The organization of frontostriatal brain wiring in non-affective early psychosis compared with healthy subjects using a novel diffusion imaging fiber cluster analysis.

BACKGROUND: Alterations in brain connectivity may underlie neuropsychiatric conditions such as schizophrenia. We here assessed the degree of convergence of frontostriatal fiber projections in 56 young adult healthy controls (HCs) and 108 matched Early Psychosis-Non-Affective patients (EP-NAs) using our novel fiber cluster analysis of whole brain diffusion magnetic resonance imaging tractography. METHODS: Using whole brain tractography and our fiber clustering methodology on harmonized diffusion magnetic resonance imaging data from the Human Connectome Project for Early Psychosis we identified 17 white matter fiber clusters that connect frontal cortex (FCtx) and caudate (Cd) per hemisphere in each group. To quantify the degree of convergence and, hence, topographical relationship of these fiber clusters, we measured the inter-cluster mean distances between the endpoints of the fiber clusters at the level of the FCtx and of the Cd, respectively. RESULTS: We found (1) in both groups, bilaterally, a non-linear relationship, yielding convex curves, between FCtx and Cd distances for FCtx-Cd connecting fiber clusters, driven by a cluster projecting from inferior frontal gyrus; however, in the right hemisphere, the convex curve was more flattened in EP-NAs; (2) that cluster pairs in the right (p = 0.03), but not left (p = 0.13), hemisphere were significantly more convergent in HCs vs EP-NAs; (3) in both groups, bilaterally, similar clusters projected significantly convergently to the Cd; and, (4) a significant group by fiber cluster pair interaction for 2 right hemisphere fiber clusters (numbers 5, 11; p = .00023; p = .00023) originating in selective PFC subregions. CONCLUSIONS: In both groups, we found the FCtx-Cd wiring pattern deviated from a strictly topographic relationship and that similar clusters projected significantly more convergently to the Cd. Interestingly, we also found a significantly more convergent pattern of connectivity in HCs in the right hemisphere and that 2 clusters from PFC subregions in the right hemisphere significantly differed in their pattern of connectivity between groups.

[175 years of anesthesia and narcosis-Towards a "human right to unconsciousness"]. / 175 Jahre Anästhesie und Narkose ­ Auf dem Weg zu einem "Menschenrecht auf Ohnmacht".

The Ether Day, a key moment in the history of mankind, commemorates its 175th anniversary on 16 October 2021. On that day the dentist William T. G. Morton successfully gave the first public ether anesthesia in Boston. From then on it was possible to save people from pain with justifiable risk and at the same time to protect them from psychological damage by inducing unconsciousness. The German philosopher Peter Sloterdijk, one of the most renowned and effective philosophers of our times, deduced that from then on humans, to some extent, had a right to unconsciousness when in psychophysical distress. This postulate unfolded from his concept of "anthropotechnics" developed around 1997, meaning the idea of treating human nature as an object of possible improvements. According to Sloterdijk, in favorable cases a synthesis of man and technology can result in a significant improvement of human capabilities in the sense of "enhancement", i.e. an increase, an improvement or even an expansion of intellectual, physical or psychological possibilities, as it were in a transgression of the human (so-called transhumanism). Man should go into vertical tension, i.e. strive for higher aims and exploit his inherent potential, he should not dwell in the horizontal. This is not meant as an appeal but as an imperative: "You must change your life!". In this context modern anesthesia may prove helpful: be operated on by others in order to undergo an enhancement. Or, in its most extreme form, the operation in the "auto-operational curved space", a person can even operate on himself as has been dramatically demonstrated by Rogozov, a young Russian physician and trainee surgeon who successfully performed a self-appendectomy under local anesthesia at the Novolazarevskaya Antarctic Station in 1961; however, the implementation of this idea is a long way off. On the one hand, many countries lack qualified personnel in sufficiently large numbers to perform even vital operations with patients under anesthesia. On the other hand, over the decades it has become clear that anesthesia is obviously beneficial for mankind in that it offers relief from pain and psychological stress but that it can also often show its dark side: substance abuse, use of anesthetics in torture and in executions. In addition, the role of anesthetics in resuscitation, palliative care, and allaying executions is unclear or controversial. Finally, the necessary formal legal steps to acknowledge a "human right to unconsciousness" have not yet been implemented.

