controlled conditions. However, mapping studies that explore the phytochemical diversity of hemp in a more realistic context are crucial to guide decisions at multiple levels, especially in areas where hemp cultivation was recently re-authorized, including Mediterranean countries. In this work, a powerful strategy was followed to map the phytochemical diversity of cultivated hemp in Greece, being the first study of its kind for this environment. A panel of 98 inflorescence samples, covering two harvesting years, eleven geographical regions and seven commonly used EU varieties, were studied using a combination of targeted and untargeted approaches. Quantitative results based on UPLC-PDA revealed relatively constant CBD/THC (total) ratios, while profiling by LC-HRMS effectively probed the phytochemical variability of samples, and led to the annotation of 88 metabolites, including a multitude of minor cannabinoids. Multivariate analysis substantiated a strong effect of harvesting year in sample discrimination and related biomarkers were revealed, belonging to fatty acids and flavonoids. The effect of geographical region and, especially, variety on chemical variation patterns was more intricate to interpret. The results of this work are envisioned to enhance our understanding of the real-world phytochemical complexity of C. sativa (hemp), with a view to maximized utilization of hemp for the promotion of human well-being., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to present the burden of cardiovascular disease (CVD) and its related risk factors based on a 20-year observation period (2002-2022)., Methods: In 2002, 3042 Greek adults (aged: 45 (12) years) free of CVD, cancer, or any other chronic infections were enrolled. In 2022, the 20-year follow-up was performed on 2169 participants (1988 had complete data for CVD). Lifetime risk for CVDs and disability-adjusted-life-years (DALYs) lost were also calculated., Results: The 20-year CVD incidence was 3600 cases/10,000 individuals (man-to-woman ratio 5:4). At the index age of 40 years, the lifetime risk for developing CVD was 68% for men and 63% for women; as the participants were getting older, the lifetime risk declined by approximately 19% and 13% for men and women, respectively, but remained at high levels, reaching 55% for both sexes. Participants between 45 and 55 years exhibited the highest CVD burden concerning aggregated DALYs. The burden was greater in men than in women, at ages below 35 years; beyond this age threshold, this trend shifted, and women exhibited a higher CVD burden., Conclusion: The burden of CVD in Greece has shown increasing trends over the past 20 years as a result of the accumulative growth of the prevalence of modifiable CVD risk factors. The disability-adjusted life-years lost are the most observed ever before, urging for efficient public health strategies and measures., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Introduction: The activity of direct oral anticoagulants (DOAC) is important in acute clinical situations. Recent studies have suggested a strong influence of DOAC on the diluted Russel's Viper Venom Time (dRVVT). Therefore, it may be a suitable screening parameter for antithrombotic plasma activity of different DOAC. This prospective study aims to evaluate the sensitivity and specificity of dRVVT to detect residual DOAC activity at recommended plasma level thresholds., Methods: A total of 80 patients were recruited, with 20 each treated with one of the four approved DOAC (apixaban, edoxaban, rivaroxaban or dabigatran), respectively. Blood plasma was collected before (baseline), at plasma peak time, and 6 and 12 h after DOAC. DRVVT was measured using the screen (LA1) and confirm (LA2) assay for lupus anticoagulant and compared with DOAC plasma levels. A reference range was calculated based on the dRVVT values of 61 healthy blood donors., Results: All DOAC significantly prolonged the dRVVT especially at higher DOAC plasma levels. The LA1 time ≥41 s had a sensitivity ≥98% to detect edoxaban, dabigatran and rivaroxaban plasma levels ≥30 ng/mL but it was only 87% for apixaban. Sensitivity was ≥98% for all DOAC with the LA2 assay ≥36 s. The negative predictive value of a DOAC plasma level <30 ng/mL and dRVVT LA2 <36 s was 99%., Conclusions: The dRVVT confirm assay (LA2) reliably detects residual DOAC plasma levels ≥30 ng/mL and could be useful to rapidly rule out relevant DOAC activity in emergency situations and to guide treatment decisions., (© 2024 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)

In the present study, we conducted a scoping review to provide an overview of the existing literature on the carbocyanine dye DiI, in human neuroanatomical tract tracing. The PubMed, Scopus, and Web of Science databases were systematically searched. We identified 61 studies published during the last three decades. While studies incorporated specimens across human life from the embryonic stage onwards, the majority of studies focused on adult human tissue. Studies that utilized peripheral nervous system (PNS) tissue were a minority, with the majority of studies focusing on the central nervous system (CNS). The most common topic of interest in previous tract tracing investigations was the connectivity of the visual pathway. DiI crystals were more commonly applied. Nevertheless, several studies utilized DiI in a paste or dissolved form. The maximum tracing distance and tracing speed achieved was, respectively, 70 mm and 1 mm/h. We identified studies that focused on optimizing tracing efficacy by varying parameters such as fixation, incubation temperature, dye re-application, or the application of electric fields. Additional studies aimed at broadening the scope of DiI use by assessing the utility of archival tissue and compatibility of tissue clearing in DiI applications. A combination of DiI tracing and immunohistochemistry in double-labeling studies have been shown to provide the means for assessing connectivity of phenotypically defined human CNS and PNS neuronal populations.

Evidence of the association between dietary habits and long-term body weight status is scarce. This study aimed to evaluate changes in Mediterranean-type diet (MTD) adherence in relation to body weight during 20 years of follow-up. Data from n = 1582 participants from the ATTICA cohort study (2002-2022) were used. MTD adherence was assessed via MedDietScore, and body weight status via body mass index (BMI) by 3 different measurements. We found that MTD adherence and changes in this adherence were inversely related to BMI at 20 years and the mean BMI during the 20-year follow-up. In multi-adjusted linear regression models, a 1/55 increase in baseline, 10-year, and 20-year MedDietScore was associated with a decrease of 0.05-0.13 kg/m 2 in BMI at 20 years and of 0.08-0.09 kg/m 2 in the mean BMI. Being consistently close to the MTD for 20 years was associated with a >90% decreased risk of maintaining overweight/obesity during the 20-year period. Strong, protective, long-lasting effects of the MTD were observed, even in those who deviated from the MTD in the follow-up (41% of the sample). Our results highlight the need to focus on the overall diet quality to minimize the risk of maintaining an excessive body weight during the life-course.

