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Methicillin-Resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections (HAI). Contact isolation has been traditionally implemented to stop transmission but its impact is increasingly questioned.A single center, retrospective, nonrandomized, observational, quasi-experimental study compared MRSA HAI rates between pre-/postdiscontinuation of MRSA contact isolation in a tertiary university hospital over 68 months. Data on primary outcomes, Central line-associated bloodstream infections and MRSA LabID bacteremia events, were analyzed by interrupted time series design using segmented Poisson regression modeling. As secondary outcomes catheter-associated urinary tract infections , ventilator-associated pneumonia , surgical site infections and hospital-associated pneumonia were compared using Fisher's exact tests. Current savings due to discontinuation were calculated based on gown use.Two hundred and ninty-five patients developed 399 HAIs. Infection rates between pre- and postinterventions were as follows: Central line-associated bloodstream infections: (0.02% vs 0.02%; P-value = .64), MRSA LabID events: (0.01% vs 0.02%; P-value = .32), hospital-associated pneumonia: (0.01% vs 0.01%; P-value = .64), catheter-associated urinary tract infections: (0% vs 0.01%; P-value = .56), ventilator-associated pneumonia: (0.01% vs 0.01%; P-value = .32), surgical site infections (0.55% vs 0.15%; P-value = .03). Savings amount to $139,228 annually.Discontinuing CP did not negatively impact endemic MRSA HAI rates between pre-postdiscontinuation periods and saved costs for isolation materials.

ZusammenfassungZahlreiche Studien haben gezeigt, dass die mediterrane Ernährung vor ernährungsmitbedingten Erkrankungen wie Übergewicht, Diabetes mellitus Typ 2, Herz-Kreislauf-Erkrankungen und verschiedenen Krebsentitäten, einschließlich Brustkrebs, schützen kann. Die zugrunde liegenden Mechanismen sind jedoch weitgehend unklar. Bislang wurde vor allem die Rolle antiinflammatorischer Fettsäuren diskutiert. In der vorliegenden Übersichtsarbeit soll am Beispiel des genetisch determinierten sowie des sporadischen Brustkrebses der Frage nachgegangen werden, welche Rolle das Darmmikrobiom spielen könnte, dessen Zusammensetzung und Funktion durch die mediterrane Ernährung verändert wird.

Background: Patients with cirrhosis have significant morbidity and mortality, as well as substantial symptom burden. Objective: We investigated the relationship between symptom burden and inpatient health care utilization among patients with cirrhosis. Methods: Adult patients with cirrhosis being evaluated for or awaiting liver transplantation at an academic institution in the United States completed the Edmonton Symptom Assessment Scale (ESAS), a validated symptom evaluation tool with total scores ranging from 0 to 90. The outcomes of interest were emergency department (ED) visits, nonelective hospitalizations, hospital days, intensive care unit (ICU) admissions, and 30-day readmissions within 6 months. Adjusted incidence rate ratios (IRRs) were used to examine the relationship between ESAS scores and outcomes. Results: Of 233 patients (43% female, median age 61), the median total ESAS score was 16 (interquartile range 6–30). Higher total scores on the ESAS were associated with increased ED visits, hospitalizations, hospital days, and ICU days (all p

Background Along with significant case transmission, hospitalizations, and mortality experienced during the global Sars-CoV-2 (COVID-19) pandemic, there existed a disruption in the delivery of health care across multiple specialties. We studied the effect of the pandemic on inpatients with diabetic foot problems in a level-one trauma center in Central Ohio. Methods A retrospective chart review of patients necessitating a consultation by the foot and ankle surgery service were reviewed from the first 8 months of 2020. A total of 270 patients met the inclusion criteria and divided into pre-pandemic (n = 120) and pandemic groups (n = 150). Demographics, medical history, severity of current infection, and medical or surgical management were collected and analyzed. Results The odds of undergoing any level of amputation was 10.8 times higher during the pandemic versus before the pandemic. The risk of major amputations (below-the-knee or higher) likewise increased with an odds ratio of 12.5 among all patients in the foot and ankle service during the pandemic. Of the patients undergoing any amputation, the odds for receiving a major amputation was 3.1 times higher than before the pandemic. Additionally, the severity of infections increased during the pandemic and a larger proportion of the cases were classified as emergent in the pandemic group compared to the pre-pandemic group. Conclusions The effect of the pandemic on the health-care system has had a deleterious effect on people with diabetes-related foot problems resulting in more severe infections, more emergencies, and necessitating more amputations. When an amputation was performed, the likelihood it was a major amputation also increased.Editor's Note: This Original Article accompanies "Diabetes-Related Amputations: A Pandemic within a Pandemic," by Lee C. Rogers, DPM, Robert J. Snyder, DPM, and Warren S. Joseph, DPM, FIDSA, available at https://doi.org/10.7547/20-248.

Perioperative myocardial ischemia (PMI) after non-cardiac surgery remains a serious postoperative complication. This study analyzed the risk factors and outcomes of patients who suffered from PMI after elective aortic surgery.Data from 863 patients who underwent elective aortic surgery for aneurysms or Leriche syndrome were retrospectively analysed with regard to PMI. The diagnosis of PMI was based on a positive serum troponin diagnostic test. According to the clinical signs and symptoms, the patients with PMI were divided into two groups: symptomatic and asymptomatic patients. Comorbidities, preoperative medication, intraoperative parameters, postoperative complications, mortality, length of intensive care stay and hospitalisation, as well as the long-term follow-up, were compared in a matched-pair analysis (1:3) with patients without PMI. Logistic regression analyses were performed to identify independent risk factors for PMI.Thirty-two patients with PMI were identified. Cardiac comorbidities (previous myocardial ischemia, P = 0.0099; left ventricular systolic dysfunction, P = 0.0429), ASA score ≥III (P = 0.0114) and preoperative elevated creatinine (P = 0.0194) were more common in patients who suffered PMI. The regression analysis confirmed that peripheral artery disease and prolonged operative duration180 min are significant predictors of PMI. Surgical complications (wound healing deficit, P = 0.0027; rate of secondary interventions during primary admission, P = 0.0057) and medical complications (pneumonia, P = 0.0002; renal dysfunction, P = 0.0041) were more common in patients with PMI compared to the control group. Patients who suffered PMI remained in intensive care for a significantly longer period (P = 0.0001) and were also hospitalized for longer (P = 0.0001) than the control group. The long-term survival of patients who suffered PMI after aortic surgery was significantly worse than the control group (P0.0001, median 53 vs. 84 months), independent of clinical ischemia-associated symptoms.PMI after aortic surgery not only affects long-term survival, but also correlates with worsening of surgical outcome. Thus, meticulous preoperative risk stratification is required for high-risk patients, together with routine postoperative monitoring of troponin levels after aortic surgery.

