Pain management after laparoscopic cholecystectomy: A systematic review and procedure-specific postoperative pain management (PROSPECT) recommendations.

Laparoscopic cholecystectomy can be associated with significant postoperative pain that is difficult to treat. We aimed to evaluate the available literature and develop updated recommendations for optimal pain management after laparoscopic cholecystectomy. A systematic review was performed using the procedure-specific postoperative pain management (PROSPECT) methodology. Randomised controlled trials and systematic reviews published in the English language from August 2017 to December 2022 assessing postoperative pain after laparoscopic cholecystectomy using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases. From 589 full text articles, 157 randomised controlled trials and 31 systematic reviews met the inclusion criteria. Paracetamol combined with NSAIDs or cyclo-oxygenase-2 inhibitors should be given either pre-operatively or intra-operatively, unless contraindicated. In addition, intra-operative intravenous (i.v.) dexamethasone, port-site wound infiltration or intraperitoneal local anaesthetic instillation are recommended, with opioids used for rescue analgesia. As a second-line regional technique, the erector spinae plane block or transversus abdominis plane block may be reserved for patients with a heightened risk of postoperative pain. Three-port laparoscopy, a low-pressure pneumoperitoneum, umbilical port extraction, active aspiration of the pneumoperitoneum and saline irrigation are recommended technical aspects of the operative procedure. The following interventions are not recommended due to limited or no evidence on improved pain scores: single port or mini-port techniques, routine drainage, low flow insufflation, natural orifice transluminal endoscopic surgery (NOTES), infra-umbilical incision, i.v. clonidine, nefopam and regional techniques such as quadratus lumborum block or rectus sheath block. Several interventions provided better pain scores but are not recommended due to risk of side effects: spinal or epidural anaesthesia, gabapentinoids, i.v. lidocaine, i.v. ketamine and i.v. dexmedetomidine.

Evaluation of score-based tertiary triage policies during the COVID-19 pandemic: simulation study with real-world intensive care data.

OBJECTIVE: The explicit prohibition of discontinuing intensive care unit (ICU) treatment that has already begun by the newly established German Triage Act in favor of new patients with better prognoses (tertiary triage) under crisis conditions may prevent saving as many patients as possible and therefore may violate the international well-accepted premise of undertaking the "best for the most" patients. During the COVID-19 pandemic, authorities set up lockdown measures and infection-prevention strategies to avoid an overburdened health-care system. In cases of situational overload of ICU resources, when transporting options are exhausted, the question of a tertiary triage of patients arises. METHODS: We provide data-driven analyses of score- and non-score-based tertiary triage policies using simulation and real-world electronic health record data in a COVID-19 setting. Ten different triage policies, for example, based on the Simplified Acute Physiology Score (SAPS II), are compared based on the resulting mortality in the ICU and inferential statistics. RESULTS: Our study shows that score-based tertiary triage policies outperform non-score-based tertiary triage policies including compliance with the German Triage Act. Based on our simulation model, a SAPS II score-based tertiary triage policy reduces mortality in the ICU by up to 18 percentage points. The longer the queue of critical care patients waiting for ICU treatment and the larger the maximum number of patients subject to tertiary triage, the greater the effect on the reduction of mortality in the ICU. CONCLUSION: A SAPS II score-based tertiary triage policy was superior in our simulation model. Random allocation or "first come, first served" policies yield the lowest survival rates, as will adherence to the new German Triage Act. An interdisciplinary discussion including an ethical and legal perspective is important for the social interpretation of our data-driven results.

Less Invasive Surfactant Administration in Preterm Infants in Tertiary Neonatal Intensive Care Units in Germany: A Survey.

INTRODUCTION: The European guideline for treatment of respiratory distress syndrome recommends less invasive surfactant administration (LISA) as the preferred method of surfactant administration in spontaneously breathing preterm infants. However, there is limited evidence on practical aspects such as sedation and catheter types, leading to considerable variability between centers. METHODS: An anonymous online survey (www.soscisurvey.de) was sent to 164 tertiary neonatal intensive care units (NICUs) in Germany including 43 questions on practical aspects of LISA. RESULTS: Of 122 (74%) participating NICUs, 117 (96%) reported experience with LISA with 82% of those reporting LISA as their preferred method of surfactant administration. Indications for surfactant administration differed widely between NICUs. Most (89%) used FiO2-thresholds only or in combination with other criteria, such as Silverman score/signs of dyspnea (41%) or lung ultrasound findings (3%). Prophylactic surfactant was administered by 42%. Differences in use of LISA in extremely immature infants were reported (e.g., 36% did not perform LISA in infants below 24-26 weeks). Preferred drugs for sedation were (Es-)Ketamine, followed by Propofol and Midazolam. Minimum time interval between subsequent LISA procedures was 4 (2-6) h. Catheters specifically designed for LISA were used by most NICUs (69%). CONCLUSION: This survey shows that LISA is common practice in German NICUs, but with considerable variability in practical aspects. These data may serve as a guidance for NICUs that have not yet implemented LISA and might be helpful design clinical trials with the aim to standardize and/or optimize LISA.

Evidence and Perspectives for Choline Supplementation during Parenteral Nutrition-A Narrative Review.

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms "choline" and "parenteral nutrition", resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants.

Hot Carrier Nanowire Transistors at the Ballistic Limit.

We demonstrate experimentally nonequilibrium transport in unipolar quasi-1D hot electron devices reaching the ballistic limit at room temperature. The devices are realized with heterostructure engineering in nanowires to obtain dopant- and dislocation-free 1D-epitaxy and flexible bandgap engineering. We show experimentally the control of hot electron injection with a graded conduction band profile and the subsequent filtering of hot and relaxed electrons with rectangular energy barriers. The number of electrons passing the barrier depends exponentially on the transport length with a mean-free path of 200-260 nm, and the electrons reach the ballistic transport regime for the shortest devices with 70% of the electrons flying freely through the base electrode and the barrier reflections limiting the transport to the collector.

In Silico Design of Heterogeneous Microvascular Trees Using Generative Adversarial Networks and Constrained Constructive Optimization.

OBJECTIVE: Designing physiologically adequate microvascular trees is of crucial relevance for bioengineering functional tissues and organs. Yet, currently available methods are poorly suited to replicate the morphological and topological heterogeneity of real microvascular trees because the parameters used to control tree generation are too simplistic to mimic results of the complex angiogenetic and structural adaptation processes in vivo. METHODS: We propose a method to overcome this limitation by integrating a conditional deep convolutional generative adversarial network (cDCGAN) with a local fractal dimension-oriented constrained constructive optimization (LFDO-CCO) strategy. The cDCGAN learns the patterns of real microvascular bifurcations allowing for their artificial replication. The LFDO-CCO strategy connects the generated bifurcations hierarchically to form microvascular trees with a vessel density corresponding to that observed in healthy tissues. RESULTS: The generated artificial microvascular trees are consistent with real microvascular trees regarding characteristics such as fractal dimension, vascular density, and coefficient of variation of diameter, length, and tortuosity. CONCLUSIONS: These results support the adoption of the proposed strategy for the generation of artificial microvascular trees in tissue engineering as well as for computational modeling and simulations of microcirculatory physiology.

Joint recommendations on cost calculation and estimation in paediatric clinical trials.

The conduct of clinical trials in paediatrics is essential to improve drug therapy in children. In Europe, paediatric clinical trials have been supported by the European Paediatric Regulation since 2007, but there is still a great need for high-quality clinical trials. The personnel and time required to conduct clinical trials in accordance with EU Regulations 536/2014 and 745/2017 is considerably higher compared to other studies, such as observational studies. It is important that this additional workload for the trial centre is fully compensated, also taking into account EU state aid rules. In paediatric trials, it is necessary to take into account the special requirements of paediatric and adolescent medicine when calculating the additional costs. Within the framework of the pan-European paediatric study network c4c/GermanNetPaeT, a working group dealt with specific aspects of cost calculation in order to support paediatric study centres in internal cost calculation as well as in the subsequent preparation of financing requirements for industrial sponsors or public funders. In several workshops the working group developed a cost calculation template with the content derived from the "Joint recommendations for a total services account as a factor in simplifying contracts" of the Deutsche Hochschulmedizin (DHM, German University Medicine), the Netzwerk der Koordinierungszentren für Klinische Studien (KKS Network, Network of Coordinating Centres for Clinical Trials) and the Verband Forschender Arzneimittelhersteller (vfa, German Association of Research-Based Pharmaceutical Companies). By estimating the specific time required for measures and investigations as part of a sample study, the background to the increased time required was discussed and a list with aspects to be considered for cost calculation was compiled together with the study centres. The paediatrics-specific aspects mentioned in detail are intended to increase understanding of the particular problem of higher costs for clinical trials involving children and adolescents and the need for correspondingly appropriate remuneration. This transparent and comprehensible presentation of the higher financial requirements for both the study centres and the financial supporters is intended to promote the high-quality conduct of clinical trials in paediatric study centres in the long term.

Harmonized analysis of PBMC by mass cytometry.

Mass cytometry permits the high dimensional analysis of cellular systems at single-cell resolution with high throughput in various areas of biomedical research. Here, we provide a state-of-the-art protocol for the analysis of human peripheral blood mononuclear cells (PBMC) by mass cytometry. We focus on the implementation of measures promoting the harmonization of large and complex studies to aid robustness and reproducibility of immune phenotyping data.

Pulse oximetry signal loss during hypoxic episodes in preterm infants receiving automated oxygen control.

The aim of this study was to analyze signal loss (SL) resulting from low signal quality of pulse oximetry-derived hemoglobin oxygen saturation (SpO2) measurements during prolonged hypoxemic episodes (pHE) in very preterm infants receiving automatic oxygen control (AOC). We did a post hoc analysis of a randomized crossover study of AOC, programmed to set FiO2 to "back-up FiO2" during SL. In 24 preterm infants (median (interquartile range)) gestational age 25.3 (24.6 to 25.6) weeks, recording time 12.7 h (12.2 to 13.6 h) per infant, we identified 76 pHEs (median duration 119 s (86 to 180 s)). In 50 (66%) pHEs, SL occurred for a median duration of 51 s (33 to 85 s) and at a median frequency of 2 (1 to 2) SL-periods per pHE. SpO2 before and after SL was similar (82% (76 to 88%) vs 82% (76 to 87%), p = 0.3)).  Conclusion: SL is common during pHE and must hence be considered in AOC-algorithm designs. Administering a "backup FiO2" (which reflects FiO2-requirements during normoxemia) during SL may prolong pHE with SL.  Trial registration: The study was registered at www. CLINICALTRIALS: gov under the registration no. NCT03785899. WHAT IS KNOWN: • Previous studies examined SpO2 signal loss (SL) during routine manual oxygen control being rare, but pronounced in lower SpO2 states. • Oxygen titration during SL is unlikely to be beneficial as SpO2 may recover to a normoxic range. WHAT IS NEW: • Periods of low signal quality of SpO2 are common during pHEs and while supported with automated oxygen control (SPOC), FiO2 is set to a back-up value reflecting FiO2 requirements during normoxemia in response to SL, although SpO2 remained below target until signal recovery. • FiO2 overshoots following pHEs were rare during AOC and occurred with a delayed onset; therefore, increased FiO2 during SL does not necessarily lead to overshoots.

Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial.

BACKGROUND: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. METHODS: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. FINDINGS: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. INTERPRETATION: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. FUNDING: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

Cathodoluminescence investigations of dark-line defects in platelet-based InGaN nano-LED structures.

We have investigated the optical properties of heterostructured InGaN platelets aiming at red emission, intended for use as nano-scaled light-emitting diodes. The focus is on the presence of non-radiative emission in the form of dark line defects. We have performed the study using hyperspectral cathodoluminescence imaging. The platelets were grown on a template consisting of InGaN pyramids, flattened by chemical mechanical polishing. These templates are defect free, whereas the dark line defects are introduced in the lower barrier and tend to propagate through all the subsequent layers, as revealed by the imaging of different layers in the structure. We conclude that the dark line defects are caused by stacking mismatch boundaries introduced by multiple seeding and step bunching at the edges of the as-polished, dome shaped templates. To avoid these defects, we suggest that the starting material must be flat rather than dome shaped.

Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission.

Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability of disease flares impedes their study. Addressing this critical knowledge gap, we use the experimental medicine approach of immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes allowing detailed characterisation. Exploratory mass cytometry analyses reveal three circulating cellular subsets heralding the onset of arthritis flare - CD45RO+PD1hi CD4+ and CD8+ T cells, and CD27+CD86+CD21- B cells - further characterised by single-cell sequencing. Distinct lymphocyte subsets including cytotoxic and exhausted CD4+ memory T cells, memory CD8+CXCR5+ T cells, and IGHA1+ plasma cells are primed for activation in flare patients. Regulatory memory CD4+ T cells (Treg cells) increase at flare onset, but with dysfunctional regulatory marker expression compared to drug-free remission. Significant clonal expansion is observed in T cells, but not B cells, after drug cessation; this is widespread throughout memory CD8+ T cell subsets but limited to the granzyme-expressing cytotoxic subset within CD4+ memory T cells. Based on our observations, we suggest a model of immune dysregulation for understanding RA flare, with potential for further translational research towards novel avenues for its treatment and prevention.

Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome - a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BACKGROUND: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45-50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol - a xanthine oxidase inhibitor - reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. METHODS/DESIGN: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. RESULTS: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and ."will be stratified for the two treatment groups. DISCUSSION: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.

MICA Procedure vs Open Chevron Osteotomy for Hallux Valgus Correction: A Prospective Cohort Study.

Background: Currently, more than 150 surgical techniques have been described for the treatment of hallux valgus. The abundance of techniques indicates that there is no technique that has been designated as a gold standard. In recent years, a particular interest in the use of minimally invasive techniques has grown. The aim of this study was to prospectively compare clinical, radiologic, and postoperative outcomes between the MICA technique and open chevron technique over a 1-year follow-up period. Methods: Between January 2016 and August 2020, data were prospectively collected from consecutive patients preoperatively and at 6 weeks, 3 months, and 12 months following minimally invasive chevron and Akin (MICA) or open chevron osteotomies. Radiographic outcomes were measured using weightbearing radiographs preoperatively and at 3 and 12 months postoperatively. Clinical outcomes were measured using the American Orthopaedic Foot & Ankle Society (AOFAS), Manchester-Oxford Foot Questionnaire (MOXFQ), VAS (visual analog scale), Foot Function Index (FFI), Foot and Ankle Outcome Score (FAOS), and Euro-QoL-5D (EQ5D) questionnaires. Results: Of the 68 patients, 42 patients (62%) underwent a MICA surgery and 26 patients (38%) underwent open chevron osteotomy. Both groups showed significant improvement in HVA, IMA, and DMAA at the 1-year follow-up. Our findings show that both clinical and radiologic outcomes of the MICA technique are comparable to the conventional open technique. No significant differences were found in clinical outcomes (VAS, AOFAS, MOXFQ, FFI, and FAOS), complication rate, and operative times. Conclusion: These results show that MICA is a safe alternative for chevron osteotomy. The clinical and radiologic outcomes of these 2 techniques by 12 months are comparable. Level of Evidence: Level II, prospective cohort study.

Immune signatures of checkpoint inhibitor-induced autoimmunity-A focus on neurotoxicity.

BACKGROUND: Neurologic immune-related adverse events (irAE-n) are rare but severe toxicities of immune checkpoint inhibitor (ICI) treatment. To overcome diagnostic and therapeutic challenges, a better mechanistic understanding of irAE-n is paramount. METHODS: In this observational cohort study, we collected serum and peripheral blood samples from 34 consecutive cancer patients with irAE-n (during acute illness) and 49 cancer control patients without irAE-n (pre- and on-ICI treatment, n = 44 without high-grade irAEs, n = 5 with high-grade nonneurologic irAEs). Patients received either anti-programmed cell death protein (PD)-1 or anti-PD ligand-1 monotherapy or anti-PD-1/anti-cytotoxic T-lymphocyte-associated protein-4 combination therapy. Most common cancers were melanoma, lung cancer, and hepatocellular carcinoma. Peripheral blood immune profiling was performed using 48-marker single-cell mass cytometry and a multiplex cytokine assay. RESULTS: During acute illness, patients with irAE-n presented higher frequencies of cluster of differentiation (CD)8+ effector memory type (EM-)1 and central memory (CM) T cells compared to controls without irAEs. Multiorgan immunotoxicities (neurologic + nonneurologic) were associated with higher CD8+ EM1 T cell counts. While there were no B cell changes in the overall cohort, we detected a marked decrease of IgD- CD11c+ CD21low and IgD- CD24+ CD21high B cells in a subgroup of patients with autoantibody-positive irAE-n. We further identified signatures indicative of enhanced chemotaxis and inflammation in irAE-n patients and discovered C-X-C motif chemokine ligand (CXCL)10 as a promising marker to diagnose high-grade immunotoxicities such as irAE-n. CONCLUSIONS: We demonstrate profound and partly subgroup-specific immune cell dysregulation in irAE-n patients, which may guide future biomarker development and targeted treatment approaches.

Perioperative pain management for cleft palate surgery: a systematic review and procedure-specific postoperative pain management (PROSPECT) recommendations.

BACKGROUND/IMPORTANCE: Cleft palate surgery is associated with significant postoperative pain. Effective pain control can decrease stress and agitation in children undergoing cleft palate surgery and improve surgical outcomes. However, limited evidence often results in inadequate pain control after cleft palate surgery. OBJECTIVES: The aim of this review was to evaluate the available evidence and to develop recommendations for optimal pain management after cleft palate surgery using procedure-specific postoperative pain management (PROSPECT) methodology. EVIDENCE REVIEW: MEDLINE, Embase, and Cochrane Databases were searched for randomized controlled trials and systematic reviews assessing pain in children undergoing cleft palate repair published in English language from July 2002, through August 2023. FINDINGS: Of 1048 identified studies, 19 randomized controlled trials and 4 systematic reviews met the inclusion criteria. Interventions that improved postoperative pain, and are recommended, include suprazygomatic maxillary nerve block or palatal nerve block (if maxillary nerve block cannot be performed). Addition of dexmedetomidine to local anesthetic for suprazygomatic maxillary nerve block or, alternatively, as intravenous administration perioperatively is recommended. These interventions should be combined with a basic analgesic regimen including acetaminophen and nonsteroidal anti-inflammatory drugs. Of note, pre-incisional local anesthetic infiltration and dexamethasone were administered as a routine in several studies, however, because of limited procedure-specific evidence their contribution to pain relief after cleft palate surgery remains unknown. CONCLUSION: The present review identified an evidence-based analgesic regimen for cleft palate surgery in pediatric patients. PROSPERO REGISTRATION NUMBER: CRD42022364788.

Choline and Betaine Levels in Plasma Mirror Choline Intake in Very Preterm Infants.