Background: Toxic renal effects of myoglobin following rhabdomyolysis can cause acute kidney injury (AKI) with the necessity of kidney replacement therapy (KRT). Fast elimination of myoglobin seems notable to save kidney function and intensify kidney repair. Clinical data regarding efficacy of KRT in critical care patients with rhabdomyolysis and AKI are limited. This retrospective analysis aimed to identify differences between conservative therapy and different modalities of KRT regarding myoglobin elimination and clinical outcome., Methods: This systematic, retrospective, single-center study analyzed 328 critical care patients with rhabdomyolysis (myoglobin > 1000 µg/l). Median reduction rate of myoglobin after starting KRT was calculated and compared for different modalities. Multivariate logistic regression models were established to identify potential confounder on hospital mortality. Filter lifetime of the various extracorporeal circuits was analyzed by Kaplan-Meier curves., Results: From 328 included patients 171 required KRT. Health condition at admission of this group was more critical compared to patient with conservative therapy. Myoglobin reduction rate did not differ between the groups (KRT 49% [30.8%; 72.2%] vs. conservative treatment (CT) 61% [38.5%; 73.5%]; p = 0.082). Comparison between various extracorporeal procedures concerning mortality showed no significant differences. Hospital mortality was 55.6% among patients with KRT and 18.5% with CT (p < 0.001). Multivariate logistic regression model identified requirement for KRT (OR: 2.163; CI: 1.061-4.407); p = 0.034) and the SOFA Score (OR: 1.111; CI: 1.004-1.228; p = 0.041) as independent predictive factors for hospital mortality. When comparing specific KRT using multivariate regression, no benefit was demonstrated for any treatment modality. Life span of the extracorporeal circuit was shorter with CVVH compared to that of others (log-Rank p = 0.017)., Conclusions: This study emphasizes that AKI requiring KRT following rhabdomyolysis is accompanied by high mortality rate. Differences in myoglobin reduction rate between various KRTs could not be confirmed, but CVVH was associated with reduced filter lifetime compared to other KRTs, which enable myoglobin elimination, too., (© 2024. The Author(s).)

Background: The Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) is a self-administered questionnaire that categorizes patients according to symptom severity. We aimed to translate and adapt the English IBS-SSS, validate the Greek version, and detect factors predictive of IBS severity., Methods: The original English version was obtained from the Rome Foundation, and the final Greek version arose through a process of translation, comprehensibility evaluation and back-translation. The 141 participants enlisted in the study were enrolled from 2 tertiary hospitals and were divided into 2 groups (98 patients and 43 healthy volunteers). We evaluated the questionnaire properties based on COSMIN criteria., Results: The recruited patients reported either diarrhea-predominant (34.7%), constipation-predominant (28.6%), or mixed subtype (36.7%) IBS. No significant variations were found regarding the frequency and intensity of abdominal pain and flatulence among the 3 IBS subtypes. Severity scores among healthy volunteers were significantly lower compared to IBS patients, irrespective of their disease subtype (P<0.001). The Cronbach coefficient (α) was calculated at 0.953, suggesting high inter-item internal consistency. The intraclass correlation coefficient was calculated and found to be high, suggesting good responsiveness of the questionnaire. Two-way MANOVA evaluation showed that demographic variables (age, family status, body mass index [BMI], smoking, and alcohol consumption) in the Greek population affect the IBS-SSS score and syndrome severity., Conclusions: The Greek version of IBS-SSS is a reliable, valid and responsive tool for assessing Greek IBS patients' symptom severity. Older age, smoking, alcohol use and higher BMI are indicative of greater symptom severity., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Introduction: Recombinant porcine factor VIII (rpFVIII) is a treatment option for break-through bleeds in patients with congenital haemophilia A with inhibitors (CHAwI) on emicizumab. However, there are limited data about the measurement of rpFVIII in the presence of emicizumab., Aim: To analyse whether rpFVIII can be measured with a chromogenic assay with bovine component (bCSA) in plasma from CHAwI on emicizumab treatment., Methods: In the first part of the study, FVIII deficient plasma was spiked with rpFVIII, in the second part, commercial plasma from CHAwI was spiked with emicizumab and rpFVIII, and in the third part, plasma from CHAwI on emicizumab treatment was spiked with rpFVIII. FVIII was then measured with bCSA and a chromogenic assay with human component (hCSA). Thrombin generation (TG) and clot-waveform analysis (CWA) were also carried out., Results: The recovery of rpFVIII measured with bCSA is approximately 80% and is further influenced by the presence of an anti-porcine inhibitor. rpFVIII assessed with hCSA was influenced by emicizumab. CWA and TG showed a weak correlation with baseline emicizumab concentration, but peak thrombin and CWA correlated well with increasing emicizumab concentrations and rpFVIII activities., Conclusion: This study indicates that rpFVIII can be measured in the presence of emicizumab with a bCSA. A calibration curve for the measurement of rpFVIII with bCSA should be established., (© 2024 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Introduction: Cannabis sativa L. is attracting worldwide attention due to various health-promoting effects. Extraction solvent type is critical for the recovery of bioactive compounds from the plant, especially cannabinoids. However, the choice of solvent is varied and not adequately warranted elsewhere, causing confusion in involved fields., Objective: The present work aimed to investigate the effect of extraction solvent on C. sativa (hemp) with regard to cannabinoid recovery and phytochemical profile of the extracts, considering most of the related solvents., Methodology: The majority of solvents reported for C. sativa (n = 14) were compared using a representative hemp pool. Quantitative results for major and minor cannabinoids were rapidly and reliably obtained using ultrahigh-performance liquid chromatography coupled with photodiode array detection (UPLC-PDA). In parallel, high-performance thin-layer chromatographic (HPTLC) fingerprinting was employed, involving less toxic mobile phase than in relevant reports. Various derivatisation schemes were applied for more comprehensive comparison of extracts., Results: Differential selectivity towards cannabinoids was observed among solvents. MeOH was found particularly efficient for most cannabinoids, in addition to solvent systems such as n-Hex/EtOH 70:30 and ACN/EtOH 80:20, while EtOH was generally inferior. For tetrahydrocannabinol (THC)-type compounds, EtOAc and n-Hex/EtOAc 60:40 outperformed n-Hex, despite its use in the official EU method. Solvents that tend to extract more lipids or more polar compounds were revealed based on HPTLC results., Conclusion: Combining the observations from UPLC quantitation and HPTLC fingerprinting, this work allowed comprehensive evaluation of extraction solvents, in view of robust quality assessment and maximised utilisation of C. sativa., (© 2023 The Authors. Phytochemical Analysis published by John Wiley & Sons Ltd.)

This second position paper of the Section Metabolism and Nutrition of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) provides recommendations on the laboratory monitoring of macro- and micronutrient intake as well as the use of indirect calorimetry in the context of medical nutrition therapy of critically ill adult patients. In addition, recommendations are given for disease-related or individual (level determination) substitution and (high-dose) pharmacotherapy of vitamins and trace elements., (© 2023. The Author(s).)

