CD52-negative T cells predict acute graft-versus-host disease after an alemtuzumab-based conditioning regimen.

Allogeneic haematopoietic stem cell transplantation (HSCT) after a reduced-intensity conditioning (RIC) regimen with fludarabine, melphalan and alemtuzmab is an effective therapy for haematological malignancies. Alemtuzumab, a monoclonal antibody against CD52, a glycosylphosphatidylinositol-anchor-bound surface protein on lymphocytes, depletes T cells to prevent graft-versus-host disease (GVHD). Despite this, acute and chronic GVHD (a/cGVHD) remain life-threatening complications after HSCT. The aim of the present study was to identify parameters to predict GVHD. In 69 patients after HSCT, T-cell subsets were functionally analysed. Reconstitution of CD52neg T cells and CD52neg regulatory T cells (Tregs) correlated with onset, severity and clinical course of aGVHD. Patients with aGVHD showed significantly lower levels of CD52pos T cells compared to patients with cGVHD or without GVHD (P < 0·001). Analysis of T-cell reconstitution revealed a percentage of <40% of CD52pos CD4pos T cells or CD52pos Tregs at day +50 as a risk factor for the development of aGVHD. In contrast, CD52neg Tregs showed significant decreased levels of glycoprotein A repetitions predominant (GARP; P < 0·001), glucocorticoid-induced TNFR-related protein (GITR; P < 0·001), chemokine receptor (CXCR3; P = 0·023), C-C chemokine receptor type 5 (CCR5; P = 0·004), but increased levels of immunoglobulin-like transcript 3 (ILT3; P = 0·001), as well as a reduced suppressive capacity. We conclude that reconstitution of CD52neg T cells and CD52neg Tregs is a risk factor for development of aGVHD.

Awake tracheal intubation in routine airway management: A retrospective analysis in a tertiary centre.

INTRODUCTION: While awake tracheal intubation (ATI) is regarded as the gold standard for difficult airway management according to current guidelines, there seems to be a reluctance in its application. This retrospective cohort study, conducted at a German tertiary hospital over a 2-year period, aimed to demonstrate that integrating awake tracheal intubation using flexible bronchoscopy (ATI:FB) into routine airway management makes it a successful and safe approach. MATERIALS AND METHODS: In 2019 and 2020, records from the data acquisition system (DAQ) and archived anesthesia records were screened to evaluate the specifics of ATI:FB procedures, focusing on overall success and safety. Analysis included complications, time required for ATI:FB, and potential influencing factors such as patient characteristics, indication, medical/operative specialty, sedation technique, route and experience of anesthesiologist. Logistic regression assessed the impact of various variables on occurrence of complications and linear regression, with log(time) as the dependent variable, evaluated median time required to perform ATI:FB. RESULTS: ATI:FB constituted 4.3 % (n = 1,911) of all airway management procedures, predominantly observed in dental, oral, and maxillofacial surgery (46.5 %) and otorhinolaryngology (38.4 %). The success rate for ATI:FB was notably high at 99.6 %, with only 5.4 % of cases experiencing complications, including technical issues, agitation, and visibility obstruction due to mucous secretion. Complication risk was influenced by the medical specialty and the experience of the anesthesiologist. A strong effect was observed in otorhinolaryngology (OR = 4.54, 95 % CI [1.64; 14.06]). The median time required for ATI:FB was 16 minutes (IQR: 11 to 23), with factors such as indication (p < 0.0001), experience of anesthesiologist (p < 0.0001), sedation technique (p = 0.0408), priority of the procedure (p = 0.0134), and medical/operative specialty (p < 0.0001) affecting the duration. The median time required for ATI:FB differed significantly based on the experience of the anesthesiologist (p < 0.0001). CONCLUSION: ATI:FB proves successful and safe, with low complications and manageable procedural time. Experience of the anesthesiologist is a modifiable factor enhancing safety, emphasizing the need for ATI:FB integration into routine airway management.

Shape of the art: TCR-repertoire after allogeneic hematopoietic cell transplantation.

The human adaptive immune repertoire is characterized by specificity and diversity to provide immunity against past and future tasks. Such tasks are mainly infections but also malignant transformations of cells. With its multiple lines of defense, the human immune system contains both, rapid reaction forces and the potential to capture, disassemble and analyze strange structures in order to teach the adaptive immune system and mount a specific immune response. Prevention and mitigation of autoimmunity is of equal importance. In the context of allogeneic hematopoietic cell transplantation (HCT) specific challenges exist with the transfer of cells from the adapted donor immune system to the immunosuppressed recipient. Those challenges are immunogenetic disparity between donor and host, reconstitution of immunity early after HCT by expansion of mature immune effector cells, and impaired thymic function, if the recipient is an adult (as it is the case in most HCTs). The possibility to characterize the adaptive immune repertoire by massively parallel sequencing of T-cell receptor gene rearrangements allows for a much more detailed characterization of the T-cell repertoire. In addition, high-dimensional characterization of immune effector cells based on their immunophenotype and single cell RNA sequencing allow for much deeper insights in adaptive immune responses. We here review, existing - still incomplete - information on immune reconstitution after allogeneic HCT. Building on the technological advances much deeper insights into immune recovery after HCT and adaptive immune responses and can be expected in the coming years.

Evaluation of gender differences in postoperative sore throat and hoarseness following the use of Ambu AuraGain laryngeal mask: the randomised controlled LadyLAMA trial study protocol.

