Improvement of Predictive Scores in Burn Medicine through Different Machine Learning Approaches.

The mortality of severely burned patients can be predicted by multiple scores which have been created over the last decades. As the treatment of burn injuries and intensive care management have improved immensely over the last years, former prediction scores seem to be losing accuracy in predicting survival. Therefore, various modifications of existing scores have been established and innovative scores have been introduced. In this study, we used data from the German Burn Registry and analyzed them regarding patient mortality using different methods of machine learning. We used Classification and Regression Trees (CARTs), random forests, XGBoost, and logistic regression regarding predictive features for patient mortality. Analyzing the data of 1401 patients via machine learning, the factors of full-thickness burns, patient's age, and total burned surface area could be identified as the most important features regarding the prediction of patient mortality following burn trauma. Although the different methods identified similar aspects, application of machine learning shows that more data are necessary for a valid analysis. In the future, the usage of machine learning can contribute to the development of an innovative and precise predictive score in burn medicine and even to further interpretations of relevant data regarding different forms of outcome from the German Burn registry.

Nucleated red blood cells are a predictor of mortality in patients under extracorporeal membrane oxygenation.

BACKGROUND: The presence of Nucleated Red Blood Cells (NRBCs) in critically ill patients is associated with higher mortality and poor prognosis. Although patients on extracorporeal support such as veno-venous or veno-arterial extracorporeal membrane oxygenation (VV/VA-ECMO) are severely ill, NRBCs have rarely been investigated regarding their predictive value so far. METHODS: As part of a retrospective study, we examined all cardiothoracic surgery patients from July 2019 to September 2020 who received ECMO treatment during their inpatient stay. The aim of this study was to investigate the occurrence of NRBCs during ECMO support in terms of their predictive value for mortality. RESULTS: In total 30 patients (age at admission: 62.7 ± 14.3 year; 26 male; ECMO duration: 8.5 ± 5.1 days; ICU duration: 18.0 ± 14.5 days) were included. 16 patients (53.3%) died during their inpatient stay. There were no significant differences in demographic characteristics between VA- or VV- ECMO patients. NRBCs occurred in all patients while under ECMO support. NRBC value was significant higher in those who died (2299.6 ± 4356.6 µl) compared to the surviving patients (133.6 ± 218.8 µl, p < 0.001). Univariate analysis found that patients with a cutoff value of ≥ 270 NRBCs/µl during ECMO support were 39 times more likely to die (OR 39.0, 95% CI 1.5-997.5, p < 0.001). 12 out of 13 patients (92.3%) with ≥ 270 NRBCs/µl died. The area under the curve (AUC) of the receiver operating characteristic curve was 0.85 (95% CI 0.69-0.96) with a sensitivity of 75.0% and a specificity of 92.9%. CONCLUSION: NRBCs appear to be an accurate biomarker for mortality in patients with ECMO support. They may be helpful in deciding if therapy becomes futile. Trial registration DRKS00023626 (December 20th 2020).

Shank2 identifies a subset of glycinergic neurons involved in altered nociception in an autism model.

BACKGROUND: Autism Spectrum Disorders (ASD) patients experience disturbed nociception in the form of either hyposensitivity to pain or allodynia. A substantial amount of processing of somatosensory and nociceptive stimulus takes place in the dorsal spinal cord. However, many of these circuits are not very well understood in the context of nociceptive processing in ASD. METHODS: We have used a Shank2-/- mouse model, which displays a set of phenotypes reminiscent of ASD, and performed behavioural and microscopic analysis to investigate the role of dorsal horn circuitry in nociceptive processing of ASD. RESULTS: We determined that Shank2-/- mice display increased sensitivity to formalin pain and thermal preference, but a sensory specific mechanical allodynia. We demonstrate that high levels of Shank2 expression identifies a subpopulation of neurons in murine and human dorsal spinal cord, composed mainly by glycinergic interneurons and that loss of Shank2 causes the decrease in NMDAR in excitatory synapses on these inhibitory interneurons. In fact, in the subacute phase of the formalin test, glycinergic interneurons are strongly activated in wild type (WT) mice but not in Shank2-/- mice. Consequently, nociception projection neurons in laminae I are activated in larger numbers in Shank2-/- mice. LIMITATIONS: Our investigation is limited to male mice, in agreement with the higher representation of ASD in males; therefore, caution should be applied to extrapolate the findings to females. Furthermore, ASD is characterized by extensive genetic diversity and therefore the findings related to Shank2 mutant mice may not necessarily apply to patients with different gene mutations. Since nociceptive phenotypes in ASD range between hyper- and hypo-sensitivity, diverse mutations may affect the circuit in opposite ways. CONCLUSION: Our findings prove that Shank2 expression identifies a new subset of inhibitory interneurons involved in reducing the transmission of nociceptive stimuli and whose unchecked activation is associated with pain hypersensitivity. We provide evidence that dysfunction in spinal cord pain processing may contribute to the nociceptive phenotypes in ASD.

