Humoral immune response as an indicator for protection against Covid-19 after anti-SARS-COV2-booster vaccination in hematological and oncological patients.

Cancer patients are at a higher risk to develop severe COVID-19 symptoms after SARS-CoV-2 infection compared to the general population and regularly show an impaired immune response to SARS-CoV-2 vaccination. In our oncological center, 357 patients with hematological and oncological diseases were monitored for neutralizing antibodies from October 2021 over 12 months. All patients had received three anti-SARS-CoV-2 vaccinations with an mRNA-(Comirnaty/BionTech or Spikevax/Moderna) or a vector vaccine (Vakzevria/AstraZeneca or JCOVDEN/Johnson&Johnson). Neutralizing anti-SARS-CoV-2 IgG antibodies in the patients' sera were detected within 3 months before, 3-10 weeks and 5-7 months after the booster vaccination (third vaccination). 112 patients developed a breakthrough SARS-CoV-2 infection during the observation period. High anti-SARS-Cov-2 antibody levels before infection significantly protected against symptomatic Covid-19 disease (p = .003). The median antibody titer in patients with asymptomatic Covid-19 disease was 2080 BAU/ml (binding antibody units per Milliliter) and 765 BAU/ml in symptomatic patients. 98% of the solid tumor patients reached seroconversion after the booster vaccination in comparison to 79% of the hematological patients. High antibody titers of >2080 BAU/ml after the booster vaccination were detected in 61% of the oncological and 34.8% of the hematological patients. 7-10 months after the booster vaccination, the anti-SARS-CoV-2 antibody titer declined to an average of 849 BAU/ml. Considering the heterogenous humoral immune response of cancer patients observed in this study, an individual vaccination strategy based on regular measurement of anti-SARS-CoV-2 antibody levels should be considered in contrast to fixed vaccination intervals.

Deventilation Syndrome in COPD Patients Receiving Long-Term Home Noninvasive Ventilation: A Systematic Scoping Review.

The treatment of patients with COPD and chronic hypercapnic respiratory failure using noninvasive ventilation (NIV) is well established. A "deventilation syndrome" (DVS) has been described as acute dyspnea after cessation of NIV therapy. A systematic scoping review reporting according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) searching Embase was conducted in September 2021. A final manual search followed in February 2023. Literature synthesis was blinded using Rayyan by three different reviewers. A total of 2,009 studies were screened. Five studies met the eligibility criteria. Four articles presented original data. Three articles examined potential treatment options. Three studies were prospective; none were randomized. A total of 122 patients were included. DVS was defined differently in all studies. Seventy-four patients were identified to suffer from DVS (48 controls). Patients were evaluated by blood gas analysis, transcutaneous TcCO2 measurement, spirometry, whole-body plethysmography, respiratory muscle assessments, diaphragmatic electromyography, ultrasound, 6-min walk test, polysomnography, and questionnaires. Treatment approaches studied were minimization of "patient-ventilator asynchrony" (PVA) and use of pursed- lip breathing ventilation. Pathophysiological mechanisms discussed were PVA, high inspiratory positive airway pressure, hyperinflation, respiratory muscle impairment, and increased respiratory rates. Compared with controls, patients with DVS appeared to suffer from more severe airway obstruction, hyperinflation, and PaCO2 retention; worse exercise test scores; and poorer quality of life. The available evidence does not allow for definite conclusions about pathophysiological mechanisms, ethology, or therapeutic options. Future studies should focus on a consistent definition and possible pathomechanisms.

[Pulmonary involvement in idiopathic inflammatory myopathies]. / Pulmonale Beteiligung bei idiopathischen inflammatorischen Myopathien.

Idiopathic inflammatory myopathies are rare systemic diseases with different types of pulmonary manifestations depending on the underlying aetiology; here, interstitial lung diseases (ILD) are the most frequently found patterns depending on the underlying disorder. There is a lack of sufficient prospective studies on this heterogeneous group of patients, particularly in case of ILD being involved. The diagnosis is based upon guideline recommendations for ILD and requires a multidisciplinary discussion within a team with specific expertise in this field. Myositis specific antibodies and myositis associated antibodies form an essential part of the diagnostic tools and may also be associated with a certain phenotype or disease progression. Anti-t-RNA-synthetase antibodies (Anti-ARS) and anti-melanoma differentiation-associated gene 5 antibodies (MDA5) play an important clinical role for treatment the estimation of response and prognosis. The most common ILD patterns are nonspecific interstitial pneumonia (NSIP) and organising pneumonia (OP) or a mixed pattern of both. Treatment is based on systemic steroids and early initiation of other immunosuppressant drugs. Evidence for this is, however, sparse, since most of the studies having investigated treatment modalities are of retrospective nature, even though some new prospective data may be useful for the establishment of treatment pathways in the future.

