Deep abdominal breathing reduces heart rate and symptoms during orthostatic challenge in patients with postural orthostatic tachycardia syndrome.

BACKGROUND AND PURPOSE: This study investigated the effects of deep abdominal breathing on cardiovascular parameters and symptoms in patients with postural orthostatic tachycardia syndrome (POTS) during head-up tilt-table (HUT) challenge. METHODS: Thirty POTS patients completed two consecutive rounds of 10-min HUT in a crossover design. One round was HUT without intervention, and one round combined the HUT with deep breathing at a rate of 6 breaths/min. Cardiovascular parameters, including mean blood pressure and maximum and mean heart rate (HR), were measured supine and standing. Symptoms were assessed using the Vanderbilt Orthostatic Symptom Score (VOSS). RESULTS: During the breathing technique, the mean HR increase was -7.35 bpm (95% confidence interval [CI] = -11.71 to -2.98), and the maximum HR increase was -6.27 bpm (95% CI = -11.85 to -0.68, p = 0.041), significantly lower compared to normal breathing. Additionally, improvements were observed in all absolute cardiovascular parameters during standing, with VOSS symptoms simultaneously and significantly decreasing by -5.38 (95% CI = -10.43 to -0.36). CONCLUSIONS: Slow deep abdominal breathing can act as a simple technique to reduce the standing HR increase upon HUT in patients with POTS. This suggests that modulation of the cardiopulmonary neurocircuits and the respiratory pump may reduce HR increase and symptoms in patients with POTS. The findings of this study highlight the use of a safe, zero-cost, and simple behavioral tool to suggest to POTS patients for symptom relief apart from standard treatment. The observed improvements in cardiovascular parameters and symptoms offer a promising therapeutic approach for patients in times of inadequate treatment options.

The German Multicenter Registry for ME/CFS (MECFS-R).

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystemic disease characterized by a complex, incompletely understood etiology. Methods: To facilitate future clinical and translational research, a multicenter German ME/CFS registry (MECFS-R) was established to collect comprehensive, longitudinal, clinical, epidemiological, and laboratory data from adults, adolescents, and children in a web-based multilayer-secured database. Results: Here, we present the research protocol and first results of a pilot cohort of 174 ME/CFS patients diagnosed at two specialized tertiary fatigue centers, including 130 (74.7%) adults (mean age 38.4; SD 12.6) and 43 (25.3%) pediatric patients (mean age 15.5; SD 4.2). A viral trigger was identified in 160/174 (92.0%) cases, with SARS-CoV-2 in almost half of them. Patients exhibited severe functional and social impairment, as reflected by a median Bell Score of 30.0 (IQR 30.0 to 40.0) and a poor health-related quality of life assessed with the Short Form-36 health survey, resulting in a mean score of 40.4 (SD 20.6) for physical function and 59.1 (SD 18.8) for mental health. Conclusions: The MECFS-R provides important clinical information on ME/CFS to research and healthcare institutions. Paired with a multicenter biobank, it facilitates research on pathogenesis, diagnostic markers, and treatment options. Trial registration: ClinicalTrials.gov NCT05778006.

Pediatric and adult patients with ME/CFS following COVID-19: A structured approach to diagnosis using the Munich Berlin Symptom Questionnaire (MBSQ).

A subset of patients with post-COVID-19 condition (PCC) fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To establish the diagnosis of ME/CFS for clinical and research purposes, comprehensive scores have to be evaluated. We developed the Munich Berlin Symptom Questionnaires (MBSQs) and supplementary scoring sheets (SSSs) to allow for a rapid evaluation of common ME/CFS case definitions. The MBSQs were applied to young patients with chronic fatigue and post-exertional malaise (PEM) who presented to the MRI Chronic Fatigue Center for Young People (MCFC). Trials were retrospectively registered (NCT05778006, NCT05638724). Using the MBSQs and SSSs, we report on ten patients aged 11 to 25 years diagnosed with ME/CFS after asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19. Results from their MBSQs and from well-established patient-reported outcome measures indicated severe impairments of daily activities and health-related quality of life.    Conclusions: ME/CFS can follow SARS-CoV-2 infection in patients younger than 18 years, rendering structured diagnostic approaches most relevant for pediatric PCC clinics. The MBSQs and SSSs represent novel diagnostic tools that can facilitate the diagnosis of ME/CFS in children, adolescents, and adults with PCC and other post-infection or post-vaccination syndromes. What is Known: • ME/CFS is a debilitating disease with increasing prevalence due to COVID-19. For diagnosis, a differential diagnostic workup is required, including the evaluation of clinical ME/CFS criteria. • ME/CFS after COVID-19 has been reported in adults but not in pediatric patients younger than 19 years. What is New: • We present the novel Munich Berlin Symptom Questionnaires (MBSQs) as diagnostic tools to assess common ME/CFS case definitions in pediatric and adult patients with post-COVID-19 condition and beyond. • Using the MBSQs, we diagnosed ten patients aged 11 to 25 years with ME/CFS after asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19.