Stretch Evolution of Electronic Coupling of the Thiophenyl Anchoring Group with Gold in Mechanically Controllable Break Junctions.

The current-voltage characteristics of a single-molecule junction are determined by the electronic coupling Γ between the electronic states of the electrodes and the dominant transport channel(s) of the molecule. Γ is profoundly affected by the choice of the anchoring groups and their binding positions on the tip facets and the tip-tip separation. In this work, mechanically controllable break junction experiments on the N,N'-bis(5-ethynylbenzenethiol-salicylidene)ethylenediamine are presented, in particular, the stretch evolution of Γ with increasing tip-tip separation. The stretch evolution of Γ is characterized by recurring local maxima and can be related to the deformation of the molecule and sliding of the anchoring groups above the tip facets and along the tip edges. A dynamic simulation approach is implemented to model the stretch evolution of Γ, which captures the experimentally observed features remarkably well and establishes a link to the microscopic structure of the single-molecule junction.

Individualized flow-controlled versus conventional pressure-controlled ventilation in on-pump heart surgery (FLOWVENTIN HEARTSURG): study protocol for a randomized controlled trial.

BACKGROUND: In on-pump cardiac surgery, lungs are at high risk of periprocedural organ impairment because of atelectasis formation, ventilator-induced lung injury, and hyperinflammation due to the cardiopulmonary bypass which results in postoperative pulmonary complications in half of this patient population. The new ventilation mode flow-controlled ventilation (FCV) uniquely allows full control of ins- and expiratory airway flows. This approach reduces the mechanical power of invasive ventilation as a possible cause of ventilator-induced lung injury. The scope of FLOWVENTIN HEARTSURG is to compare perioperative individualized FCV with best clinical practice pressure-controlled ventilation (PVC) modes in patients with elective on-pump cardiac surgery procedures. We hypothesize that the postoperative inflammatory response can be reduced by the perioperative application of FCV compared to PCV. METHODS: FLOWVENTIN HEARTSURG is a single-center, randomized, parallel-group trial with two intervention arms: perioperative PCV modes (n = 70, PCV group) with an individualized positive end-expiratory pressure (PEEP) and a tidal volume of 6-8 ml/kg predicted bodyweight compared to perioperative FCV (n = 70, FCV group) with an individualized PEEP and driving pressure, resulting in a liberal tidal volume. As the primary study endpoint interleukin 8 plasma level is assessed 6 h after cardiopulmonary bypass as a surrogate biomarker of systemic and pulmonary inflammation. As secondary aims clinically relevant patient outcomes are analyzed, e.g., perioperative lung function regarding oxygenation indices, postoperative pulmonary and extra-pulmonary complications, SIRS-free days as well as ICU and total inpatient stays. As additional sub-studies with an exploratory approach perioperative right ventricular function parameters are assessed by echocardiography and perioperative lung aeration by electrical impedance tomography. DISCUSSION: Current paradigms regarding protective low tidal volume ventilation are consciously left in the FCV intervention group in order to reduce mechanical power as a determinant of ventilator-induced lung injury in this high-risk patient population and procedures. This approach will be compared in a randomized controlled trial with current best clinical practice PCV in FLOWVENTIN HEARTSURG. TRIAL REGISTRATION: German Clinical Trials Register DRKS00018956 . Registered on 12 June 2020 (Version 1), last update on 22 August 2022 (Version 4).