International audience; In hospitals through Europe and worldwide, the practices regarding hospital diets are very heterogeneous. Hospital diets are rarely prescribed by physicians, and sometimes the choices of diets are based on arbitrary reasons. Often prescriptions are made independently from the evaluation of nutritional status, and without taking into account the nutritional status. Therapeutic diets (low salt, gluten-free, texture and consistency modified, …) are associated with decreased energy delivery (i.e. underfeeding) and increased risk of malnutrition. The European Society for Clinical Nutrition and Metabolism (ESPEN) proposes here evidence-based recommendations regarding the organization of food catering, the prescriptions and indications of diets, as well as monitoring of food intake at hospital, rehabilitation center, and nursing home, all of these by taking into account the patient perspectives. We propose a systematic approach to adapt the hospital food to the nutritional status and potential food allergy or intolerances. Particular conditions such as patients with dysphagia, older patients, gastrointestinal diseases, abdominal surgery, diabetes, and obesity, are discussed to guide the practitioner toward the best evidence based therapy. The terminology of the different useful diets is defined. The general objectives are to increase the awareness of physicians, dietitians, nurses, kitchen managers, and stakeholders towards the pivotal role of hospital food in hospital care, to contribute to patient safety within nutritional care, to improve coverage of nutritional needs by hospital food, and reduce the risk of malnutrition and its related complications.

ZusammenfassungDie Mukoviszidose (zystische Fibrose, CF) gilt als häufigste, früh zum Tod führende angeborene Erkrankung in der weißen Bevölkerung. Die Beteiligung der Lunge ist wesentlich für die eingeschränkte Lebensqualität und das vorzeitige Versterben der Betroffenen verantwortlich. In der Bildgebung der letzten 10 Jahre wird – immer häufiger und wann immer möglich – die strahlenfreie MRT den Bildgebungsverfahren mit ionisierender Strahlung vorgezogen.

Regionalization of specialty medical services may necessitate an interfacility transfer. Prepatching is a model of care adopted by critical care transport organizations to reduce the transfer time to specialty care. In this model, paramedics communicate with a transport medical physician before arrival at the sending hospital to discuss a patient's condition and management plan, allowing paramedics to focus solely on packaging the patient when he or she arrives at the sending hospital. The objective of this study was to assess the impact of prepatching on paramedic in-hospital time for emergent interfacility transfers of patients requiring mechanical ventilation or vasopressor support.This is a retrospective cohort study of all emergent interfacility transfers by Ornge, the provincial critical care transport organization in Ontario, Canada, over a 4-year period. All patients over 18 years old who were either intubated or on vasopressor medications were included in the study population. Quantile regression was used to evaluate the impact of prepatching as well as patient and paramedic characteristics on paramedic in-hospital time.A total of 4,466 emergent interfacility transports were included. Of these, 1,898 were completed with prepatching, and 2,568 were not. Vasopressor use was associated with significantly higher prepatching rates. Overall, prepatching reduced in-hospital time by 9 minutes at the 90th quantile across all patients. Increased in-hospital time was noted for patients on mechanical ventilation, on vasopressor medications, and transported by a fixed wing vehicle by 38, 29, and 49 minutes at the 90th quantile, respectively (P.05). Conversely, patients transported by a critical care paramedic crew configuration were associated with a 27-minute decrease in in-hospital time at the 90th quantile compared with transport by an advanced care paramedic crew configuration (P.05).Prepatching reduced paramedic in-hospital time for emergent interfacility transports for patients who were mechanically ventilated or require vasopressors. These results suggest that prepatching can reduce the overall time to definitive care in high-risk patients, potentially improving patient outcomes in critically ill patients.

Objectives To investigate the adherence of randomised controlled trial (RCT) protocols evaluating non-regulated interventions (including dietary interventions, surgical procedures, behavioural and lifestyle interventions, and exercise programmes) in comparison with regulated interventions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement. Methods We conducted a repeated cross-sectional investigation in a random sample of RCT protocols approved in 2012 (n = 257) or 2016 (n = 292) by research ethics committees in Switzerland, Germany, or Canada. We investigated the proportion of accurately reported SPIRIT checklist items in protocols of trials with non-regulated as compared to regulated interventions. Results Overall, 131 (24%) of trial protocols tested non-regulated interventions. In 2012, the median proportion of SPIRIT items reported in these protocols (59%, interquartile range [IQR], 53%-69%) was lower than in protocols with regulated interventions (median, 74%, IQR, 66%-80%). In 2016, the reporting quality of protocols with non-regulated interventions (median, 75%, IQR, 62%-83%) improved to the level of regulated intervention protocols, which had not changed on average. Conclusions Reporting of RCT protocols evaluating non-regulated interventions improved between 2012 and 2016, although remained suboptimal. SPIRIT recommendations need to be further endorsed by researchers, ethics committees, funding agencies, and journals to optimize reporting of RCT protocols.

Summary Background This practical guideline is based on the ESPEN Guidelines on Chronic Intestinal Failure in Adults. Methodology ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists, and nurses working with patients with chronic intestinal failure. Results This practical guideline consists of 112 recommendations with short commentaries for the management and treatment of benign chronic intestinal failure, including home parenteral nutrition and its complications, intestinal rehabilitation, and intestinal transplantation. Conclusion This practical guideline gives guidance to health care providers involved in the management of patients with chronic intestinal failure.

Zusammenfassung Hintergrund Adipositas und die assoziierten Folgeerkrankungen führen nicht nur zu einer erhöhten Morbidität und Mortalität, sondern auch zu einer Reduktion der Lebensqualität. Obwohl ein multimodaler Therapieansatz die leitliniengerechte Therapie der Wahl für die meisten Patienten ist, fehlen in Deutschland flächendeckend geeignete Programme und die Ansprechraten unstrukturierter Interventionen sind unzureichend. Material und Methodik Das ZEPmax-Programm ist ein konservatives, multimodales, 1-jähriges Therapieprogramm mit initialer Formuladiätphase für Erwachsene mit Adipositas. Die Patienten treffen sich jede Woche für 3,5 Stunden am Zentrum. Die Daten der ersten 136 konsekutiv eingeschlossenen Patienten wurden hier als Intention-to-treat-Analyse ausgewertet. Neben Gewicht und BMI wurden Faktoren des metabolischen Syndroms untersucht. Ergebnisse Die Teilnehmer hatten einen durchschnittlichen BMI von 43,0 kg/m2. 11,8 % brachen das Programm im ersten Jahr ab. 87,5 % erreichten das primäre Therapieziel einer Gewichtsreduktion von > 10 % des Ausgangsgewichts bei einem durchschnittlichen Gewichtsverlust von 24,7 kg (19 % des Ausgangsgewichts). 72 % der Diabetespatienten (n = 18) erreichten eine vollständige Remission, d. h. einen normwertigen HbA1c ohne spezifische Diabetesmedikation. Der systolische Blutdruck der Hypertoniepatienten (n = 53) sank im Mittel um 22 mmHg. Das Gesamtcholesterin der Patienten mit Hyperlipidämie (n = 66) konnte um 23 mg/dl und das LDL-Cholesterin um 17 mg/dl gesenkt werden. Schlussfolgerung Die vorliegende Arbeit zeigt, dass mit Hilfe des strukturierten, formuladiätbasierten, multimodalen Adipositas-Therapieprogramms ZEPmax ein nachhaltiger Gewichtsverlust mit hohen Ansprechraten erreicht werden kann. Durch erfolgreiche Therapie der Adipositas konnten die assoziierten Folgeerkrankungen Diabetes mellitus Typ 2, arterielle Hypertonie und Hyperlipidämie mit hohen Remissionsquoten behandelt werden. Die vorliegende Arbeit belegt den Stellenwert einer professionell durchgeführten konservativen Adipositastherapie in Deutschland.

