Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

Journal of Clinical Immunology - Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable...     

Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real-time PCR

Minimal (i.e. submicroscopic) residual disease (MRD) predicts outcome in childhood acute lymphoblastic leukaemia (ALL). To be used clinically, MRD assays must be reliable and accurate. Two well-established techniques, flow cytometry (FC) and polymerase chain reaction (PCR), can detect leukaemic cells with a sensitivity of 0.01% (10(-4)). We analysed diagnostic samples of 45 ALL-patients (37 B-lineage ALL, eight T-lineage ALL) by four-colour FC and real-time PCR. Leukaemia-associated immunophenotypes, at a sensitivity of MRD detection by FC at the 0.01% level, were identified in 41 cases (91%); antigen-receptor gene rearrangements suitable for MRD detection with a sensitivity of 0.01% or better by PCR were identified in 38 cases (84%). The combined use of FC and PCR allowed MRD monitoring in all 45 patients. In 105 follow-up samples, MRD estimates by both methods were highly concordant, with a deviation factor of <5 by Bland-Altman analysis. Importantly, the concordance between FC and PCR was also observed in regenerating bone marrow samples containing high proportions of CD19(+) cells, and in samples studied 24 h after collection. We conclude that both MRD assays yield generally concordant results. Their combined use should enable MRD monitoring in virtually all patients and prevent false-negative results due to clonal evolution or phenotypic shifts.     

Oxygen uptake plateau occurrence depends on oxygen kinetics and oxygen deficit accumulation

We tested the hypothesis that participants with an oxygen uptake () plateau during incremental exercise exhibit a lower VO₂‐deficit (VO_2DEF)‐accumulation in the submaximal intensity domain due to faster ramp and square wave O₂‐kinetics. Twenty‐six male participants performed a standard ramp test (increment: 30 W·min^?1), a ramp test with an individualized ramp slope and a two‐step (moderate and severe) square wave exercise followed by a ‐verification bout. VO_2DEF was calculated by the difference between individualized ramp test O₂ and O₂‐demand estimated from steady‐state O₂‐kinetics. Twenty‐four participants verified their O_2max in the verification test. Ten of them showed a plateau in the individualized ramp test. VO_2DEF at the end of this ramp test (4.34 ± 0.60 vs 4.54 ± 0.43 L) was not different between the plateau and the non‐plateau group (P > 0.05). The plateau group had a significantly (P < 0.05) lower VO_2DEF 2 minutes before termination of the individualized ramp test (2.24 ± 0.40 vs 2.78 ± 0.33 L). This coincided with a shorter mean response time (43 ± 9 vs 53 ± 7 seconds), a higher increase in O₂ per W (10.1 ± 0.2 vs 9.2 ± 0.5 mL·min^?1·W^?1) at the individualized ramp test as well as shorter time constants of moderate (36 ± 6 vs 48 ± 7 seconds) and severe (62 ± 9 vs 86 ± 10 seconds) square wave kinetics (all P < 0.05). We conclude that the O₂‐plateau occurrence requires a fast O₂‐kinetics and a low VO_2DEF‐accumulation at intensities below O_2max.     

RAS diseases in children

RAS genes encode a family of 21 kDa proteins that are an essential hub for a number of survival, proliferation, differentiation and senescence pathways. Signaling of the RAS-GTPases through the RAF-MEK-ERK pathway, the first identified mitogen-associated protein kinase (MAPK) cascade is essential in development. A group of genetic syndromes, named “RASopathies”, had been identified which are caused by heterozygosity for germline mutations in genes that encode protein components of the RAS/MAPK pathway. Several of these clinically overlapping disorders, including Noonan syndrome, Noonan-like CBL syndrome, Costello syndrome, cardio-facio-cutaneous (CFC) syndrome, neurofibromatosis type I, and Legius syndrome, predispose to cancer and abnormal myelopoiesis in infancy. This review focuses on juvenile myelomonocytic leukemia (JMML), a malignancy of early childhood characterized by initiating germline and/or somatic mutations in five genes of the RAS/MAPK pathway: PTPN11, CBL, NF-1, KRAS and NRAS. Natural courses of these five subtypes differ, although hematopoietic stem cell transplantation remains the only curative therapy option for most children with JMML. With whole-exome sequencing studies revealing few secondary lesions it will be crucial to better understand the RAS/MAPK signaling network with its crosstalks and feed-back loops to carefully design early clinical trials with novel pharmacological agents in this still puzzling leukemia.     

Stellenwert der Arthroskopie bei Gonarthrose

The relevance of arthroscopic surgery in patients with advanced osteoarthritis of the knee has been discussed controversially in recent years. Even though the idea of joint lavage in order to reduce the inflammatory component of the affected joint has not been proven to provide sufficient long-term effects, there are a variety of copathologies that can efficiently be addressed by arthroscopic surgery. The present article summarizes the indications for arthroscopic surgery in patients with osteoarthritis of the knee joint and discusses the scientific literature available on this controversial topic.     

Recurrent B-cell non-Hodgkin's lymphoma in two brothers with X-linked lymphoproliferative disease without evidence for Epstein-Barr virus infection

We present two male siblings suffering from recurrent manifestations of B-cell non-Hodgkin's lymphoma (NHL) and recurrent infections of the lower respiratory tract associated with bronchiectasis. Immunodeficiency could not be demonstrated by any laboratory investigation. In both patients, lymphomas developed without evidence for Epstein-Barr virus (EBV) infection, i.e. no antibody response to EBV-specific antigens, negative EBV-PCR (polymerase chain reaction) in peripheral blood cells, and absence of latent membrane protein (LMP) and EBV-encoded RNA (EBER) in lymphoma cells. Molecular analysis of the SH2D1A, the gene for X-linked lymphoproliferative disease (XLP) led to the identification of a deletion in the first exon in both patients. Therefore, we postulate that the genetic defect and the following dysregulation of the B-/T-cell interaction rendered these patients susceptible to the early onset of B-cell NHL and that EBV infection is not an obligate prerequisite.