Background: Meat consumption has shown from detrimental to beneficial effects against cardiovascular disease (CVD) incidence, mainly depending on the type of meat studied (i.e., red/white, processed/unprocessed) and quantity consumed., Objective: To examine the associations between meat type consumption patterns and incident CVD among apparently healthy adults., Design: ATTICA study was conducted in the greater metropolitan Athens area, Greece, during 2001-2002 studying adults free-of-CVD at baseline. Twenty-year follow-up was performed in n = 1988 participants (n = 718 incident cases). Meat consumption during the follow-up period was categorized as: never/rare meat consumption (i.e., <1 time/week), mostly red meat (i.e., compared to other types of meat or processed meat), mostly white meat, and mostly processed meat products (e.g., bacon, sausage)., Results: Approximately 38% of the participants reported rare or no consumption of any type of meat, 31% consumed mostly red meat, 19% mostly white meat and the remainder 12% mostly processed meat. In multivariate analysis, compared to never/rarely consuming any type of meat, consuming mostly processed meat [HR: 2.89, 95%CI: 1.05, 7.89], but not red meat [HR: 1.22, 95%CI: 0.81, 1.82], was positively associated with incident CVD during 20 years of follow-up, while consuming mostly white meat was inversely associated with incident CVD [HR: 0.35, 95%CI: 0.17, 0.71]., Conclusions: The findings of this study suggest that the type of meat, irrespective of the frequency of consumption, plays a role in the risk of developing CVD. In clinical practice, emphasis should be placed on avoiding processed meat and replacing it with white unprocessed meat., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The present systematic scoping review aimed at mapping and analyzing the available literature on biological fluid (biofluid) biomarkers showing promise in the prediction of chronic subdural hematoma (cSDH) recurrence and the prognosis of neurological/functional patient outcome. Twenty-three studies published between 2003 and 2023 investigating a diverse range of biomarkers in hematoma fluid and/or the circulation in 3749 patients were included. Immune cell populations and inflammatory/anti-inflammatory cytokines comprised the most studied category of biomarkers displaying significant findings. A notable time trend in biomarker studies was a recent shift in research focus towards the analysis of circulating biomarkers. Several biomarkers were indicated as independent predictors of cSDH recurrence and/or functional/neurological outcome, including circulating fibrinogen degradation products (FDP), brain natriuretic peptide (BNP-1) and high-density lipoprotein (HDL), as well as blood urea nitrogen (BUN) and the ratios of blood neutrophil to lymphocyte (NLR) or red blood cell distribution width to platelet count (RPR). While studies on cSDH prognostic biomarkers have gained, in recent years, momentum, additional multicenter prospective studies are warranted to confirm and extend their findings. The identification of prognostic biofluid biomarkers in cSDH is an active field of research that may provide future tools, guiding clinical decisions and allowing for the design of treatments based on risk stratification.

Thrombotic thrombocytopenic purpura (TTP), which comprises thrombocytopenia, elevated lactate dehydrogenase levels, and anemia in the combination of organ involvement, is a rare but life-threatening condition associated with an extremely high lethality in the acute phase if left untreated. Using the example of a 49-year-old woman admitted to the hospital with unexplained abdominal symptoms and subfebrile temperatures, recommendations for the emergency situation are presented. Increased awareness of the disease and targeted further diagnostics with determination of the PLASMIC score or ADAMTS13 activity may lead directly to diagnosis of TTP; delayed diagnosis is usually associated with secondary complications., (© 2022. The Author(s).)

The cooperative aerial and device-to-device (D2D) networks employing non-orthogonal multiple access (NOMA) are expected to play an essential role in next-generation wireless networks. Moreover, machine learning (ML) techniques, such as artificial neural networks (ANN), can significantly enhance network performance and efficiency in fifth-generation (5G) wireless networks and beyond. This paper studies an ANN-based unmanned aerial vehicle (UAV) placement scheme to enhance an integrated UAV-D2D NOMA cooperative network.The proposed placement scheme selection (PSS) method for integrating the UAV into the cooperative network combines supervised and unsupervised ML techniques. Specifically, a supervised classification approach is employed utilizing a two-hidden layered ANN with 63 neurons evenly distributed among the layers. The output class of the ANN is utilized to determine the appropriate unsupervised learning method-either k-means or k-medoids-to be employed. This specific ANN layout has been observed to exhibit an accuracy of 94.12%, the highest accuracy among the ANN models evaluated, making it highly recommended for accurate PSS predictions in urban locations. Furthermore, the proposed cooperative scheme allows pairs of users to be simultaneously served through NOMA from the UAV, which acts as an aerial base station. At the same time, the D2D cooperative transmission for each NOMA pair is activated to improve the overall communication quality. Comparisons with conventional orthogonal multiple access (OMA) and alternative unsupervised machine-learning based-UAV-D2D NOMA cooperative networks show that significant sum rate and spectral efficiency gains can be harvested through the proposed method under varying D2D bandwidth allocations.

Sepsis is one of the most common and lethal conditions in intensive care medicine. Besides adequate treatment of the infection, timely hemodynamic management is essential to treat tissue hypoperfusion due to sepsis. Adequate fluid resuscitation plays a central role, and this should be carried out with dynamic monitoring of the hemodynamic response. However, a positive fluid balance is associated with poor outcome. Vasopressor therapy is required in case of inadequate response to fluid resuscitation, with norepinephrine considered the first choice. With increasing norepinephrine dose, addition of hydrocortisone or vasopressin may contribute to maintaining the hemodynamic state, although the prognostic advantage of these drugs has not been demonstrated. While dobutamine may be considered in patients with septic cardiomyopathy, the evidence for inotropic therapy in sepsis is limited., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The clinical heterogeneity regarding the response profile of the antitumor necrosis factor (anti-TNF) in patients with Crohn's disease (CD) and psoriasis (PsO) is attributed, amongst others, to genetic factors that influence the regulatory mechanisms which orchestrate the inflammatory response. Here, we investigated the possible associations between the MIR146A rs2910164 and MIR155 rs767649 variants and the response to anti-TNF therapy in a Greek cohort of 103 CD and 100 PsO patients. We genotyped 103 CD patients and 100 PsO patients via the PCR-RFLP method, utilizing the de novo formation of a restriction site for the SacI enzyme considering the MIR146A rs2910164, while Tsp45I was employed for the MIR155 rs767649 variant. Additionally, we investigated the potential functional role of the rs767649 variant, exploring in silico the alteration of transcription factor binding sites (TFBSs) mapped on its genomic location. Our single-SNP analysis displayed a significant association between the rare rs767649 A allele and response to therapy (Bonferroni-corrected p value = 0.012) in patients with PsO, a result further enhanced by the alteration in the IRF2 TFBS caused by the above allele. Our results highlight the protective role of the rare rs767649 A allele in the clinical remission of PsO, implying its utilization as a pharmacogenetic biomarker.