Phenotype- and species-specific skin proteomic signatures for incision-induced pain in humans and mice.

BACKGROUND: Acute pain after surgery is common and often leads to chronic post-surgical pain, but neither treatment nor prevention is currently sufficient. We hypothesised that specific protein networks (protein-protein interactions) are relevant for pain after surgery in humans and mice. METHODS: Standardised surgical incisions were performed in male human volunteers and male mice. Quantitative and qualitative sensory phenotyping were combined with unbiased quantitative mass spectrometry-based proteomics and protein network theory. The primary outcomes were skin protein signature changes in humans and phenotype-specific protein-protein interaction analysis 24 h after incision. Secondary outcomes were interspecies comparison of protein regulation as well as protein-protein interactions after incision and validation of selected proteins in human skin by immunofluorescence. RESULTS: Skin biopsies in 21 human volunteers revealed 119/1569 regulated proteins 24 h after incision. Protein-protein interaction analysis delineated remarkable differences between subjects with small (low responders, n=12) and large incision-related hyperalgesic areas (high responders, n=7), a phenotype most predictive of developing chronic post-surgical pain. Whereas low responders predominantly showed an anti-inflammatory protein signature, high responders exhibited signatures associated with a distinct proteolytic environment and persistent inflammation. Compared to humans, skin biopsies in mice habored even more regulated proteins (435/1871) 24 h after incision with limited overlap between species as assessed by proteome dynamics and PPI. Immunohistochemistry confirmed the expression of high priority candidates in human skin biopsies. CONCLUSIONS: Proteome profiling of human skin after incision revealed protein-protein interactions correlated with pain and hyperalgesia, which may be of potential significance for preventing chronic post-surgical pain. Importantly, protein-protein interactions were differentially modulated in mice compared to humans opening new avenues for successful translational research.

Conditioned pain modulation and offset analgesia: Influence of sex, sex hormone levels and menstrual cycle on the magnitude and retest reliability in healthy participants.

BACKGROUND: Conditioned pain modulation (CPM) and offset analgesia quantify impairment of endogenous pain modulation, but magnitude and reliability vary broadly between studies, indicating influencing factors that are not currently controlled for. The aim of this study was to quantify magnitude and retest reliability of CPM and offset analgesia in healthy participants, while investigating the influence of sex and sex hormone levels. METHODS: Sixty-two participants (30 female) completed the study. We tested CPM (heat-cold paradigm) and offset analgesia on 6 days within two menstrual cycles (tests were performed in each phase of two subsequent menstrual cycles, with similar time points for men). RESULTS: Median offset effect was -29.4% in female and - 22.5% in male participants (as change from initial stimulus). Median early CPM effects were - 16.7% for women versus -13.3% for men. Reliability (intra-class correlation coefficient [ICC]) was similar between the main measures, offset effect (female: 0.48, male: 0.47) and early CPM effect (female: 0.49, male: 0.43). There was significant variance between individual experimental parameters within protocols but not between sexes or menstrual phases. While oestradiol and progesterone did not correlate with the magnitude of effect within sexes, we found that testosterone levels explained an estimated 5%-10% of variance within individual responses in all sexes. CONCLUSIONS: Our results show that the reliability of both CPM effect and offset analgesia was independent of sex and menstrual cycle phase. The magnitude of CPM and offset effects was weakly influenced by sex and testosterone levels, indicating an area for future research, rather than clinical significance. SIGNIFICANCE: This study investigated CPM and offset analgesia in parallel, across sexes and during two menstrual cycles while assessing the impact of sex hormones. Reliability seems to depend on experimental parameters rather than participant characteristics, while the magnitude of effect could be weakly linked to sex hormones and sex.

Perioperative ketamine for postoperative pain management in patients with preoperative opioid intake: A systematic review and meta-analysis.

