The Efficiency of Increased HCV Testing and Treatment Strategies in Spain to Achieve Elimination Goals.

BACKGROUND: In 2015, Spain launched a national eradication strategy for hepatitis C virus (HCV), resulting in the highest treatment rate in Europe and substantial reductions in HCV prevalence. However, to achieve the goal of HCV elimination, it is necessary to scale-up the diagnosis, treatment, and management of HCV infection. OBJECTIVE: Our aim was to assess the prevalence, incidence, and cost effectiveness of scaling-up compared with status quo scenarios. METHODS: A compartmental dynamic transmission model was developed comprising of a cascade of care and a liver progression module. Cost and quality-of-life inputs were sourced from the literature. Key outcomes were the prevalence and incidence of HCV and the incremental cost per quality-adjusted life-year (QALY) and per life-year (LY). Outcomes for a hypothetical elimination strategy were compared with the status quo. RESULTS: The base-case analysis found that scaling-up testing and treatment reduced both the prevalence and incidence of HCV over time, resulting in incremental costs per QALY and LY of €13,291 and €12,285 respectively, compared with the status quo. The main drivers of the cost-effectiveness results included cost of diagnosis, cost of treatment, proportion of people who are unaware, percentage of population who inject drugs, and calibration parameters related to HCV infection prevalence. CONCLUSIONS: This analysis demonstrated that scaling-up testing and treatment with direct-acting antivirals may be an efficient strategy for reducing the incidence and prevalence of HCV and may help achieve HCV elimination goals in Spain.

Comprehensive frailty assessment with multidimensional frailty domains as a predictor of mortality among vascular and cardiac surgical patients.

Purpose: The frailty concept has become a fundamental part of daily clinical practice. In this study our purpose was to create a risk estimation method with a comprehensive aspect of patients' preoperative frailty. Patients and methods: In our prospective, observational study, patients were enrolled between September 2014 and August 2017 in the Department of Cardiac Surgery and Department of Vascular Surgery at Semmelweis University, Budapest, Hungary. A comprehensive frailty score was built from four main domains: biological, functional-nutritional, cognitive-psychological and sociological. Each domain contained numerous indicators. In addition, the EUROSCORE for cardiac patients and the Vascular POSSUM for vascular patients were calculated and adjusted for mortality. Results: Data from 228 participants were included for statistical analysis. A total of 161 patients underwent vascular surgery, and 67 underwent cardiac surgery. The preoperatively estimated mortality was not significantly different (median: 2.700, IQR (interquartile range): 2.000-4.900 vs. 3.000, IQR: 1.140-6.000, P = 0.266). The comprehensive frailty index was significantly different (0.400 (0.358-0.467) vs. 0.348 (0.303-0.460), P = 0.001). In deceased patients had elevated comprehensive frailty index (0.371 (0.316-0.445) vs. 0.423 (0.365-0.500), P < 0.001). In the multivariate Cox model an increased risk for mortality in quartiles 2, 3 and 4 compared with quartile 1 as a reference was found (AHR (95% CI): 1.974 (0.982-3.969), 2.306 (1.155-4.603), and 3.058 (1.556-6.010), respectively). Conclusion: The comprehensive frailty index developed in this study could be an important predictor of long-term mortality after vascular or cardiac surgery. Accurate frailty estimation could make the traditional risk scoring systems more accurate and reliable.

Mapping Immune Correlates and Surfaceome Genes in BRAF Mutated Colorectal Cancers.

