Autoimmune cytopenias (AIC) such as immune thrombocytopenia or autoimmune hemolytic anemia are claimed to be essentially driven by a dysregulated immune system. Using next-generation immunosequencing ...we profiled 59 T and B cell repertoires (
and
) of 25 newly diagnosed patients with primary or secondary (lymphoma-associated) AIC to test the hypothesis if these patients present a disease-specific immunological signature that could reveal pathophysiological clues and eventually be exploited as blood-based biomarker. Global
and
repertoire metrics as well as
gene usage distribution showed uniform characteristics for all lymphoma patients (high clonality and preferential usage of specific
- and
genes), but no AIC-specific signature. Since T cell immune reactions toward antigens are unique and polyclonal, we clustered TCRβ clones
based on target recognition using the GLIPH (grouping of lymphocyte interactions by paratope hotspots) algorithm. This analysis revealed a considerable lack of physiological T cell clusters in patients with primary AIC. Interestingly, this signature did not discriminate between the different subentities of AIC and was also found in an independent cohort of 23 patients with active autoimmune hepatitis. Taken together, our data suggests that the identified T cell cluster signature could represent a blood biomarker of autoimmune conditions in general and should be functionally validated in future studies.
In multiple myeloma, circulating "clonotypic" B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential ..."feeder" cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10(-3), this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology.
The surgical complexities of our current population have pushed the technological limits of healthcare, urging for minimally invasive approaches. For ventral hernias, in particular, robotic assisted ...laparoscopic repairs have been met with conflict. Cost and longer operative times are among the arguments against robotic surgery, although thorough evaluation of patient outcomes could potentially advocate for use of this tool. We attempted to approach this by retrospectively reviewing our own data. We reviewed charts between September 2016 and February 2017 of patients receiving complex hernia repairs, either a standard open repair (SOR) or robotic-assisted repair (RAR). Data collected included preoperative, perioperative, and postoperative care. Of the 43 patients reviewed, 16 were SOR, versus 27 RAR. Patients were comparable in age, gender, BMI, diabetes as a comorbidity; average hernia defect size was similar between the two groups. Although operative times were longer in the RAR group, estimated blood loss (EBL) was less. Hospital stay was also shorter in the RAR group, at 3.0 ± 1.9 days versus 9.6 ± 8.4 days for the OAR group. Of those requiring critical care management, only one patient had a robotic assisted repair, versus half of the patients who received an open repair. Of the patients who presented to the emergency department within 30 days of surgery, each group had four patients, and two from the OAR group required admission. Our data is consistent with other literature supporting shorter lengths of stays. Although the robotic approach did required a longer operative time, the resulting improved patient outcomes support this technique for complex ventral hernia repairs.
A recall campaign for commercial, orange flowering petunia varieties in spring 2017 caused economic losses worldwide. The orange varieties were identified as undeclared genetically engineered ...(GE)-plants, harboring a maize dihydroflavonol 4-reductase (
), which was used in former scientific transgenic breeding attempts to enable formation of orange pelargonidin derivatives from the precursor dihydrokaempferol (DHK) in petunia. How and when the
cDNA entered the commercial breeding process is unclear. We provide an in-depth analysis of three orange petunia varieties, released by breeders from three countries, with respect to their transgenic construct, transcriptomes, anthocyanin composition, and flavonoid metabolism at the level of selected enzymes and genes. The two possible sources of the
cDNA in the undeclared GE-petunia can be discriminated by PCR. A special version of the
gene, the
type 2 allele, is present, which includes, at the 3'-end, an additional 144 bp segment from the non-viral transposable
sequence, which does not add any functional advantage with respect to DFR activity. This unequivocally points at the first scientific GE-petunia from the 1980s as the
source, which is further underpinned e.g., by the presence of specific restriction sites, parts of the untranslated sequences, and the same arrangement of the building blocks of the transformation plasmid used. Surprisingly, however, the GE-petunia cannot be distinguished from native red and blue varieties by their ability to convert DHK in common
enzyme assays, as DHK is an inadequate substrate for both the petunia and maize DFR. Recombinant maize DFR underpins the low DHK acceptance, and, thus, the strikingly limited suitability of the
protein for a transgenic approach for breeding pelargonidin-based flower color. The effect of single amino acid mutations on the substrate specificity of DFRs is demonstrated. Expression of the
gene is generally lower than the petunia
expression despite being under the control of the strong, constitutive p
promoter. We show that a rare constellation in flavonoid metabolism-absence or strongly reduced activity of both flavonol synthase and B-ring hydroxylating enzymes-allows pelargonidin formation in the presence of DFRs with poor DHK acceptance.
Auch die Bevölkerung < 60 Jahre ist von einer signifikanten Krankheitslast durch die saisonale Influenza betroffen, einhergehend mit einer hohen wirtschaftlichen Belastung, insbesondere bedingt durch ...Influenza-assoziierte Produktivitätsverluste der arbeitenden Gesellschaft. Konventionelle eibasierte Influenzaimpfstoffe können aufgrund von Eiadaptation eine beeinträchtigte Impfeffektivität aufweisen. Zellkulturbasierte Influenzaimpfstoffe weisen seltener Antigenanpassungen an das Wirtssystem auf und zeigten über mehrere Saisons eine bessere Effektivität bei 4‑ bis 64-Jährigen gegenüber konventionellen eibasierten Influenzaimpfstoffen unter realen Bedingungen. Der präferenzielle Einsatz von zellkulturbasierten vs. konventionelle Influenzaimpfstoffe könnte zu einer Verringerung der Influenza-bedingten Krankheitslast und wirtschaftlichen Belastung in der deutschen Bevölkerung < 60 Jahre führen.
Zusammenfassung
Auch die Bevölkerung < 60 Jahre ist von einer signifikanten Krankheitslast durch die saisonale Influenza betroffen, einhergehend mit einer hohen wirtschaftlichen Belastung, ...insbesondere bedingt durch Influenza-assoziierte Produktivitätsverluste der arbeitenden Gesellschaft. Konventionelle eibasierte Influenzaimpfstoffe können aufgrund von Eiadaptation eine beeinträchtigte Impfeffektivität aufweisen. Zellkulturbasierte Influenzaimpfstoffe weisen seltener Antigenanpassungen an das Wirtssystem auf und zeigten über mehrere Saisons eine bessere Effektivität bei 4‑ bis 64-Jährigen gegenüber konventionellen eibasierten Influenzaimpfstoffen unter realen Bedingungen. Der präferenzielle Einsatz von zellkulturbasierten vs. konventionelle Influenzaimpfstoffe könnte zu einer Verringerung der Influenza-bedingten Krankheitslast und wirtschaftlichen Belastung in der deutschen Bevölkerung < 60 Jahre führen.
The population < 60 years of age is also affected by a significant disease burden from seasonal influenza. It carries a high economic burden, mainly driven by influenza-associated productivity losses ...in the working population. Conventional egg-based influenza vaccines may experience reduced effectiveness due to antigen adaptation in eggs. In contrast, cell-based influenza vaccines are less likely to be affected by antigenic adaptations to the host system and showed better effectiveness in individuals 4-64 years old over several seasons compared to conventional egg-based influenza vaccines under real-world conditions. Preferential use of cell-based influenza vaccines, as opposed to conventional egg-based vaccines, could reduce the burden of influenza-related symptoms on individuals and alleviate the economic impact on the German population < 60 years of age.
Seasonal influenza poses a significant burden of disease, affecting not only older adults but also individuals under the age of 60. It carries a high economic burden, mainly driven by ...influenza-associated productivity losses in the working population. Conventional egg-based influenza vaccines may have reduced effectiveness due to antigen adaptation in eggs. In contrast, cell-based influenza vaccines are less likely to be affected by such antigen adaptation. This review aims to present real-world data (RWD) comparing the effectiveness of quadrivalent cell-based (QIVc) and egg-based (QIVe) influenza vaccines over three consecutive seasons.
A comprehensive review was conducted, analyzing RWD from retrospective cohort and case-control studies on the relative vaccine effectiveness (rVE) of QIVc versus QIVe during the 2017/18-2019/20 seasons.
This study included six retrospective cohort studies and one case-control study, with a combined total of approximately 29 million participants. A cohort study involving people aged ≥4 years during the 2017/18 season showed a statistically significant rVE of QIVc compared to QIVe in preventing influenza-like illness, with a value of 36.2%. QIVc demonstrated statistically significant superiority over QIVe in preventing outpatient and inpatient medical encounters as observed in two cohort studies conducted during the 2018/19 and 2019/20 seasons. The rVE of QIVc compared to QIVe was found to be 7.6% in individuals aged ≥4 years and 9.5% in individuals aged ≥18 years. Three additional cohort studies conducted between 2017/18-2019/20 reported a statistically significant improvement in rVE (5.3-14.4%) of QIVc compared to QIVe in preventing influenza-related hospitalizations and emergency department visits due to influenza in individuals aged 4-64 years. In a case-control study across all three seasons, QIVc showed statistically significantly higher effectiveness compared to QIVe in preventing test-confirmed influenza, with rVEs of 10.0-14.8%.
RWD from the 2017/18-2019/20 seasons demonstrated that QIVc is more effective than QIVe in preventing influenza-related outcomes in individuals aged 4-64 years. Preferential use of cell-based influenza vaccines, as opposed to conventional egg-based vaccines, could reduce the burden of influenza-related symptoms on individuals and alleviate the economic impact on the German population under 60 years of age.
Background
The aging of our societies leads to a higher prevalence of multimorbidity and therefore polypharmacy, which often results in inappropriate drug treatment. To address this issue, numerous ...listing approaches, such as the Fit fOR The Aged (FORTA) list have been developed. FORTA’s positive impact on the quality of medications and relevant clinical outcomes has been shown. Based on new emerging evidence and experiences with the existing FORTA lists, we aimed to update the FORTA lists in several European countries/regions.
Methods
Two-step Delphi consensus procedures were conducted in Poland, UK/Ireland, Italy, Spain, the Nordic countries, The Netherlands and France. The existing European FORTA lists served as survey proposals.
Results
Thirty-two experts agreed to take part in this study (return rate: 96.9%). The country/region-specific overall consensus for all items and participants after the first round was > 90%. FORTA lists from six participating countries, plus the FORTA list for the German-speaking countries, were collated into the new EURO-FORTA List, which now contains 267 items aligned to 27 indications. Three items were added to the EURO-FORTA List, and no drugs were deleted. Eight FORTA items were relabeled, and 96.9% of the labels remained unchanged.
Conclusion
In this study, seven new country/region specific FORTA lists, as well as a new overarching EURO-FORTA List, were developed. An overall increase in the mean consensus coefficient and increases for all disease-specific mean consensus coefficients show a wider consensus among participants. The new lists have the potential to improve drug therapy in older people internationally.
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