The hype about vitamin D can be traced back to the ubiquitous presence of vitamin D receptors in many organ systems, in addition to the importance for healthy bones. Large observational studies have provided indications that a vitamin D deficiency favors risks for age-associated chronic diseases, such as cancer and cardiovascular diseases. In this article the latest information on bone health in adult persons as well as cancer and cardiovascular diseases is summarized based on the current results of the large vitamin D and omega‑3 trial (VITAL).Der „Hype um Vitamin D“ ist neben der Bedeutung für die Knochengesundheit auch auf die ubiquitäre Präsenz des Vitamin-D-Rezeptors in vielen Organsystemen zurückzuführen. Große Beobachtungsstudien lieferten Hinweise, dass ein Vitamin-D-Mangel Risiken altersassoziierte chronische Erkrankungen, wie Krebs- und kardiovaskuläre Erkrankungen, begünstigt. In der vorliegenden Übersicht werden neueste Informationen, einerseits zur Knochengesundheit bei erwachsenen Menschen sowie andererseits zu Krebs- und kardiovaskulären Erkrankungen, anhand der aktuellen Resultate des großen Vitamin D and Omega‑3 Trial (VITAL) eingeordnet.

BACKGROUND: Obesity [Body Mass Index (BMI) > 30 kg/m2] is a risk factor for disease conditions enhancing hospitalization and mortality risks, but higher BMI was paradoxically reported to reduce mortality in several acute and chronic diseases. Unintentional weight loss (WL) is conversely associated with disease development and may worsen patient outcome, but the impact of weight loss and its interaction with obesity in modulating risk of death in hospitalized patients remain undefined. METHODS: We investigated the ESPEN nutritionDay database of non-critically ill hospitalized patients to assess the impact of self-reported 3-month WL (WL1:2.5-6.6%; WL2: 6.6-12.6%, WL3: >12.6%) and its interaction with BMI in modulating 30-day in-hospital mortality. Multivariate Cox regression was used to estimate hazard ratios (HR), with stable weight (WL0) as reference category. RESULTS: In 110835 nDay patients, 30-day mortality increased with increasing WL. Male gender, increasing disease severity index PANDORA score (age, nutrient intake, mobility, fluid status, cancer and main patient group) and not having had surgery also predicted 30-day mortality. HR for 30-day mortality remained significantly higher compared to WL0 for WL2 and WL3 after multiple adjustment. Adjusted HR and its increments through increasing weight loss categories were comparable in lean (BMI30 kg/m2). Impact of gender, PANDORA score and surgery on 30-day mortality were conversely comparable in the three BMI groups. CONCLUSIONS: These results indicate that self-reported WL could represent a relevant prognostic factor in every hospitalized patient. Overweight and obesity per se have no protective impact against WL-associated mortality.

Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoint in translating autoimmunity to inflammation. Zonulin family peptide (zonulin), a potent regulator for intestinal tight junctions, is highly expressed in autoimmune mice and humans and can be used to predict transition from autoimmunity to inflammatory arthritis. Increased serum zonulin levels are accompanied by a leaky intestinal barrier, dysbiosis and inflammation. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate or a cannabinoid type 1 receptor agonist inhibits the development of arthritis. Moreover, treatment with the zonulin antagonist larazotide acetate, which specifically increases intestinal barrier integrity, effectively reduces arthritis onset. These data identify a preventive approach for the onset of autoimmune disease by specifically targeting impaired intestinal barrier function., Intestinal dysbiosis is associated with an ever-growing list of autoimmune diseases. Here the authors show that both mice and humans with autoimmune arthritis can have dysbiosis and barrier leakiness prior to major signs of inflammatory arthritis, and treatment of mice with a zonulin antagonist can limit collagen-induced arthritis.

Objective: The aim of this study was to report 10-year real-world single-center experience with the GORE TAG conformable thoracic aortic graft (CTAG), focusing on rupture-free survival, aortic-related reintervention, and device-related complications during midterm and long-term follow-up (FU). Methods: This retrospective study analyzes results of thoracic endovascular aortic repair (TEVAR) performed between January 2009 and December 2018. Out of 419 TEVAR procedures within this period, 194 patients (male 57.2%, 111/194), with a mean age of 65 ± 13 years, were treated with the CTAG device. Indication for TEVAR was a thoracic aortic aneurysm in 24.7% (48/194), type B aortic dissection in 32.5% (63/194), penetrating aortic ulcer 15.5% (30/194), and miscellaneous 27.3% (53/194). Emergently were operated 43.8% (85/194) patients. Median follow-up (FU) including computed tomography imaging was 43.5 months (Q1-Q3: 8.6–67.0) and was completed in 91.2% (177/194) of patients. Results: Overall survival rates were 75.8% (95% confidence interval [CI] = [0.76–0.70]) and 56.6% (95% CI = [0.57–0.50]) at 12 and 60 months, respectively. Cumulative incidence for aortic rupture was 11.9% (95% CI = [0.07–0.17]) at 60 and 90 months, respectively. Cumulative incidence for aortic-related reintervention was 27.5% (95% CI = [0.21–0.34]) at 60 and 90 months. Cumulative incidence for migration was 2.8% (95% CI = [0.004–0.05]) and 3.9% (95% CI = [0.007–0.07]) at 60 and 90 months, respectively. New endograft infections or material fatigue were not observed. Conclusions: The herein reported 10-year real-world single-center experience with the CTAG observed favorable long-term outcome. Thus, the device demonstrates appropriate persistent safety, efficacy, and clinical durability up to long-term FU in the treatment of diverse thoracic aortic pathologies.

ZusammenfassungEtwa ein Drittel aller Patienten, die sich einem operativen Eingriff unterziehen, nehmen chronisch Psychopharmaka ein. Neben Depressionen und Psychosen stellen chronische Schmerzen sowie Angst- und Panikstörungen die häufigsten Indikationen dar. In den vergangenen 30 Jahren stieg die Häufigkeit der Verordnung von Psychopharmaka um das 7-Fache. Fast alle Psychopharmaka interagieren mit Medikamenten, die perioperativ häufig gegeben werden, beispielsweise mit 5-HT3-Antagonisten, Sympathomimetika oder Opioiden. Einige der Medikamente weisen eine enge therapeutische Breite auf und nicht alle Medikamente können perioperativ pausiert werden. Im Rahmen der präoperativen Risikoevaluation ist daher eine Prüfung im Einzelfall notwendig. Der Anästhesist muss zudem bei Gabe bestimmter Medikamente während der Narkose besondere Vorsicht walten lassen oder ganz auf diese verzichten.Bei der Therapie vieler neurologischer Erkrankungen stellen Medikamente die zentrale Säule dar. Häufig begegnen dem Anästhesisten Patienten mit einer Epilepsie, mit Morbus Parkinson oder mit einer Myasthenia gravis, die eine entsprechende medikamentöse Therapie erhalten. Das perioperative Pausieren der Medikamente lässt zumeist eine Befundverschlechterung der neurologischen Grunderkrankung befürchten. Auf die möglichst rasche postoperative Einnahme der Dauermedikation ist daher besonderer Wert zu legen.