Despite the impressive results obtained with immunotherapy in several cancer types, a significant fraction of patients remains unresponsive to these treatments. In colorectal cancer (CRC), B-RafV600 mutations have been identified in 8-15% of the patients. In this work we interrogated a public dataset to explore the surfaceome of these tumors and found that several genes, such as GP2, CLDN18, AQP5, TM4SF4, NTSR1, VNN1, and CD109, were upregulated. By performing gene set enrichment analysis, we also identified a striking upregulation of genes (CD74, LAG3, HLA-DQB1, HLA-DRB5, HLA-DMA, HLA-DMB, HLA-DPB1, HLA-DRA, HLA-DOA, FCGR2B, HLA-DQA1, HLA-DRB1, and HLA-DPA1) associated with antigen processing and presentation via MHC class II. Likewise, we found a strong correlation between PD1 and PD(L)1 expression and the presence of genes encoding for proteins involved in antigen presentation such as CD74, HLA-DPA1, and LAG3. Furthermore, a similar association was observed for the presence of dendritic cells and macrophages. Finally, a low but positive relationship was observed between tumor mutational burden and neoantigen load. Our findings support the idea that a therapeutic strategy based on the targeting of PD(L)1 together with other receptors also involved in immuno-modulation, such as LAG3, could help to improve current treatments against BRAF-mutated CRC tumors.

Evaluation of a transbronchial cryoprobe for the ablation of pulmonary nodules: an in vitro pilot study.

BACKGROUND: Ablation of malignant pulmonary nodules is a novel therapeutic option for patients who cannot undergo surgery. Current transthoracic approaches cause pneumothorax and/or bleeding in a significant number of cases. OBJECTIVE: Our purpose with this study was to evaluate cryoablation under in vitro conditions with a commercially available cryosurgery system. METHODS: We used ballistic gelatin to model the thermal conduction of lung tissue. The cryoprobe was inserted in the ballistic gelatin with two thermal sensors, they were placed 0.5 cm and 1.0. cm from the probe, respectively, temperature was measured on both sides. We used single-, double- and triple-freeze protocols to see if we could freeze it to -20 °C. RESULTS: We achieved - 18.6 ± 3.26 °C on the closer sensor (sensor 1) and - 3.7 ± 4.61 °C on the sensor further away (sensor 2) after 15 min using the single-freeze protocol. Using the dual-freeze protocol, we achieved - 23.2 ± 2,23 °C on sensor 1 and - 16.5 ± 2.82 °C on sensor 2. With the triple-freeze protocol we obtained - 23.5 ± 2.38 °C on sensor 1 and - 19.05 ± 3.22 °C on sensor 2. CONCLUSION: With dual-freeze, values above - 20 °C were achieved using nearer sensor data, but a plateau phase occurred as with continuous freezing. Using triple freeze, we reached - 20 °C at a distance of 0.5 cm from the probe, but not at 1 cm; therefore, we did not expand the diameter of the predicted necrosis zone.

The Actigraphy-Based Identification of Premorbid Latent Liability of Schizophrenia and Bipolar Disorder.

(1) Background and Goal: Several studies have investigated the association of sleep, diurnal patterns, and circadian rhythms with the presence and with the risk states of mental illnesses such as schizophrenia and bipolar disorder. The goal of our study was to examine actigraphic measures to identify features that can be extracted from them so that a machine learning model can detect premorbid latent liabilities for schizotypy and bipolarity. (2) Methods: Our team developed a small wrist-worn measurement device that collects and identifies actigraphic data based on an accelerometer. The sensors were used by carefully selected healthy participants who were divided into three groups: Control Group (C), Cyclothymia Factor Group (CFG), and Positive Schizotypy Factor Group (PSF). From the data they collected, our team performed data cleaning operations and then used the extracted metrics to generate the feature combinations deemed most effective, along with three machine learning algorithms for categorization. (3) Results: By conducting the training, we were able to identify a set of mildly correlated traits and their order of importance based on the Shapley value that had the greatest impact on the detection of bipolarity and schizotypy according to the logistic regression, Light Gradient Boost, and Random Forest algorithms. (4) Conclusions: These results were successfully compared to the results of other researchers; we had a similar differentiation in features used by others, and successfully developed new ones that might be a good complement for further research. In the future, identifying these traits may help us identify people at risk from mental disorders early in a cost-effective, automated way.

Association between Hepatic Venous Congestion and Adverse Outcomes after Cardiac Surgery.