One-year follow-up of young people with ME/CFS following infectious mononucleosis by Epstein-Barr virus.

Background: Infectious mononucleosis after primary infection with Epstein-Barr virus (EBV-IM) has been linked to the development of myalgic encephalomyelitis/chronic fatigue-syndrome (ME/CFS) in children, adolescents, and young adults. Here, we present clinical phenotypes and follow-up data from a first German cohort of young people with ME/CFS following EBV-IM. Methods: 12 adolescents and 13 young adults were diagnosed with IM-triggered ME/CFS at our specialized tertiary outpatient service by clinical criteria requiring post-exertional malaise (PEM) and a history of confirmed EBV primary infection as triggering event. Demographic information, laboratory findings, frequency and severity of symptoms, physical functioning, and health-related quality of life (HRQoL) were assessed and re-evaluated 6 and 12 months later. Results: Young adults displayed more severe symptoms as well as worsening of fatigue, physical and mental functioning, and HRQoL throughout the study, compared to adolescents. After one year, 6/12 (54%) adolescents no longer met the diagnostic criteria for ME/CFS while all young adults continued to fulfill the Canadian consensus criteria. Improvement in adolescents was evident in physical functioning, symptom frequency and severity, and HRQoL, while young adults showed little improvement. EBV serology and EBV DNA load did not correlate with distinct clinical features of ME/CFS, and clinical chemistry showed no evidence of inflammation. Remarkably, the median time from symptom onset to ME/CFS diagnosis was 13.8 (IQR: 9.1-34.9) months. Conclusions: ME/CFS following EBV-IM is a severely debilitating disease often diagnosed late and with limited responses to conventional medical care, especially in adults. Although adolescents may have a better prognosis, their condition can fluctuate and significantly impact their HRQoL. Our data emphasize that biomarkers and effective therapeutic options are also urgently needed to improve medical care and pave the way to recovery.

Customized 3D printed bioreactors for decellularization-High efficiency and quality on a budget.

Decellularization (DC) of biomaterials with bioreactors is widely used to produce scaffolds for tissue engineering. This study uses 3D printing to develop efficient but low-cost DC bioreactors. Two bioreactors were developed to decellularize pericardial patches and vascular grafts. Flow profiles and pressure distribution inside the bioreactors were optimized by steady-state computational fluid dynamics (CFD) analysis. Printing materials were evaluated by cytotoxicity assessment. Following evaluation, all parts of the bioreactors were 3D printed in a commercial fused deposition modeling printer. Samples of bovine pericardia and porcine aortae were decellularized using established protocols. An immersion and agitation setup was used as a control. With histological assessment, DNA quantification and biomechanical testing treatment effects were evaluated. CFD analysis of the pericardial bioreactor revealed even flow and pressure distribution in between all pericardia. The CFD analysis of the vessel bioreactor showed increased intraluminal flow rate and pressure compared to the vessel's outside. Cytotoxicity assessment of the used printing material revealed no adverse effect on the tissue. Complete DC was achieved for all samples using the 3D printed bioreactors while DAPI staining revealed residual cells in aortic vessels of the control group. Histological analysis showed no structural changes in the decellularized samples. Additionally, biomechanical properties exhibited no significant change compared to native samples. This study presents a novel approach to manufacturing highly efficient and low budget 3D printed bioreactors for the DC of biomaterials. When compared to standard protocols, the bioreactors offer a cost effective, fast, and reproducible approach, which vastly improves the DC results.