Microbe-host interplay in atopic dermatitis and psoriasis

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.Peer reviewe

Temperature management after cardiac arrest, postanoxic injury and neurological recovery

In patients admitted alive to hospital after cardiac arrest the most common mode of death is withdrawal of life sustaining therapy due to brain injury. This decicion is preceeed by multimodal neuroprognostication, which includes clinical examination, neurophysiological tests, imagning and serum markers of braininjury. The search for methods to ameliorate the brain injury after cardiac arrest is ongoing. Target temperature manegemnt (TTM) is a neuroprotective stratery recommended by guidelines.This thesis investigates the characteristics of and neuroprognostic value of time until awakening (I) and clinical seizures (II) at two levels of TTM (33°C vs 36°C). It also investigates the potential bed-side use of simplified continuous electroencephalogram (cEEG) in the ICU (III) and whether electrographic status epilepticus diagnosed on cEEG results in additional brain injury (IV). The thesis is designed to reflect the collaboration between anesthesiologists, neurologists and neurophysiologists in this area of medicine.Data were collected during the TTM-trial, an international, randomized, parallel group, assessor-blinded trial designed to evaluate outcome in comatose survivors of cardiac arrest after TTM at 33°C or 36°C with no difference in long-term neurological outcome between intervention arms.Late awakening is common and patients often has a good long-term neurological outcome. Time to awakening was longer in TTM at 33°C than at 36°C. The difference could not be attributed to sedative drugs administered during the first 48 h after cardiac arrest or severity of brain injury. Independent predictors of late awakening were: TTM at 33°C, level of consciousness on admission and clinical seizures. Results may be explained by the effect of body temperature on pharmacokinetics of sedative drugs.Clinical seizures are common after cardiac arrest and associated with a poor outcome. There were no differences in outcome between early and late onset clinical seizures. Level of TTM did not affect the prevalence or prognostic significance of clinical seizures Good outcomes occur, even in early status myoclonus.After cardiac arrest, preliminary bedside interpretations of simplified cEEGs by trained ICU physicians may allow earlier detection of clinically relevant cEEG changes and prompt evaluation by an EEG-expert. Bedside interpretation of cEEG by ICU physicians requires awareness of limitations of both the simplified electrode montage and the cEEG interpretations performed by ICU physicians.After cardiac arrest, ESE is associated with higher levels of serum neurofilament light chain suggesting more severe neuronal injury possibly caused by ESE, which can potentially be mitigated by treatment with antiepileptic drugs. Associations with glial fibrillary acidic protein and glial injury are less clear

Mentorskap - Det reflektiva lärandet mellan mentor och adept

Vi fick av företaget Cardo i uppdrag att analysera deras mentorprogram, vilket ingick i deras managementprogram, CIMP 2005. Då deltagarna hade olika bakgrund och erfarenhet och därmed olika förutsättningar, bestod vårt uppdrag av att analysera och finna eventuella skillnader mellan deltagare som fått utbildning och handledning jämfört med dem som inte fått detta. Vårt syfte var att med utgångspunkt i deltagarnas upplevelser av mentorprogrammet, analysera deltagarnas reflektiva lärande, utifrån både ett adept- och mentorperspektiv. Med denna utgångspunkt valde vi att använda oss av ett kvalitativt angreppssätt med en empirisk och en teoretisk del. Den empiriska delen inleddes med en kort e-postintervju till samtliga deltagare. E-postintervjun följdes upp av åtta semistrukturerade intervjuer, fyra adepter och fyra mentorer, utan inbördes relation. Vårt abduktivt influerade arbetssätt resulterade i att vi valde Jarvis teori om reflektion och lärande. Vi såg en klar tendens att den grupp som fick handledning, påverkades mest av mentorprogrammet i form av personlig och professionell utveckling. Den mentorgrupp med tidigare erfarenhet av mentorprogram påverkades något mindre, medan den grupp utan vare sig erfarenhet eller handledning påverkades minst