INTRODUCTION: Hepatic venous flow patterns reflect pressure changes in the right ventricle and are also markers of systemic venous congestion. Fluid management is crucial in patients undergoing cardiac surgery. METHODS: Our goal was to determine which factors are associated with the increased congestion of the liver as measured by Doppler ultrasound in patients undergoing cardiac surgery. This prospective, observational study included 41 patients without preexisting liver disease who underwent cardiac surgery between 1 January 2021 and 30 September 2021 at a tertiary heart center. In addition to routine echocardiographic examination, we recorded the maximal velocity and velocity time integral (VTI) of the standard four waves seen in the common hepatic vein (flow profile) using Doppler ultrasound preoperatively and at the 20-24th hour of the postoperative period. The ratios of the retrograde and anterograde hepatic venous waves were calculated, and the waveforms were compared to the baseline value and expressed as a delta ratio. Demographic data, pre- and postoperative echocardiographic parameters, intraoperative variables (procedure, cardiopulmonary bypass time), postoperative factors (fluid balance, vasoactive medication requirement, ventilation time and parameters) and perioperative laboratory parameters (liver and kidney function tests, albumin) were used in the analysis. RESULTS: Of the 41 patients, 20 (48.7%) were males, and the median age of the patients was 65.9 years (IQR: 59.8-69.9 years). Retrograde VTI growth showed a correlation with positive fluid balance (0.89 (95% CI 0.785-0.995) c-index. After comparing the postoperative echocardiographic parameters of the two subgroups, right ventricular and atrial diameters were significantly greater in the "retrograde VTI growth" group. The ejection fraction and decrement in ejection fraction to preoperative parameters were significantly different between the two groups. (p = 0.001 and 0.003). Ventilation times were longer in the retrograde VTI group. The postoperative vs. baseline delta VTI ratio of the hepatic vein correlated with positive fluid balance, maximum central venous pressure, and ejection fraction. (B = -0.099, 95% CI = -0.022-0.002, p = 0.022, B = 0.011, 95% CI = 0.001-0.021, p = 0.022, B = 0.091, 95% CI = 0.052-0.213, p = 0.002, respectively.) Conclusion: The increase of the retrograde hepatic flow during the first 24 h following cardiac surgery was associated with positive fluid balance and the decrease of the right ventricular function. Measurement of venous congestion or venous abdominal insufficiency seems to be a useful tool in guiding fluid therapy and hemodynamic management.

Correction of overexposure in laser speckle contrast imaging.

Laser speckle contrast imaging (LSCI) is a method to visualize and quantify tissue perfusion and blood flow. A common flaw in LSCI variants is their sensitivity to the optical setup parameters and that they operate well only on statistics of undistorted laser speckle patterns. The signal saturation of the sensors makes the contrast calculation misleading; hence the illumination level must be well controlled. We describe the theoretical explanation for the saturation-caused degradation. We introduce a linear extrapolation method to eliminate the overexposure induced error up to an extent of 60-70% saturated pixel count. This, depending on the contrast value and use case, enables to use 3-8 times higher external illumination level with no deterioration of the contrast calculation and thus the measured blood flow index. Our method enables a higher signal-to-noise ratio in darker areas by allowing the use of higher illumination, utilizing a larger portion of the dynamic range of the sensors, and making the illumination level setting less cumbersome.

[Case report: molecular analysis of congenital glioblastoma in a newborn]. / Esettanulmány: molekuláris vizsgálatok újszülöttkori glioblasztómában.

BACKGROUND: Congenital glioblastoma (cGBM) is a brain tumor very rarely observed in newborns and young infants, and differs in several respects from glioblastoma (GBM) of childhood and adulthood. Our aim was the presentation of a cGBM case with 14 days of postnatal survival at the Pediatric Oncology Center of the Markusovszky University Teaching Hospital in 2004. We investigated formalin-fixed, paraffin-embedded autoptic tumor samples of the newborn by immunohistochemical and molecular genetic (FISH and pyrosequencing) methods. We found polysomy of chromosome 2 and 5' deletion of the ALK gene in the glioma cells by ALK FISH. This result indicates the importance of molecular analyses in the diagnostic evaluation of cGBM, and raises the possibility of a personalized, targeted therapy (crizotinib, alectinib).