[Long-term health-related quality of life of patients after prolonged weaning depending on weaning status]. / Lebensqualität im Langzeitverlauf nach prolongiertem Weaning in Abhängigkeit vom Weaning-Status.

INTRODUCTION: Long-term outcome in patients with prolonged weaning is known to be impaired, particularly against the background of their weaning status; however, data on their health-related quality of life (HRQL) are sparse. METHODS: HRQL was measured in patients with prolonged weaning using the Severe Respiratory Insufficiency Questionnaire (SRI). RESULTS: Overall, 39 out of 83 patients with prolonged weaning filled in the SRI questionnaire. The median interval between discharge from hospital and HRQL assessment was 3.5 years (IQR 2.4-4.5 years). In the total group, the median SRI summary score was 56.4 (IQR 38.8-73.5). Patients with unsuccessful weaning and subsequent invasive home mechanical ventilation (N=15) had worse HRQL as estimated from the SRI summary score when compared to those with successful weaning both without (n=13) and with subsequent long-term non-invasive ventilation (NIV) (n=11); Kruskal-Wallis-Test: H (2, n=39) = 7,875446; P=0.0195. Statistically significant differences indicating worse HRQL in patients with invasive home mechanical ventilation were particularly evident in the following SRI subscales: Social relationships (P=0.0325), Anxiety (P=0.0096), and Psychological well-being (P=0.0079). CONCLUSIONS: HRQL is substantially impaired in patients with unsuccessful prolonged weaning and subsequent invasive home mechanical ventilation compared to those with successful prolonged weaning. Further studies incorporating higher case numbers are needed to assess other conditions potentially affecting HRQL in patients with prolonged weaning.

GANBISS: a new GPU accelerated N-body code for binary star systems.

We present a GPU accelerated N-body integrator using the Bulirsch-Stoer method, called GANBISS (GPU accelerated n-body code for binary star systems). It is designed to simulate the dynamical evolution of planetesimal disks in binary star systems which contain some thousand disk objects. However, it can also be used for studies of non-interacting massless bodies where up to 50 million objects can be studied in a simulation. GANBISS shows the energy and angular momentum conservation behavior of non-symplectic integration methods. The code is written in CUDA C and can be run on NVIDIA GPUs of compute capability of at least 3.5. A comparison of GPU and CPU computations indicates a speed-up of the GPU performance of up to 100 times-depending on the number of disk objects.

[Neuralgic amyotrophy: a common cause of unilateral and bilateral diaphragmatic pareses]. / Die neuralgische Amyotrophie: eine häufige Ursache uni- oder bilateraler Zwerchfellparesen.

There are several causes for unilateral or bilateral diaphragmatic paresis. The most common cause is an (intraoperative) injury to the phrenic nerve.However, in up to 20% of cases, no explanation can be found despite extensive workup. Neuralgic amyotrophy (NA, also known as Parsonage-Turner syndrome) is a common underdiagnosed multifocal autoimmune-inflammatory disease that predominantly affects proximal nerve segments of the upper extremities. Classic symptoms include acute onset of severe pain in the shoulder girdle with delayed onset of paresis of the shoulder and arm muscles. In at least 7% of cases, the phrenic nerve is also affected. Based on the annual incidence of NA of 1:1000, the entity as a cause of diaphragmatic dysfunction is probably not as uncommon as previously thought. However, clinical experience shows that this diagnosis is often not considered, and diaphragmatic paresis gets wrongly classified as idiopathic.This is particularly disastrous because in the early stage of NA, medical therapy with corticosteroids is mostly not considered and the possibility that surgical repair of the diaphragm may be performed prematurely, given that the condition may resolve spontaneously many months after symptom onset.The aim of the present article is to raise awareness of the entity of NA as a cause of diaphragmatic paresis and to establish a standardized approach to diagnosis and treatment.

Neuralgic Amyotrophy: A Commonly Overlooked Cause of Acute Shoulder Pain.