Choline is essential for cell membrane formation and methyl transfer reactions, impacting parenchymal and neurological development. It is therefore enriched via placental transfer, and fetal plasma concentrations are high. In spite of the greater needs of very low birth weight infants (VLBWI), choline content of breast milk after preterm delivery is lower (median (p25-75): 158 mg/L (61-360 mg/L) compared to term delivery (258 mg/L (142-343 mg/L)). Even preterm formula or fortified breast milk currently provide insufficient choline to achieve physiological plasma concentrations. This secondary analysis of a randomized controlled trial comparing growth of VLBWI with different levels of enteral protein supply aimed to investigate whether increased enteral choline intake results in increased plasma choline, betaine and phosphatidylcholine concentrations. We measured total choline content of breast milk from 33 mothers of 34 VLBWI. Enteral choline intake from administered breast milk, formula and fortifier was related to the respective plasma choline, betaine and phosphatidylcholine concentrations. Plasma choline and betaine levels in VLBWI correlated directly with enteral choline intake, but administered choline was insufficient to achieve physiological (fetus-like) concentrations. Hence, optimizing maternal choline status, and the choline content of milk and fortifiers, is suggested to increase plasma concentrations of choline, ameliorate the choline deficit and improve growth and long-term development of VLBWI.

Validation of secondary triage algorithms for mass casualty incidents : A simulation-based study-English version.

BACKGROUND: In the event of a mass casualty incident (MCI), the situation-related shortage of medical resources does not end when the patients are transported from the scene of the incident. Consequently, an initial triage is required in the receiving hospitals. In the first step, the aim of this study was to create a reference patient vignette set with defined triage categories. This allowed a computer-aided evaluation of the diagnostic quality of triage algorithms for MCI situations in the second step. METHODS: A total of 250 case vignettes validated in practice were entered into a multistage evaluation process by initially 6 and later 36 triage experts. This algorithm-independent expert evaluation of all vignettes-served as the gold standard for analyzing the diagnostic quality of the following triage algorithms: Manchester triage system (MTS module MCI), emergency severity index (ESI), Berlin triage algorithm (BER), the prehospital algorithms PRIOR and mSTaRT, and two project algorithms from a cooperation between the Federal Office of Civil Protection and Disaster Assistance (BBK) and the Hashemite Kingdom of Jordan-intrahospital Jordanian-German project algorithm (JorD) and prehospital triage algorithm (PETRA). Each patient vignette underwent computerized triage through all specified algorithms to obtain comparative test quality outcomes. RESULTS: Of the original 250 vignettes, a triage reference database of 210 patient vignettes was validated independently of the algorithms. These formed the gold standard for comparison of the triage algorithms analyzed. Sensitivities for intrahospital detection of patients in triage category T1 ranged from 1.0 (BER, JorD, PRIOR) to 0.57 (MCI module MTS). Specificities ranged from 0.99 (MTS and PETRA) to 0.67 (PRIOR). Considering Youden's index, BER (0.89) and JorD (0.88) had the best overall performance for detecting patients in triage category T1. Overtriage was most likely with PRIOR, and undertriage with the MCI module of MTS. Up to a decision for category T1, the algorithms require the following numbers of steps given as the median and interquartile range (IQR): ESI 1 (1-2), JorD 1 (1-4), PRIOR 3 (2-4), BER 3 (2-6), mSTaRT 3 (3-5), MTS 4 (4-5) and PETRA 6 (6-8). For the T2 and T3 categories the number of steps until a decision and the test quality of the algorithms are positively interrelated. CONCLUSION: In the present study, transferability of preclinical algorithm-based primary triage results to clinical algorithm-based secondary triage results was demonstrated. The highest diagnostic quality for secondary triage was provided by the Berlin triage algorithm, followed by the Jordanian-German project algorithm for hospitals, which, however, also require the most algorithm steps until a decision.