Distally Tilted Implants According to the All-on-Four® Treatment Concept for the Rehabilitation of Complete Edentulism: A 3.5-Year Retrospective Radiographic Study of Clinical Outcomes and Marginal Bone Level Changes.

Bone grafting procedures during the use of dental implants may be avoided by the use of tilted implants in the maxilla and the mandible; advantages of angled implants are associated with the extension of the distal cantilever, leading to better implant survival rates. However, the bending effect on the single tilting implants may increase the marginal bone stress. The purpose of the present study was to retrospectively assess the clinical success and proximal bone loss rate following the implantation of distally tilted implants according to the All-on-Four™ prosthetic concept­based on radiographic findings­in a single-center experience, in addition to the assessment of the outcomes in the context of various clinico-epidemiological correlates. During the study period, n = 36 patients (24 males and 12 females) with complete records of periapical radiographs, received a full-arch fixed bridge supported by two axial and two distal tilted implants; overall n = 144 and n = 144 implants (Nobel B) were place in the maxilla and mandibles of patients, respectively. Mean age of patients at the time of fixture installation was 58.75 ± 13.71 years; n =11 patients presented with relevant underlying conditions/habits. To assess peri-implant bone-level changes, matched and calibrated orthopantomogram (OPT) images were taken at follow-ups after 1.5 years, 2.5 years, and 3.5 years post-restoration, and marginal bone levels were assessed on the mesio- (MA) and disto-approximal (DA) aspects. All implants were successful, resulting in a 100% overall survival rate. The radiographic mean bone loss levels at baseline (mean ± SEM) were 0.181 ± 0.011 mm and 0.178 ± 0.017 mm in the maxilla and mandible, respectively, while by the 3.5-year mark, bone loss was 0.770 ± 0.029 mm and 0.713 ± 0.026 mm in the maxilla and mandible (p > 0.05), respectively; bone-level changes were significant over time (p = 0.035 and p = 0.033). Peri-implant bone loss was more aggressive around titled distal implants versus mesial actual position implants. The effect of smoking and other underlying conditions showed significantly higher (p < 0.05) bone resorption levels when assessed on an individual implant-level, while during patient-level analysis, only a tendency was shown for higher bone loss rates for both MA and DA implants (p > 0.05). Within its limitations, our study has concluded that the use of All-on-Four™ prosthetic concept for total arch rehabilitation yields higher bone loss in association with tilted implants and, in some cases, on the MA surfaces at vertically positioned implants after >40 months in function.

Association between Preoperative Retrograde Hepatic Vein Flow and Acute Kidney Injury after Cardiac Surgery.

