Itch, sleep loss, depressive symptoms, fatigue, and productivity loss in patients with moderate-to-severe atopic dermatitis: Analyses of TREATgermany registry data.

BACKGROUND: TREATgermany is a multicenter registry including patients with moderate-to-severe atopic dermatitis (AD) from currently 74 study centers (university clinics, hospitals and practices) in Germany. As of August 31, 2021, 1,230 adult patients were enrolled. METHODS: In TREATgermany, patients and physicians fill in questionnaires pertaining to symptoms, disease severity, quality of life, depressiveness, and fatigue. In particular, limitations in work performance are assessed using the Work Limitations Questionnaire (WLQ). To assess associations between occupational performance/work limitations and symptoms, correlations and regression models were calculated. RESULTS: The examined sample of 228 employed patients reported an average of 6% at-work productivity loss within the past two weeks prior to enrolment in the registry. The WLQ productivity loss score was moderately associated with itch (r = 0.32) and sleep loss (r = 0.39) and strongly associated with depressive symptoms (r = 0.68) and fatigue (r = 0.60). CONCLUSIONS: The analyses of the registry data show that moderate-to-severe atopic dermatitis has a negative impact on the work productivity of the patients. The analyses further point out the relevant associations between work productivity, depressive symptoms, and fatigue highlighting the disease burden caused by the psychological components of AD.

Functional characterization, localization, and inhibitor sensitivity of the TPR-FGFR1 fusion in 8p11 myeloproliferative syndrome.

Myeloid and lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) abnormalities, also known as 8p11 myeloproliferative syndrome (EMS), represent rare and aggressive disorders, associated with chromosomal aberrations that lead to the fusion of FGFR1 to different partner genes. We report on a third patient with a fusion of the translocated promoter region (TPR) gene, a component of the nuclear pore complex, to FGFR1 due to a novel ins(1;8)(q25;p11p23). The fact that this fusion is a rare but recurrent event in EMS prompted us to examine the localization and transforming potential of the chimeric protein. TPR-FGFR1 localizes in the cytoplasm, although the nuclear pore localization signal of TPR is retained in the fusion protein. Furthermore, TPR-FGFR1 enables cytokine-independent survival, proliferation, and granulocytic differentiation of the interleukin-3 dependent myeloid progenitor cell line 32Dcl3, reflecting the chronic phase of EMS characterized by myeloid hyperplasia. 32Dcl3 cells transformed with the TPR-FGFR1 fusion and treated with increasing concentrations of the tyrosine kinase inhibitors ponatinib (AP24534) and infigratinib (NVP-BGJ398) displayed reduced survival and proliferation with IC50 values of 49.8 and 7.7 nM, respectively. Ponatinib, a multitargeted tyrosine kinase inhibitor, is already shown to be effective against several FGFR1-fusion kinases. Infigratinib, tested only against FGFR1OP2-FGFR1 to date, is also efficient against TPR-FGFR1. Taking its high specificity for FGFRs into account, infigratinib could be beneficial for EMS patients and should be further investigated for the treatment of myeloproliferative neoplasms with FGFR1 abnormalities.

Prioritization and Resource Allocation in the Context of the COVID-19 Pandemic: Recommendations for Colorectal and Pancreatic Cancer in Germany.

In the context of the COVID-19 pandemic, there has been a scarcity of resources with various effects on the care of cancer patients. This paper provides an English summary of a German guideline on prioritization and resource allocation for colorectal and pancreatic cancer in the context of the pandemic. Based on a selective literature review as well as empirical and ethical analyses, the research team of the CancerCOVID Consortium drafted recommendations for prioritizing diagnostic and treatment measures for both entities. The final version of the guideline received consent from the executive boards of nine societies of the Association of Scientific Medical Societies in Germany (AWMF), 20 further professional organizations and 22 other experts from various disciplines as well as patient representatives. The guiding principle for the prioritization of decisions is the minimization of harm. Prioritization decisions to fulfill this overall goal should be guided by (1) the urgency relevant to avoid or reduce harm, (2) the likelihood of success of the diagnostic or therapeutic measure advised, and (3) the availability of alternative treatment options. In the event of a relevant risk of harm as a result of prioritization, these decisions should be made by means of a team approach. Gender, age, disability, ethnicity, origin, and other social characteristics, such as social or insurance status, as well as the vehemence of a patient's treatment request and SARS-CoV-2 vaccination status should not be used as prioritization criteria. The guideline provides concrete recommendations for (1) diagnostic procedures, (2) surgical procedures for cancer, and (3) systemic treatment and radiotherapy in patients with colorectal or pancreatic cancer within the context of the German healthcare system.