Background: The optimal dose of tinzaparin for prophylaxis in obese medical patients is not well defined., Objectives: To evaluate the anti-Xa activity in obese medical patients on tinzaparin prophylaxis adjusted for actual bodyweight., Methods: Patients with a body mass index of ≥30 kg/m 2 treated with 50 IU/kg tinzaparin once daily were prospectively included. Anti-Xa and anti-IIa activity; von Willebrand factor antigen and von Willebrand activity; factor VIII activity; D-dimer, prothrombin fragments; and thrombin generation were measured 4 hours after subcutaneous injection between days 1 and 14 after the initiation of tinzaparin prophylaxis., Results: We included 121 plasma samples from 66 patients (48.5% women), with a median weight of 125 kg (range, 82-300 kg) and a median body mass index of 41.9 kg/m 2 (range, 30.1-88.6 kg/m 2 ). The target anti-Xa activity of 0.2 to 0.4 IU/mL was achieved in 80 plasma samples (66.1%); 39 samples (32.2%) were below and 2 samples (1.7%) above the target range. The median anti-Xa activity was 0.25 IU/mL (IQR, 0.19-0.31 IU/mL), 0.23 IU/mL (IQR, 0.17-0.28 IU/mL), and 0.21 IU/mL (IQR, 0.17-0.25 IU/mL) on days 1 to 3, days 4 to 6, and days 7 to 14, respectively. The anti-Xa activity did not differ among the weight groups ( P  = .19). Injection into the upper arm compared to the abdomen resulted in a lower endogenous thrombin potential, a lower peak thrombin, and a trend to a higher anti-Xa activity., Conclusion: Dosing of tinzaparin adjusted for actual bodyweight in obese patients achieved anti-Xa activity in the target range for most patients, without accumulation or overdosing. In addition, there is a significant difference in thrombin generation depending on the injection site., (© 2023 The Authors.)

Objectives: Radiation therapy is the treatment of choice for cats with sinonasal carcinomas. Different protocols have been described in the literature, though a clear consensus regarding the optimal protocol is lacking. The aim of the study was to describe the tolerability, efficacy and outcome of cats treated with a cyclical hypofractionated protocol., Methods: Cats with histologically diagnosed sinonasal carcinomas in a single institution were retrospectively included. All patients were treated with a cyclical hypofractionated protocol ('QUAD shot' regime). Cats were treated with 4 Gray (Gy) delivered in four fractions within 48 h, with a minimum of 6 h between two treatments, and repeated every 3-4 weeks for a total dose of 48 Gy in three cycles., Results: Seven cats met the inclusion criteria. Nasal discharge and sneezing were the most common presenting complaints. All cats presented with advanced stage of disease with CT examination (three with modified Adams stage 3 and four with stage 4). Clinical improvement was seen in six cats. Five cats had a follow-up CT; one had a complete response, two had partial responses, one had stable disease and one had progressive disease. Two cats were still alive at the time of writing while four were euthanased owing to tumour-related causes. The median overall survival time was 460 days. The 1-year survival time was 80% and the 2-year survival time was 0%. Severe acute or late toxicity was not reported., Conclusions and Relevance: This is the first report of a cyclical hypofractionated protocol in the veterinary literature that can provide prolonged survival in cats with advanced stage sinonasal carcinoma. Its use should be considered in patients when prolonged hospitalisation can be detrimental to quality of life, while still delivering a therapeutic total dose of radiation therapy.

Pulsed electric field (PEF) and osmotic dehydration (OD) pretreatment can accelerate the time-consuming drying process and minimize its high energy demands. The effect of PEF and OD pre-processing conditions and osmotic solution composition on mass transfer kinetics (water loss, solid gain, water activity) and quality properties (color, texture, total sensory quality) during OD and subsequent air-drying (AD) of pumpkin was studied. Application of PEF (2.0 kV/cm-1500 pulses) significantly enhanced mass transfer during subsequent air-drying (increased effective diffusivity coefficient D es and drying rate k drying , respectively). PEF and OD treatments led to a significant reduction of the processing time by 12 and 10%, respectively (p < 0.05). The maximum reduction of processing time by 27% (p < 0.05) (compared to untreated sample) resulted in combined use of PEF and OD as pretreatments prior to AD. When PEF pretreatment was combined with OD prior to AD, the corresponding energy was by 50% less than the respective energy required for nonprocessed samples. PRACTICAL APPLICATION: Pulsed electric fields (PEF) and osmotic dehydration (OD) can be applied for the production of air-dried pumpkin cuts of superior quality (in terms of quality and sensory characteristics) and reduced energy requirements (as a result of total processing time decrease)., (© 2022 Institute of Food Technologists.)

Background: Management of critically ill nontrauma (CINT) patients in the resuscitation room of the emergency department (ED) is very challenging. Detailed data describing the patient characteristics and management of this population are lacking. This observational study describes the epidemiology, management and outcome in CINT ED patients in the resuscitation room., Methods: This prospective, single center observational study included all adult patients who were consecutively admitted to the ED resuscitation room during 2 periods of 1 year (September 2014-August 2015 vs. September 2017- August 2018). Patient characteristics, out-of-hospital/in-hospital treatment, admission-related conditions, time intervals for diagnostics and interventions and outcome were recorded using a self-developed questionnaire., Results: A total of 34,303 patients in the first and 35,039 patients in the second study period were admitted to the ED, of whom 532 and 457 patients, respectively, were admitted to the nontrauma resuscitation room due to acute life-threatening conditions. The patient characteristics did not differ significantly between the study periods (male: 58% vs. 59%, age: 68 ± 17 years vs. 65 ± 17 years). Time intervals for diagnostic and therapeutic interventions were similar. The CINT patients during the second study period were treated faster compared to the first study period (end of ED management: 53 ± 33 min vs. 41 ± 24 min, p < 0.0001). The 30-day all-cause mortality was comparable (34.0% vs. 36.3%)., Conclusion: Observation of critically ill patient management in the ED resuscitation room showed reliable results between both study periods. Structured ED management guidelines for CINT patients may provide comparable results at one institution., (© 2021. The Author(s).)