[The anesthetist's view on Jethro Tull's Aqualung]. / Der Blick des Anästhesisten auf Jethro Tulls Aqualung.

In 1971 the British rock band Jethro Tull published their milestone album Aqualung with a song of the same title. The song tells the story of a character also named "Aqualung", a homeless person, who spends a cold day on a bench in a park in London. Nothing much happens: he watches little girls playing, bends to pick up a cigarette butt, walks to a public restroom, is offered a cup of tea by the Salvation Army, is scared by and flees from a young prostitute called "cross-eyed Mary", and then finally dies with "rattling last breaths with deep-sea diver sounds". Apparently, Aqualung is severely ill. He might suffer from pulmonary edema, peripheral artery disease, posttraumatic stress disorder and possibly from many other diseases typical of the homeless. The description of his final breaths may remind the anesthetist of the death rattle. One avenue for mediating medical knowledge to physicians is to link data and facts on diseases to elements of popular culture. This essay strives to use a still extremely popular rock song to sensitize and educate anesthetists and intensive care physicians regarding diseases of the homeless relevant to critical care.

[A critical carol : Being an essay on anemia, suffocation, starvation, and other forms of intensive care, after the manner of Dickens]. / Eine kritische Weihnachtsgeschichte : Essay über Anämie, Ersticken, Verhungern und andere Behandlungsverfahren der Intensivmedizin ­ im Stil von Dickens.

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.

Potential Leukemic Cells Engraftment After Hematopoietic Stem Cell Transplantation From Unrelated Donors With Undiagnosed Chronic Leukemia.

BACKGROUND: Donor-related neoplasms are a potential complication of treatment strategies involving stem cell transplantation. Although mechanisms for detection of short-term complications after these procedures are well developed, complications with delayed onset, notably transmission of chronic diseases such as chronic myeloid leukemia (CML), have been difficult to assess. Consequently, we studied the potential of human CML cells to engraft hematopoietic tissues after intravenous implantation in mice. METHODS: Human peripheral blood cells, collected from CML patients presenting with moderately increased white blood cells count before treatment, were transplanted into sub-lethally irradiated, immunodeficient mice. Five weeks after transplantation the nuclear cells were isolated from the murine bone marrow, spleen, and peripheral blood and were used to quantitatively detect human CD45 antigen by flow cytometry; qRT-PCR was used to detect the BCR-ABL1 fusion gene, and the human or murine beta-glucuronidase housekeeping gene was used to examine human-murine chimerism. RESULTS: We found that all evaluated animals had donor chimerism at the selected interval after transplant and the presence of a specific BCR-ABL1 fusion gene transcript was also detected. CONCLUSIONS: Our results suggest that the risk of neoplasm transmission cannot be eliminated during hematopoietic stem cell transplantation from undiagnosed CML donors with borderline leukocytosis. The obtained data confirms the potential of leukemic cells to viably engraft the hematopoietic organs post-transplantation in an immunosuppressed recipient.

Coexistence of JAK2 or CALR mutation is a rare but clinically important event in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.

INTRODUCTION: There are 7 designated conditions under the category of myeloproliferative neoplasms (MPN), including chronic myelogenous leukemia (CML) and classical MPN, that is, polycythemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF). Recently, reports about Philadelphia and JAK2 V617F-positive MPN cases have been described in literature. The coexistence of different molecular defects may change the clinical and laboratory manifestation of MPN and may result in an inappropriate interpretation of the response to treatment with tyrosine kinase inhibitors in CML patients. METHODS: The morphological, cytogenetic, and molecular genetic data from a retrospective analysis of 592 adult patients aged 18-86 years diagnosed with CML were analyzed. RESULTS: In 5 CML patients, the presence of JAK2 V617F or CALR mutation was confirmed. Three of 4 TKI-treated patients did not reach complete hematologic response due to the persistence of thrombocytosis and/or splenomegaly. In all of them (in 3 with JAK2 V617F mutation and 1 with CALR mutation), thrombocytosis was present at the time when complete cytogenetic response was documented. In 3 out of 4 reported CML patients, thrombocytosis and/or splenomegaly were still present even at the time when deep molecular response was reached. CONCLUSION: In our opinion, a detailed evaluation and appropriate interpretation of clinical and laboratory data in such a category of patients seem to be extremely important, especially when a decision about the TKI change due to therapy failure is considered.

