The impact of the COVID-19 pandemic on administrative eating disorder prevalence in the outpatient sector and on severity of anorexia nervosa.

The COVID-19 pandemic appears to have had a considerable impact on the mental health of children and adolescents, particularly regarding eating disorders. However, it remains unclear whether the pandemic affected only the frequency or also the severity of eating disorders. We examined potential pandemic-related changes in the administrative prevalence of eating disorders in the outpatient sector compared with other mental disorders using German statutory health insurance data for the age group 10 to 16 years. We also examined disorder severity of anorexia nervosa using data from the multicenter German Registry of Children and Adolescents with Anorexia Nervosa in the same age group. Our results showed a marked increase in the administrative prevalence of eating disorders (based on documented diagnoses) in the outpatient sector among girls but not among boys. A similar pattern was found for internalizing disorders, whereas the administrative prevalences of externalizing disorders decreased. Regarding the severity of anorexia nervosa among inpatients, we found no pandemic-related changes in body mass index standard deviation score at admission, body weight loss before admission, psychiatric comorbidities and psychopharmacological medication. Given the administrative prevalence increase in the outpatient sector, the lack of impact of the pandemic on the inpatient sector may also be partly due to a shift in healthcare utilization towards outpatient services during the pandemic. Thus, the higher number of children and adolescents requiring specialized and timely outpatient care may be a major concern under pandemic conditions.

High-level competition exercise and related fatigue are associated with stride and jumping characteristics in eventing horses.

BACKGROUND: Fatigue and related injuries to the musculoskeletal system are among the most frequent reasons for the withdrawal of high-level eventing horses from the sport. The safety of both horse and rider is very important, and early detection of fatigue is crucial. OBJECTIVES: To investigate elite eventing horses in competitive events focusing on biomechanical, cardiovascular and metabolic variables across the cross-country test and to identify their potential associations with fatigue. STUDY DESIGN: Prospective observational exploratory field study. METHODS: Observations on 54 cross-country tests of 33 horses at five competitive, high-level events were evaluated using sternal accelerometric analysis of stride parameters between and at the jumps. Blood lactate concentration and heart rate were determined 10 min after finishing. The differences in kinematic parameters between the course start and end were analysed with mixed models for repeated measures. Associations between blood lactate and heart rate recovery with the kinematic variables were quantified with Pearson correlation coefficients. RESULTS: We observed numerous stride characteristics between the jumps and the jumps changing over time during the courses. Blood lactate concentrations were positively correlated with the mean maximal strike power at the jumps in the last minute of the course (r = 0.41; p < 0.001), and the latter was negatively correlated with the mean stride height over the jumps (r = -0.41; p = 0.003). MAIN LIMITATIONS: The sample contained horses of varying breeds, sexes and ages, and different horses participated in different events. CONCLUSIONS: We identified several kinematic changes during a cross-country test depending on event, speed and fatigue.

BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial.

Background: Replacement of carmustine (BCNU) in the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) with bendamustine (BendaEAM) before autologous stem cell transplantation (ASCT) is feasible in lymphoma. However, randomised trials are lacking. Here, we present the first trial addressing this topic. Methods: This multicentre, randomised, phase 2 study (BEB-trial) conducted at four haematological centres in Austria and Switzerland compares BEAM with BendaEAM in patients with relapsed lymphoma. Both regimens were administered intravenously before ASCT, in BEAM according to the standard protocol (300 mg/m2 BCNU on day -6), in BendaEAM, BCNU was replaced by 200 mg/m2 bendamustine given on days -7 and -6. Eligible patients were aged 18-75 years and had mantle cell lymphoma, diffuse large B-cell lymphoma, or follicular lymphoma in first or second remission or chemosensitive relapse. The primary endpoint of the study was to evaluate whether replacement of BCNU by bendamustine reduces lung toxicity, defined as a decrease of the diffusion capacity of the lung for carbon monoxide by at least 20% at three months after ASCT. Data analyses were performed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02278796, and is complete. Findings: Between April 20, 2015, and November 28, 2018, 108 patients were enrolled; of whom 53 were randomly assigned to receive BendaEAM (36 male, 17 female) and 55 to receive BEAM (39 male, 16 female). All patients engrafted rapidly. Lung toxicity did not differ between groups (BendaEAM: n = 8, 19.5%; BEAM: n = 11, 25.6%; risk difference = -6.1%: 95% confidence interval: -23.9% to 11.7%). Acute toxicities of at least grade 3 were comparable in both groups (BendaEAM: 35.8%, BEAM: 30.9%). Overall survival (BendaEAM: 92.5%, BEAM: 89.1%) and complete remission (BendaEAM: 76.7%, BEAM: 74.3%) after 1 year (median follow-up: 369 days) were similar. No difference in quality of life was observed. Interpretation: Results were similar for both regimens in terms of survival and response rates. A phase 3 non-inferiority study is required to investigate whether BendaEAM can be considered as an alternative to BEAM. Funding: Mundipharma.