STUDY OBJECTIVE: Postoperative pain management in opioid users remains challenging. The perioperative administration of ketamine might lead to favourable pain outcomes in these patients. STUDY DESIGN: A systematic review of randomised controlled trials (RCT) with meta-analysis and assessment of the quality of evidence by GRADE was performed. SETTING: Perioperative pain treatment. PATIENTS: Adult opioid users undergoing surgery. INTERVENTIONS: Perioperative administration of ketamine. MEASUREMENTS: Primary outcomes were postoperative acute pain at rest/during movement after 24 h and number of patients with ketamine-related adverse events. MAIN RESULTS: Nine RCTs (802 patients with at least two weeks opioid-intake) were included. There is low-quality evidence that ketamine may slightly reduce postoperative pain during movement after 24 h (mean difference: -0.79; 95% confidence interval (CI): -1.22 to -0.36). Based on a very low-quality of evidence, we are uncertain on any effect of ketamine on pain at rest after 24 h and incidences of adverse events like hallucinations and confusion within 48 h. However, perioperative ketamine reduced cumulative mean opioid consumption by 97.3 mg (95%CI: -164.8 to -29.7) after 24 h and 186.4 mg (95%CI: -347.6 to -25.2) after 48 h. The relative risks (RR) for opioid-related adverse events were significantly different for sedation within 24 h (RR: 0.54; 95%CI 0.37 to 0.78). CONCLUSIONS: There is currently limited evidence for a reduced postoperative pain intensity using perioperative ketamine in preoperative opioid-consuming patients. However, a clinically relevant opioid-sparing effect was evident associated with a reduced risk for postoperative sedation and without increased harm. Therefore, ketamine might be a useful anti-hyperalgesic adjuvant in these patients. Nevertheless, with clinical heterogeneity being considerable, it's too premature to suggest any specific ketamine protocol. Furthermore, many questions (like ideal dosing, treatment duration and more favourable patient-related outcome measures including long-term effects) remain open and need to be addressed in future studies. PROTOCOL REGISTRATION: Prospero CRD42020185497.

Efficacy of Auricular Acupuncture and Lavender Oil Aromatherapy in Reducing Preinterventional Anxiety in Cardiovascular Patients: A Randomized Single-Blind Placebo-Controlled Trial.

Introduction: Auricular acupuncture at the "relaxation point" and lavender oil aromatherapy can reduce preoperative anxiety associated with increased mortality and morbidity. Data on the effect of combined auricular acupuncture and lavender oil aromatherapy in patients undergoing cardiovascular interventions with the use of local anesthesia or under conscious sedation are sparse. The authors sought to evaluate the efficacy of auricular acupuncture and lavender oil aromatherapy in reducing preinterventional anxiety in cardiovascular patients. Materials and Methods: Data of 80 consecutive patients undergoing diagnostic coronary angiography (n = 56) with or without percutaneous coronary intervention (n = 9) and right heart catheterization (n = 6), transcatheter aortic valve replacement (n = 17) and percutaneous mitral valve repair (MitraClip; n = 2) were analyzed. Patients were prospectively randomized to receive either preinterventional auricular acupuncture and lavender oil (Lavandula angustifolia) aromatherapy (verum group, n = 39) or combined sham auricular acupuncture and placebo oil aromatherapy (placebo group, n = 41). For the verum group bilateral auricular acupuncture was performed at the "relaxation point." State anxiety and blood pressure were assessed before and at 30 min after acupuncture and presternal oil application. State anxiety was defined as primary outcome measure and assessed using the Spielberger State Anxiety Inventory (STAI) for Adults form Y6. Intervention-specific anxiety was assessed by a 10-point numerical rating scale, and perceived treatment success by a single dichotomous question. Clinical blood pressure was further assessed. Results: After the intervention, the verum group had significantly decreased anxiety on the STAI compared with the placebo group (Δ = -4.18; 95% confidence interval = -8.31 to -0.05; p = 0.047). Significantly more patients reported subjective treatment success in the verum group (87.2%) than in the placebo group (65.9%, p = 0.035). No significant differences were observed regarding intervention-specific anxiety and blood pressure between the two groups. No serious adverse events occurred in any group. Conclusions: Combined auricular acupuncture and lavender oil aromatherapy can decrease preinterventional anxiety in cardiovascular patients and requires further investigation. German Clinical Trials Register (registration no. DRKS00023686).