Key questions: Is there a predictive value of hepatic venous flow patterns for postoperative acute kidney injury (AKI) after cardiac surgery? Key findings: In patients who underwent cardiac surgery, retrograde hepatic venous waves (A, V) and their respective ratio to anterograde waves showed a strong association with postoperative AKI, defined as the percentage change of the highest postoperative serum creatinine from the baseline preoperative concentration (%ΔCr). The velocity time integral (VTI) of the retrograde A wave and the ratio of the retrograde and anterograde waves' VTI were independently associated with AKI after adjustment for disease severity. Take-home message: A higher ratio of retrograde/antegrade waves in hepatic venous retrograde waves, which are related to hepatic stasis, may predict AKI after cardiac surgery. Introduction: Hepatic venous flow patterns reflect pressure changes in the right ventricle and are also markers of systemic venous congestion. Pulsatility of the inferior caval vein was used to predict the risk of acute kidney injury (AKI) after cardiac surgery. Aims: Our objective was to evaluate the association between preoperative hepatic venous flow patterns and the risk of AKI in patients after cardiac surgery. Methods: This prospective, observational study included 98 patients without preexisting liver disease who underwent cardiac surgery between 1 January 2018, and 31 March 2020, at a tertiary heart center. In addition to a routine echocardiographic examination, we recorded the maximal velocity and velocity time integral (VTI) of the standard four waves in the common hepatic vein with Doppler ultrasound. Our primary outcome measure was postoperative AKI, defined as the percentage change of the highest postoperative serum creatinine from the baseline preoperative concentration (%ΔCr). The secondary outcome was AKI, defined by KDIGO (Kidney Disease Improving Global Outcomes) criteria. Results: The median age of the patients was 69.8 years (interquartile range [IQR 25−75] 13 years). Seventeen patients (17.3%) developed postoperative AKI based on the KDIGO. The VTI of the retrograde A waves in the hepatic veins showed a strong correlation (B: 0.714; p = 0.0001) with an increase in creatinine levels after cardiac surgery. The velocity time integral (VTI) of the A wave (B = 0.038, 95% CI = 0.025−0.051, p < 0.001) and the ratio of VTI of the retrograde and anterograde waves (B = 0.233, 95% CI = 0.112−0.356, p < 0.001) were independently associated with an increase in creatinine levels. Conclusions: The severity of hepatic venous regurgitation can be a sign of venous congestion and seems to be related to the development of AKI.

Primary Founder Mutations in the PRKDC Gene Increase Tumor Mutation Load in Colorectal Cancer.

The clonal composition of a malignant tumor strongly depends on cellular dynamics influenced by the asynchronized loss of DNA repair mechanisms. Here, our aim was to identify founder mutations leading to subsequent boosts in mutation load. The overall mutation burden in 591 colorectal cancer tumors was analyzed, including the mutation status of DNA-repair genes. The number of mutations was first determined across all patients and the proportion of genes having mutation in each percentile was ranked. Early mutations in DNA repair genes preceding a mutational expansion were designated as founder mutations. Survival analysis for gene expression was performed using microarray data with available relapse-free survival. Of the 180 genes involved in DNA repair, the top five founder mutations were in PRKDC (n = 31), ATM (n = 26), POLE (n = 18), SRCAP (n = 18), and BRCA2 (n = 15). PRKDC expression was 6.4-fold higher in tumors compared to normal samples, and higher expression led to longer relapse-free survival in 1211 patients (HR = 0.72, p = 4.4 × 10-3). In an experimental setting, the mutational load resulting from UV radiation combined with inhibition of PRKDC was analyzed. Upon treatments, the mutational load exposed a significant two-fold increase. Our results suggest PRKDC as a new key gene driving tumor heterogeneity.

Relationship between the Biofilm-Forming Capacity and Antimicrobial Resistance in Clinical Acinetobacter baumannii Isolates: Results from a Laboratory-Based In Vitro Study.

The relationship between the multidrug-resistant (MDR) phenotype and biofilm-forming capacity has been a topic of extensive interest among biomedical scientists, as these two factors may have significant influence on the outcomes of infections. The aim of the present study was to establish a possible relationship between biofilm-forming capacity and the antibiotic-resistant phenotype in clinical Acinetobacter baumannii (A. baumannii) isolates. A total of n = 309 isolates were included in this study. Antimicrobial susceptibility testing and the phenotypic detection of resistance determinants were carried out. The capacity of isolates to produce biofilms was assessed using a crystal violet microtiter-plate-based method. Resistance rates were highest for ciprofloxacin (71.19%; n = 220), levofloxacin (n = 68.61%; n = 212), and trimethoprim-sulfamethoxazole (n = 66.02%; n = 209); 42.72% (n = 132) of isolates were classified as MDR; 22.65% (n = 70) of tested isolates were positive in the modified Hodge-test; the overexpression of efflux pumps had significant effects on the susceptibilities of meropenem, gentamicin, and ciprofloxacin in 14.24% (n = 44), 6.05% (n = 19), and 27.51% (n = 85), respectively; 9.39% (n = 29), 12.29% (n = 38), 22.97% (n = 71), and 55.35% (n = 170) of isolates were non-biofilm-producing and weak, moderate, and strong biofilm producers, respectively. A numerical, but statistically not significant, difference was identified between the MDR and non-MDR isolates regarding their biofilm-forming capacity (MDR: 0.495 ± 0.309 vs. non-MDR: 0.545 ± 0.283; p = 0.072), and no association was seen between resistance to individual antibiotics and biofilm formation. Based on numerical trends, MER-resistant isolates were the strongest biofilm producers (p = 0.067). Our study emphasizes the need for additional experiments to assess the role biofilms have in the pathogenesis of A. baumannii infections.