Characterizing cognitive heterogeneity on the schizophrenia-bipolar disorder spectrum.

BACKGROUND: Current group-average analysis suggests quantitative but not qualitative cognitive differences between schizophrenia (SZ) and bipolar disorder (BD). There is increasing recognition that cognitive within-group heterogeneity exists in both disorders, but it remains unclear as to whether between-group comparisons of performance in cognitive subgroups emerging from within each of these nosological categories uphold group-average findings. We addressed this by identifying cognitive subgroups in large samples of SZ and BD patients independently, and comparing their cognitive profiles. The utility of a cross-diagnostic clustering approach to understanding cognitive heterogeneity in these patients was also explored. METHOD: Hierarchical clustering analyses were conducted using cognitive data from 1541 participants (SZ n = 564, BD n = 402, healthy control n = 575). RESULTS: Three qualitatively and quantitatively similar clusters emerged within each clinical group: a severely impaired cluster, a mild-moderately impaired cluster and a relatively intact cognitive cluster. A cross-diagnostic clustering solution also resulted in three subgroups and was superior in reducing cognitive heterogeneity compared with disorder clustering independently. CONCLUSIONS: Quantitative SZ-BD cognitive differences commonly seen using group averages did not hold when cognitive heterogeneity was factored into our sample. Members of each corresponding subgroup, irrespective of diagnosis, might be manifesting the outcome of differences in shared cognitive risk factors.

First Complete Genome Sequences of Zika Virus Isolated from Febrile Patient Sera in Ecuador.

Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, EcEs062_16 and EcEs089_16, isolated from the sera of febrile patients in Esmeraldas City, in the northern coastal province of Esmeraldas, Ecuador, in April 2016. These are the first complete ZIKV genomes to be reported from Ecuador.

[The old man and the I sea U : Essay on faith, fate and evidence - after the manner of Hemingway]. / Der alte Mann und die "I sea U" : Essay über Vertrauen, Schicksal und Evidenz ­ im Stil von Hemingway.

Robert Bartlett, emeritus Professor of surgery at the University of Michigan in Ann Arbor, USA, transformed classical works of world literature (Charles Dickens: A Christmas Carol, Lewis Carroll: Alice in Wonderland) into teaching aids for advanced training in intensive care medicine. He recently turned his hand to the well-known work of Ernest Hemingway: the Nobel Prize winning novel The Old Man and the Sea. Subsequent to Robert Bartlett's essay this article provides background information and comments on the current problems in modern intensive care medicine addressed in his essay.

Potential Clinical Utility of Copeptin (C-terminal provasopressin) measurements in clinical medicine.

Copeptin is a 39-amino-acids containing glycosylated peptide derived from the C-terminal part of the arginine vasopressin (AVP) precursor. In the process of proteolysis the AVP precursor is processed to AVP, neurophysin II, and copeptin in equimolar amounts. In contrast to AVP, copeptin remains stable for several days at room temperature in serum or plasma. Hence, copeptin serves as a bona fide biomarker of AVP release. We briefly summarise clinical utility of copeptin in the diagnosis of diabetes insipidus. We also discuss potential applications of copeptin measurements in hyponatraemic states, assessment of an anterior pituitary function, as well as a wide range of several acute and chronic medical conditions, such as myocardial infarction, stroke or diabetes mellitus.

S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders : Revision 2015: S2e guideline of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI).