Chronic Pain Following Fracture-Related Surgery: Posttraumatic Rather Than Postsurgical Origin Promotes Chronification-A Prospective Observational Study With 1-Year Follow-up.

BACKGROUND: Chronic posttraumatic/postsurgical pain (CPSP) is common after traumatic or surgical damage. Exposure to both trauma and surgery, with the potential for repeated bone and nerve damage, may increase the risk of CPSP after fracture-related surgery. But the (long-term) incidences of CPSP and neuropathic CPSP and the ensuing burdens are unknown. Therefore, the patients were prospectively assessed within 1 year, and the patient-specific characteristics were explored. METHODS: Between 2017 and 2018, 127 patients (age: 52.9 ± 17.1 years, male: 55.1%) with traumatic fractures needing osteosynthesis (extremities: 91.3%) were assessed posttrauma (before surgery), postsurgery at days 1 to 5, 6 weeks, 3 and 12 months. The primary outcomes are as follows: incidence at 3 and 12 months of CPSP (defined as pain intensity on a numerical rating scale [NRS: 0-10] ≥3), secondary exploration: neuropathic CPSP (NRS ≥3 and Douleur Neuropathique 4 interview [DN4i] score ≥3 [Douleur Neuropathique interview: 0-7]); burden: quality of life (QoL, the EuroQOL five dimensions questionnaire [EQ-5D-3L] descriptive system); and inter alia, the number of analgesics (trial registration: DRKS00011601). RESULTS: The incidence of CPSP was 57.1% (52/91, n/N) at 3 and 42.7% (35/82) at 12 months postsurgery, including neuropathic CPSP 7.7% (4/52) and 17.1% (6/35), respectively. Descriptively, posttraumatic higher pain intensity at rest (difference of 0.9 ± 1.8 NRS) and the need for more frequent analgesics (by 34.3%) were associated with CPSP a year after surgery compared to those without. As soon as week 6, these patients had developed descriptively a 15% more impaired QoL, with 25% more impairment after 1 year. The patients with CPSP presented with at least 1 neuropathic symptom 12 months later in 68.6% (24/35) of cases, mainly with an early posttraumatic occurrence (without fulfilling the definition of neuropathic CPSP). CONCLUSIONS: After early fracture-related surgery, high incidences of CPSP (43%) were prospectively observed 1 year postsurgery, up to approximately 1 in 5 patients who had neuropathic CPSP. At the same time, CPSP was accompanied with an impacted QoL and analgesic dependence, both indicating clinical relevance. Moreover, the high incidence and the early posttraumatic occurrence of more intense pain suggest that the initial fracture-related trauma, rather than the surgical trauma, may predominantly trigger CPSP at Y1 (1 year). Therefore, these exploratory results set the direction of required future research. A future clinical hypothesis might be: treat first what hurts first.

Electrical Characterization of Germanium Nanowires Using a Symmetric Hall Bar Configuration: Size and Shape Dependence.

The fabrication of individual nanowire-based devices and their comprehensive electrical characterization remains a major challenge. Here, we present a symmetric Hall bar configuration for highly p-type germanium nanowires (GeNWs), fabricated by a top-down approach using electron beam lithography and inductively coupled plasma reactive ion etching. The configuration allows two equivalent measurement sets to check the homogeneity of GeNWs in terms of resistivity and the Hall coefficient. The highest Hall mobility and carrier concentration of GeNWs at 5 K were in the order of 100 cm2/(Vs) and 4×1019cm-3, respectively. With a decreasing nanowire width, the resistivity increases and the carrier concentration decreases, which is attributed to carrier scattering in the region near the surface. By comparing the measured data with simulations, one can conclude the existence of a depletion region, which decreases the effective cross-section of GeNWs. Moreover, the resistivity of thin GeNWs is strongly influenced by the cross-sectional shape.

Isoflurane not at the expense of postoperative nausea and vomiting in cardiac anesthesia - an observational study.