This review gives an overview of current screening practices for cervical cancer. In the introduction, we will cover approaches of population screening focusing on high-risk Human Papilloma Virus (hrHPV) and the need for a better triage assay. We will further assess the impact of current vaccination programs on screening. Subsequently, the review will cover various technological aspects of nucleic acid- and protein-based biomarker assays. We will then detail different molecular markers in view of their use in triage assays, emphasizing epigenetic and protein markers. Finally, we will place this in the context of cost-effectiveness considerations in view of their implementation in high- as well as in low- to middle-income countries. Introduction: Cervical cancer remains a significant healthcare problem, notably in low- to middle-income countries. While a negative test for hrHPV has a predictive value of more than 99.5%, its positive predictive value is less than 10% for CIN2+ stages. This makes the use of a so-called triage test indispensable for population-based screening to avoid referring women, that are ultimately at low risk of developing cervical cancer, to a gynecologist. This review will give an overview of tests that are based on epigenetic marker panels and protein markers. Areas covered: There is a medical need for molecular markers with a better predictive value to discriminate hrHPV-positive women that are at risk of developing cervical cancer from those that are not. Areas covered are epigenetic and protein markers as well as health economic considerations in view of the fact that most cases of cervical cancer arise in low-to-middle-income countries. Expert opinion: While there are biomarker assays based on changes at the nucleic acid (DNA methylation patterns, miRNAs) and at the protein level, they are not widely used in population screening. Combining nucleic acid-based and protein-based tests could improve the overall specificity for discriminating CIN2+ lesions that carry a low risk of progressing to cervical cancer within the screening interval from those that carry an elevated risk. The challenge is to reduce unnecessary referrals without an undesired increase in false-negative diagnoses resulting in cases of cervical cancer that could have been prevented. A further challenge is to develop tests for low-and middle-income countries, which is critical to reduce the worldwide burden of cervical cancer.

Purpose Emerging evidence suggests that the progesterone-mediated receptor activator of nuclear factor κB (RANK)/soluble RANK ligand (sRANKL)/osteoprotegerin (OPG) pathway plays an important role in mammary carcinogenesis and is hyperactivated in germline (g)BRCA1/2 mutation carriers. We analyzed the effects of a 3-month intensive lifestyle intervention within the LIBRE-1 study on the serum levels of OPG and sRANKL and hypothesized that the intervention program provides a beneficial impact on the biomarkers by increasing OPG and reducing sRANKL serum concentrations. Methods Serum levels of OPG and sRANKL of 49 gBRCA1/2 mutation carriers were quantified using enzyme-linked immunosorbent assays. We used previously collected blood samples from participants of the prospective LIBRE-1 study, who were randomized into an intervention group (IG), increasing physical activity and adherence to the Mediterranean diet (MedD) through supervised sessions from study entry to the first study visit after 3 months and a usual-care control group (CG). Differences in biomarker levels before and after the 3-month intervention were tested within and between study groups. Results The lifestyle intervention resulted in a significant increase in OPG for participants in both the IG (q = 0.022) and CG (q = 0.002). sRANKL decreased significantly in the IG (q = 0.0464) and seemed to decrease in the CG (q = 0.5584). An increase in the intake of Omega-3 polyunsaturated fatty acids was significantly associated with an increase in OPG (r = 0.579, q = 0.045). Baseline serum levels of sRANKL were a strong predictor for the change of sRANKL in the course of the intervention (ß-estimate = − 0.70; q = 0.0018). Baseline physical fitness (assessed as VO2peak) might predict the change of OPG in the course of the intervention program (ß-estimate = 0.133 pg/ml/ml/min/kg; p = 0.0319; q = 0.2871). Conclusion Findings from this pilot study seem to confirm our hypothesis by showing an increase in OPG and decrease in sRANKL over a 3-month lifestyle intervention and suggest that increased physical activity and adherence to the MedD are potent modulators of the biomarkers OPG and potentially sRANKL.

The use of the appendix for diagnosis of Total Colonic Aganglionosis (TCA) remains controversial. This study aimed to categorize the presence of ganglion cells in the appendix and determine its reliability as a histological specimen for the diagnosis of TCA. This was a combined retrospective and prospective study. Permanent histological specimens of normal appendices removed during appendectomy for malrotation or falsely presumed appendicitis, and from patients with short segment Hirschsprung’s disease (HD) or TCA were included. Permanent specimens of the appendix tip from Malone procedures were prospectively collected. All specimens were independently reviewed by two experienced pathologists in a standardized manner to assess for the presence of ganglion cells. A total of 112 appendices were evaluated. Nine came from patients with a diagnosis of TCA, and five from patients with HD. Ganglion cells were present in all specimens from patients with diagnoses other than TCA and were absent in all specimens from patients with TCA. In the correct clinical setting, the absence of ganglion cells in the appendix can allow for a reliable diagnosis of TCA.

Pediatric colorectal conditions require complex medical care and can require lifelong support. Caregivers often seek medical information on the internet. The aim of this study was to characterize the use of three social media platforms for information sharing about pediatric colorectal conditions. A systematic study of Instagram, Facebook, and Twitter was performed using standardized search terms. Accounts with activity within the last year were included. Quantitative data were collected. Accounts were qualitatively assessed and assigned a functional category. Group differences were tested via Kruskal–Wallis test and Fisher’s exact tests for continuous and categorical variables, respectively. A total of 96 Instagram accounts, 57 Twitter accounts, 49 Facebook pages, and 45 Facebook groups were identified. Accounts originated from 24 countries and the greatest number of accounts was created in 2013. The most common source of information on Instagram was from personal accounts (74.0%), on Facebook was from support groups (45.7%), and on Twitter was from health care providers (35.1%), (p

Severely injured patients benefit from early identification and trauma centre treatment. Ontario has provincial prehospital trauma triage guidelines identifying patients who require direct trauma centre transport. Trauma patients not identified as meeting this provincial trauma triage standard are brought to the closest non-trauma hospital and may later be transferred to a trauma centre by a secondary interfacility transfer. Secondary interfacility transfers cause significant delays in receiving definitive care which have been associated with worse outcomes. The objective of this study was to determine the frequency that patients who underwent emergent secondary interfacility trauma transfer initially met prehospital trauma triage guidelines, as well as to assess the approximate delay to trauma centre care. Health record review of all injured patients undergoing interfacility transfer to a trauma centre by the provincial critical care transport organization in Ontario, Canada over a 1-year period. The primary outcome of interest was the frequency that patients met the triage standards and which specific criteria were satisfied. Times from patient arrival at the initial non-trauma hospital to initiation of interfacility transfer and from patient arrival at initial non-trauma hospital to arrival at trauma centre were calculated. A total of 460 were included in the study, 372 (80.8%) of whom met the prehospital triage standard. The largest missed criteria were age greater than 55 years, high-risk motor vehicle collisions, and decreased Glasgow Coma Scale. The median time from initial hospital arrival to trauma centre was 5.7 h for those patients requiring secondary interfacility transport. Patients who meet trauma triage criteria that end up undergoing secondary interfacility transfer experience significant delays. We recommend adding recreational vehicle collisions as a triage criterion. Emergency physicians should work with their local paramedic services to ensure severely injured patients are identified early to expedite transport.

