Gastric intramucosal pH-guided therapy in patients after elective repair of infrarenal abdominal aneurysms: is it beneficial?

Objective: To determine if gastric intramucosal pH (pHi)-guided therapy reduces the number of complications and length of stay in the intensive care unit (ICU) or the hospital after elective repair of infrarenal abdominal aortic aneurysms. Design: Prospective, randomized study. Setting: Surgical intensive care unit (SICU) of a University Hospital. Patients: Fifty-five consecutive patients randomized to group 1 (pHi-guided therapy) or to group 2 (control). Interventions: Patients of group 1 with a pHi of lower than 7.32 were treated by means of a prospective protocol in order to increase their pHi to 7.32 or more. Measurements and results: pHi was determined in both groups on admission to the SICU and thereafter at 6-h intervals. In group 2, the treating physicians were blinded for the pHi values. Complications, APACHE II scores, duration of endotracheal intubation, fluid and vasoactive drug treatment, treatment with vasoactive drugs, length of stay in the SICU and in the hospital and hospital mortality were recorded. There were no differences between groups in terms of the incidence of complications. We found no differences in APACHE II scores on admission, the duration of intubation, SICU or hospital stay, or hospital mortality. In the two groups the incidence of pHi values lower than 7.32 on admission to the SICU was comparable (41 % and 42 % in groups 1 and 2, respectively). Patients with pHi lower than 7.32 had more major complications during SICU stay (p<0.05), and periods more than 10 h of persistently low pHi values (< 7.32) were associated with a higher incidence of SICU complications (p<0.01). Conclusions: Low pHi values (<7.32) and their persistence are predictors of major complications. Treatment to elevate low pHi values does not improve postoperative outcome. Based on these data, we cannot recommend the routine use of gastric tonometers for pHi-guided therapy in these patients. Further studies are warranted to determine adequate treatment of low pHi values that results in beneficial effects on the patient's postoperative course and outcom

Fulminant neuroleptic malignant syndrome after perioperative withdrawal of antiParkinsonian medication

Neuroleptic malignant syndrome is a rare complication when using neuroleptic drugs. We report the case of a patient with severe Parkinson's disease who developed neuroleptic malignant syndrome after withdrawal of his antiParkinsonian medication for elective coronary artery bypass grafting. Sodium dantrolene may be a therapeutic option in severe case

Transthoracic echocardiography for perioperative haemodynamic monitoring

Transoesophageal echocardiography (TOE) is valuable for perioperative monitoring in patients at risk from haemodynamic disturbance. However, its use is not practicable in patients undergoing surgical procedures under regional anaesthesia. We describe two cases showing that transthoracic echocardiography (TTE) has the same advantages as TOE and thus may be valuable for monitoring awake patients. TTE should be considered when extended perioperative haemodynamic monitoring is needed but TOE is not possibl

Ethische Fallbesprechungen auf der Intensivstation: Vom Versuch zur Routine

Zusammenfassung: Hintergrund: Der Berufsalltag vieler Mitarbeitender im Gesundheitswesen ist in den letzten Jahren anspruchsvoller geworden, und die Anforderungen werden immer größer. Häufig stellen sich neben rein fachlichen auch ethische Fragen, z.B. nach der Sinnhaftigkeit einer Therapie am Lebensende. So genannte "medical futility", eine nutzlose, aussichtslose Therapie, wird von Pflegenden und Ärzten auf Intensivstationen häufig wahrgenommen. Das medizinethische Modell METAP (Akronym aus Module, Ethik, Therapieentscheidung, Allokation und Prozess) stellt Verfahren und Kriterien zur Verfügung, die es dem Behandlungsteam ermöglichen, diese Fragen gemeinsam, eigenständig und lösungsorientiert zu bearbeiten. Material und Methode: Alle Protokolle der 44 ethischen Fallbesprechungen (eFB), die zwischen Januar 2011 und Juni 2012 auf einer chirurgischen Intensivstation stattfanden, wurden zusammengefasst. Ein kurzer Fragebogen an alle Teilnehmenden erfasste deren Beurteilung des Nutzens für den Patienten und das Team sowie die Wahrnehmung der Reduktion persönlicher Belastung. Ergebnisse: Interprofessionelle eFB finden regelmäßig statt (ca. 2/Monat). Von den 41 in der eFB behandelten Patienten verstarben im Verlauf 23. Die Befragten (Rücklaufquote 52 %) schätzen den Nutzen für Patienten und Team als hoch ein (Ärzte etwas höher als Pflegende). Mehr als zwei Drittel der Pflegenden und die Hälfte der Ärzte nehmen eine Reduktion der Belastung durch die eFB wahr. Schlussfolgerungen: Eine methodisch strukturierte ethische Entscheidungsfindung kann in die klinische Routine integriert werden, wenn sie einen festen Platz im Alltag erhält, die ärztliche und die pflegerische Leitung die Implementierung unterstützen sowie die Verantwortung für die Organisation und Durchführung festgelegt ist