Neuron-specific enolase and long-term neurological outcome after OHCA – A validation study

Aims: To investigate what NSE levels predict long-term neurological prognosis at 24, 48 and 72 hours after ROSC in a cohort of out-of-hospital cardiac arrest and to validate previously suggested NSE cut-offs, including the latest ERC guidelines (2021). Methods: Patients admitted to intensive care units in four hospitals in Southern Sweden between 2014–2018 were included. Blood samples were handled by a single local laboratory. The primary outcome was neurological outcome according to the Cerebral Performance Category (CPC) scale at 2–6 months after cardiac arrest. Results: 368 patients were included for analysis. A ≤2% false positive rate for the prediction of poor neurological outcome was achieved with an NSE cut-off value of >101 μg/L at 48 hours and >80 μg/L at 72 hours. The cut-off suggested by the recent ERC guidelines of >60 μg/L at 48 and/or 72 hours generated a false positive rate of 4.3% (95 %CI 0.9–7.4%). Conclusion: A local validation study of the ability of serum levels of neuron-specific enolase to predict long-term poor neurological outcome after out-of-hospital cardiac arrest generated higher cut-offs than suggested by previous publications

Hypothermia versus normothermia after out-of-hospital cardiac arrest; the effect on post-intervention serum concentrations of sedatives and analgesics and time to awakening

Background: This study investigated the association of two levels of targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) with administered doses of sedative and analgesic drugs, serum concentrations, and the effect on time to awakening. Methods: This substudy of the TTM2-trial was conducted at three centers in Sweden, with patients randomized to either hypothermia or normothermia. Deep sedation was mandatory during the 40-hour intervention. Blood samples were collected at the end of TTM and end of protocolized fever prevention (72 hours). Samples were analysed for concentrations of propofol, midazolam, clonidine, dexmedetomidine, morphine, oxycodone, ketamine and esketamine. Cumulative doses of administered sedative and analgesic drugs were recorded. Results: Seventy-one patients were alive at 40 hours and had received the TTM-intervention according to protocol. 33 patients were treated at hypothermia and 38 at normothermia. There were no differences between cumulative doses and concentration and of sedatives/analgesics between the intervention groups at any timepoint. Time until awakening was 53 hours in the hypothermia group compared to 46 hours in the normothermia group (p = 0.09). Conclusion: This study of OHCA patients treated at normothermia versus hypothermia found no significant differences in dosing or concentration of sedatives or analgesic drugs in blood samples drawn at the end of the TTM intervention, or at end of protocolized fever prevention, nor the time to awakening

In-hospital versus out-of-hospital cardiac arrest : Characteristics and outcomes in patients admitted to intensive care after return of spontaneous circulation

Introduction: Cardiac arrest is characterized depending on location as in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA). Strategies for Post Cardiac Arrest Care were developed based on evidence from OHCA. The aim of this study was to compare characteristics and outcomes in patients admitted to intensive care after IHCA and OHCA. Methods: A retrospective multicenter observational study of adult survivors of cardiac arrest admitted to intensive care in southern Sweden between 2014–2018. Data was collected from registries and medical notes. The primary outcome was neurological outcome according to the Cerebral Performance Category (CPC) scale at 2–6 months. Results: 799 patients were included, 245 IHCA and 554 OHCA. IHCA patients were older, less frequently male and less frequently without comorbidity. In IHCA the first recorded rhythm was more often non-shockable, all delay-times (ROSC, no-flow, low-flow, time to advanced life support) were shorter and a cardiac cause of the arrest was less common. Good long-term neurological outcome was more common after IHCA than OHCA. In multivariable analysis, witnessed arrest, age, shorter arrest duration (no-flow and low-flow times), low lactate, shockable rhythm, and a cardiac cause were all independent predictors of good long-term neurological outcome whereas location of arrest (IHCA vs OHCA) was not. Conclusion: In patients admitted to intensive care after cardiac arrest, patients who suffered IHCA vs OHCA differed in demographics, co-morbidities, cardiac arrest characteristics and outcomes. In multivariable analyses, cardiac arrest characteristics were independent predictors of outcome, whereas location of arrest (IHCA vs OHCA) was not