BACKGROUND: Neuralgic amyotrophy (NA) is a multifactorial, monophasic neuritis that mainly affects the nerves of the shoulder girdle. It is characterized by very severe pain and by weakness that arises some time after the pain. Its reported incidence is high (100 cases per 100 000 persons per year), but our data suggest that many or most cases are diagnosed late or not at all. METHODS: This review of the epidemiology, pathophysiology, diagnosis, and treatment of NA is based on pertinent publications retrieved by a selective literature search, and on data provided by the scientific institute of AOK, a German statutory health-insurance carrier. RESULTS: It is currently thought that the combination of a genetic predisposition, an immunological trigger factor, and mechanical stress on the affected nerve segment(s) is pathophysiologically determinative. The prognosis of untreated NA is poor, with 25% of patients remaining unable to work at three years. The main form of treatment is with corticosteroids that are administered as early as possible. If there is evidence of nerve constriction or torsion, surgery may also help. There have only been six controlled cohort studies on the treatment of NA, and no randomized trials. It is not uncommon for the acute phase to develop into a chronic pain syndrome requiring multidimensional treatment. CONCLUSION: Particularly in view of the high incidence and improved therapeutic options, NA should be included in the differential diagnosis of all patients with suggestive symptoms.

Clinical relevance of positively determined myositis antibodies in rheumatology: a retrospective monocentric analysis.

BACKGROUND: The increased availability of myositis autoantibodies represents new possibilities and challenges in clinical practice (Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76:1955-64. https://doi.org/10.1136/annrheumdis-2017-211468 .). The aim of this study was to perform a retrospective data analysis of patient cases with positive myositis autoantibodies to analyse their significance in routine rheumatology practice. METHODS: A monocentric analysis of all the orders used to determine myositis autoantibodies from July 2019 to May 2022 in the Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany, was carried out. RESULTS: In the defined time interval, a total of 71,597 laboratory values for the antibodies mentioned above were obtained. A total of 238 different positive autoantibodies ​​were detected in 209 patients. Idiopathic inflammatory myopathy was diagnosed in 37 patients (18%), and inflammatory rheumatic diseases other than idiopathic inflammatory myopathy were diagnosed in 90 patients (43%). No inflammatory rheumatic disease was diagnosed in 82 patients (39%). General clusters of clinical manifestations were observed. CONCLUSIONS: In our cohort, we were able to show that a relevant proportion of patients with positive myositis antibodies did not have idiopathic inflammatory myopathies or inflammatory rheumatic diseases. This finding indicates the importance of myositis autoantibodies in this group of patients. However, further studies on the course of symptoms and examination results in patients without inflammatory rheumatic diseases and with positive myositis antibodies are necessary.

A clinical phenotype of VEXAS syndrome with pleural effusion, infiltrates, and systemic inflammation in a 76-year-old patient: a case report.

INTRODUCTION: VEXAS syndrome, characterized by a UBA1 gene mutation, is a rare and severe systemic inflammatory disease predominantly affecting men. Since its initial description in 2020, it has been noted for its broad clinical phenotype and frequent misdiagnosis. CASE PRESENTATION: A 76-year-old Caucasian male patient diagnosed with VEXAS syndrome is presented in this case report. He presented with typical symptoms including pulmonary manifestations (infiltrates and effusions), systemic inflammation, and haematological abnormalities. The diagnosis was challenging due to the disease's heterogeneous presentation, often resembling autoimmune or haematological diseases. This patient's case featured ground-glass opacities and pleural effusions, underlining the significant pulmonary involvement seen in 50-67% of VEXAS patients. His condition was further complicated by recurrent fever and systemic inflammation affecting multiple organs. CONCLUSION: VEXAS syndrome demands an aggressive treatment approach due to its high mortality rate and refractory nature. This case underscores the importance of including VEXAS syndrome in differential diagnoses, particularly for patients with systemic inflammation and pulmonary symptoms, and calls for multidisciplinary management and extensive research to understand its full range of clinical phenotypes.

Adherence-enhancing interventions for pharmacological and oxygen therapy in patients with COPD: a systematic review and component network meta-analyses.