The German Society of Anesthesiology and Intensive Care Medicine (DGAI) commissioneda revision of the S2 guidelines on "positioning therapy for prophylaxis or therapy of pulmonary function disorders" from 2008. Because of the increasing clinical and scientificrelevance the guidelines were extended to include the issue of "early mobilization"and the following main topics are therefore included: use of positioning therapy and earlymobilization for prophylaxis and therapy of pulmonary function disorders, undesired effects and complications of positioning therapy and early mobilization as well as practical aspects of the use of positioning therapy and early mobilization. These guidelines are the result of a systematic literature search and the subsequent critical evaluation of the evidence with scientific methods. The methodological approach for the process of development of the guidelines followed the requirements of evidence-based medicine, as defined as the standard by the Association of the Scientific Medical Societies in Germany. Recently published articles after 2005 were examined with respect to positioning therapy and the recently accepted aspect of early mobilization incorporates all literature published up to June 2014.

[Short version S2e guidelines: "Positioning therapy and early mobilization for prophylaxis or therapy of pulmonary function disorders"]. / Kurzversion S2e-Leitlinie - "Lagerungstherapie und Frühmobilisation zur Prophylaxe oder Therapie von pulmonalen Funktionsstörungen".

The German Society of Anesthesiology and Intensive Care Medicine (DGAI) commissioned a revision of the S2 guidelines on "positioning therapy for prophylaxis or therapy of pulmonary function disorders" from 2008. Because of the increasing clinical and scientific relevance the guidelines were extended to include the issue of "early mobilization" and the following main topics are therefore included: use of positioning therapy and early mobilization for prophylaxis and therapy of pulmonary function disorders, undesired effects and complications of positioning therapy and early mobilization as well as practical aspects of the use of positioning therapy and early mobilization. These guidelines are the result of a systematic literature search and the subsequent critical evaluation of the evidence with scientific methods. The methodological approach for the process of development of the guidelines followed the requirements of evidence-based medicine, as defined as the standard by the Association of the Scientific Medical Societies in Germany. Recently published articles after 2005 were examined with respect to positioning therapy and the recently accepted aspect of early mobilization incorporates all literature published up to June 2014.

Genome sequence analysis of Ebola virus in clinical samples from three British healthcare workers, August 2014 to March 2015.

We determined complete viral genome sequences from three British healthcare workers infected with Ebola virus (EBOV) in Sierra Leone, directly from clinical samples. These sequences closely resemble those previously observed in the current Ebola virus disease outbreak in West Africa, with glycoprotein and polymerase genes showing the most sequence variation. Our data indicate that current PCR diagnostic assays remain suitable for detection of EBOV in this epidemic and provide confidence for their continued use in diagnosis.

Dangers resulting from DNA profiling of biological materials derived from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with regard to forensic genetic analysis.

The study documents the risk that comes with DNA analysis of materials derived from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in forensic genetics. DNA chimerism was studied in 30 patients after allo-HSCT, based on techniques applied in contemporary forensic genetics, i.e. real-time PCR and multiplex PCR-STR with the use of autosomal DNA as well as Y-DNA markers. The results revealed that the DNA profile of the recipient's blood was identical with the donor's in the majority of cases. Therefore, blood analysis can lead to false conclusions in personal identification as well as kinship analysis. An investigation of buccal swabs revealed a mixture of DNA in the majority of recipients. Consequently, personal identification on the basis of stain analysis of the same origin may be impossible. The safest (but not ideal) material turned out to be the hair root. Its analysis based on autosomal DNA revealed 100% of the recipient's profile. However, an analysis based on Y-chromosome markers performed in female allo-HSCT recipients with male donors demonstrated the presence of donor DNA in hair cells - similarly to the blood and buccal swabs. In the light of potential risks arising from DNA profiling of biological materials derived from persons after allotransplantation in judicial aspects, certain procedures were proposed to eliminate such dangers. The basic procedures include abandoning the approach based exclusively on blood collection, both for kinship analysis and personal identification; asking persons who are to be tested about their history of allo-HSCT before sample collection and profile entry in the DNA database, and verification of DNA profiling based on hair follicles in uncertain cases.

[Patron saints of anesthesia]. / Schutzheilige der Anästhesie.