Haploidentical transplant with posttransplant cyclophosphamide vs matched related and unrelated donor transplant in acute myeloid leukemia and myelodysplastic neoplasm.

Hematopoietic cell transplantation from haploidentical donors (haploHCT) has facilitated treatment of AML and MDS by increasing donor availability and became more feasible since the introduction of post-transplant cyclophosphamide (ptCY). In our single-center retrospective analysis including 213 patients with AML or MDS, we compare the outcome of haploHCT (n = 40) with ptCY with HCT from HLA-identical MRD (n = 105) and MUD (n = 68). At 2 years after transplantation, overall survival (OS) after haploHCT was not significantly different (0.59; 95% confidence interval 0.44-0.79) compared to MRD (0.77; 0.67-0.88) and MUD transplantation (0.72; 0.64-0.82, p = 0.51). While progression-free survival (PFS) was also not significantly different (haploHCT: 0.60; 0.46-0.78, MRD: 0.55; 0.44-0.69, MUD: 0.64; 0.55-0.74, p = 0.64), non-relapse mortality (NRM) was significantly higher after haploHCT (0.18; 0.08-0.33) vs. MRD (0.029; 0.005-0.09) and MUD (0.06; 0.02-0.12, p < 0.05). Higher NRM was mainly caused by a higher rate of fatal infections, while deaths related to GvHD or other non-relapse reasons were rare in all groups. As most fatal infections occurred early and were bacterial related, one potential risk factor among many was identified in the significantly longer time to neutrophil engraftment after haploHCT with a median of 16 days (interquartile range; 14.8-20.0) vs. 12 days (10.0-13.0) for MRD and 11 days (10.0-13.0) for MUD (p = 0.01).

Indications and Outcomes of Patients Receiving Therapeutic Plasma Exchange under Critical Care Conditions: A Retrospective Eleven-Year Single-Center Study at a Tertiary Care Center.

Background: Therapeutic plasma exchange (TPE) is frequently performed in critical care settings for heterogenous indications. However, specific intensive care unit (ICU) data regarding TPE indications, patient characteristics and technical details are sparse. Methods: We performed a retrospective, single-center study using data from January 2010 until August 2021 for patients treated with TPE in an ICU setting at the University Hospital Zurich. Data collected included patient characteristics and outcomes, ICU-specific parameters, as well as apheresis-specific technical parameters and complications. Results: We identified n = 105 patients receiving n = 408 TPEs for n = 24 indications during the study period. The most common was thrombotic microangiopathies (TMA) (38%), transplant-associated complications (16.3%) and vasculitis (14%). One-third of indications (35.2%) could not be classified according to ASFA. Anaphylaxis was the most common TPE-related complication (6.7%), while bleeding complications were rare (1%). The median duration of ICU stay was 8 ± 14 days. Ventilator support, renal replacement therapy or vasopressors were required in 59 (56.2%), 26 (24.8%), and 35 (33.3%) patients, respectively, and 6 (5.7%) patients required extracorporeal membrane oxygenation. The overall hospital survival rate was 88.6%. Conclusion: Our study provides valuable real-world data on heterogenous TPE indications for patients in the ICU setting, potentially supporting decision-making.

Cell Cycle-Mediated Regulation of Secondary Ig Diversification.

Secondary Ig diversification in B cells requires the deliberate introduction of DNA damage into the Ig genes by the enzyme activation-induced cytidine deaminase (AID) and the error-prone resolution of AID-induced lesions. These processes must be tightly regulated because they may lead to lymphomagenesis if they act on genes other than the Ig genes. Since B cells may limit secondary Ig diversification mechanisms during the cell cycle to minimize genomic instability, we restricted the activity of AID specifically to the G1 or S/G2 phase to investigate the cell cycle contribution to the regulation of somatic hypermutation, class switch recombination, and Ig gene conversion in human, murine, and avian B cells, respectively. The efficient induction of AID in different cell cycle phases allowed us for the first time, to our knowledge, to discriminate G1- from S/G2-specific events of regulation. We show that the processes of Ig gene conversion and C/G mutagenesis during somatic hypermutation can be achieved throughout the cell cycle, whereas A/T mutagenesis and class switch recombination require AID-mediated deamination in G1. Thus, AID activity in G1, but not in S/G2, leads to the efficient accomplishment of all mechanisms of secondary Ig diversification. Our findings refine the current state-of-the-art knowledge in the context of the regulation of secondary Ig diversification.

Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report.

BACKGROUND: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell therapy in patients with central nervous system (CNS) lymphoma remain limited. MAIN BODY: We here report occurrence of a Guillain-Barré-like syndrome (GBS) and central diabetes insipidus (cDI) following tisagenlecleucel therapy for relapsed high-grade lymphoma with CNS involvement. Both complications were refractory to standard treatment of ICANS. Weakness of respiratory muscles required mechanical ventilation and tracheostomy while cDI was treated with desmopressin substitution for several weeks. Muscle-nerve biopsy and nerve conduction studies confirmed an axonal pattern of nerve damage. T cell-rich infiltrates and detection of the CAR transgene in muscle-nerve sections imply a direct or indirect role of CAR-T cell-mediated inflammation. In line with current treatment guidelines for GBS, intravenous immunoglobulin was administered and gradual but incomplete recovery was observed over the course of several months. CONCLUSIONS: This case report highlights the risk of rare but severe neurological adverse events, such as acute GBS or cDI, in patients treated with CAR-T cells. It further underlines the importance of appropriate patient surveillance and systematic reporting of rare complications to eventually improve treatment.

Posttraumatic stress disorder and diabetes-related outcomes in patients with type 1 diabetes.

Mental comorbidities in patients with type 1 diabetes mellitus (T1D) are common, and can have a negative impact on acute blood glucose levels and long-term metabolic control. Information on the association of T1D and comorbid posttraumatic stress disorder (PTSD) with diabetes-related outcomes is limited. The aim was to examine the associations between a clinical diagnosis of PTSD and diabetes-related outcomes in patients with T1D. Patients with T1D and comorbid documented PTSD from the DPV database (n = 179) were compared to a group with T1D without PTSD (n = 895), and compared to a group with T1D without comorbid mental disorder (n = 895) by matching demographics (age, gender, duration of diabetes, therapy and migration background) 1:5. Clinical diabetes-related outcomes {body mass index (BMI), hemoglobin A1c (hbA1c), daily insulin dose, diabetic ketoacidosis (DKA), hypoglycemia, number of hospital admissions, number of hospital days} were analyzed, stratified by age groups (≤ 25 years vs. > 25 years). Patients with comorbid PTSD aged ≤ 25 years compared with patients without PTSD or patients without mental disorders had significantly higher HbA1c (8.71 vs. 8.30 or 8.24%), higher number of hospital admissions (0.94 vs. 0.44 or 0.32 per year) and higher rates of DKA (0.10 vs. 0.02 or 0.01 events/year). Patients with comorbid PTSD aged ≤ 25 years compared with patients without PTSD had significantly higher BMI (0.85 vs. 0.59) and longer hospital stays (15.89 vs.11.58 days) than patients without PTSD. Patients with PTSD > 25 years compared with patients without PTSD or without any mental comorbidities had significantly fewer hospital admissions (0.49 vs. 0.77 or 0.69), but a longer hospital length of stay (20.35 vs. 11.58 or 1.09 days). We found that PTSD in younger patients with T1D is significantly related to diabetes outcome. In adult patients with T1D, comorbid PTSD is associated with fewer, but longer hospitalizations. Awareness of PTSD in the care of patients with T1D should be raised and psychological intervention should be provided when necessary.

Antibody response to a third SARS-CoV-2 vaccine dose in recipients of an allogeneic haematopoietic cell transplantation.

Allogeneic haematopoietic cell transplantation (allo-HCT) recipients show impaired antibody (Ab) response to a standard two-dose vaccination against severe acute respiratory syndrome coronavirus-2 and currently a third dose is recommended as part of the primary vaccination regimen. By assessing Ab titres 1 month after a third mRNA vaccine dose in 74 allo-HCT recipients we show sufficient neutralisation activity in 77% of the patients. Discontinuation of immunosuppression before the third vaccine led to serological responses in 50% of low responders to two vaccinations. Identifying factors that might contribute to better vaccine responses in allo-HCT recipients is critical to optimise current vaccination strategies.