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Background: During the current second wave of COVID-19, the radiologists are expected to face great challenges in differentiation between COVID-19 and other virulent influenza viruses, mainly H1N1. Accordingly, this study was performed in order to find any differentiating CT criteria that would help during the expected clinical overlap during the current Influenza season.
Results: This study was retrospectively conducted during the period from June till November 2020, on acute symptomatic 130 patients with no history of previous pulmonary diseases; 65 patients had positive PCR for COVID-19 including 50 mild patients and 15 critical or severe patients; meanwhile, the other 65 patients had positive PCR for H1N1 including 50 mild patients and 15 critical or severe patients. They included 74 males and 56 females (56.9%:43.1%). Their age ranged 14–90 years (mean age 38.9 ± 20.3 SD). HRCT findings were analyzed by four expert consultant radiologists in consensus. All patients with COVID-19 showed parenchymal or alveolar HRCT findings; only one of them had associated airway involvement. Among the 65 patients with H1N1; 56 patients (86.2%) had parenchymal or alveolar HRCT findings while six patients (9.2%) presented only by HRCT signs of airway involvement and three patients (4.6%) had mixed parenchymal and airway involvement. Regarding HRCT findings of airway involvement (namely tree in bud nodules, air trapping, bronchial wall thickening, traction bronchiectasis, and mucous plugging), all showed significant p value (ranging from 0.008 to 0.04). On the other hand, HRCT findings of parenchymal or alveolar involvement (mainly ground glass opacities) showed no significant relation.
Conclusion: HRCT can help in differentiation between non-severe COVID-19 and H1N1 based on signs of airway involvement.
The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity
(2017)
Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics. However, there is no approved pharmacological treatment for CIPN available. Among other substances, oxaliplatin causes CIPN in up to 80% of treated patients. Here, we report the involvement of the G-protein coupled receptor G2A (GPR132) in oxaliplatin-induced neuropathic pain in mice. We found that mice deficient in the G2A-receptor show decreased mechanical hypersensitivity after oxaliplatin treatment. Lipid ligands of G2A were found in increased concentrations in the sciatic nerve and dorsal root ganglia of oxaliplatin treated mice. Calcium imaging and patch-clamp experiments show that G2A activation sensitizes the ligand-gated ion channel TRPV1 in sensory neurons via activation of PKC. Based on these findings, we conclude that targeting G2A may be a promising approach to reduce oxaliplatin-induced TRPV1-sensitization and the hyperexcitability of sensory neurons and thereby to reduce pain in patients treated with this chemotherapeutic agent.
Highligthts
• Marburg virus infects and replicates in primary human proximal tubular cells (PTC).
• Transcriptome analyses at multiple time points revealed a profound inflammatory response by IFNα, -y and TNFα signaling.
• Among the strongly downregulated gene sets were targets of the transcription factors MYC and E2F, the G2M checkpoint, as well as oxidative phosphorylation.
• Importantly, the downregulated factors comprise PGC-1α, a key factor in mitochondrial biogenesis and renal energy homeostasis, to be substantially downregulated in MARV-infected PTC.
• Our results suggest inflammation-induced changes in tubular energy metabolism as a possible factor in MARV-associated tubular dysfunction.
Abstract
Marburg virus, a member of the Filoviridae, is the causative agent of Marburg virus disease (MVD), a hemorrhagic fever with a case fatality rate of up to 90 %. Acute kidney injury is common in MVD and is associated with increased mortality, but its pathogenesis in MVD remains poorly understood. Interestingly, autopsies show the presence of viral proteins in different parts of the nephron, particularly in proximal tubular cells (PTC). These findings suggest a potential role for the virus in the development of MVD-related kidney injury. To shed light on this effect, we infected primary human PTC with Lake Victoria Marburg virus and conducted transcriptomic analysis at multiple time points. Unexpectedly, infection did not induce marked cytopathic effects in primary tubular cells at 20 and 40 h post infection. However, gene expression analysis revealed robust renal viral replication and dysregulation of genes essential for different cellular functions. The gene sets mainly downregulated in PTC were associated with the targets of the transcription factors MYC and E2F, DNA repair, the G2M checkpoint, as well as oxidative phosphorylation. Importantly, the downregulated factors comprise PGC-1α, a well-known factor in acute and chronic kidney injury. By contrast, the most highly upregulated gene sets were those related to the inflammatory response and cholesterol homeostasis. In conclusion, Marburg virus infects and replicates in human primary PTC and induces downregulation of processes known to be relevant for acute kidney injury as well as a strong inflammatory response.