Patron saints act as facilitators between God and humans. Humans appeal to patron saints for support in devastating, often futile situations in life. Patron saints may intercede for trade and professional guilds, every so often they hold a protective hand over objects. Saint Barbara is venerated as the patron saint of surgeons. In anesthesia she also oversees barbiturates, protects anesthetized patients, anesthetists and anesthesia nursing personnel. Within the Anglo-American language area Saint René is venerated by anesthetists and anesthesia nursing personnel. During anesthesia or critical care treatment patient safety and welfare are entirely in the hands of anesthetists and intensivists. Especially in the borderland of critical illness and imminent death, it may be reassuring for religiously or spiritually orientated physicians and nurses that they can turn to "their" patron saints to intercede so that upcoming anesthetic procedures or intensive care interventions will meet with success. Hereby, the heavy burden of responsibility may be borne more easily and equanimously.

Our paper 20 years later: Inhaled nitric oxide for the acute respiratory distress syndrome--discovery, current understanding, and focussed targets of future applications.

INTRODUCTION: More than 20 years have passed since we reported our results of treating patients with the acute respiratory distress syndrome (ARDS) with inhaled nitric oxide (iNO). The main finding was that iNO alleviated pulmonary hypertension (PH) by selective vasodilation of pulmonary vessels in ventilated lung areas. This, in turn, improved arterial oxygenation. METHODS: We now set out to review the time span between the discovery of NO in 1987 and today in order to identify and describe interesting areas of research and clinical practice surrounding the application of iNO. MAJOR FINDINGS: Enhancement of ventilation-perfusion matching and alleviation of PH in ARDS, treatment of PH of the newborn, and treatment of perioperative PH in congenital heart disease serve as just a few exciting examples for the successful use of iNO. Breathing NO prevents PH induced by stored blood transfusions or sickle cell disease. Exploiting the anti-inflammatory properties of NO helps to treat malaria. DISCUSSION: Regarding the use of iNO in ARDS, there remains the unresolved question of whether important outcome parameters can be positively influenced. At first glance, several randomized controlled trials and meta-analyses seem to send the clear message: "There is none!" Careful analyses, however, leave sufficient room for doubt that the ideal study to produce the unequivocal proof for the inability of iNO to positively impact on important outcome parameters has, as yet, not been conducted. CONCLUSION: In summary, the discovery of and research on the many positive effects of iNO has improved care of critically ill patients worldwide. It is a noble effort to continue on this path.

Cognitive variability in psychotic disorders: a cross-diagnostic cluster analysis.

BACKGROUND: Cognitive dysfunction is a core feature of psychotic disorders; however, substantial variability exists both within and between subjects in terms of cognitive domains of dysfunction, and a clear 'profile' of cognitive strengths and weaknesses characteristic of any diagnosis or psychosis as a whole has not emerged. Cluster analysis provides an opportunity to group individuals using a data-driven approach rather than predetermined grouping criteria. While several studies have identified meaningful cognitive clusters in schizophrenia, no study to date has examined cognition in a cross-diagnostic sample of patients with psychotic disorders using a cluster approach. We aimed to examine cognitive variables in a sample of 167 patients with psychosis using cluster methods. METHOD: Subjects with schizophrenia (n = 41), schizo-affective disorder (n = 53) or bipolar disorder with psychosis (n = 73) were assessed using a battery of cognitive and clinical measures. Cognitive data were analysed using Ward's method, followed by a K-means cluster approach. Clusters were then compared on diagnosis and measures of clinical symptoms, demographic variables and community functioning. RESULTS: A four-cluster solution was selected, including a 'neuropsychologically normal' cluster, a globally and significantly impaired cluster, and two clusters of mixed cognitive profiles. Clusters differed on several clinical variables; diagnoses were distributed amongst all clusters, although not evenly. CONCLUSIONS: Identification of groups of patients who share similar neurocognitive profiles may help pinpoint relevant neural abnormalities underlying these traits. Such groupings may also hasten the development of individualized treatment approaches, including cognitive remediation tailored to patients' specific cognitive profiles.