INTRODUCTION: Adherence to COPD management strategies is complex, and it is unclear which intervention may enhance it. OBJECTIVES: We aim to evaluate the effectiveness of adherence-enhancing interventions, alone or compared to interventions, for patients with COPD. METHODS: This review comprises a component network meta-analysis with a structured narrative synthesis. We searched MEDLINE, Embase, CENTRAL, CINAHL and trial registries on 9 September 2023. We included controlled studies that explored adherence in patients with COPD. Two review authors independently performed the study selection, data extraction and the risk of bias assessment. We involved patients with COPD in developing this systematic review through focus group interviews and displayed the findings in pre-designed logic models. RESULTS: We included 33 studies with 5775 participants. We included 13 studies in the component network meta-analysis that explored adherence. It was mainly assessed through questionnaires. As a continuous outcome, there was a tendency mainly for education (standardised mean difference 1.26, 95% CI 1.13-1.38, very low certainty of evidence) and motivation (mean difference 1.85, 95% CI 1.19-2.50, very low certainty of evidence) to improve adherence. As a dichotomous outcome (e.g. adherent/non-adherent), we found a possible benefit with education (odds ratio 4.77, 95% CI 2.25-10.14, low certainty of evidence) but not with the other components. We included six studies that reported quality of life in the component network meta-analysis. Again, we found a benefit of education (mean difference -9.70, 95% CI -10.82- -8.57, low certainty of evidence) but not with the other components. CONCLUSIONS: Education may improve adherence and quality of life in COPD patients. Patient focus group interviews indicated that interventions that strengthen patients' self-efficacy and help them to achieve individual goals are the most helpful.

Ambulatory Long-Term Oxygen Therapy in Patients with Severe COPD: A Randomized Crossover Trial to Compare Constant-Minute-Volume and Constant-Bolus Systems.

Background and Methods: Constant-minute-volume and constant-bolus devices serve as two different means of portable oxygen conservation. A prospective randomised crossover study was conducted in COPD GOLD IV patients to investigate the effect of these two devices on dyspnea, oxygenation and 6-minute walking test (6MWT) distance. The primary endpoint was the final operating level required (operating level range 1-5 for both devices) by either device to meet the success criteria for mobile oxygen therapy, as outlined in the British Thoracic Society guidelines (SpO2 ≥90% throughout 6MWT; ≥10% increase in walking distance from baseline; improvement in BORG of at least 1 point from baseline). Results: Twenty-five patients were enrolled in the study and randomly assigned to one of two sequences involving the use of each type of portable oxygen conservation device. 14 female, 67.9 years (±7.8); FEV1: 27.3%pred. (±8.4); PaO2 at rest without oxygen: 50.3mmHg (±5.9). For both systems, 24/25 patients (96%) were successfully recruited. The mean operating-level difference when success criteria were met was -0.58 in favor of the constant bolus device (95% CI: -0.88 to -0.28, P <0.001). Secondary endpoints (walking distance, respiratory rate and BORG dyspnea) showed no statistically significant or clinically relevant differences. An algorithm created especially for this study showed a high success rate in terms of titration for the required operating level. Conclusion: Both portable oxygen-conserving devices met the success criteria in 96% of patients in the 6MWT when they were titrated to the correct level. The constant-bolus device required a significantly lower operating level to achieve the success criteria, hereby reducing energy consumption. Individual titration of the respective device is recommended, which can be facilitated by the novel titration algorithm described here.

[Leukemia caused by collision with a wild pig?] / Leukämie durch Kollision mit Wildschwein?

HISTORY: A 23 years old, previously healthy woman was admitted to our clinic with neutropenic fever to rule out acute leukemia. Upon admission the patient reported that a few days ago the carcass of a pig had fallen on her from above, so that she experienced strong back pain. FINDINGS AND DIAGNOSIS: The blood count showed thrombocytopenia and marked neutropenia of 0.04G/L. Moreover, laboratory work up demonstrated increased C-reactive protein, procalcitonin as well as serum creatinine levels. THERAPY AND COURSE: Broad antiinfective therapy was initiated immediately. During the further course of disease the patient developed signs of acute cholecystitis, which was managed conservatively. Only after repeated specific investigation and after initially denying, the patient reported to have taken 1 g of metamizole as self-medication after her initial accident. All symptoms and laboratory parameters gradually improved and finally completely resolved to normal, and the patient could be released from hospital after seven days. CONCLUSIONS: In retrospect all signs and symptoms reported here can be interpreted as an infectious complication during an episode of agranulocytosis caused by a single dose of metamizole, underscoring the importance of carefully judging indication when using this otherwise highly useful substance.