Endocrine Management and Hormone Replacement Therapy in Cardiac Donor Management: A Retrospective Observational Study.

BACKGROUND: Pituitary dysfunction after brainstem death can cause various hormone deficiencies in potential heart donors. The aim of this study was to evaluate the relationship between hormone replacement therapy (HRT; including antidiuretic hormone analog, thyroid hormone, and methylprednisolone) in heart donors and the recipients' outcomes after heart transplantation (HTx). METHODS: We retrospectively analyzed HTxs performed between January 2012 and October 2018. Donor and recipient characteristics were retrieved with a focus on endocrine parameters and HRT. The primary outcome was primary graft dysfunction (PGD). Secondary outcomes were the 30-day and 2-year mortality of the recipients. Univariate and multivariate Cox regression analyses were applied. RESULTS: The study included 297 HTxs. PGD occurred in 56 recipients (18.9%). In the multivariable Cox analysis, methylprednisolone and thyroxine treatment in donors were associated with a lower odds for PGD (odds ratio [OR], 0.43; 95% CI, 0.19-1.01; P = .052; and OR,: 0.34; 95% CI, 0.15-0.76; P = .009, respectively). In multivariate analysis, thyroxine treatment in donors was associated with a lower odds of PGD (OR, 0.38; 95% CI, 0.17-0.86; P = .020). Donor thyroxine supplementation also had a beneficial effect on recipients' 2-year survival (OR, 0.53; 95% CI, 0.29-0.96; P = .036). CONCLUSIONS: Combined thyroxine and methylprednisolone treatment could be a protective factor against PGD. Thyroxine administration was associated with better 2-year survival in recipients.

Mini-thoracotomy in redo mitral valve surgery: safety and efficacy of a standardized procedure.

BACKGROUND: Re-operative mitral valve surgery is sometimes burdened by a greater technical difficulty and a higher complications rate than the first operation. Minimally invasive cardiac surgery has become routine, and it could significantly reduce the surgical risk in redo surgery. The objective of our retrospective observational study is to assess the results of cardiac reoperations in patients with mitral valve disease approached trough a 5-7 cm right mini-thoracotomy. METHODS: From February 2017 to December 2019, 65 patients underwent re-operative mitral valve surgery in our institution. Cardiopulmonary bypass (CPB) was started by cannulation of the femoral and jugular vein and femoral artery or alternatively right axillary artery. Patients enrolled had a mean age of 66.6±11.5 years. Patients were divided into three groups based on the procedure adopted: external aortic cross-clamp (EAC), EndoAortic balloon occlusion (EABO) and ventricular fibrillation (VF). Major complications were evaluated and compared with a propensity matched population of patients undergoing elective isolated mitral valve surgery via right minithoracotomy (MVS). RESULTS: The average time between last operation and reoperation was 7.1±3.4 years. Fourteen patients (21%) underwent mitral valve repair and 51 patients (78%) underwent mitral valve replacement; 9 patients (14%) received tricuspid valve surgery. There was no statistically significant difference in CPB time between the groups. Seven patients (11%) had a postoperative renal failure, 5 patients (8%) underwent surgical reopening for bleeding; incidence of post-operative stroke and pace-maker implantation was 3% for both. No deaths were registered during in-hospital stay and at 30-days echocardiographic control all patients respect the criterions of device success according with MVARC. Propensity matched patients of group redo had a longer CPB time (100.8±42.7 versus 72.8±16.7 min, P<0.001) and cross-clamp time (71.9±30.7 versus 59±10.7 min, P<0.001) respect to first operation mitral valve surgery patients. CONCLUSIONS: Minimally invasive mitral valve redo surgery is a safe procedure. Less invasive techniques in redo surgery could minimize morbidity and mortality without prolonging the duration of CPB.