Background The diagnostic value of cardiac magnetic resonance imaging (MRI) employing the 2018 Lake Louise criteria in pediatric and adolescent patients with acute myocarditis is undefined. Objective To evaluate the diagnostic value of the Lake Louise criteria in pediatric and adolescent patients with suspected acute myocarditis and to show the utility of cardiac MRI for follow-up in this patient cohort. Materials and methods Forty-three patients (age range: 8–21 years) with suspected acute myocarditis and 13 control patients who underwent cardiac MRI were retrospectively analyzed. T2-weighted and late gadolinium enhancement imaging were performed in all patients. T1 and T2 mapping were available in 26/43 patients (60%). The Lake Louise criteria were assessed. In 27/43 patients (63%), cardiac MRI follow-up was available. Receiver operating characteristic analysis, Pearson’s correlation coefficient and paired Student’s t-test were used for statistical analysis. Results In the total cohort, the Lake Louise criteria achieved a sensitivity of 86% (95% confidence interval [CI]: 72–95%) and a specificity of 100% (95% CI: 79–100%) for the diagnosis of acute myocarditis. In the subgroup of patients with available mapping parameters, the diagnostic performance of the Lake Louise criteria was higher when mapping parameters were implemented into the score (area under the receiver operating characteristic curve: 0.944 vs. 0.870; P=0.033). T2 relaxation times were higher in patients with admission to the intermediate care unit and were associated with the length of intermediate care unit stay (r=0.879, P=0.049). Cardiac MRI markers of active inflammation decreased on follow-up examinations (e.g., T1 relaxation times: 1,032±39 ms vs. 975±33 ms, PP=0.003). Conclusion The Lake Louise criteria have a high diagnostic performance for the diagnosis of acute myocarditis and are a valuable tool for follow-up in pediatric and adolescent patients. The mapping techniques enhance the diagnostic performance of the 2018 Lake Louise criteria.

OBJECTIVES The aim of this study was to evaluate technical/clinical outcomes of the Gore TAG Conformable Thoracic Stent Graft with Active Control System (CTAG with ACS) in thoracic aortic disease since its introduction in Europe in 2017. METHODS Patients undergoing thoracic endovascular aortic repair (TEVAR) with the device between 2017 and 2020 were identified from a prospectively maintained single-centre database and retrospectively analysed. Predominant indications were aortic dissection (n = 46), thoracic/thoraco-abdominal aneurysm (n = 20/n = 7), penetrating ulcer (n = 14) and intramural haematoma (n = 12). Emergency procedures were performed in 47% (54/115). The primary outcome was technical success. Secondary outcomes were clinical success, serious adverse events and procedure-related reintervention. ACS was assessed regarding angulation, accuracy and apposition. The median follow-up was 8.46 months (interquartile range: 3.18–16.89 months). RESULTS A total of 115 consecutive patients (82 males, median age 63; interquartile range: 53–74 years) have been included. Technical success was achieved in 95.7% (110/115). Clinical success rate was 80.9% (93/115); mostly due to procedure-related death (n = 14). Overall mortality was 19.1% (22/115), with significant differences between elective/emergency procedures (log-rank: P CONCLUSIONS This single-centre study shows encouraging performance of the CTAG with ACS in an array of aortic pathologies. Although longer-term data must be awaited, ACS leads to overall favourable device placement. Despite ongoing advances in device technology, TEVAR remains challenging and is associated with significant burden inherent to the underlying disease.

The accurate processing of complex liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) data from biological samples is a major challenge for metabolomics, proteomics, and related approaches. Here, we present the pipelines and systems for threshold-avoiding quantification (PASTAQ) LC-MS/MS preprocessing toolset, which allows highly accurate quantification of data-dependent acquisition LC-MS/MS datasets. PASTAQ performs compound quantification using single-stage (MS1) data and implements novel algorithms for high-performance and accurate quantification, retention time alignment, feature detection, and linking annotations from multiple identification engines. PASTAQ offers straightforward parameterization and automatic generation of quality control plots for data and preprocessing assessment. This design results in smaller variance when analyzing replicates of proteomes mixed with known ratios and allows the detection of peptides over a larger dynamic concentration range compared to widely used proteomics preprocessing tools. The performance of the pipeline is also demonstrated in a biological human serum dataset for the identification of gender-related proteins.

Summary This ESPEN practical guideline will inform physicians, nurses, dieticians, pharmacists, caregivers and other home enteral nutrition (HEN) providers in a concise way about the indications and contraindications for HEN, as well as its implementation and monitoring. This guideline will also inform interested patients requiring HEN. Home parenteral nutrition is not included but will be addressed in a separate ESPEN guideline. The guideline is based on the ESPEN scientific guideline published before, which consists of 61 recommendations that have been reproduced and renumbered, along with the associated commentaries that have been shorted compared to the scientific guideline. Evidence grades and consensus levels are indicated. The guideline was commissioned and financially supported by ESPEN and the members of the guideline group were selected by ESPEN.

The coronavirus disease 2019 (COVID-19) and the imposed lockdowns in order to control the pandemic, had undoubtedly influenced the lifestyle of millions of people worldwide. The period of confinement, which was characterized by seizing most business activities and allowing only for e-classes at schools and universities, leading also to a lower physical activity, could have affected eating behaviors of people of all ages. In this study we aimed to investigate the impact of the first lockdown period (March-May 2020) on body weight (BW) and on body mass index (BMI) in both adults and adolescents (>16 years old). A systematic literature search was conducted in PubMed®, Scopus®, Web of Science® and EMBASE® databases and 36 observational (35 cross-sectional and one cohort) studies were included. BW and BMI changes after/during the lockdown period were examined. BW was stated as increased in a significant part of the individuals (11.1-72.4%), although a range of 7.2-51.4% of individuals reported weight loss. A significant higher BW was observed with a weighted mean between-group difference (WMD) 1.57 (95% CI 1.01 to 2.14) in the post-lockdown period compared to the before lockdown time and higher BMI, 0.31 WMD (95% CI, 0.17 to 0.45) was identified before the lockdown period. At variance with general trends, one study in older adults (>60 years old) notably reported a significant BW loss, suggesting a higher risk for lockdown-induced weight loss and potentially malnutrition in the elderly population. Overall increments in BW are an alarming effect of lockdown during the COVID-19 pandemic, leading to potential higher incidence of overweight, obesity and related health-risks as well as other noncommunicable diseases. Further studies are needed to assess potential group-specific impacts, with particular regard to weight gain in younger people and risk of weight loss, malnutrition and sarcopenia in older adults.

BACKGROUND Despite the widespread use of superior vena cava (SVC) flow as a marker of systemic blood flow from the upper body, no previous studies have systematically evaluated the correlation between SVC flow and other echocardiography measures of systemic blood flow in the context of different patterns of patent ductus arteriosus (PDA) shunt direction METHODS: A retrospective cohort study of preterm infants (

Background In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed–platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed–platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed–platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab. Patients and methods Eligible patients were randomized 2 : 1 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks (for up to 35 cycles, ∼2 years) plus four cycles of pemetrexed (500 mg/m2) and investigators’ choice of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg·min/ml) every 3 weeks, followed by pemetrexed until progression. Patients assigned to placebo plus pemetrexed–platinum could cross over to pembrolizumab upon progression if eligibility criteria were met. The primary endpoints were OS and PFS. Results After a median follow-up of 31.0 months, pembrolizumab plus pemetrexed–platinum continued to improve OS [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.46-0.69] and PFS (HR, 0.49; 95% CI, 0.41-0.59) over placebo plus pemetrexed–platinum regardless of programmed death-ligand 1 expression. Objective response rate (ORR) (48.3% versus 19.9%) and time to second/subsequent tumor progression on next-line treatment (PFS2; HR, 0.50; 95% CI, 0.41-0.61) were improved in patients who received pembrolizumab plus pemetrexed–platinum. Eighty-four patients (40.8%) from the placebo plus pemetrexed–platinum group crossed over to pembrolizumab on-study. Grade 3-5 adverse events occurred in 72.1% of patients receiving pembrolizumab plus pemetrexed–platinum and 66.8% of patients receiving placebo plus pemetrexed–platinum. Fifty-six patients completed 35 cycles (∼2 years) of pembrolizumab; ORR was 85.7% and 53 (94.6%) were alive at data cut-off. Conclusions Pembrolizumab plus pemetrexed–platinum continued to show improved efficacy outcomes compared with placebo plus pemetrexed–platinum, with manageable toxicity. These findings support first-line pembrolizumab plus pemetrexed–platinum in patients with previously untreated metastatic nonsquamous NSCLC.

