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Somewhere in the USA, shortly before Christmas, tipsy Charlie Cratchit intends to cross a street but is hit by an oncoming city bus und suffers severe trauma: serial rib fracture, femoral fracture, fibula fracture, splenic, pancreatic and bowel ruptures. He is operated on in a maximum care hospital and then transferred to the critical care unit. From then on, an anonymous, very experienced physician continuously takes care of him. Four nights before Christmas, the ghost of the famous British physiologist Ernest Henry Starling appears at the patient's bed. The ghost involves the anonymous physician in a dialogue and is very interested in the inserted Swan-Ganz catheter, then he disappears. He repeats his visits the next 3 nights. On the first occasion he is displeased with Cratchit's low haematocrit, the second time he dislikes the mechanical ventilator settings, and on his final visit he is concerned with Cratchit's clinical nutrition. At first, the anonymous physician is indignant with the ghost's criticism and indoctrinations, but then recognizes that ultimately they are the key to Cratchit's convalescence and acts accordingly. Successfully! Following the ghost's proposals, he changes the ventilator settings, transfuses 3 units of packed red blood cells, and starts clinical nutrition. Shortly thereafter, Cratchit's trachea is extubated, and on New Year's Day he is ready to be discharged from the critical care unit. In this essay, Robert Bartlett transposed Charles Dickens' "Christmas Carol" into the world of critical care. Its intention is to encourage the intensivist to scrutinize common therapeutic measures, such as mechanical ventilation, haemodynamic interventions and transfusion of blood products. Background information and comments on the addressed problems of modern intensive care are provided subsequent to the essay.Irgendwo in den USA – Einige Tage vor Heiligabend wird der angetrunkene Charlie Cratchit bei dem Versuch, eine Straße zu überqueren, von einem Bus angefahren und schwer verletzt: Rippenserienfraktur, Femur- und Fibulafraktur, Milz- und Pankreaslazeration, Darmrisse. In einem US-amerikanischen Krankenhaus der Maximalversorgung wird er operativ versorgt und anschließend auf die Intensivtherapiestation verlegt und dort kontinuierlich von einem namenlosen, sehr erfahrenen Arzt betreut. Vier Tage vor Heiligabend, erscheint am Patientenbett der Geist des berühmten britischen Physiologen Ernest Henry Starling. Er tritt in einen Dialog mit dem namenlosen Arzt, interessiert sich sehr für den Swan-Ganz-Katheter und verschwindet dann wieder. Die Besuche wiederholen sich in den kommenden 3 Nächten. Einmal kritisiert er Cratchits niedrigen Hämatokrit, beim nächsten Mal zeigt er sich unzufrieden mit der Respiratoreinstellung, und beim letzten Besuch ist er äußerst besorgt über den Ernährungszustand des Patienten. Der namenlose Arzt ist zunächst indigniert über des Geistes Kritik und Belehrungen, erkennt aber, dass darin der Schlüssel zu Cratchits Genesung liegt und handelt letztlich nach seinen Vorschlägen. Mit Erfolg: Nach der vom Geist Starlings angeregten Umstellung der maschinellen Ventilation, Gabe von 3 Erythrozytenkonzentraten und Aufnahme einer parenteralen Ernährung kann Charlie Cratchit am Weihnachtsabend extubiert und am Neujahrstag von der Intensivtherapiestation entlassen werden. In diesem Essay hat Robert Bartlett Charles Dickens’ „Weihnachtsgeschichte“ in die Welt der Intensivmedizin verlegt. Sie soll den Intensivmediziner anregen, therapeutische Interventionen wie maschinelle Ventilation, hämodynamische Interventionen und Gabe von Blutprodukten kritisch zu hinterfragen. Hintergrundinformationen und Kommentare zu den angesprochenen aktuellen Problemen der modernen Intensivmedizin ergänzen den Essay.

BACKGROUND: Cognitive impairments are an emerging treatment target in mood disorders but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations.; METHODS: The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials.; RESULTS: We identified 16 RCTs (N=859) investigating cognitive remediation (CR; k=6; N=311), direct current or repetitive magnetic stimulation (k=3; N=127), or pharmacological interventions (k=7; N=421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome, and no information on allocation sequence masking.; CONCLUSIONS: Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions, and include neuroimaging. This article is protected by copyright. All rights reserved.

Students were asked for their reasons for not re-enrolling at the University of New South Wales. Of the 1216 students in this category 72 percent did not reply, but those who did indicated three motivating factors: the effect of the course or school on them as individuals; pressures of employment or distance; change in personal situation. (LBH)

Context\ud \ud Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs).\ud \ud \ud \ud Objective\ud \ud To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients.\ud \ud \ud \ud Design\ud \ud 12-year prospective, observational study.\ud \ud \ud \ud Participants & Setting\ud \ud We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases.\ud \ud \ud \ud Interventions & Outcome\ud \ud AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310).\ud \ud \ud \ud Results\ud \ud Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650).\ud \ud \ud \ud Conclusions\ud \ud Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.

Objectives Cognitive dysfunction affects a significant proportion of people with bipolar disorder (BD), but the cause, trajectory and correlates of such dysfunction remains unclear. Increased understanding of these factors is required to progress treatment development for this symptom dimension. Methods This paper provides a critical overview of the literature concerning the trajectories and emerging correlates of cognitive functioning in BD. It is a narrative review in which we provide a qualitative synthesis of current evidence concerning clinical, molecular, neural and lifestyle correlates of cognitive impairment in BD across the lifespan (in premorbid, prodromal, early onset, post-onset, elderly cohorts). Results There is emerging evidence of empirical links between cognitive impairment and an increased inflammatory state, brain structural abnormalities and reduced neuroprotection in BD. However, evidence regarding the progressive nature of cognitive impairment is mixed, since consensus between different cross-sectional data is lacking and does not align to the outcomes of the limited longitudinal studies available. Increased recognition of cognitive heterogeneity in BD may help to explain some inconsistencies in the extant literature. Conclusions Large, longitudinally focussed studies of cognition and its covariation alongside biological and lifestyle factors are required to better define cognitive trajectories in BD, and eventually pave the way for the application of a precision medicine approach for individual patients in clinical practice.