At the time of admission to an intensive or intermediate care unit, assessment of the patients' nutritional status may have both prognostic and therapeutic relevance with regard to the planning of individualized medical nutrition therapy (MNT). MNT has definitely no priority in the initial treatment of a critically ill patient, but is often also neglected during the course of the disease. Especially with prolonged length of stay, there is an increasing risk of malnutrition with considerable prognostic macro- and/or micronutrient deficit. So far, there are no structured, evidence-based recommendations for assessing nutritional status in intensive or intermediate care patients. This position paper of the Section Metabolism and Nutrition of the German Interdisciplinary Association for Intensive and Emergency Medicine (DIVI) presents consensus-based recommendations for the assessment and technical monitoring of nutritional status of patients in intensive and intermediate care units. These recommendations supplement the current S2k guideline "Clinical Nutrition in Intensive Care Medicine" of the German Society for Nutritional Medicine (DGEM) and the DIVI., (© 2022. The Author(s).)

Background: Patients with cancer are at increased risk of thromboembolic events contributing significantly to cancer-related morbidity and mortality. Because cholangiocarcinoma is a rare type of cancer, the incidence of thromboembolism in this patient population is not well defined., Methods: Patients with cholangiocarcinoma treated at the University Cancer Center Leipzig between January 2014 and December 2018 were analyzed retrospectively regarding the incidence of arterial and venous thromboembolism., Results: A total of 133 newly and consecutively diagnosed patients were included, of whom 22% had stage IV disease. Thromboembolism was diagnosed in 39 (29.3%), with 48% of the events occurring between 60 days prior and 30 days after the initial diagnosis. Arterial thrombosis accounted for 19% and portal venous thrombosis for 33% of the events, while the rest of events occurred in the non-portal venous system. In multivariable analysis, an ONKOTEV score ≥ 2 was the only independent predictor for thromboembolism. Serum CA 19-9 was available in 87 patients (65.4%). In this subgroup, CA 19-9 above the median of 97.7 U/ml and vascular or lymphatic compression were independent predictors for thromboembolism in the first year and CA 19-9 alone remained a significant predictor over the whole observation period. An ONKOTEV score ≥ 2 and increasing age were predictors of survival., Conclusions: A very high thromboembolic risk was observed in cholangiocarcinoma, comparable to the risk situation in pancreatic and gastric cancer. The ONKOTEV score and serum CA 19-9 are independent predictors of thromboembolic events. Prospective validation of our observations in this patient population is warranted., (© 2021. The Author(s).)

Autotaxin (ATX) is the ectoenzyme producing the bulk of lysophosphatidic acid (LPA) in circulation. ATX and LPA-mediated signaling (the ATX-LPA axis) play critical roles in the vascular and nervous system development. In adults, this axis contributes to diverse processes, including coagulation, inflammation, fibroproliferation and angiogenesis under physiological and/or pathophysiological conditions. Given evidence implicating several of these processes in chronic subdural hematoma (CSDH) pathogenesis and development, we assessed ATX activity in CSDH patients. Twenty-eight patients were recruited. Blood and hematoma fluid were collected. Enzymatic assays were used to establish serum and hematoma ATX activity. Enzyme-linked immunosorbent assays were used to establish hematoma beta trace (BT) levels, a cerebrospinal fluid (CSF) marker, in a hematoma. ATX activity was nearly three folds higher in hematoma compared to serum (P < 0.001). There was no significant correlation between BT levels and ATX activity in a hematoma. The present results show, for the first time, that ATX is catalytically active in the hematoma fluid of CSDH patients. Moreover, our findings of significantly elevated ATX activity in hematoma compared to serum, implicate the ATX-LPA axis in CSDH pathophysiology. The CSF origin of ATX could not be inferred with the present results. Additional research is warranted to establish the significance of the ATX-LPA axis in CSDH and its potential as a biomarker and/or therapeutic target.

Objectives: This study explores the potential of gene polymorphisms in the canonical and noncanonical NF-kB signaling pathway as a prediction biomarker of anti-tumor necrosis factor (TNF)α response in Crohn's patients., Materials and Methods: A total of 109 Greek patients with Crohn's disease (CD) were recruited, and the genotype of TLR2 rs3804099, LTA rs909253, TLR4 rs5030728, and MAP3K14/NIK rs7222094 single nucleotide polymorphisms was investigated for association with response to anti-TNFα therapy. Patient's response to therapy was based on the Crohn's Disease Activity Index, depicting the maximum response within 24 months after initiation of treatment., Results: Seventy-three patients (66.7%) were classified as responders while 36 as nonresponders (33.3%). Comparing allelic frequencies between responders and nonresponders, the presence of TLR2 rs3804099 T allele was associated with nonresponse (P = 0.003), even after stratification by anti-TNFα drugs (infliximab: P = 0.032, adalimumab: P = 0.026). No other association was identified for the rest of the polymorphisms under study. Haplotype analysis further enhanced the association of rs3804099 T allele with loss of response, even though the results were NS (P = 0.073)., Conclusion: Our results suggest that polymorphisms in the canonical NF-kB pathway genes could potentially act as a predictive biomarker of anti-TNFα response in CD., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Monitoring of vitamin K antagonist treatment with the international normalized ratio (INR) is obligatory, whereas this only applies to direct oral anticoagulants (DOAC) or low molecular weight heparin in the context of selected clinical scenarios. For DOAC the focus is on the determination of trough and peak plasma levels of the drug but for low molecular weight heparins the focus is on anti-Xa activity. The timing of blood sampling in relation to drug intake is essential for the interpretation of the results. A new-onset thrombocytopenia during hospitalization is common. The cause can frequently be identified based on the classification of the underlying disease, the day of onset and documentation of the dynamics of thrombocytopenia as well as the medication history. The importance of thrombophilia testing following a venous thromboembolism has decreased in the absence of clear therapeutic consequences; however, antiphospholipid antibody syndrome must not be overlooked as both the duration of treatment and the choice of anticoagulant depend on this., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