Wnt pathway markers in low-grade and high-grade gliomas.

BACKGROUND AND PURPOSE: Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to determine as to what degrees some Wnt markers are expressed in gliomas of different grades, lineages and molecular subtypes. METHODS: Nine grade II, 10 grade III and 72 grade IV surgically removed, formalin-fixed paraffin-embedded glioma specimens were included. Mutation status of IDH1 codon 132 was defined by immunohistochemistry and pyrosequencing in all tumors. Grade II and III astrocytic and oligodendroglial tumors were further tested for the expression of p53 and ATRX by immunohistochemistry, and codeletion of 1p19q by fluorescent in situ hybridization. Expression levels of the non-canonical Wnt5a and Fzd2, and the canonical Wnt3a and beta-catenin Wnt pathway markers were determined by immunohistochemistry, and compared between subgroups stratified according to grade, lineage and the presence or absence of IDH1 R132H/C mutations. RESULTS: In the normal brain - grade II-IV glioma comparisons, a gradual increase was observed for the expressions of Wnt5a, Wnt3a, Fzd2 and beta-catenin. In the astroglial and oligodendroglial lineages of grade II and III gliomas, only the Wnt5a expression was significantly higher in the astroglial subgroup. Stratification according to the IDH1 status resulted in a significant increase of the Wnt3 expression in the wild type grade II-IV gliomas. CONCLUSION: These data extend previous observations and show a correlation of Wnt pathway activity with glioma grade. Further investigations of the Wnt marker expression regulation according to glioma lineage or IDH gene mutational status are in progress by using more exact molecular approaches.

Ensemble averaging laser speckle contrast imaging: statistical model of improvement as function of static scatterers.

The appearance of the common artifacts of laser speckle contrast imaging (LSCI), namely the granularity in flow rate estimation caused by static scatterers, is a well-known phenomenon. This artifact can be greatly reduced in spatial speckle contrast calculation using interframe decorrelated illumination, forcing true ensemble averaging. We propose a statistical model, which describes the effect of multiple image acquisitions on the contrast map quality when the illumination stable and when the illumination is decorrelated frame by frame. We investigate the improvement as a function of the ratio of dynamic and static scatterers by formulating a statistical distribution based model, using in simulation, flow phantom and in vivo experiments. Our main finding is that the ensemble averaging yields limited improvement in several practical cases due to the highly heterogeneous scatterer structure of living tissues.

Preoperative nutritional state is associated with mid- and long-term mortality after cardiac surgery.

BACKGROUND: The frailty score has been developed to determine physiological functioning capacity. The aim of our research was to explore the relationship between frailty factors and mortality in cardiac surgery patients. METHODS: Our research is an observational, single-center, prospective cohort study (registered on ClinicalTrials.gov: NCT02224222), and we studied 69 patients who underwent elective cardiac surgery between 2014 and 2017. Thirty days before the surgery, they completed a questionnaire that contained questions related to social support, self-reported life quality-happiness, cognitive functions, anxiety and depression. Demographic, anthropometric and medical data were widely collected. The Geriatric Nutritional Risk Index (GNRI) and the Comprehensive Geriatric Assessment (CGA)-based frailty index were calculated as a sum and the domains, respectively. Cox regression and the Kaplan-Meier tests were applied to analyze survival and relative risk. The primary outcome was mid-term mortality. RESULTS: The patients' mean age was 65.43 years [standard deviation (SD): 9.81 years]. The median follow-up was 1,656 days of survival [interquartile range (IQR), 1,336-2,081 years], during this period 14 patients died. The median of EuroSCORE II was 1.56 (1.00-2.58) points. The median preoperative albumin level was 32.80 g/L (IQR, 29.9-35.8 g/L). Major adverse cardiovascular and cerebral events (MACCEs) occurred 7 times during follow-up. The nutrition score of the CGA was significantly associated with worse long-term survival [score; hazard ratio (HR): 5.35; 95% CI: 1.10-25.91, P=0.037]. After adjustment for EuroSCORE II and postoperative complications the noncardiovascular CGA score was associated with overall mortality [adjusted hazard ratio (AHR): 1.44, 95% CI: 1.02-2.04, P=0.036]. In the multivariable Cox regression, GNRI <91 showed an increased risk for mortality (AHR: 4.76, 95% CI: 1.52-14.92, P=0.007). CONCLUSIONS: The CGA-based noncardiovascular score and nutritional status should be assessed before cardiac surgery prehabilitation and may help decrease long-term mortality.