Understanding the unique needs of patients seen in clinic versus at home can help palliative care (PC) teams choose how to maximize available resources.To compare the characteristics and PC needs of patients seen by PC teams in clinic versus at home.We analyzed data from the Palliative Care Quality Network between August 2016 and September 2019 and compared demographics, diagnosis, reason for referral, PC needs, functional status, self-reported symptoms, and patient-reported quality of life.Compared to patients receiving PC in clinic, patients receiving PC at home were more likely to be of age 80 years or older (odds ratio [OR] 7.5, 95% CI 5.0, 10.9, P 0.0001), have lower functional status (mean Palliative Performance Scale score 53% vs. 68%, P 0.0001), and were less likely to screen positive for needing pain management (OR 0.31, 95% CI 0.22, 0.42, P 0.0001) or other symptom management (OR 0.61, 95% CI 0.41, 0.90, P = 0.01). Patients receiving care at home were more likely to be referred for care planning (goals of care discussions or advance care planning) (OR 11.5, 95% CI 8.3, 16.0 P 0.0001) and patient/family support (OR 5.9, 95% CI 4.2, 8.3, P 0.0001).Patients seen by PC teams at home had worse function and were more likely to be referred for care planning, while patients seen in clinic had more PC needs related to pain and symptom management. Despite these differences, both populations have significant PC needs that support routine assessment and require appropriately staffed interdisciplinary teams to address these needs.

The effect of medical nutrition on serum metabolomics has been poorly explored. The aim of the study was to investigate the relation between energy supply and metabolic profiles in critically ill patients.Twenty mechanically ventilated patients on enteral nutrition (EN) or enteral/parenteral nutrition (EN/PN) were randomized into two groups. One group received an individual energy supply based on indirect calorimetry (IC group, n = 9), the other group received a standard energy supply based on a formula, the standard care group (SC group, n = 11). Targeted metabolomics was performed in early-, late- and post-acute metabolic phase.Individual versus standard care energy supply resulted in a metabolite class separation between the IC and the SC group (P 0.001). In the SC group concentrations of four glucogenic amino acids and three biogenic amines increased between the early- and late-acute metabolic phase (P 0.05). The metabolomics pattern differed between the routes of nutrition administration (P 0.01).The amount of energy supply by EN or PN, besides other factors, seems to modulate serum metabolites. Nutrition therapy based on individualized energy supply is associated with a reduction of metabolites reflecting catabolism. Therefore, metabolomics could be a new tool to determine metabolic phases in critically ill patients.

Purpose Food-derived bioactive peptides may influence important physiological functions. An important example is beta-casomorphins, which are opioid peptides derived from A1 beta-casein in bovine milk and have been associated to be risk factors for non-communicable diseases in humans. A1 and A2 beta-casein are different with respect to the release of bioactive peptides, in particular BCM-7. However, evidence from human studies is limited and could be complemented with evidence derived from animal studies. We conducted a scoping review to identify animal studies investigating the effects of A1 beta-casein or BCM-7 compared to A2 beta-casein or any other intervention on health-related outcomes. Methods We systematically searched for relevant studies in two electronic databases (Medline, Embase; last search performed March 2020). Two reviewers independently undertook study selection and data extraction of included references. Results were summarized tabularly and narratively. Results We included 42 studies investigating various animal models, including rats, mice, rabbits, and dogs. Six studies investigated health-related outcomes of A1- vs. A2 milk, while most studies (n = 36) reported on physiological properties (e.g., analgesic effect) of BCM-7 as an opioid peptide. Included studies were extremely heterogeneous in terms of the study population, type of intervention and dose, and type of outcome measures. Conclusions Only a few studies comparing the effects of A1- and A2 milk were identified. More studies addressing this research question in animal models are needed to provide essential information to inform research gaps. Results from future studies could eventually complement research for humans, particularly when the body of evidence remains uncertain as is the case in the A1- and A2 milk debate.

ObjectiveOur aim was to determine whether right ventricular (RV) dysfunction at 24-hour postnatal age predicts adverse developmental outcome among patients with hypoxic ischaemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH).DesignNeonates≥35 weeks with HIE/TH were enrolled in a physiological study in the neonatal period (n=46) and either died or underwent neurodevelopmental follow-up at 18 months (n=43). The primary outcome was a composite of death, diagnosis of cerebral palsy or any component of the Bayley Scores of Infant Development IIIResultsNine patients died and 34 patients were followed up at a mean age of 18.9±1.4 months. Both indices of RV systolic performance were abnormal in 15 (35%) patients, TAPSE ConclusionsThe role of postnatal cardiovascular function on neurological outcomes among patients with HIE who receive TH merits further study. Quantitative measurement of RV function at 24 hours may provide an additional neurological prognostic tool.

Background: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (vs 25·0–49·9 nmol/L vs 50·0–74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of vs 400–1000 IU vs 1001–2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (vs 1·00–15·99 years vs 16·00–64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. Findings: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0–95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86–0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65–0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400–1000 IU (0·70 [0·55–0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72–0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00–15·99 years at enrolment (0·71 [0·57–0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86–1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. Interpretation: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400–1000 IU for up to 12 months, and age at enrolment of 1·00–15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. Funding: None.

Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2.

Background MDR organisms (MDROs) pose a relevant risk for patients in modern healthcare. Although ownership of pet animals is common and owners and pets commonly live in close contact, it is still unclear whether pet ownership may be considered as a risk factor for MDRO acquisition prior to hospitalization. Methods We performed three separate meta-analyses in accordance with the PRISMA guidelines, assessing contact to pets as a risk factor for acquisition of MRSA, VRE and MDR Gram-negatives [namely third-generation cephalosporin-resistant Enterobacterales (3GCRE) and carbapenem-resistant Enterobacterales (CRE)]. Results We calculated an increased risk of MRSA carriage for dog owners [risk ratio (RR) 2.28, 95% CI 1.47–3.56]. Meta-analysis did not show a significantly higher risk for 3GCRE colonization among owners of different pet species compared with non-pet owners (RR 1.18, 95% CI 0.83–1.68 for pet owners in general, RR 0.88, 95% CI 0.56–1.40 for dog owners, RR 1.16, 95% CI 0.58–2.34 for cat owners, RR 1.34, 95% CI 0.43–4.18 for rodent owners, RR 0.91, 95% CI 0.38–2.18 for bird owners, and RR 2.34, 95% CI 0.33–16.63 for lizard/frog owners). For VRE, there were insufficient data to perform a meta-analysis. Conclusions Our analyses suggest contact to pet animals is a risk factor for MRSA, but not for 3GCRE/CRE acquisition. Evaluation of the underlying literature suggested a possible role of pet animals as: (i) vectors for the transmission of MDROs between livestock and humans; as well as (ii) a reservoir for MDROs. Pets, therefore, may promote transmission and reinfection of humans.