The human immune system is determined by the functionality of the human lymph node. With the use of high-throughput techniques in clinical diagnostics, a large number of data is currently collected. The new data on the spatiotemporal organization of cells offers new possibilities to build a mathematical model of the human lymph node - a virtual lymph node. The virtual lymph node can be applied to simulate drug responses and may be used in clinical diagnosis. Here, we review mathematical models of the human lymph node from the viewpoint of cellular processes. Starting with classical methods, such as systems of differential equations, we discuss the values of different levels of abstraction and methods in the range from artificial intelligence techniques formalism.
Highlights
• Constrictional structures range from dome-and-basin folds to coeval folds and boudins.
• Under bulk constriction, the competent layer rotates slower than a passive plane.
• Extension-parallel and –perpendicular folds grow simultaneously.
• Extension-perpendicular folds affect previous boudins.
Abstract
We conducted scaled analogue modelling to show the influence of varying single layer initial orientation on the geometry of folds and boudins in a bulk constrictional strain field. The initial angle between the plane of shortening and the competent layer (θZ(i)) was incrementally increased from 0° to 90° by multiples of 11.25°. While the amount of layer thickening decreased with increasing θZ(i), the deformation structures produced range from pure dome-and-basin folds to coeval folds and boudins. Based on the attitude of fold axes, there are extension-parallel (FEPR) and extension-perpendicular (FEPP) folds, with axes subparallel and subperpendicular to the principal stretching axis (X), respectively. Coeval growth of FEPR folds and boudins occurred when θZ(i) > ca. 25°. The FEPP folds can be subdivided into a first type which affect the entire layer (if θZ(i) ranges between 11.25 and 78.75°) and a second type, referred to as FBEPP folds, which are affecting pre-existing boudins if θZ(i) > 45°. The interlimb angle of all types of folds increases with increasing θZ(i). Folds and boudins similar to the ones produced in this study can be found in salt domes and in tectonites of subduction zones.
Background/Objective: Evidence-based clinical pathways can be a useful tool for guideline implementation. However, there seem to be barriers to the use of clinical pathways. The aim of the present questionnaire survey was to assess the perceived usability of the clinical pathway “Overweight/obesity in children and adolescents at primary care level” and to identify factors promoting and hindering the use of the clinical pathway.
Methods: In January 2020, an online questionnaire survey was sent out to 3,916 general practitioners and 470 pediatricians in Austria. The data collected were analysed descriptively.
Results: A total of 148 people took part in the questionnaire survey (response rate 3.7 %). The majority of respondents indicated that they, in general, perceive evidence-based clinical pathways as helpful (90 %) and also make use of them (57 %). Few respondents (9 %) felt well-informed about new clinical pathways developed in Austria. Most of the respondents considered the clinical pathway “Overweight/obesity in children and adolescents at primary care level” as a useful support (60 %), as a reference work (72 %) or as a facilitator for justifying their approach to their patients (68 %). However, a large proportion of the respondents stated that the clinical pathway is not easily applicable in everyday practice. The three most frequently cited barriers to using the clinical pathway were lack of time resources, lack of structures and lack of financial incentives. Other display and access options (e. g., individualisation, integration into practice software) were most frequently cited as factors that might promote the use of the pathway.
Conclusion: Although the majority of the respondents had positive expectations regarding the use of the clinical pathway “Overweight/obesity in children and adolescents at primary care level”, many of them still perceived its usability in everyday clinical practice as difficult. The necessary next steps to improve the use of evidence-based clinical pathways seem to be: an economic and practicable design, easy accessibility of clinical pathways and the creation of framework conditions that facilitate their use in everyday practice.
Although exercise guidelines now recommend exercise for patients with MCI, the long-term effects of exercise in patients with MCI has not been reviewed systematically. The aim was to assess (1) the effectiveness of exercise and physical activity (EXPA) interventions in improving long-term patient-relevant cognitive and non-cognitive outcomes in people with mild cognitive impairment, (2) how well the included trials reported details of the intervention, and (3) the extent to which reported endpoints were in line with patient preferences that were assessed in patient workshops. Following PRISMA guidelines, we performed a systematic review and meta-analysis including randomized controlled trials. A total of ten studies were included after searching in six electronic sources from 1995 onwards. There is a trend that 6 + -month EXPA interventions improve global cognition 12 months after initiation. Evidence on long-term effects of EXPA interventions on non-cognitive health outcomes could not be meaningfully pooled and the individual studies reported mixed results. Workshop participants considered freedom from pain and stress, mood, motivation and self-efficacy to be important, but these outcomes were rarely addressed. Too little information is available on intervention details for EXPA programs to be replicated and confidently recommended for patients with MCI. PROSPERO registration in December, 2021 (CRD42021287166).