Mental burden and moral distress among oncologists and oncology nurses in Germany during the third wave of the COVID-19 pandemic: a cross-sectional survey.

PURPOSE: There is evidence for mental burden and moral distress among healthcare workers during the pandemic. However, there is scarcity of analyses regarding possible correlations of mental burden and moral distress in this context. This study provides data to quantify mental burden and possible associations with moral distress among physicians and nurses working in oncology in Germany. METHODS: We conducted a cross-sectional online survey with physicians and nurses working in oncology in Germany between March and July 2021. Next to sociodemographic characteristics and working conditions, mental burden and moral distress were assessed using standardized instruments. Binary multivariate logistic regression using the enter method was performed in order to explore the relationship between mental burden and moral distress. RESULTS: 121 physicians and 125 nurses were included in the study. Prevalence of clinically relevant depressive symptoms, anxiety, somatic symptoms, burnout symptoms and moral distress was 19.2, 14.5, 12.7, 46.0 and 34.7% in physicians and 41.4, 24.0, 46.8, 46.6 and 60.0% in nurses respectively. Mental burden was significantly associated with moral distress, being female/diverse, younger age < 40 and increase in workload. Nurses who felt sufficiently protected from COVID-19 reported significantly less moral distress. CONCLUSION: To improve pandemic resilience, there is a need to ensure safe working environment including psychosocial support. Further evidence on risk and protective factors for moral distress is needed to be able to develop and implement strategies to protect healthcare workers within and beyond the pandemic.

Enhancing Anticoagulation Monitoring and Therapy in Patients Undergoing Microvascular Reconstruction in Maxillofacial Surgery: A Prospective Observational Trial.

BACKGROUND: In reconstructive surgery, loss of a microvascular free flap due to perfusion disorders, especially thrombosis, is a serious complication. In recent years, viscoelastic testing (VET) has become increasingly important in point-of-care (POC) anticoagulation monitoring. This paper describes a protocol for enhanced anticoagulation monitoring during maxillofacial flap surgery. OBJECTIVE: The aim of the study will be to evaluate, in a controlled setting, the predictive value of POC devices for the type of flap perfusion disorders due to thrombosis or bleeding. VET, Platelet monitoring (PM) and standard laboratory tests (SLT) are comparatively examined. METHODS/DESIGN: This study is an investigator-initiated prospective trial in 100 patients undergoing maxillofacial surgery. Patients who undergo reconstructive surgery using microvascular-free flaps will be consecutively enrolled in the study. All patients provide blood samples for VET, PM and SLT at defined time points. The primary outcome is defined as free flap loss during the hospital stay. Statistical analyses will be performed using t-tests, including the Bonferroni adjustment for multiple comparisons. DISCUSSION: This study will help clarify whether VET can improve individualized patient care in reconstruction surgery. A better understanding of coagulation in relation to flap perfusion disorders may allow real-time adaption of antithrombotic strategies and potentially prevent flap complications.

Evaluation of Flexible and Integrative Psychiatric Treatment Models in Germany-A Mixed-Method Patient and Staff-Oriented Exploratory Study.

Contrary to the practice in some countries, access to flexible and integrated forms of psychiatric care (FIT models) is limited in Germany. Several legislations have been introduced to improve this situation, notably the recent §64b (flexible and integrative treatment model; FIT64b) of the German Social Code, which allows for a capitation-based accounting of fees for services. The aim of this study was to explore the effects of FIT64b implementation on various stakeholders (patients, informal caregivers and staff) in 12 psychiatric hospital departments across Germany. Structural as well as quantitative and qualitative data are included, with integration of different methodological approaches. In all departments, the implementation of the new accounting system resulted into a relatively stable set of structural and processual changes where rigid forms of mainly inpatient care shifted to more flexible and integrated types of outpatient and outreach treatments. These changes were more likely to be perceived by patients and staff, and likewise received better evaluations, in those departments showing higher level or longer duration of implementation. Patients' evaluations, furthermore, were largely influenced by the advent of continuous forms of care, better accessibility, and by their degree of autonomy in steering of their services.

A patient severely affected by spinal neurofibromas carries a recurrent splice site mutation in the NF1 gene.

Spinal neurofibromas are found in up to 38% of NF1 patients. However, they cause clinical implications only in about 5% of the patients. In contrast, multiple symptomatic spinal neurofibromas are the main clinical finding in patients with familial spinal neurofibromatosis. Familial spinal neurofibromatosis has been considered to be a distinct clinical form of neurofibromatosis. Linkage analysis in two families and identification of a NF1 gene mutation in a third family strongly associate spinal neurofibromatosis with the NF1 gene. We describe a NF1 patient who satisfies the NIH diagnostic criteria and has severe spinal involvement with bilateral spinal root neurofibromas at every level. A recurrent splice site mutation (IVS19b-3C>G) was identified in the NF1 gene in the patient. We discuss the possibility that the clinical picture of this patient represents an additional example of spinal neurofibromatosis. By comparison of the clinical expression of NF1 in this patient and that in another patient with the identical mutation the hypothesis that spinal neurofibromatosis is associated with a particular mutation is highly unlikely. The involvement of other genes linked to the NF1 gene or modifying genes is currently the most likely explanation for the clinical phenotype of spinal neurofibromatosis.

Primary gastric mantle cell lymphoma in a patient with long standing history of Crohn's disease.

The stomach is the most common site of primary extranodal lymphoma. Virtually all cases are of B-cell lineage, including extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma) and diffuse large B-cell lymphomas. While secondary gastric involvement from nodal mantle cell lymphoma (MCL) or in the course of primary intestinal MCL (lymphomatous polyposis) have been described, primary gastric MCL has not been reported so far. A 74-year-old man with a 14 year-history of Crohn's disease was admitted at a general hospital due to epigastric pain refractory to therapy with proton-pump inhibitors. Endoscopy disclosed a large polypoid tumor with an ulcerated surface at the greater curvature of the gastric antrum. Endosonography demonstrated the tumor to be limited to the stomach with only local lymph node involvement. Histology of gastric biopsies revealed a dense atypical lymphoid infiltrate composed of small to medium sized cells with slightly irregular nuclear contours. Immunohistochemichally, the cells were positive for CD20, CD79a, CD43 and cyclin D1, but negative for CD3, CD5 and bcl-6. They stained for IgM and showed lambda-light chain restriction. Fluorescent in situ hybridisation studies showed the presence of the t(11;14) characteristic for MCL. No further evidence of lymphoma was found on extensive clinical staging. Following chemotherapy the patient is disease free at 24 months after diagnosis. This is the first case of a primary localized gastric MCL. The lack of CD5 expression underscores the importance of performing thorough immunohistochemical studies, particularly to exclude MALT lymphoma.

Acute effects of cigarette smoking on cerebral oxygenation and hemodynamics: a combined study with near-infrared spectroscopy and transcranial Doppler sonography.

Cigarette smoking has been shown to increase cerebral blood flow velocity (CBFV) and reduce vasomotor reactivity temporarily. The aim of our study was to clarify whether this results from dilation of resistance vessels alone with subsequent increase in regional cerebral blood flow (rCBF), or an additional constriction of basal cerebral arteries. In 24 healthy smokers (mean age+/-S.D., 32.7+/-10.5 years), cerebral oxygenation and hemodynamics were monitored by transcranial Doppler sonography and near-infrared spectroscopy before, during, and after smoking a cigarette (nicotine 0.9 mg). We simultaneously recorded CBFV of both middle cerebral arteries, mean arterial blood pressure, skin blood flow, end-tidal CO(2), changes in concentration of cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (micromol/l), and a cerebral tissue oxygenation index. Smoking increased CBFV (p<0.01), oxyhemoglobin (p<0.01), and total hemoglobin (p<0.01). After smoking, the increase in CBFV and total hemoglobin persisted (p<0.01), while oxyhemoglobin returned to baseline. Deoxyhemoglobin and cerebral tissue oxygenation index did not change during the whole procedure. During, but not after smoking, CBFV increase was correlated to ipsilateral changes in oxyhemoglobin and total hemoglobin (p<0.05). The increase in oxyhemoglobin only during smoking and the lack of changes in deoxyhemoglobin and cerebral tissue oxygenation index indicate that smoking did not substantially increase rCBF. The smoking-induced elevation in CBFV might therefore be due to an additional constriction of the middle cerebral artery. The combined effects of smoking on basal cerebral arteries and arterioles might contribute to the increased stroke risk in smokers.

Evaluation of a Frequentist Hierarchical Model to Estimate Prevalence when sampling from a large geographic area using Pool Screening.

We present a frequentist Bernoulli-Beta hierarchical model to relax the constant prevalence assumption underlying the traditional prevalence estimation approach based on pooled data. This assumption is called into question when sampling from a large geographic area. Pool screening is a method that combines individual items into pools. Each pool will either test positive (at least one of the items is positive) or negative (all items are negative). Pool screening is commonly applied to the study of tropical diseases where pools consist of vectors (e.g. black flies) that can transmit the disease. The goal is to estimate the proportion of infected vectors. Intermediate estimators (model parameters) and estimators of ultimate interest (pertaining to prevalence) are evaluated by standard measures of merit, such as bias, variance and mean squared error making extensive use of expansions. Using the hierarchical model an investigator can determine the probability of the prevalence being below a prespecified threshold value, a value at which no reemergence of the disease is expected. An investigation into the least biased choice of the α parameter in the Beta (α, ß) prevalence distribution leads to the choice of α = 1.

In-hospital cardiology consultation and evidence-based care for nursing home residents with heart failure.

OBJECTIVES: To determine the association between cardiology consultation and evidence-based care for nursing home (NH) residents with heart failure (HF). PARTICIPANTS: Hospitalized NH residents (n = 646) discharged from 106 Alabama hospitals with a primary discharge diagnosis of HF during 1998-2001. DESIGN: Observational. MEASUREMENTS OF EVIDENCE-BASED CARE: Preadmission estimation of left ventricular ejection fraction (LVEF) for patients with known HF (n = 494), in-hospital LVEF estimation for HF patients without known LVEF (n = 452), and discharge prescriptions of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs or ARBs) to systolic HF (LVEF <45%) patients discharged alive who were eligible to receive those drugs (n = 83). Eligibility for ACEIs or ARBs was defined as lack of prior allergy or adverse effect, serum creatinine lower than 2.5 mg/dL, serum potassium lower than 5.5 mEq/L, and systolic blood pressure higher than 100 mm Hg. RESULTS: Preadmission LVEF was estimated in 38% and 12% of patients receiving and not receiving cardiology consultation, respectively (adjusted odds ratio [AOR], 3.49; 95% CI, 2.16-5.66; P < .001). In-hospital LVEF was estimated in 71% and 28% of patients receiving and not receiving cardiology consultation, respectively (AOR, 6.01; 95% CI, 3.69-9.79; P < .001). ACEIs or ARBs were prescribed to 62% and 82% of patients receiving and not receiving cardiology consultation, respectively (AOR, 0.24; 95% CI, 0.07-0.81; P = .022). CONCLUSION: In-hospital cardiology consultation was associated with significantly higher odds of LVEF estimation among NH residents with HF; however, it did not translate into higher odds of discharge prescriptions for ACEIs or ARBs to NH residents with systolic HF who were eligible for the receipt of these drugs.

Accurate and flexible power calculations on the spot: Applications to genomic research.

Often investigators need to calculate power to demonstrate feasibility of proposed genetic studies for grant proposals or simply to aid in their own study planning. Frequently, power can be easily calculated using a closed form formula. However, in some situations such formulae for calculating power have not been derived and derivation on demand may be difficult if not impossible. In these situations investigators typically perform simulations specific to the study. Yet such simulations can be computationally extensive and take weeks to months depending on the circumstances. Here, we provide a simple method to rapidly estimate power when one has power estimates available for corresponding situations that differ from the situation of interest only in sample size and/or alpha (type I error) level desired. We show by application to multiple published results from the genomics field that these methods are generally very accurate and applicable to a broad range of genomic studies.

Vascular endothelial growth factor: the major factor for tumor neovascularization and edema formation in meningioma patients.

BACKGROUND: Peritumoral brain edema (PTBE) may be crucial in the clinical outcome of meningioma patients. The underlying pathogenetic key mechanism has so far not been determined. Sex, age, tumor size, location, involvement of other structures, or the histological appearance was not found to sufficiently explain PTBE formation in meningiomas. OBJECTIVE: As PTBE formation is widely accepted to be vasogenic, we investigated the role of vascular endothelial growth factor (VEGF) and pial supplying vessels in a series of World Health Organization (WHO) grade I meningiomas. METHODS: A total of 79 patients with WHO grade I meningiomas were immunohistochemically studied for VEGF and MIB-1. Pre- and postoperative magnetic resonance imaging including 3-dimensional reconstruction of 1.3-mm thick layers, with calculation of tumor and edema volume, was performed. Intraoperatively, the vascular supply and arachnoidal state were noted by the neurosurgeon. RESULTS: VEGF was found to be exclusively confined to meningioma tumor cells. We identified 4 different patterns. VEGF and supplying pial vessels were found in 14 meningioma patients, pial vascular supply only in 3, VEGF expression only in 46, and neither VEGF expression nor supplying pial vessels in 16. Only the occurrence of both pial vascular supply and tumor VEGF expression was found to be correlated with PTBE formation (P<.002). CONCLUSION: Our data suggest that VEGF may be crucial in angiogenesis and therefore indirectly in PTBE formation in World Health Organization grade I meningiomas.

Fluorescent in situ hybridization and ex vivo 1H magnetic resonance spectroscopic examinations of meningioma tumor tissue: is it possible to identify a clinically-aggressive subset of benign meningiomas?

OBJECTIVE: Although histologically benign, Grade I meningiomas can sometimes behave aggressively. The clinically-aggressive subset of Grade I meningiomas is typically indistinguishable from clinically-benign Grade I meningiomas in vivo. We compared molecular genetic and biochemical findings to clinical, pathological, and immunohistochemical information in a series of clinically-aggressive Grade I meningiomas with a series of clinically-benign meningiomas to identify characteristics that may be used to distinguish between these two groups. METHODS: Tumor tissue samples from 30 patients with Grade I meningiomas were harvested. Half of the sample was embedded in paraffin to be used for fluorescent in situ hybridization to examine aberrations of chromosomes 1p, 14q, and 22q; the other half was snap frozen and examined with proton magnetic resonance spectroscopy to identify concentrations of key metabolites in the tissue ex vivo. Clinical and pathological parameters were retrospectively reviewed as part of routine clinical management. These data were evaluated for potential unique associations with diagnostic significance. RESULTS: Molecular genetic and biochemical findings correlated with clinical behavior of the two Grade I meningioma groups. Specific chromosomal abnormalities correlated with the aggressive phenotype: homogeneous loss of 1p, homogeneous loss of 14q, and the presence of any of the examined chromosomal aberrations (P < 0.05). The presence of aberrations also influenced meningioma regrowth after subtotal resection. The ratio of choline to glutamate correlated with histopathological subtype (P < 0.05). The ratio of glutamine to glutamate, and the ratio of glycine to total glutamine and glutamate, and creatine correlated with recurrence. Alanine was decreased in meningiomas with chromosomal aberrations in tumors that recurred. CONCLUSION: Distinct molecular genetic and biochemical alterations differentiated clinically-aggressive Grade I meningiomas from clinically-benign Grade I meningiomas.

Noninvasive monitoring of cerebral oxygenation during vasomotor reactivity tests by a new near-infrared spectroscopy device.

BACKGROUND: Spatially resolved spectroscopy is a recently developed technique for noninvasive monitoring of cerebral tissue oxygenation using the photon diffusion theory. METHODS: We studied this technique with a new, commercial near-infrared spectroscopy (NIRS) device during vasomotor reactivity tests in 28 healthy volunteers (mean age 31.0 years; SD 10.6 years) and compared it with values assessed by the modified Beer-Lambert law and indices from simultaneous transcranial Doppler sonography of both middle cerebral arteries. We measured O(2) reactivity as percentage change of cerebral blood flow velocity (CBFV), as absolute change in the concentrations (measured in micromol/l) of oxygenated (HbO(2)), deoxygenated (Hb) and total hemoglobin (HbT), and as change in the tissue oxygenation index (TOI) during inhalation of 100% oxygen. CO(2) reactivity was calculated as percentage change of CBFV (NCR), as absolute change in the concentrations of HbO(2), Hb, and HbT (micromol/l), and as change in TOI (%) per 1% increase in end-tidal CO(2). RESULTS: One hundred percent oxygen inhalation lead to a decrease in CBFV (mean +/- SD: left -8.0 +/- 7.0%, p = 0.000; right -9.6 +/- 7.6%, p = 0.000), an increase in HbO(2) (0.99 +/- 1.07 micromol/l), Hbdiff (2.23 +/- 1.72 micromol/l), and TOI (3.1 +/- 1.5%), and a decrease in Hb (-1.22 +/- 0.74 micromol/l), significant from baseline values (p = 0.0000). CO(2) reactivity was: NCR left 25.4 +/- 14.7%; NCR right 25.9 +/- 13.4%; HbO(2) 1.99 +/- 0.97 micromol/l; Hb -1.24 +/- 0.81 micromol/l; HbT 0.81 +/- 1.0 micromol/l, and TOI 3.7 +/- 2.2%. O(2) reactivity in TCD did not correlate with NIRS reactivities (Pearson p > 0.05), but NCR did correlate with changes in HbO(2), Hb, and TOI (Pearson p < 0.01). TOI was closely related to indices derived from the Beer-Lambert law (Pearson p < 0.03), but not with mean arterial blood pressure or skin blood flow during vasomotor reactivity tests. CONCLUSION: Spatially resolved spectroscopy provides an encouraging, noninvasive new tool to study cerebral tissue oxygenation during vasomotor reactivity tests consistent with physiological changes.