INTRODUCTION: Postoperative sore throat (POST) is a comparatively minor but very common side effect of general anaesthesia with a supraglottic airway device. The patient considers these side effects a mirror of the quality of anaesthesia. The aims of this study are to evaluate gender-specific differences in the incidence of POST and to assess whether the effects of known risk factors vary between genders. METHODS AND ANALYSIS: The LadyLAMA trial is a single-centre, patient-blinded, randomised controlled trial. Consecutive patients requiring ophthalmological surgery under general anaesthesia with a second generation Ambu AuraGain laryngeal mask are randomly allocated to either cuff pressure of 45 cmH2O or cuff pressure of 60 cmH2O. We estimate the difference in POST between the genders at 20% and we hypothesised that a reduction of cuff pressure would reduce POST by 10%. A total of 800 patients will be recruited, with each subgroup including 200 patients to achieve 80% power for detecting a difference at the 5% significance level. Primary endpoints are gender differences in the incidence of POST within 24 hours postoperatively, as well as comparison of cuff pressure 45 cmH2O to 60 cmH2O with respect to POST. The main secondary objective is the effect of cuff pressure on POST stratified by gender. Further secondary endpoints are gender-specific differences in POST and hoarseness in postanaesthesia care unit (PACU) at 48 and 72 hours (or until freedom of discomfort). The parameter cuff pressure serves as key-secondary endpoint. ETHICS AND DISSEMINATION: The project is approved by the local ethics committee of the Medical Association of the Rhineland Palatine state (Nr. 2021-15835). The results of this study will be made available in the form of manuscripts for publication and presentations at national and international meetings. TRIAL REGISTRATION NUMBER: NCT04915534.

Big data: Airway management at a university hospital over 16 years; a retrospective analysis.

PURPOSE: Little is known about the current practice of airway management in Germany and its development over the last decades. The present study was, therefore, designed to answer the following questions. Which airway management procedures have been performed over the last 16 years and how has the frequency of these procedures changed over time? Is there a relationship between patient characteristics or surgical specialisation and the type of airway management performed? METHODS: In the present study, we used our in-house data acquisition and accounting system to retrospectively analyse airway management data for all patients who underwent a surgical or medical procedure with anaesthesiological care at our tertiary care facility over the past 16 years. 340,748 airway management procedures were analysed by type of procedure, medical/surgical specialty, and type of device used. Logistic regression was used to identify trends over time. RESULTS: Oral intubation was the most common technique over 16 years (65.7%), followed by supraglottic airway devices (18.1%), nasal intubation (7.5%), mask ventilation (1.6%), tracheal cannula (1.3%), double lumen tube (0.7%), and jet ventilation (0.6%). On average, the odds ratio of using supraglottic airway devices increased by 17.0% per year (OR per year = 1.072, 95% CI = 1.071-1.088) while oral intubation rates decreased. In 2005, supraglottic airway devices were used in about 10% of all airway management procedures. Until 2020, this proportion steadily increased by 27%. Frequency of oral intubation on the other hand decreased and was about 75% in 2005 and 53% in 2020. Over time, second-generation supraglottic airway devices were used more frequently than first-generation supraglottic airway devices. While second-generation devices made up about 9% of all supraglottic airway devices in 2010, in 2020 they represented a proportion of 82%. The use of fibreoptic intubation increased over time in otorhinolaryngology and dental, oral, and maxillofacial surgery, but showed no significant trends over the entire 16-year period. CONCLUSION: Our data represent the first large-scale evaluation of airway management procedures over a long time. There was a significant upward trend in the use of supraglottic airway devices, with an increase in the use of second-generation masks while a decrease in oral intubations was observed.

Video Laryngoscopy Using King Vision™ aBlade™ and Direct Laryngoscopy in Paediatric Airway Management: A Randomized Controlled Study about Device Learning by Anaesthesia Residents.

Background: Airway management in children is challenging due to anatomical and physiological differences. This randomized trial investigates whether anaesthesia residents can intubate the paediatric trachea more quickly and with a higher success rate using the King Vision™ Paediatric aBlade™ video laryngoscope (KVL) compared to conventional direct laryngoscopy (DL). Methods: Eleven anaesthesia residents (mean age: 31 years, mean training status 47 months) were each asked to perform intubations with the KVL and DL in paediatric patients. The primary outcome was the first-attempt success rate. Secondary outcomes were the time to best view (TTBV), time to placement of the tracheal tube (TTP), time to ventilation (TTV), and participant-reported ease of use on a Likert scale. Results: 105 intubations with the KVL and 106 DL were performed by the residents. The success rate on the first attempt with the KVL was 81%, and the success rate on the first attempt within a given time limit of 30 s was 45%, which was lower than with DL (93% and 77% with time limit, p < 0.01). The median TTBV [IQR] on the first attempt with KVL was 7 [5−10] s, the median TTP was 28 [19−44] s, and the median TTV was 51 [39−66] s. DL-mediated intubation was significantly faster (TTP: 17 [13−23] s; p < 0.0001 and TTV: 34 [28−44] s; p < 0.001). Application of the KVL was rated as difficult or very difficult by 60% of the residents (DL: 5%). Conclusion: In contrast to promising data on the paediatric training manikin, residents took longer to intubate the airway in children with the KVL and were less successful compared to the DL. Therefore, the KVL should not be recommended for learning paediatric intubation by residents.