Klinische Alltagsethik - Unterstützung im Umgang mit moralischem Disstress?: Evaluation eines ethischen Entscheidungsfindungsmodells für interprofessionelle klinische Teams

Zusammenfassung: Hintergrund: Hochleistungsmedizin und Kostenrationierung können zu moralischem Disstress und Burn-out-Syndromen führen - mit z.T. schwerwiegenden Konsequenzen für die direkt Betroffenen, die Qualität der Patientenversorgung und die Institutionen. Das multimodale Modell METAP (Modul, Ethik, Therapieentscheide, Allokation, Prozess) wurde als maßgeschneiderte klinische Alltagsethik entwickelt und unterstützt die interprofessionelle ethische Entscheidungsfindung. Die Besonderheit des Modells liegt in der Ausbildung einer Ethikkompetenz im Umgang mit schwierigen Therapieentscheiden. METAP wurde zur Qualitätsprüfung evaluiert. Methode: Es wurde untersucht, ob METAP im Umgang mit moralischem Disstress Unterstützung bietet. Auf 3 intensivmedizinischen und 3 geriatrischen Abteilungen wurden 24 Ärzte, 44 Pflegende und 9 Personen anderer Berufsgruppen in 33 Einzel- und 9 Gruppeninterviews befragt. Ein zusätzlicher Fragebogen wurde von 122 Personen (Rücklauf: 57 %) beantwortet. Ergebnisse: Zwei Drittel der Interview- sowie 55 % der Fragebogenaussagen zeigen, dass durch METAP als klinische Alltagsethik der Umgang mit moralischem Disstress unterstützt wird. Dies gilt v.a. in der interdisziplinären Kommunikation und Zusammenarbeit sowie der Explikation und Evaluation von Behandlungszielen. METAP wirkt bei Personen, die selten mit ethischen Problemen konfrontiert sind oder das Verfahren noch nicht lange genug anwenden, nicht unterstützend. Schlussfolgerungen: Moralischer Disstress ist bis zu einem gewissen Grad unvermeidbar und muss als interprofessionelles Problem angegangen werden. Eine klinische Alltagsethik zur Förderung von ethischer Entscheidungskompetenz kann gezielte Unterstützung leisten

Evaluation of treatment outcomes for Stenotrophomonas maltophilia bacteraemia

Objective: The goal of this study was to retrospectively collect data about treatment outcomes in patients diagnosed with Stenotrophomonas maltophilia bacteraemia over a period of 20years and evaluate these data with respect to the efficacy of treatment options. Methods: The setting was a 700-bed tertiary care hospital in a large urban area. Hospital databases and medical records provided information about episodes of S. maltophilia, patient characteristics and treatment outcomes. Patients with at least one positive blood culture for S. maltophilia were included in the study. Data were analysed with respect to clinical improvement and mortality ≤30days after the onset of infection. We compared patient characteristics, laboratory values and treatments by using the Chi-square or Fisher's exact tests and the Mann-Whitney test. Results: We investigated 27 patients with S. maltophilia bacteraemia. The focus of infection was a central venous catheter in 18 (67%) cases. The 30-day mortality rate was 11%. All patients who were treated with an antibiotic that was effective in vitro against the pathogen recovered clinically and survived ≥30days after the onset of infection. The most frequently used antibiotic was trimethoprim-sulfamethoxazole administered alone or in combination with a fluoroquinolone. Conclusions: Despite the fact that S. maltophilia is resistant to multiple antibiotics, the prognosis for patients with S. maltophilia bacteraemia is good when they are treated with antibiotics that are effective against this pathogen in vitro

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020

Background: Women are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Aim: We assessed the impact of sex and gender on PASC in a Swiss population. Method: Our multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030). Conclusion: Specific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection

SARS-CoV-2 outbreak in a tri-national urban area is dominated by a B.1 lineage variant linked to a mass gathering event.

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503

Global Genomic Analysis of SARS-CoV-2 RNA Dependent RNA Polymerase Evolution and Antiviral Drug Resistance.

A variety of antiviral treatments for COVID-19 have been investigated, involving many repurposed drugs. Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive. However, the potential emergence of antiviral resistance poses a threat to the efficacy of any successful therapies on a wide scale. Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir. We show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare in circulating lineages, and that those mutations, where present, do not destabilise RdRp. In more than 56,000 viral genomes from 105 countries from the first pandemic wave, we found negative selective pressure affecting nsp12 (Tajima's D = -2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic