High attack rate in a large care home outbreak of SARS-CoV-2 BA.2.86, East of England, August 2023.

We investigated an outbreak of SARS-CoV-2 variant BA.2.86 in an East of England care home. We identified 45 infections (33 residents, 12 staff), among 38 residents and 66 staff. Twenty-nine of 43 PCR swabs were sequenced, all of which were variant BA.2.86. The attack rate among residents was 87%, 19 were symptomatic, and one was hospitalised. Twenty-four days after the outbreak started, no cases were still unwell. Among the 33 resident cases, 29 had been vaccinated 4 months earlier.

[Functional characterization of patients with isolated post-capillary or combined post-capillary and pre-capillary pulmonary hypertension]. / Funktionelle Charakterisierung von Patienten mit isoliert postkapillärer oder kombiniert post- und präkapillärer pulmonaler Hypertonie.

BACKGROUND: The World Conference on PH recommended differentiation of isolated postcapillary (Ipc) and combined post- and precapillary (Cpc) PH according to pulmonary vascular resistance alone. The aim of this study was the haemodynamic and functional characterization of patients diagnosed IpcPH and CpcPH according to the current recommendation of the latest World Symposium on Pulmonary Hypertension (PH) with an exploratory data analysis. METHODS: We evaluated all consecutive patients presenting at the PH outpatient clinic of Mission Medical Hospital from 2008-2015. All received a complete diagnostic work-up according to the guidelines. We analyzed data of patients with mPAP ≥ 25 mmHg and pulmonary capillary wedge pressure (PCWP  > 15 mmHg. We compared anthropometric, hemodynamic and functional data of six-minute walking test (6 MWT), cardiopulmonary exercise testing (CPET) and echocardiography of patients with IpcPH and CpcPH. RESULTS: Out of 726 patients 58 showed a postcapillary PH: IpcPH: n = 20; CpcPH: n = 38. Patients with IpcPH had a significantly lower mPAP and PVR than patients with CpcPH. Cardiac index was lower in the Cpc-PH group compared to the IpcPH group. Functional capacity did not differ. CpcPH patients showed a higher right/left atrial area (RA/LA)-ratio. DISCUSSION AND CONCLUSION: Although CpcPH patients showed higher values of mPAP and PVR functional capacity was not worse than in patients with IpcPH. In patients with PH due to left heart disease an elevated RA/LA ratio may indicate CpcPH and invasive diagnostic work-up should be considered.

Flow cytometry datasets consisting of peripheral blood and bone marrow samples for the evaluation of explainable artificial intelligence methods.

Three different Flow Cytometry datasets consisting of diagnostic samples of either peripheral blood (pB) or bone marrow (BM) from patients without any sign of bone marrow disease at two different health care centers are provided. In Flow Cytometry, each cell rapidly passes through a laser beam one by one, and two light scatter, and eight surface parameters of more than 100.000 cells are measured per sample of each patient. The technology swiftly characterizes cells of the immune system at the single-cell level based on antigens presented on the cell surface that are targeted by a set of fluorochrome-conjugated antibodies. The first dataset consists of N=14 sample files measured in Marburg and the second dataset of N=44 data files measured in Dresden, of which half are BM samples and half are pB samples. The third dataset contains N=25 healthy bone marrow samples and N=25 leukemia bone marrow samples measured in Marburg. The data has been scaled to log between zero and six and used to identify cell populations that are simultaneously meaningful to the clinician and relevant to the distinction of pB vs BM, and BM vs leukemia. Explainable artificial intelligence methods should distinguish these samples and provide meaningful explanations for the classification without taking more than several hours to compute their results. The data described in this article are available in Mendeley Data [1].

Reproducible measurable residual disease detection by multiparametric flow cytometry in acute myeloid leukemia.

Measurable residual disease (MRD) detected by multiparametric flow cytometry (MFC) is associated with unfavorable outcome in patients with AML. A simple, broadly applicable eight-color panel was implemented and analyzed utilizing a hierarchical gating strategy with fixed gates to develop a clear-cut LAIP-based DfN approach. In total, 32 subpopulations with aberrant phenotypes with/without expression of markers of immaturity were monitored in 246 AML patients after completion of induction chemotherapy. Reference values were established utilizing 90 leukemia-free controls. Overall, 73% of patients achieved a response by cytomorphology. In responders, the overall survival was shorter for MRDpos patients (HR 3.8, p = 0.006). Overall survival of MRDneg non-responders was comparable to MRDneg responders. The inter-rater-reliability for MRD detection was high with a Krippendorffs α of 0.860. The mean time requirement for MRD analyses at follow-up was very short with 04:31 minutes. The proposed one-tube MFC approach for detection of MRD allows a high level of standardization leading to a promising inter-observer-reliability with a fast turnover. MRD defined by this strategy provides relevant prognostic information and establishes aberrancies outside of cell populations with markers of immaturity as an independent risk feature. Our results imply that this strategy may provide the base for multicentric immunophenotypic MRD assessment.

Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells.

With the advent of novel, highly effective therapies for multiple myeloma (MM), classical serologic monitoring appears insufficient for response assessment and prediction of relapse. Moreover, serologic studies in MM are hampered by interference of therapeutic antibodies. The detection of malignant plasma cell clones by next generation sequencing (NGS) or multiparameter flow cytometry (MFC) circumvents these difficulties and can be performed in the peripheral blood (pB) by targeting circulating cell-free DNA (cfDNA) or circulating plasma cells (CPCs), thus also avoiding an invasive sampling procedure. Here, we applied NGS of VJ light chain (LC) rearrangements in cfDNA and MFC of magnetically-enriched CD138-positive CPCs (me-MFC) to investigate disease burden in unselected MM patients. Sequencing was successful for 114/130 (87.7%) cfDNA samples and me-MFC results were analyzable for 196/205 (95.6%) samples. MM clones were detectable in 38.9% of samples taken at initial diagnosis or relapse (ID/RD), but only in 11.8% of samples taken during complete remission (CR). Circulating MM plasma cells were present in 83.3% of ID/RD samples and 9.9% of CR samples. Residual disease assessment by NGS or me-MFC in samples taken during very good partial remission or CR was 80% concordant. Notably, 4/4 (NGS) and 5/8 (me-MFC) positive CR samples were from patients with oligo- or non-secretory myeloma. The time to progression was shorter if there was evidence of residual myeloma in the pB. Together, our findings indicate that our two novel analytical approaches accurately indicate the course of MM and may be particularly valuable for monitoring patients with serologically non-trackable disease.

Ibrutinib- and bortezomib-extended R-CHOP induction in elderly higher-risk patients newly diagnosed with diffuse large B-cell lymphoma - first analysis of toxicity and efficacy signals.

Diffuse large-cell B-cell lymphoma (DLBCL) is the most common lymphoid malignancy. About 30-40% of the patients will not be cured by standard Rituximab (R)-CHOP-like immune-chemotherapy, and many of them experience relapse and eventually succumb to their disease. Enhancing first-line efficacy in patients at higher risk, among them many elderly, is key to improve long-term outcomes. Numerous attempts to combine R-CHOP with targeted agents failed in large randomized phase III trials. The addition of Ibrutinib enhanced survival in younger patients, but increased toxicity across all age groups, especially in the elderly. Older DLBCL patients impose particular challenges, since they often present with more advanced disease, and exhibit treatment-relevant comorbidities. ImbruVeRCHOP trial aims at identifying patients who need that benefit from rationally augmented first-line regimens without experiencing overt toxicity and detecting their molecular signatures of response. This first analysis presents encouraging feasibility, safety, and preliminary response data in elderly high-risk DLBCL patients.

Phase Transitions in a Perovskite Thin Film Studied by Environmental In Situ Heating Nano-Beam Electron Diffraction.

The rich phase diagram of bulk Pr1-x Cax MnO3 resulting in a high tunability of physical properties gives rise to various studies related to fundamental research as well as prospective applications of the material. Importantly, as a consequence of strong correlation effects, electronic and lattice degrees of freedom are vigorously coupled. Hence, it is debatable whether such bulk phase diagrams can be transferred to inherently strained epitaxial thin films. In this paper, the structural orthorhombic to pseudo-cubic transition for x = 0.1 is studied in ion-beam sputtered thin films and differences to the respective bulk system are pointed out by employing in situ heating nano-beam electron diffraction to follow the temperature dependence of lattice constants. In addition, it is demonstrated that controlling the environment during heating, that is, preventing oxygen loss, is crucial in order to avoid irreversible structural changes, which is expected to be a general problem of compounds containing volatile elements under non-equilibrium conditions.

Effects of cultivation practice on floristic and flowering diversity of spontaneously growing plant species on arable fields.

In the past, the floristic diversity of arable fields has been described in terms of species diversity (SD) and their degree of coverage (C), but never in combination with the recording of the actually flowered species (FS) and their flowering intensity (FI) to striking differences in the cultivation methods on arable land. In relation to SD and C, however, FS and FI may provide important additional information on the functional biodiversity of fields. The aim was therefore to investigate the effects of (a) conventional, (b) organic, and (c) smallholder (never application of herbicides) on the floristic diversity. Using a region in Germany, we investigated SD, C, FS, and FI synchronously in (a), (b), and (c), by 356 vegetation surveys (5 × 5 m plots) conducted in spring and summer in 2019 in winter cereals. Statistical tests were used to analyze the differences between (a), (b), and (c). The medians were used to compare the floristic diversity of (a), (b), and (c) and finally relationships of FS and FI to SD were analyzed in relation to the cultivation methods. Significant differences in SD, C, FS, and FI were found between the (a), (b), and (c) in spring and summer characterized by sharp declines from (c) to (b) to (a). A drastic reduction in floristic diversity from (c) 100 to (b) 52 to (a) 3 was determined. Plants in flower (FS, FI) were very poorly in (a), moderately well to well in (b), and well to very well represented in (c). (C) to (a) was characterized by a sharp decline and from (a) to (b) by sharp increase in floristic diversity. With current acreage proportions of (a) in mind, this would affect, about one third of land area in Germany, associated with a drastic reduction in functional biodiversity for insects.

[Functional characterization of patients with isolated post-capillary or combined post-capillary and pre-capillary pulmonary hypertension]. / Funktionelle Charakterisierung von Patienten mit isoliert postkapillärer oder kombiniert post- und präkapillärer pulmonaler Hypertonie.

BACKGROUND: The World Conference on PH recommended differentiation of isolated postcapillary (Ipc) and combined post- and precapillary (Cpc) PH according to pulmonary vascular resistance alone. The aim of this study was the haemodynamic and functional characterization of patients diagnosed IpcPH and CpcPH according to the current recommendation of the latest World Symposium on Pulmonary Hypertension (PH) with an exploratory data analysis. METHODS: We evaluated all consecutive patients presenting at the PH outpatient clinic of Mission Medical Hospital from 2008-2015. All received a complete diagnostic work-up according to the guidelines. We analyzed data of patients with mPAP≥ 25 mmHg and pulmonary capillary wedge pressure (PCWP) > 15 mmHg. We compared anthropometric, hemodynamic and functional data of six-minute walking test (6 MWT), cardiopulmonary exercise testing (CPET) and echocardiography of patients with IpcPH and CpcPH. RESULTS: Out of 726 patients 58 showed a postcapillary PH: IpcPH: n = 20; CpcPH: n = 38. Patients with IpcPH had a significantly lower mPAP and PVR than patients with CpcPH. Cardiac index was lower in the Cpc-PH group compared to the IpcPH group. Functional capacity did not differ. CpcPH patients showed a higher right/left atrial area (RA/LA)-ratio. DISCUSSION AND CONCLUSION: Although CpcPH patients showed higher values of mPAP and PVR functional capacity was not worse than in patients with IpcPH. In patients with PH due to left heart disease an elevated RA/LA ratio may indicate CpcPH and invasive diagnostic work-up should be considered.

Classification of acute appendicitis (CAA): treatment directed new classification based on imaging (ultrasound, computed tomography) and pathology.

PURPOSE: Acute appendicitis (AA) is amongst the most common causes of acute abdominal pain. In spite of progress based on risk stratifications, "negative" appendectomies are performed in up to 30% of patients whilst the appendix perforates in others. Preoperative classification of AA based on imaging is therefore recommended. The aim was to classify AA based on imaging (ultrasound/US, computed tomography/CT), surgical pathology, and/or histopathology in order to differentiate between complicated and uncomplicated AA. A new classification of acute appendicitis (CAA) shall be illustrated by typical US and CT images and be employed in a diagnostic and therapeutic algorithm. METHODS: Medline, Embase, and the Cochrane Library were searched. Any study after 1970, which investigated clinical scores, pathology, US, CT, magnetic resonance imaging, and treatment of AA, was included. Typical images were taken from the author's image database. RESULTS: Five main types of AA are defined, normal appendix (type 0), nonvisualised appendix (type X), uncomplicated AA (type 1), complicated AA without perforation (type 2), and complicated AA with perforation (type 3). The imaging modality is indicated by an additional letter, e.g., type p3b for free perforation on pathology. Standardised reporting of the appendix evaluation by US and CT is presented, as well as algorithms for AA management. Imaging features indicating imminent perforation, as well as likely recurrence, were both classified as complicated AA. CONCLUSION: Imaging is mandatory in suspected AA. The CAA clearly separates uncomplicated from complicated forms of AA allowing nonoperative management in selected patients with uncomplicated forms of AA.

Aberrant CD3-Positive, CD8-Low, CD7-Negative Lymphocytes May Appear During Viral Infections and Mimic Peripheral T-Cell Lymphoma.

Flow cytometry (FC) facilitates diagnosis of peripheral T-cell non-Hodgkin lymphoma (T-NHL), but overlapping features between reactive and neoplastic T-cell proliferations often hamper a rapid assessment. One hundred forty peripheral blood samples submitted to diagnostic FC for T-cell immunophenotyping were retrospectively analyzed. A T-cell population with a conspicuous aberrant surface epitope expression pattern was observed in 18 cases and diagnostic follow up was performed. The aberrant T-cell population exhibited a low scatter profile, a CD7-negative/low, CD8-low and CD3-positive immunophenotype, and monoclonal T-cell receptor expansion. T-NHL was ruled out by follow up in all cases. Epstein-Barr virus infection was diagnosed in 12 cases, cytomegalovirus infection in three cases; one patient had been vaccinated. The irregular subpopulation disappeared spontaneously within days or weeks. We describe a novel peripheral blood T-cell subpopulation with a low light scatter and CD8-low, CD7-negative/low and CD3-positive marker expression profile, which indicates reactive T-cell expansion in patients who present with peripheral lymphadenopathy and/or B symptoms.

Improving treatment of patients with inflammatory bowel diseases: a controlled trial of a multifaceted intervention in two German cities.

PURPOSE: Many recommendations from clinical practice guidelines are not implemented. We aimed to develop and evaluate a multifaceted strategy for the implementation of guidelines for Crohn's disease (CD) and ulcerative colitis (UC). METHODS: In the intervention region (Berlin, Germany), a continuing medical education course was held, brief guidelines for practice were distributed to all family physicians and gastroenterologists, and patient guidelines were distributed to all surveyed patients. Educational outreach visits with local opinion leaders were also conducted. No specific interventions were performed in the control region (Hamburg, Germany). Prior to the intervention and 1 year later, 1900 members of three statutory sickness funds were asked about their treatment according to guidelines with (1) long-term aminosalicylates and (2) immunosuppressants, (3) whether they took long-term glucocorticoids for maintenance of remission, (4) if they smoked, in CD patients, and (5) about the surveillance colonoscopies, in UC patients. RESULTS: Response rate after implementation was 20.1%. Responders differed between intervention and control region by age and by distribution between patients with UC or CD. After 1 year, more patients were treated according to clinical practice guidelines in the control region than in the intervention region. More patients in the intervention region took immunosuppressants after 1 year, and fewer had a surveillance colonoscopy. However, no before-after comparison was statistically significant. CONCLUSIONS: This implementation strategy of UC and CD guidelines did not result in a statistically significant effect. Future implementation of guidelines for inflammatory bowel disease might need thorough evaluation of barriers and the support of theory-based concepts.

Guideline recommendations for treatment of patients with inflammatory bowel diseases are not implemented in clinical practice-results of a non-representative survey.

PURPOSE: There is a growing evidence for over-, under-, or misuse of health care in patients with inflammatory bowel disease. Most studies looked at treatment variability or used quality measures, which mostly capture supportive interventions rather than treatment of IBD in itself. We aimed to evaluate if current recommendations in clinical practice guidelines regarding the medical treatment of patients with inflammatory bowel diseases are being followed in Germany. METHODS: A questionnaire was sent to 1901 patients insured with two large German statutory sickness funds and an ICD 10 diagnosis of Crohn's disease (CD) or ulcerative colitis (UC). The questionnaire asked about drug treatment, indications for drug treatment, provision of surveillance endoscopies in ulcerative colitis patients, and smoking status in Crohn's disease patients. RESULTS: Out of 460 evaluable patients, 62.4% of UC patients and 53.9% of CD patients were treated with mesalamine according to guidelines, 91.3% of all patients were treated with glucocorticoids according to guideline recommendations, while only 75.6% received recommended immunosuppressive treatment. Of UC patients, 94.5% had surveillance colonoscopies at the recommended interval and 58.8% of CD patients were non-smokers. No predictor for overall treatment according to guidelines could be found while being of age older than 60 or being treated outside of a dedicated IBD clinic was associated with less immunosuppressive treatment. CONCLUSIONS: A large proportion of patients with IBD do not receive drug treatment in accordance with clinical practice guidelines. Quality improvement measures are much needed.

Moving window growth-A method to characterize the dynamic growth of crops in the context of bird abundance dynamics with the example of Skylark (Alauda arvensis).

Agricultural field crops differ in their vegetation height, coverage, and temporal development, affecting the abundances of bird species, which are often used as bioindicators. Although this relationship has been observed, no significant methodology exists to describe the dynamics of field crop growth on a landscape scale in connection with the abundance of indicator bird species that allows meaningful interpretation of bird abundance data with respect to crop vegetation parameters during the breeding season. In a field observation program, we monitored 2,900 ha of agricultural landscape to represent both the crop growth processes and the bird abundances. We measured these two parameters in the study area, dominated by winter wheat, winter rapeseed, maize, and fallow fields, and adapted the moving window approach to a new method of "moving window growth" to describe the dynamic development of height and coverage of the crops over time. Simultaneously, Skylarks (Alauda arvensis) territorial behavior was measured concurrently on the same fields and crops. Their dynamic abundance was documented over the breeding season. To test the relationship between crop growth and development and bird abundance, we applied a generalized linear model (GLM) in two ways: (a) without differentiation of crop species and (b) with differentiation of crop species. We found significant relationships between bird abundance and vegetation height and coverage with respect to both individual parameters and their interactions, even without differentiation of the agricultural crops. In general, increasing vegetation height and coverage, especially the interaction, led to decreasing bird abundance values. The model quality increased significantly by including differentiation of specific crops as an explanatory variable indicating a non-homogenous situation between crops. Separate models for individual crop species revealed larger differences in model quality with best and least goodness of fit values for fallow fields and winter rapeseed, respectively. Because of the clear interactions between bird abundance, type of field crop, and vegetation height and coverage, it follows that both habitat suitability assessments of arable fields and the definition of favorable vegetation structures for farmland birds should be crop species-specific.

Transmission of toxigenic Corynebacterium diphtheriae by a fully immunised resident returning from a visit to West Africa, United Kingdom, 2017.

In early 2017, a United Kingdom (UK)-born person in their 20s presented with a skin ulcer on the foot 3 weeks after returning from Ghana. The patient had last received a diphtheria-containing vaccine in 2013, completing the recommended course. MALDI-TOF of a cutaneous swab identified Corynebacterium diphtheriae. Real-time PCR ascertained the species and presence of the diphtheria toxin gene. An Elek test confirmed toxigenicity. The isolate was macrolide sensitive and penicillin resistant. The local Public Health England (PHE) Health Protection Team obtained the patient's clinical history and traced contacts to inform appropriate public health action. One close contact (in their early 80s with uncertain immunisation status who had not recently travelled) had a positive throat swab for toxigenic C. diphtheriae and reported a history of mild coryzal symptoms. Multilocus sequence typing revealed that strains from the index case and contact had Sequence Type 463. Diphtheria is extremely rare in the UK due to high vaccine coverage and this is the first documented transmission in 30 years. Clinicians and laboratory staff should remain highly suspicious of lesions in overseas travellers, even when patients are fully vaccinated. Older individuals who might not have completed a full immunisation course may have higher diphtheria susceptibility.

Secondary sclerosing cholangitis in cardiac surgical patients: A complication with a dismal prognosis.

OBJECTIVES: Secondary sclerosing cholangitis in critically ill patients is a rapidly progressing disease leading to biliary fibrosis and cirrhosis. We describe the course of sclerosing cholangitis in critically ill patients after cardiac surgery and compare this with matched patients. METHODS: A retrospective search for "secondary sclerosing cholangitis" and "liver and/or hepatic failure" in all adult patients (aged 18-93 years) who underwent cardiac surgery from April 2007 to March 2016 identified 192 of 8625 patients. Of those, 12 were diagnosed with sclerosing cholangitis in critically ill patients (incidence, 0.14%). A 3:1 matching was performed. Laboratory values, pharmacologic requirements, ventilation times, mechanical circulatory support, and endoscopic retrograde cholangiopancreatography studies were extracted from the hospital database. RESULTS: A total of 9 men and 3 women were affected (age 71 years; range, 59.8-75.5 years). Critically ill patients with sclerosing cholangitis required vasoconstrictors and inotropes longer than control patients (norepinephrine 356.5 hours [264.5-621] vs 68 hours [15-132.5], P = .003; enoximone 177 hours [124.3-249.5] vs 48.5 hours [12-81 hours], P < .001, respectively). Critically ill patients with sclerosing cholangitis had longer intubation time (628.5 hours [377.3-883] vs 25 hours [9.8-117.5]; P < .001) and more surgical revisions (3 [2.5-6] vs 1 [0-2], P = .003) than the matching group. Bilirubin (23.3 mg/dL [14.4-32.9] vs 1 mg/dL [0.6-2.7]; P < .001), gamma-glutamyltransferase (1082.3 U/L [259.5-2265.7] vs 53.8 U/L [35.1-146]; P < .001), and alkaline phosphatase (751.5 U/L [372-1722.3] vs 80.5 U/L [53.3-122]; P < .001) were higher in critically ill patients with sclerosing cholangitis. One critically ill patient with sclerosing cholangitis underwent successful liver transplantation. A total of 11 patients sclerosing cholangitis died (92%) versus 12 patients (33%, P < .001) in the control group. CONCLUSIONS: Sclerosing cholangitis in critically ill patients is a fatal complication in patients undergoing cardiac surgery who have a complicated postoperative course with prolonged vasoconstrictor, inotropic, and respiratory therapy, or who require frequent surgical revisions. Liver transplantation remains the only curative option but is often precluded by the age and critical state of patients undergoing cardiac surgery.

Self-collected buccal swabs and rapid, real-time PCR during a large measles outbreak in Wales: Evidence for the protective effect of prior MMR immunisation.

BACKGROUND: We describe the laboratory response to a large measles outbreak that occurred during 2012-2013 centred in mid and west Wales, UK. OBJECTIVES: To demonstrate the impact of rapid measles testing on the management of a large outbreak, to show the complex molecular epidemiology and determine the role of previous MMR immunisation on a large cohort of exposed people. STUDY DESIGN: Results from oral fluid antibody testing and self-collected buccal swabs tested by real-time PCR were reconciled and analysed to determine level of agreement and to calculate MMR vaccine efficacy during the outbreak. RESULTS: During the outbreak 1435 notifications of measles were received from across Wales. Samples were received from 70% of notified cases with a positivity rate of 56% within the outbreak compared to 15% for the rest of Wales. Measles RNA was detected in 53 cases with previous history of MMR immunisation, but viral loads were lower than those detected in unimmunised cases. The molecular epidemiology showed at least two distinct D8 strains of measles virus were introduced into Wales along with a separate introduction of a B3 strain outside the outbreak area. CONCLUSION: Molecular testing of all notified measles cases offers the most rapid way of confirming the introduction of measles into a population potentially before secondary transmission has already occurred. The outbreak data confirms the protective effect of the MMR vaccine with vaccine efficacy calculated at 96% for one dose and 99% for two doses supporting the WHO recommendations for a two dose MMR immunisation schedule.