Association between biofilm-production and antibiotic resistance in Escherichia coli isolates: A laboratory-based case study and a literature review.

Bacteria can enhance their survival by attaching to inanimate surfaces or tissues, and presenting as multicellular communities encased in a protective extracellular matrix called biofilm. There has been pronounced interest in assessing the relationship between the antibiotic resistant phenotype and biofilm-production in clinically-relevant pathogens. The aim of the present paper was to provide additional experimental results on the topic, testing the biofilm-forming capacity of Escherichia coli isolates using in vitro methods in the context of their antibiotic resistance in the form of a laboratory case study, in addition to provide a comprehensive review of the subject. In our case study, a total of two hundred and fifty (n = 250) E. coli isolates, originating from either clean-catch urine samples (n = 125) or invasive samples (n = 125) were included. The colony morphology of isolates were recorded after 24h, while antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Biofilm-formation of the isolates was assessed with the crystal violet tube-adherence method. Altogether 57 isolates (22.8%) isolates were multidrug resistant (MDR), 89 isolates (35.6%) produced large colonies (>3 mm), mucoid variant colonies were produced in 131 cases (52.4%), and 108 (43.2%) were positive for biofilm formation. Biofilm-producers were less common among isolates resistant to third-generation cephalosporins and trimethoprim-sulfamethoxazole (P = 0.043 and P = 0.023, respectively). Biofilms facilitate a protective growth strategy in bacteria, ensuring safety against environmental stressors, components of the immune system and noxious chemical agents. Being an integral part of bacterial physiology, biofilm-formation is interdependent with the expression of other virulence factors (especially adhesins) and quorum sensing signal molecules. More research is required to allow for the full understanding of the interplay between the MDR phenotype and biofilm-production, which will facilitate the development of novel therapeutic strategies.

COVIDOUTCOME-estimating COVID severity based on mutation signatures in the SARS-CoV-2 genome.

Numerous studies demonstrate frequent mutations in the genome of SARS-CoV-2. Our goal was to statistically link mutations to severe disease outcome. We used an automated machine learning approach where 1594 viral genomes with available clinical follow-up data were used as the training set (797 'severe' and 797 'mild'). The best algorithm, based on random forest classification combined with the LASSO feature selection algorithm, was employed to the training set to link mutation signatures and outcome. The performance of the final model was estimated by repeated, stratified, 10-fold cross validation (CV) and then adjusted for multiple testing with Bootstrap Bias Corrected CV. We identified 26 protein and Untranslated Region (UTR) mutations significantly linked to severe outcome. The best classification algorithm uses a mutation signature of 22 mutations as well as the patient's age as the input and shows high classification efficiency with an area under the curve (AUC) of 0.94 [confidence interval (CI): [0.912, 0.962]] and a prediction accuracy of 87% (CI: [0.830, 0.903]). Finally, we established an online platform (https://covidoutcome.com/) that is capable to use a viral sequence and the patient's age as the input and provides a percentage estimation of disease severity. We demonstrate a statistical association between mutation signatures of SARS-CoV-2 and severe outcome of COVID-19. The established analysis platform enables a real-time analysis of new viral genomes.