Objective Characterize the impact of milrinone on arterial pressure of neonates with persistent hypoxemic respiratory failure (HRF) and hypoxic ischemic encephalopathy (HIE) treated with inhaled nitric oxide and therapeutic hypothermia (TH). Study design Retrospective cohort study. Arterial pressure was assessed hourly for 24 h. The primary outcome was change in diastolic arterial pressure (DAP). Results 56 patients were included [(i) cases: HIE/TH who received milrinone (n = 9), (ii) Milrinone controls (n = 17), (iii) HIE controls (n = 30)]. Baseline demographics, severity of HRF and arterial pressure were comparable between groups. Only milrinone treated patients with HIE/TH had a marked drop in DAP in the first hour, which persisted for more than 12 h despite escalation in inotropes (p = 0.008). Conclusion Milrinone treated patients with HRF and HIE/TH develop profound reduction in DAP and require escalation of cardiovascular support. The risk benefit profile of milrinone should be considered and pharmacological studies are warranted to evaluate drug metabolism and clearance in this population.

The Enhanced Recovery After Surgery (ERAS) protocol affected traditional cardiac surgery processes and COVID-19 is expected to accelerate its scalability. The aim of this study was to assess the impact of an ERAS-based protocol on the length of hospital stay after cardiac surgery. From January 2019 to June 2020, 664 patients underwent consecutive cardiac surgery at a Latin American center. Here, 46 patients were prepared for a rapid recovery through a multidisciplinary institutional protocol based on the ERAS concept, the “TotalCor protocol”. After the propensity score matching, 46 patients from the entire population were adjusted for 12 variables. Patients operated on the TotalCor protocol had reduced intensive care unit time (P P ≤ 0.001) and length of hospital stay (P ≤ 0.001). In addition, there were no significant differences in the occurrence of complications and death between the two groups. Of the 10-central metrics of TotalCor protocol, 6 had > 70% adherences. In conclusion, the TotalCor protocol was safe and effective for a 3-day discharge after cardiac surgery. Postoperative atrial fibrillation and renal failure were predictors of postoperative stay > 5 days.

The aim of this study was to explore how the implementation of the quality management system (QM; according to DIN EN ISO 9001 : 2008) at the LIONS Eye Bank impacted the rate and reasons for discarding donated corneas. The QM system was introduced in November 2010.The rate of and reasons for discarding cornea tissues at the LIONS Eye Bank Saar-Lor-Lux,Trier/Western Palatinate from 2006 to 2016 were analysed retrospectively. 4,140 corneas from 2,084 donors were analysed. 1,640 corneas were processed before the QM system had been introduced and 2,500 corneas thereafter. Main reasons for discarding cornea tissues were endothelial quality, contamination of the medium and a positive conjunctival swab. The data was extracted from clinical files and data filing systems, entered into a Microsoft Access database and analysed statistically with SPSS.Following the implementation of a QM system, the discard rate decreased significantly from 50.1% to 39.7% (p 0.0001). Prior to the implementation of the QM system, 493 (30.1%) cornea tissues had been discarded due to endothelial quality, while this figure improved significantly to 604 (24.2%) after the QM system had been implemented (p 0.0001). Contamination was the reason for discarding tissue in 173 (10.5%) cases before implementation of the QM system, and in 124 (5.0%) cases thereafter (p 0.0001). Positive conjunctival swab was the reason for discarding tissue in 10 (0.6%) cases before the QM system had been implemented, and in 53 (2.1%) cases thereafter (p 0.0001).Implementation of a QM system significantly reduced the rate of discarded donor tissue in the LIONS Eye Bank. Better management of contamination as a reason for discarding cornea tissues can be attributed to improved standards, protocols and training that are part of this QM system.Ziel dieser Studie war es, den Einfluss der Einführung des QM-Systems (QM: Qualitätsmanagement, nach DIN EN ISO 9001 : 2008) auf die Verwerfungsrate und -gründe von Spendergewebe in einer Hornhautbank zu erforschen. Die Einführung des QM-Systems erfolgte im November 2010.Die Verwerfungsrate und -gründe wurden retrospektiv für die Jahre 2006 bis 2016 in der LIONS-Hornhautbank Saar-Lor-Lux, Trier/Westpfalz des Universitätsklinikums des Saarlandes (UKS) analysiert. 4140 Hornhäute von 2084 Spendern wurden einbezogen. 1640 Hornhäute entstammten der Zeit vor Einführung des zertifizierten QM-Systems (nach DIN EN ISO 9001 : 2008) und 2500 Hornhäute nach Einführung. Bei den analysierten Verwerfungsgründen handelte es sich um die Endothelqualität, Kontamination des Mediums und der positiven Bindehautabstriche. Die Daten der Spender und Hornhäute wurden aus klinikinternen Dokumenten und Systemen in eine Microsoft-Access-Datenbank übertragen und mittels SPSS statistisch ausgewertet.Nach Einführung des QM-Systems sank die Verwerfungsrate von 50,1 auf 39,7% (p 0,0001). Vor der Einführung wurden 493 (30,1%) der Hornhäute aufgrund der Endothelqualität verworfen, nach der Einführung waren es 604 (24,2%) (p 0,0001). Aufgrund einer Kontamination wurden vor Einführung 173 (10,5%) Hornhäute und nach Einführung 124 (5,0%) verworfen (p 0,0001). Wegen des Bindehautabstriches wurden vor Einführung 10 (0,6%) und nach Einführung 53 (2,1%) verworfen (p 0,0001).Die Verwerfungsrate in der LIONS-Hornhautbank konnte nach Einführung des QM-Systems signifikant gesenkt werden. Durch vermehrte Mitarbeiterschulungen sowie durch einheitliche und höhere Standards des QM-Systems bez. Ablauf der Entnahme und Kultivierung konnte die Kontaminationsrate signifikant reduziert werden.

OBJECTIVES Although patients with cirrhosis often experience debilitating symptoms, few are referred for palliative care. Frailty is increasingly incorporated in liver transplantation evaluation and has been associated with symptom burden in other populations. We hypothesized that frail patients with cirrhosis are highly symptomatic and thus are likely to benefit from palliative care. METHODS Patients with cirrhosis undergoing outpatient liver transplantation evaluation completed the Liver Frailty Index (grip strength, chair stands and balance) and a composite of validated measures including the Edmonton Symptom Assessment Scale, distress and quality of life (QOL) measures. RESULTS Of 233 patients (median age 61 years, 43% women), 22% were robust, 59% prefrail and 19% frail. Overall, 38% of patients reported ≥1 severe symptoms based on preestablished Edmonton Symptom Assessment Scale criteria. Higher frailty categories were associated with increased prevalence of pain, dyspnea, fatigue, nausea, poor appetite, drowsiness, depression and poor well-being (test for trend, all P < 0.05). Frail patients were also more likely to report psychological distress and poor QOL (all P < 0.01). In univariate analysis, each 0.5 increase in liver frailty index was associated with 44% increased odds of experiencing ≥1 severe symptoms [95% confidence interval (CI), 1.2-1.7, P < 0.001], which persisted (odds ratio, 1.3, 95% CI, 1.0-1.6, P = 0.004) even after adjusting for Model for End Stage Liver Disease-Sodium, ascites, hepatic encephalopathy and age. CONCLUSION In patients with cirrhosis, frailty is strongly associated with physical/psychological symptoms, including pain and depression and poor QOL. Frail patients with cirrhosis may benefit from palliative care co-management to address symptoms and improve QOL.