OBJECTIVES: Inhalative anesthesia is of common use, but is generally known to potentiate postoperative nausea and vomiting (PONV). With an internal change of anesthesia regimen from total intravenous anesthesia (TIVA) to isoflurane (in terms of myocardial protection) in cardiac anesthesia a higher incidence of PONV was to be expected. Therefore, we evaluated the incidence of PONV after the simultaneous implementation of PONV prophylaxis. METHODS: The incidence of PONV, prospectively assessed in 197 cardiac surgery patients (68 y ± 10.4, 66.5% male) having isoflurane plus dual PONV prophylaxis with dexamethasone and droperidol, was compared with previous data of 190 controls (67 y ± 9.6, 71% male) having TIVA without and with single or dual PONV prophylaxis (n = 64 dexamethasone and droperidol, n = 25 dexamethasone, n = 101 only TIVA), and the Apfel-scoring (0-4 depending on PONV-risk). DRKS00014275. Statistics: Chi2-test, p < .05 (Bonferroni). RESULTS: The incidence of PONV under isoflurane with antiemetic prophylaxis was 20.8% (95% confidence interval (CI) 15.4; 27.4) compared to 30.5% (95%CI 24; 37.6) under TIVA (p = .029; dexamethasone and droperidol 23.4% (95%CI 13.8; 35.7); dexamethasone 32% (95%CI 14.9; 53.5); only TIVA 34.7% (95%CI 25.5; 44.8)), but was not lower in high-risk patients than predicted according to Apfel-scoring 4 (71.4 vs. 78%). CONCLUSION: In cardiac anesthesia, the use of isoflurane is not at the expense of PONV when using a risk-independent two-drug-prophylaxis. It is even beneficial resulting surprisingly in a lower incidence of PONV than under TIVA unless with and without prophylaxis. Patients with the highest risk for PONV and receiving isoflurane should receive a third antiemetic prophylactic drug.

Describing chain-like assembly of ethoxygroup-functionalized organic molecules on Au(111) using high-throughput simulations.

Due to the low corrugation of the Au(111) surface, 1,4-bis(phenylethynyl)-2,5-bis(ethoxy)benzene (PEEB) molecules can form quasi interlocked lateral patterns, which are observed in scanning tunneling microscopy experiments at low temperatures. We demonstrate a multi-dimensional clustering approach to quantify the anisotropic pair-wise interaction of molecules and explain these patterns. We perform high-throughput calculations to evaluate an energy function, which incorporates the adsorption energy of single PEEB molecules on the metal surface and the intermolecular interaction energy of a pair of PEEB molecules. The analysis of the energy function reveals, that, depending on coverage density, specific types of pattern are preferred which can potentially be exploited to form one-dimensional molecular wires on Au(111).

Efficacy and adverse events of selective serotonin noradrenaline reuptake inhibitors in the management of postoperative pain: A systematic review and meta-analysis.

STUDY OBJECTIVE: Selective-serotonin-noradrenaline-reuptake inhibitors (SSNRI) might be an interesting option for postoperative pain treatment. Objective was to investigate postoperative pain outcomes of perioperative SSNRI compared to placebo or other additives in adults undergoing surgery. DESIGN: Systematic review of randomised controlled trials (RCT) with meta-analysis and GRADE assessment. SETTING: Acute and chronic postoperative pain treatment. PATIENTS: Adult patients undergoing surgery. INTERVENTIONS: Perioperative administration of SSNRI. MEASUREMENTS: Primary outcomes were postoperative acute pain at rest/during movement (measured on a scale from 0 to 10), number of patients with chronic postsurgical pain (CPSP) and with SSNRI-related adverse events. MAIN RESULTS: Fourteen RCTs (908 patients) were included. We have high-quality evidence that duloxetine has no effect on pain at rest at 2 h (MD: -0.02; 95% confidence interval (CI) -0.51 to 0.47), but probably reduces it at 48 h (MD: -1.16; 95%CI -1.78 to -0.54). There is low- and moderate-quality evidence that duloxetine has no effects on pain during movement at 2 h (MD: -0.42; 95%CI -1.53 to 0.69) and 48 h (MD: -0.91; 95% CI -2.08 to 0.26), respectively. We have very low-quality evidence that duloxetine might reduce pain at rest (MD: -0.45; 95%CI -0.74 to -0.15) and movement (MD: -1.19; 95%CI -2.32 to -0.06) after 24 h. We have low-quality evidence that duloxetine may reduce the risk of CPSP at 6 months (RR:0.35; 95%CI 0.14 to 0.90). There is moderate-quality evidence that duloxetine increases the risk of dizziness (RR:1.72; 95%CI 1.26 to 2.34). CONCLUSION: At the expense of a higher risk for dizziness, SSNRI may be effective in reducing postoperative pain between 24 and 48 h after surgery. However, the results of the meta-analyses are mostly imprecise and duloxetine might only be used in individual cases. Protocol registration: CRD42018094699.