This article on coagulation diagnostics is published in two parts covering five common clinical scenarios for coagulation diagnostics. Part 1 deals with the diagnostics prior to invasive interventions and coagulation diagnostics to clarify a tendency to bleeding. The global parameters Quick and activated partial thromboplastin time are established for monitoring certain anticoagulants; however, they are not predictive with respect to the risk of bleeding prior to elective invasive interventions. In this context, disorders of primary hemostasis are frequent, which are insufficiently detected by the global parameters. Most clinical bleeding tendencies are due to acquired causes. These include anticoagulants and diseases which can be accompanied by tendency to bleeding. For coagulation tests preanalytical issues are essential in order to avoid false results. The interpretation should always be made in the context of the current physiological state., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Chest compressions during cardiopulmonary resuscitation (CPR) may be associated with iatrogenic chest wall injuries. The extent to which these CPR-associated chest wall injuries contribute to a delay in the respiratory recovery of cardiac arrest survivors has not been sufficiently explored. In a single-center retrospective cohort study, surviving intensive care unit (ICU) patients, who had undergone CPR due to medical reasons between 1 January 2018 and 30 June 2019, were analyzed regarding CPR-associated chest wall injuries, detected by chest radiography and computed tomography. Among 109 included patients, 38 (34.8%) presented with chest wall injuries, including 10 (9.2%) with flail chest. The multivariable logistic regression analysis identified flail chest to be independently associated with the need for tracheostomy (OR 15.5; 95% CI 2.77−86.27; p = 0.002). The linear regression analysis identified pneumonia (β 11.34; 95% CI 6.70−15.99; p < 0.001) and the presence of rib fractures (β 5.97; 95% CI 1.01−10.93; p = 0.019) to be associated with an increase in the length of ICU stay, whereas flail chest (β 10.45; 95% CI 3.57−17.33; p = 0.003) and pneumonia (β 6.12; 95% CI 0.94−11.31; p = 0.021) were associated with a prolonged duration of mechanical ventilation. Four patients with flail chest underwent surgical rib stabilization and were successfully weaned from the ventilator. The results of this study suggest that CPR-associated chest wall injuries, flail chest in particular, may impair the respiratory recovery of cardiac arrest survivors in the ICU. A multidisciplinary assessment may help to identify patients who could benefit from a surgical treatment approach.

Motion Shield is an automatic crash notification system that uses a mobile phone to generate automatic alerts related to the safety of a user when the user is boarding a means of transportation. The objective of Motion Shield is to improve road safety by considering a moving vehicle's risk, estimating the probability of an emergency, and assessing the likelihood of an accident. The system, using multiple sources of external information, the mobile phone sensors' readings, geolocated information, weather data, and historical evidence of traffic accidents, processes a plethora of parameters in order to predict the onset of an accident and act preventively. All the collected data are forwarded into a decision support system which dynamically calculates the mobility risk and driving behavior aspects in order to proactively send personalized notifications and alerts to the user and a public safety answering point (PSAP) (112).

Background: The role of thrombolytic treatment in patients with intermediate high-risk pulmonary embolism (IHR-PE) remains controversial., Objectives: In this study, we assessed whether systemic thrombolysis decreases hemodynamic decompensation and mortality in a cohort of unselected patients with IHR compared with patients with conventional anticoagulation., Methods: Between January 2014 and December 2018, 137 patients with IHR-PE were identified among 539 consecutive patients treated for symptomatic PE. In 35 patients (25.5%), systemic thrombolysis was used. Propensity score matching was performed based on 17 pretreatment variables. The primary outcome was hemodynamic decompensation, defined by systolic hypotension, need for catecholamines or signs of end-organ hypoperfusion, and all-cause mortality during hospitalization. Secondary outcomes, such as 1-year survival, and safety outcomes, such as bleeding events, were analyzed., Results: The effects of systemic thrombolysis and anticoagulation were compared in 55 matched patients with IHR-PE (systemic thrombolysis n = 21; anticoagulation n = 34). Thrombolysis was associated with a reduction (0% vs. 31%; p = 0.004) of the primary outcome during hospitalization and a 1-year survival benefit (100% vs. 83.2%; p = 0.036). Severe bleeding events occurred in 4.8% vs. 0% (p = 0.382) and moderate bleeding was observed in 14.3% vs. 7.1% (p = 0.359) in patients with thrombolysis compared with anticoagulation, respectively., Conclusions: Thrombolysis was associated with a significant reduction of the combined endpoint of hemodynamic decompensation and death during hospitalization and lower all-cause mortality after 1 year in an unselected group of patients with IHR-PE. Further studies are required to improve the therapy of IHR-PE and to identify the subgroup of patients that might benefit from thrombolytic therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Patients with connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE) have an increased risk for infections. This study investigated the outcome and characteristics of CTD patients under intensive care unit (ICU) treatment for sepsis., Methods: A single-center retrospective analysis was conducted and reviewed all patients with a CTD diagnosis admitted to the ICU of a university hospital for sepsis between 2006 and 2019. Mortality was computed and multivariate logistic regression was used to detect independent risk factors for sepsis mortality. Furthermore, the positive predictive value of ICU scores such as Sequential Organ Failure Assessment (SOFA) score was evaluated., Results: This study included 44 patients with CTD (mean age 59.8 ± 16.1 years, 68.2% females), most of them with a diagnosed SLE (61.4%) followed by systemic sclerosis (15.9%). 56.8% (n = 25) were treated with immunosuppressives and 81.8% (n = 36) received glucocorticoids. Rituximab was used in 3 patients (6.8%). The hospital mortality of septic CTD patients was high with 40.9%. It was highest among systemic sclerosis (SSc) patients (85.7%). SOFA score and diagnosis of SSc were independently associated with mortality in multivariate logistic regression ( P = 0.004 and 0.03, respectively). The Simplified Acute Physiology Score II (SAPS II), SOFA and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were good predictors of sepsis mortality in the investigated cohort (SAPS II AUC 0.772, P = 0.002; SOFA AUC 0.756, P = 0.004; APACHE II AUC 0.741, P = 0.007)., Conclusions: In-hospital sepsis mortality is high in CTD patients. SSc diagnoses and SOFA were independently associated with mortality. Additionally, common ICU scores were good predictors for mortality.

Introduction: Monitoring of direct oral anticoagulants (DOACs) with calibrated anti-Xa assay is limited by the high intra- and interindividual variations of the test results. Thrombin generation (TG) is a global hemostatic assay that reflects the patient´s individual coagulation status. The aim of this study was to investigate the influence of DOACs on TG measured with a fully automated assay system., Methods: All consecutive patients under apixaban and rivaroxaban coming to the outpatient coagulation center MVZ Limbach, Magdeburg, Germany between October 2017 and April 2020 were included. DOAC plasma levels were correlated with TG assessed using the fully automated Ceveron TG analyzer., Results: A total of 703 rivaroxaban and 252 apixaban containing plasma samples were included. There was a significant correlation between DOAC plasma levels and all TG parameters except for lag time regarding apixaban. Time to peak and peak thrombin followed an exponential regression curve, while this was linear for the endogenous thrombin potential (ETP). Apixaban showed a lower correlation coefficient for all TG parameters compared with rivaroxaban, and thrombin generation was less influenced by apixaban than rivaroxaban at plasma levels >100 ng/ml. The sensitivity and negative predictive value of normal TG parameters for the prediction of DOAC plasma levels <30 ng/ml was >85%., Conclusion: The present data show a moderate predominantly nonlinear correlation between TG parameters and plasma levels of apixaban and rivaroxaban. Rivaroxaban has a stronger effect on TG than apixaban., (© 2021 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)