Postanoxic electrographic status epilepticus and serum biomarkers of brain injury

Aim: To explore if electrographic status epilepticus (ESE) after cardiac arrest causes additional secondary brain injury reflected by serum levels of two novel biomarkers of brain injury: neurofilament light chain (NfL) originating from neurons and glial fibrillary acidic protein (GFAP) from glial cells. Methods: Simplified continuous EEG (cEEG) and serum levels of NfL and GFAP, sampled at 24, 48 and 72 h after cardiac arrest, were collected during the Target Temperature Management (TTM)-trial. Two statistical methods were used: multivariable regresssion analysis; and a matched control group of patients without ESE matched for early predictors of poor neurological outcome. Results: 128 patients had available biomarkers and cEEG. Twenty-six (20%) patients developed ESE, the majority (69%) within 24 h. ESE was an independent predictor of elevated serum NfL (p < 0.001) but not of serum GFAP (p = 0.16) at 72 h after cardiac arrest. Compared to a control group matched for early predictors of poor neurological outcome, patients who developed ESE had higher levels of serum NfL (p = 0.03) and GFAP (p = 0.04) at 72 h after cardiac arrest. Conclusion: ESE after cardiac arrest is associated with higher levels of serum NfL which may suggest increased secondary neuronal injury compared to matched patients without ESE but similar initial brain injury. Associations with GFAP reflecting glial injury are less clear. The study design cannot exclude imperfect matching or other mechanisms of secondary brain injury contributing to the higher levels of biomarkers of brain injury seen in the patients with ESE

Plasma proenkephalin A 119-159 and dipeptidyl peptidase 3 on admission after cardiac arrest help predict long-term neurological outcome

BACKGROUND: A large proportion of adult survivors of cardiac arrest have a poor neurological outcome. Guidelines recommend multimodal neuro-prognostication no earlier than 72-96 hours after cardiac arrest. There is great interest in earlier prognostic markers, including very early markers at admission. The novel blood biomarkers proenkephalin A 119-159 (penKid), bioactive adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3) have not been previously investigated for the early prognosis of cardiac arrest survivors.METHODS: This multicentre observational study included adult survivors of cardiac arrest admitted to intensive care at four Swedish intensive care units (ICUs) during 2016. Blood samples were collected at ICU admission and batch analysed. The association between admission plasma penKid, bio-ADM and cDPP3 and poor long-term neurological outcome, according to the Cerebral Performance Category (CPC) scale, was assessed by binary logistic regression. Their prognostic performance was assessed using the area under the receiver operating characteristic curve (AUC).RESULTS: A total of 190 patients were included, of which 136 patients had suffered out-of-hospital and 54 patients in-hospital cardiac arrest. Poor long-term neurological outcome was associated with elevated admission plasma concentrations of penKid and cDPP3, but not with bio-ADM. The association for penKid, but not for cDPP3, remained after adjusting for clinical cardiac arrest variables with prognostic value (time to return of spontaneous circulation (ROSC), initial rhythm, admission Glasgow Coma Scale (GCS) motor score and absence of pupillary reflexes). The prognostic performance of above mentioned clinical cardiac arrest variables alone was very good with an AUC of 0.90 (95% confidence interval, CI, 0.86-0.95), but improved further with the addition of penKid resulting in an AUC of 0.93 (95% CI 0.89-0.97, p < 0.026). Plasma penKid and cDPP3 alone provided moderate long-term prognostic information with AUCs of 0.70 and 0.71, respectively.CONCLUSION: After cardiac arrest, admission plasma levels of penKid and cDPP3, but not bio-ADM, predicted long-term neurological outcome. When added to clinical cardiac arrest variables, penKid further improved prognostic performance