Place of Death Trends and Utilization of Outpatient Palliative Care at the End of Life­Analysis of Death Certificates (2001, 2011, 2017) and Pseudonymized Data From Selected Palliative Medicine Consultation Services (2017) in Westphalia, Germany.

BACKGROUND: The largest German study on place of death was performed for deaths in selected regions of Westphalia in the years 2001 and 2011. In the period thereafter, provision of palliative care was regionally expanded. This upgrade included the establishment of palliative medicine consultation services (PMCS), combining general and specialized palliative care on an outpatient basis. A follow-up place of death survey took place in 2017. The aim was to depict the trends in place of death between 2001 and 2017. A second goal was to determine how often outpatient PMCS were used by persons who died in 2017. METHODS: Descriptive analysis of place of death as specified in all death certificates (2001, 2011, 2017) issued in the cities of Bochum and Münster and the districts of Borken and Coesfeld. Comparison of pseudonymized data on deceased patients (2017) treated by the PMCS of Münster and Coesfeld with the place of death database to ascertain the rate of PMCS care at the end of life. RESULTS: A total of 38 954 death certificates were analyzed, and 5887 deaths were compared with PCMS data. The distribution of place of death was as follows: (2001, 2011, 2017; age standardized; %): own residence 27.8; 23.3; 21.3; hospital: 55.8; 51.8; 51.8; palliative care unit: 0.0; 1.0; 6.2; hospice: 1.9; 4.5; 4.8; nursing home: 13.1; 18.6; 20.4; other: 1.2; 1.2; 1.5. The rate of PMCS use was 28.8% (1694/5887). CONCLUSION: Over the period 2001-2017, the proportion of people who died at home or in the hospital went down, while the number who died in a palliative care unit, hospice, or nursing home increased. In the city of Münster and the district of Coesfeld, one fourth of the people who died in 2017 received PMCS care at the end of life.

Developing consensus on core outcome domains for assessing effectiveness in perioperative pain management: results of the PROMPT/IMI-PainCare Delphi Meeting.

ABSTRACT: Postoperative pain management is still insufficient, leading to major deficits, including patient suffering, impaired surgical recovery, long-term opioid intake, and postsurgical chronic pain. Yet, identifying the best treatment options refers to a heterogeneous outcome assessment in clinical trials, not always reflecting relevant pain-related aspects after surgery and therefore hamper evidence synthesis. Establishing a core outcome set for perioperative pain management of acute pain after surgery may overcome such limitations. An international, stepwise consensus process on outcome domains ("what to measure") for pain management after surgery, eg, after total knee arthroplasty, sternotomy, breast surgery, and surgery related to endometriosis, was performed. The process, guided by a steering committee, involved 9 international stakeholder groups and patient representatives. The face-to-face meeting was prepared by systematic literature searches identifying common outcome domains for each of the 4 surgical procedures and included breakout group sessions, world-café formats, plenary panel discussions, and final voting. The panel finally suggested an overall core outcome set for perioperative pain management with 5 core outcome domains: physical function (for a condition-specific measurement), pain intensity at rest, pain intensity during activity, adverse events, and self-efficacy. Innovative aspects of this work were inclusion of the psychological domain self-efficacy, as well as the specific assessment of pain intensity during activity and physical function recommended to be assessed in a condition-specific manner. The IMI-PROMPT core outcome set seeks to improve assessing efficacy and effectiveness of perioperative pain management in any clinical and observational studies as well as in clinical practice.