Introduction/background: Vasculitis patients have a high risk for infections that may require intensive care unit (ICU) treatment in case of resulting sepsis. Since data on sepsis mortality in this patient group is limited, the present study investigated the clinical characteristics and outcomes of vasculitis patients admitted to the ICU for sepsis., Methods: The medical records of all necrotizing vasculitis patients admitted to the ICU of a tertiary hospital for sepsis in a 13-year period have been reviewed. Mortality was calculated and multivariate logistic regression was used to determine independent risk factors for sepsis mortality. Moreover, the predictive power of common ICU scores was further evaluated., Results: The study included 34 patients with necrotizing vasculitis (mean age 69 ± 9.9 years, 35.3% females). 47.1% (n = 16) were treated with immunosuppressives (mostly cyclophosphamide, n = 35.3%) and 76.5% (n = 26) received glucocorticoids. Rituximab was used in 4 patients (11.8%).The in-hospital mortality of septic vasculitis patients was 41.2%. The Sequential Organ Failure Assessment (SOFA) score (p = 0.003) was independently associated with mortality in multivariate logistic regression. Acute Physiology And Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II) and SOFA scores were good predictors of sepsis mortality in the investigated vasculitis patients (APACHE II AUC 0.73, p = 0.02; SAPS II AUC 0.81, p < 0.01; SOFA AUC 0.898, p < 0.0001)., Conclusions: Sepsis mortality was high in vasculitis patients. SOFA was independently associated with mortality in a logistic regression model. SOFA and other well-established ICU scores were good mortality predictors.

Background: The antithrombotic effect of direct oral anticoagulants (DOAC) in specific clinical scenarios is difficult to assess., Objective: This study aimed to evaluate the effect of DOAC on thrombin generation (TG) in relation to their plasma level., Methods: Eighty patients newly started on anticoagulation were included, 20 patients for each DOAC-apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma was sampled before DOAC (baseline), at plasma peak time, 6 and 12 hours after starting DOAC for quantification of drug levels and TG., Results: The baseline TG before DOAC intake showed inter-individual variability. All DOACs significantly prolonged lag time (LT) and time to peak (TTP), but did not change endogenous thrombin potential (ETP). Anti-Xa inhibitors but not dabigatran reduced thrombin peak, but the effect of apixaban at plasma peak was less pronounced (factor 1.6). LT and TTP prolongation of dabigatran was lower compared to anti-Xa inhibitors. All DOACs showed a nonlinear dose-response relationship, with the greatest antithrombotic effect at lower DOAC plasma levels. The inhibition of TG parameters between baseline and peak was parallel between individual patients but the coefficient of variation of TG was lower compared to drug levels., Conclusion: The antithrombotic effect at DOAC peak plasma level measured by TG depends on the patient-specific baseline TG level and the drug-specific inhibition by the particular DOAC. Although peak plasma levels have a high variability, the variation of TG is lower compared to drug levels. Therefore, TG assays may be superior to plasma levels in the assessment of the intensity of anticoagulation., (© 2021 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)

The objective of this study was to assess the diagnostic and prognostic utility of feline neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte ratios (LMR) in a variety of underlying diseases. Five-year medical records from cats presenting to the internal medicine unit of a veterinary teaching hospital were retrospectively reviewed. Cats were considered for inclusion based on complete medical records. ADVIA 120 was used for the complete blood counts; the NLR and LMR were calculated by dividing the absolute numbers of the respective leucocytes. Two hundred and nineteen sick and 20 healthy cats were included in the study. The median NLR and LMR were significantly (P < 0.05) elevated and decreased, respectively, in cats with infectious, neoplastic and chronic kidney diseases compared to controls. Additionally, cats with neoplasia had significantly higher median NLR compared to cats with urinary tract and gastrointestinal diseases. Non-survivors had significantly higher NLR and lower LMR compared to survivors. Both ratios had suboptimal prognostic performance for the outcome of sick cats (NLR sensitivity: 37.9%, specificity: 86.4%; LMR sensitivity: 69.0%, specificity: 61.0%). Many different disease categories were associated with increased NLR and decreased LMR compared to controls, but the overall prognostic performance of the two leucocyte ratios was suboptimal.

Vitamin C, a water-soluble compound, is a natural antioxidant in many plant-based products, possessing important nutritional benefits for human health. During fruit and vegetable processing, this bioactive compound is prone to various modes of degradation, with temperature and oxygen being recognised as the main factors responsible for this nutritional loss. Consequently, Vitamin C is frequently used as an index of the overall quality deterioration of such products during processing and post-processing storage and handling. Traditional preservation methods, such as thermal processing, drying and freezing, are often linked to a substantial Vitamin C loss. As an alternative, novel techniques or a combination of various preservation steps ("hurdles") have been extensively investigated in the recent literature aiming at maximising Vitamin C retention throughout the whole product lifecycle, from farm to fork. In such an integrated approach, it is important to separately study the effect of each preservation step and mathematically describe the impact of the prevailing factors on Vitamin C stability, so as to be able to optimise the processing/storage phase. In this context, alternative mathematical approaches have been applied, including more sophisticated ones that incorporate parameter uncertainties, with the ultimate goal of providing more realistic predictions.