Objectives: Patient-level factors that influence compliance with a recommendation for CBT in nursing home residents diagnosed with depression were identified.
Methods: Within a cluster-randomized trial on stepped care for depression in nursing homes (DAVOS-study, Trial registration: DRKS00015686), participants received an intake interview administered by a licensed psychotherapist. If psychotherapy was required, patients were offered a referral for CBT. Sociodemographic characteristics, severity of depression, loneliness, physical health, antidepressant medication, prior experience with psychotherapy, and attitudes towards own aging were assessed. A binary regression determined predictors of compliance with referral.
Results: Of 123 residents receiving an intake interview, 80 were recommended a CBT. Forty-seven patients (58.8 %) followed the recommendation. The binary logistic regression model on compliance with recommended CBT was significant, χ2(9) = 21.64, p = .010. Significant predictors were age (Odds Ratio (OR) = 0.9; 95 % Confidence Interval (CI) = 0.82, 0.99; p = .024) and depression (OR = 1.33; 95 % CI = 1.08, 1.65; p = .008).
Conclusion: Within the implemented setting compliance rate was comparable to other age groups. Future interventions should include detailed psychoeducation on the benefits of psychotherapy on mild depressive symptoms in older age and evidence-based interventions to address the stigma of depression. Interventions such as reminiscence-based methods or problem-solving could be useful to increase compliance with referral, especially in very old patients (80+). Language barriers and a culturally sensitive approach should be considered when screening residents.
Association of mortality and early tracheostomy in patients with COVID-19: a retrospective analysis
(2022)
COVID-19 adds to the complexity of optimal timing for tracheostomy. Over the course of this pandemic, and expanded knowledge of the disease, many centers have changed their operating procedures and performed an early tracheostomy. We studied the data on early and delayed tracheostomy regarding patient outcome such as mortality. We performed a retrospective analysis of all tracheostomies at our institution in patients diagnosed with COVID-19 from March 2020 to June 2021. Time from intubation to tracheostomy and mortality of early (≤ 10 days) vs. late (> 10 days) tracheostomy were the primary objectives of this study. We used mixed cox-regression models to calculate the effect of distinct variables on events. We studied 117 tracheostomies. Intubation to tracheostomy shortened significantly (Spearman’s correlation coefficient; rho = − 0.44, p ≤ 0.001) during the course of this pandemic. Early tracheostomy was associated with a significant increase in mortality in uni- and multivariate analysis (Hazard ratio 1.83, 95% CI 1.07–3.17, p = 0.029). The timing of tracheostomy in COVID-19 patients has a potentially critical impact on mortality. The timing of tracheostomy has changed during this pandemic tending to be performed earlier. Future prospective research is necessary to substantiate these results.
Aim: To evaluate the influence of the width of keratinized tissue (KT) on the prevalence of peri-implant diseases, and soft- and hard-tissue stability.
Materials and methods: Clinical studies reporting on the prevalence of peri-implant diseases (primary outcome), plaque index (PI), modified plaque index (mPI), bleeding index (mBI), bleeding on probing (BOP), probing pocket depths (PD), mucosal recession (MR), and marginal bone loss (MBL) and/or patient-reported outcomes (PROMs; secondary outcomes) were searched. The weighted mean differences (WMD) were estimated for the assessed clinical and radiographic parameters by employing a random-effect model that considered different KT widths (i.e., <2 and ≥2 mm).
Results: Twenty-two articles describing 21 studies (15 cross-sectional, five longitudinal comparative studies, and one case series with pre–post design) with an overall high to low risk of bias were included. Peri-implant mucositis and peri-implantitis affected 20.8% to 42% and at 10.5% to 44% of the implants with reduced or absent KT (i.e., <2 mm or 0 mm). The corresponding values at the implant sites with KT width of ≥2 mm or >0 mm were 20.5% to 53% and 5.1% to 8%, respectively. Significant differences between implants with KT < 2 mm and those with KT ≥ 2 mm were revealed for WMD for BOP, mPI, PI, MBL, and MR all favoring implants with KT ≥ 2 mm.
Conclusion: Reduced KT width is associated with an increased prevalence of peri-implantitis, plaque accumulation, soft-tissue inflammation, mucosal recession, marginal bone loss, and greater patient discomfort.