Die hier aufgefuhrten „Choosing-wisely“-Empfehlungen zur Behandlung der akuten und chronischen Typ-Stanford-B-Dissektion basieren auf den Leitlinien und Konsensusempfehlungen in der publizierten Literatur der letzten 10 Jahre. Es existieren neben ADSORB und INSTEAD keine randomisierten Studien zum Therapievergleich „best medical treatment“ (BMT) versus „TEVAR“ („thoracic endovascular aortic repair“). Die Literatur zur offenen Chirurgie der Aortendissektion ist mittlerweile historisch, da im Falle der Indikation zur invasiven Therapie TEVAR seit mehr als einem Jahrzehnt die Methode der Wahl ist. Die Positivempfehlungen adressieren insbesondere Differenzialdiagnose, Diagnostik und Indikationsstellung sowie TEVAR und Nachsorge. Die Negativempfehlungen fokussieren auf das State-of-the-Art-Management der konservativen Therapie, dem sog. „best medical treatment“, die Pravention der schwerwiegenden Komplikation der Paraplegie und die elektive Indikationsstellung der chronisch expandierenden Typ-B-Dissektion. Der Artikel stellt die Komplexitat der Therapieentscheidungen mit der anspruchsvollen Diagnosestellung und der komplikationsreichen invasiven Therapie am Beispiel der Aortendissektion Typ Stanford B ab. Ein Risiko der endovaskularen Uberversorgung besteht bei Patienten mit unkomplizierter Typ-B-Dissektion. Eine Gefahr der Unterversorgung besteht sowohl im Hinblick auf die primare Diagnosestellung und Diagnosesicherung als auch hinsichtlich der Nachsorge und Uberwachung wahrend des Follow-ups.

The incidence of abdominal wall defects like gastroschisis and omphalocele are relatively rare. Gastroschisis occurs approximately in 2 to 3 births in every 5,000, and omphalocele occurs in fewer than 2 births in every 10,000. However, our Level III NICU was informed that we were going to receive 2 infants with gastroschisis and one infant with an omphalocele in the same year. Because of the infrequency of these defects, our novice NICU nurses expressed concern about their lack of exposure to and familiarity with these defects. It became apparent that a thorough review of the clinical care and emergency interventions was needed before the anticipated deliveries. The challenge, however, was to develop an innovative, interactive learning experience for the NICU nurse that would provide both a didactic review and hands-on education to care for these patients. We opted to employ simulation. Infant mannequins were used along with moulage to create realistic-looking loops of bowel, herniated bowel segments, and umbilical cord. Scenarios were created that covered the various unpredictable clinical directions these cases could take. These scenarios included the emergency equipment, maneuvers, and interventions that could be required for the anticipated deliveries. Ten sessions for each abdominal wall defect were held; 51 NICU nurses participated in each simulation. NICU nurses reported increased comfort and readiness to care for each infant.

Objectives A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled. Material and methods Patients with resectable NSCLC stage II/IIIA were included. Two cycles of pembrolizumab (200 mg intravenously once every 3 weeks) were administered prior to surgery. The primary objectives were to assess the feasibility and safety of neoadjuvant pembrolizumab therapy and to evaluate antitumor activity. We analyzed the clinical parameters as well as pathological and radiological tumor response data. Results The NSCLC histology was adenocarcinoma for 13 patients and squamous cell carcinoma for 2 patients. All patients but two underwent 2 cycles of pembrolizumab prior to surgery. Four patients (27 %) presented a major pathologic response. Significant tumor target response in positron emission tomography computed tomography (PET-CT) was detected in all 4 pathologic responders. Nevertheless, the PET findings mismatched the tumor load in some patients. A PD-L1 expression ≥10 % in the pretreatment biopsy was associated with at least major pathologic response. Five patients (33 %) presented grade 2–3 treatment related adverse events (TRAE), the overall postoperative morbidity was 7 % and 30-day mortality was 0 %. Conclusion Neoadjuvant pembrolizumab is a feasible therapy in surgical lung cancer patients. It was associated with tolerable toxicity and did not compromise tumor resection.

Background In selected patients with early-stage malignant pleural mesothelioma (MPM), a multimodal therapy that includes surgical cytoreduction, chemotherapy, and/or radiotherapy is recommended. Several clinical trials have demonstrated the beneficial effects of immune checkpoint inhibitors in pretreated MPM patients with advanced disease. Recent clinical data have suggested that the combination of chemotherapy and checkpoint inhibition might improve efficacy. Trial Design The NICITA (nivolumab with chemotherapy in pleural mesothelioma after surgery) trial is a prospective, 1:1 randomized, open-label, multicenter phase II clinical trial ( ClinicalTrials.gov identifier, NCT04177953 ). Ninety-two patients with MPM epithelioid subtype, who had undergone extended pleurectomy and decortication with or without hyperthermic intrathoracic chemoperfusion, will be included to receive adjuvant treatment. All patients will receive ≤ 4 cycles of platinum-based chemotherapy with pemetrexed (arms A and B). Patients in arm B will additionally receive nivolumab, together with the adjuvant chemotherapy, and subsequently for ≤ 12 cycles as maintenance therapy. The primary endpoint of this study is the time-to-next-treatment. The secondary endpoints include progression-free survival, overall survival, proportion of patients with treatment beyond progression, duration of treatment beyond progression in this population, and quality of life. Conclusion This prospective trial will contribute data to assess the efficacy of standard chemotherapy combined with nivolumab in the context of multimodal management of early-stage MPM. The study is currently enrolling patients.

BackgroundGermlineBRCA1/2mutation carriers (gBMC) face increased cancer risks that are modulated via non-genetic lifestyle factors whose underlying molecular mechanisms are unknown. The peptides Neurotensin (NT) and Enkephalin (ENK)—involved in tumorigenesis and obesity-related diseases—are of interest. We wanted to know whether these biomarkers differ between gBMC and women from the general population and what effect a 1-year lifestyle-intervention has in gBMC.MethodsThe stable precursor fragments pro-NT and pro-ENK were measured at study entry (SE), after 3 and 12 months for 68 women from LIBRE-1 (a controlled lifestyle-intervention feasibility trial for gBMC involving structured endurance training and the Mediterranean Diet). The SE values were compared with a cohort of the general population including female subjects with and without previous cancer disease, non-suggestive for hereditary breast and ovarian cancer (OMA-reference). For LIBRE-1, we analysed the association between the intervention-related change in the two biomarkers and certain lifestyle factors.ResultsAt SE, gBMC had a higher median pro-NT than OMA-reference (in the subgroups with previous cancer 117 vs. 91 pmol/L,p = 0.002). Non-diseased gBMC had lower median pro-ENK levels when compared to the non-diseased reference group. VO2peak and pro-NT 1-year change in LIBRE-1 were inversely correlated (r = − 0.435; CI − 0.653 to − 0.151;p = 0.004). Pro-ENK correlated positively with VO2peak at SE (r = 0.323; CI 0.061–0.544;p = 0.017). Regression analyses showed an inverse association of 1-year changes for pro-NT and Omega-6/Omega-3 (Estimate: − 37.9,p = 0.097/0.080) in multivariate analysis.ConclusionOur results give first indications for lifestyle-related modification particularly of pro-NT in gBMC.