Improvement of Superficial and Deep Cutaneous Microcirculation Due to Axillary Plexus Anesthesia Impaired by Smoking.

BACKGROUND: Understanding microvascular physiology is key to any reconstructive procedure. Current concepts in anesthesia increasingly involve regional peripheral nerve blockade during microvascular reconstructive procedures. Whereas favorable effects on perfusion due to these techniques have been reported earlier, little evidence focusing on its effects in most peripheral vascular compartments is available. METHODS: A total of 30 patients who were to receive axillary plexus blockade (APB) were included. Microcirculatory assessment of the dependent extremity was conducted utilizing combined laser-Doppler flowmetry and white light spectroscopy. Two probes (1-2 and 7-8 mm penetration depth) were used to assess changes in microcirculation. RESULTS: APB resulted in significant changes to both superficial and deep cutaneous microcirculation. Changes in blood flow were most prominent in superficial layers with a maximum increase of +617% compared to baseline values. Significantly lower values of +292% were observed in deep measurements. Consecutively, a significant enhancement in tissue oxygen saturation was observed. Further analysis revealed a significant impairment of perfusion characteristics due to reported nicotine consumption (max Bf: +936% vs. +176%). CONCLUSION: Cutaneous microcirculation is strongly affected by APB, with significant differences regarding microvascular anatomy and vascular physiology. Smoking significantly diminishes the elicited improvements in perfusion. Our findings could influence reconstructive strategies as well as dependent perioperative anesthetic management.

Prevalence of therapeutic and diagnostic procedures in the last 14 days of life in hospital patients: a single-center observational study from Germany.

BACKGROUND: The opportunities available for maintaining and prolonging life in modern medicine give rise to medical-ethical dilemmas in patients at the end of life, raising the question of whether intensified treatment and diagnosis is appropriate in these patients. This affects hospital patients in particular. METHODS: This single-center cross-sectional study from Germany analyzed hospital records of all deceased patients of a university hospital who died between October 2016 and September 2017. The prevalence of therapeutic and diagnostic procedures during the last 14 days before death was determined. In-hospital transfer practices shortly before patients' deaths were also examined. RESULTS: A total of 468 hospital patients died. The mean age at death was 76.3±13.7 years; 47.0% [220] were female; 12.0% [56] died on the day of hospital admission, 41.9% [196] 1 to 6 days and 46.1% [216] more than 6 days later; the case mix index (CMI) was 4.6. The majority of patients {57.1% [267]} died on intensive care unit (ICU). Therapeutic and diagnostic procedures within the last 14 days before death: 30.3% [142] resuscitation, 28.6% [134] surgery, 10.9% [51] extracorporeal membrane oxygenation (ECMO), 23.7% [111] renal replacement therapy, 4.3% [20] tracheostomy, 2.8% [13] PTCA/cardiac stenting, 1.9% [9] chemotherapy, 29.3% [137] transfusion of packed red blood cells, 13.7% [64] transfusion of prothrombin complex concentrate, 5.3% [25] cardiac catheter examination, 7.5% [35] upper gastrointestinal endoscopy, 79.1% [370] chest X-ray, 41.9% [196] computed tomography. In-hospital transfer from ICU to PCU before patients' death: 1.5% (4/274 ICU patients). CONCLUSIONS: Intensified therapeutic and diagnostic procedures are often performed at the end of life in hospital patients. Closer interdisciplinary cooperation between intensive care and palliative care would be beneficial to improve in-patient care for these patients.

Control over self-assembled Janus clusters by the strength of magnetic field in [Formula: see text].

Colloidal Janus microparticles can be propelled by controlled chemical reactions on their surfaces. Such microswimmers have been used as model systems for the behavior on the microscale and as carriers for cargo to well-defined positions in hard-to-access areas. Here we demonstrate the propagation motion of clusters of magnetic Janus particles driven by the catalytic decomposition of [Formula: see text] on their metallic caps. The magnetic moments of their caps lead to certain spatial arrangements of Janus particles, which can be influenced by external magnetic fields. We investigate how the arrangement of the particles and caps determines the driven motion of the particle clusters. In addition, we show the influence of confining walls on the cluster motion, which will be encountered in any real-life biological system.