Background: Abnormal admission blood glucose was reported as a useful predictor of outcome in critically ill patients., Objectives: To identify patients at higher risk, this study aimed to evaluate the relationship between admission blood glucose levels and patient mortality during the management of nontraumatic critically ill patients in the emergency department (ED)., Methods: In this prospective, single-center observational study in a German university ED, all adult patients admitted to the resuscitation room of the ED were included between September 1, 2014 and August 31, 2015. Directly after resuscitation room admission, blood samples for admission blood glucose were taken, and adult patients were divided into groups according to predefined cut-offs between the admission blood glucose. Study endpoint was in-hospital mortality., Results: During the study period, 532 patients were admitted to the resuscitation room. The data of 523 patients (98.3%) were available for analysis. The overall in-hospital mortality was 34.2%. In comparison with an in-hospital mortality of 25.2% at an admission blood glucose of 101-136 mg/dL (n = 107), admission blood glucose of ≤ 100 mg/dL (n = 25, odds ratio [OR] 6.30, 95% confidence interval [CI] 2.44-16.23, p < 0.001), 272-361 mg/dL (n = 63, OR 2.53, 95% CI 1.31-4.90, p = 0.007), and ≥ 362 mg/dL (n = 44, OR 2.96, 95% CI 1.42-6.18, p = 0.004) were associated with a higher mortality., Conclusions: Abnormal admission blood glucose is associated with a high in-hospital mortality. Admission blood glucose is an inexpensive and rapidly available laboratory parameter that may predict mortality and help to identify critically ill patients at risk in a general nontraumatic critically ill ED patient cohort. The breakpoint for in-hospital mortality may be an admission blood glucose ≤ 100 and ≥ 272 mg/dL., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bleeding is associated with an increased morbidity and mortality. Anatomic and hemostatic causes play a central role in the pathophysiology of bleeding, with anatomic causes being by far more common. While trauma and invasive procedures are the leading causes of bleeding in surgical disciplines, gastrointestinal bleeding is the major cause of bleeding in internal medicine. Major bleedings lead to secondary homeostatic changes, which in turn not only contribute to further bleeding, but also to the pathogenesis of organ dysfunction. Acquired coagulopathies due to antithrombotic treatment or an underlying disease also contribute to the extent and the dynamics of bleeding, while hereditary bleeding disorders are seldom. The balance between the physiological pro- and anticoagulant pathway plays a significant role in the pathophysiology of bleeding and coagulation. Therefore, the pathophysiology of bleeding cannot be described by means of easily available laboratory coagulation workup. The aim of coagulation correction during the management of life-threatening bleeding is not to normalize coagulation, but rather to stop bleeding. Besides a careful clinical evaluation of the course of bleeding coupled with basic understanding of the physiology of coagulation, targeted laboratory coagulation workup can contribute to a rational coagulation treatment concept., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction/background: Patients with rheumatoid arthritis (RA) have a high risk of infections that may require intensive care unit (ICU) admission in case of resulting sepsis. Data regarding the mortality of these patients are very limited. This study investigated clinical characteristics and outcomes of patients with RA admitted to the ICU for sepsis and compared the results to a control cohort without RA., Methods: All patients with RA as well as sex-, age-, and admission year-matched controls admitted to the ICU of a university hospital for sepsis between 2006 and 2019 were retrospectively analyzed. Mortality was calculated for both the groups, and multivariate logistic regression was used to determine independent risk factors for sepsis mortality. The positive predictive value of common ICU scores was also investigated., Results: The study included 49 patients with RA (mean age 67.2 ± 9.0 years, 63.3% females) and 51 matched controls (mean age 67.4 ± 9.5 years, 64.7% females). Among the patients with RA, 42.9% (n = 21) were treated with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and 30.6% (n = 15) received glucocorticoids only. Seven (14.3%) patients received biologic (b) DMARDs. The hospital mortality was higher among patients with RA (42.9% vs 15.7%, P = .0016). Rheumatoid arthritis was independently associated with mortality in multivariate logistic regression ( P = .001). In patients with RA, renal replacement therapy ( P = .024), renal failure ( P = .027), and diabetes mellitus ( P = .028) were independently associated with mortality. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were good predictors of sepsis mortality in patients with RA (APACHE II area under the curve [AUC]: 0.78, P = .001; SAPS II AUC: 0.78, P < .001; SOFA AUC 0.78, P < .001), but their predictive power was higher among controls., Conclusions: Hospital sepsis mortality was higher in patients with RA than in controls. Rheumatoid arthritis itself is independently associated with an increased sepsis mortality. Renal replacement therapy, renal failure, and diabetes were associated with an increased mortality. Common ICU scores were less well predictors of sepsis mortality in patients with RA compared to non-RA controls.

Purpose: The Mid-German Sepsis Cohort (MSC) aims to investigate mid-term and long-term functional disabilities in sepsis survivors from intensive care unit (ICU) discharge until 1 year after. Secondary, post-acute mortality and morbidity, health-related quality of life and healthcare utilisation will be investigated., Participants: The MSC comprises adult (aged ≥18 years) patients who were treated for (severe) sepsis or septic shock on ICU. The participants were recruited between 15 April 2016 and 30 November 2018 from five German centres. Three thousand two hundred and ten patients with sepsis were identified, of which 1968 survived their ICU stay and were eligible for enrolment in the follow-up cohort. Informed consent for follow-up assessment was provided by 907 patients (46.1% of eligible patients)., Findings to Date: The recruitment of the participants for follow-up assessments and the baseline data collection is completed. Incidence of sepsis was 116.7 patients per 1000 ICU patients. In this cohort profile, we provide an overview of the demographics and the clinical characteristics of both the overall sepsis cohort and the ICU survivors who provided informed consent for follow-up assessment (907 out of 1968 ICU survivors (46.1%))., Future Plans: The follow-ups are conducted 3, 6 and 12 months after ICU discharge. Another yearly follow-up up to 5 years after ICU discharge is pursued. Several cooperation and satellite projects were initiated. This prospective cohort offers a unique resource for research on long-term sequelae of sepsis survivors., Trial Registration Number: German Clinical Trials Registry (DRKS00010050)., Competing Interests: Competing interests: CSH declares funding from the German Federal Joint Committee Innovations-Funds and the European Society of Intensive Care Medicine. All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cannabidiol (CBD) and cannabidiolic acid (CBDA) represent the most abundant non-psychoactive cannabinoids in fiber-type Cannabis sativa L. (hemp) and both have demonstrated high therapeutic potential. Hence, efficient extraction coupled with reliable determination of these compounds is crucial for informed utilization of hemp and is increasingly needed in the present state of harmonization efforts. In this context, a systematic approach for extraction optimization was followed, which initially involved comparison of three widely available extraction techniques, i.e. ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and dynamic maceration (DM). These were applied on samples of different hemp varieties (n = 3) using ethanol as a safe and efficient solvent. UAE showed the most promising results and was further optimized by means of response surface methodology (RSM), based on a circumscribed central composite design. The conditions maximizing CBD, CBDA, and total CBD content as well as extraction yield were determined with high desirability (0.97) and were experimentally confirmed. The optimized UAE method was also compared with a previously reported extraction procedure, demonstrating superior performance. For the quantitation of CBD and CBDA in hemp extracts, a reversed-phase UPLC-PDA method was developed and validated. Chromatographic separation was achieved in less than 10 min, while satisfactory results for linearity (R 2  > 0.996), precision (RSD < 2.0%), and accuracy (recovery rates of 93.1-101.0%) were obtained for both analytes. Limits of detection were determined as 0.07 and 0.04 μg mL -1 for CBD and CBDA, respectively, indicating sufficient sensitivity. The good performance of the method was verified by the evaluation of additional parameters (e.g. matrix effect, extraction recovery), which was largely enabled by the use of isolated standards. The whole analytical workflow, involving both optimized UAE extraction and UPLC-PDA determination, entails simplified manipulation and may offer a reliable and cost-effective approach for routine quality control of hemp regarding the principal cannabinoids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)