Imagistic Findings Using Artificial Intelligence in Vaccinated versus Unvaccinated SARS-CoV-2-Positive Patients Receiving In-Care Treatment at a Tertiary Lung Hospital.

BACKGROUND: In December 2019 the World Health Organization announced that the widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection had become a global pandemic. The most affected organ by the novel virus is the lung, and imaging exploration of the thorax using computer tomography (CT) scanning and X-ray has had an important impact. MATERIALS AND METHODS: We assessed the prevalence of lung lesions in vaccinated versus unvaccinated SARS-CoV-2 patients using an artificial intelligence (AI) platform provided by Medicai. The software analyzes the CT scans, performing the lung and lesion segmentation using a variant of the U-net convolutional network. RESULTS: We conducted a cohort study at a tertiary lung hospital in which we included 186 patients: 107 (57.52%) male and 59 (42.47%) females, of which 157 (84.40%) were not vaccinated for SARS-CoV-2. Over five times more unvaccinated patients than vaccinated ones are admitted to the hospital and require imaging investigations. More than twice as many unvaccinated patients have more than 75% of the lungs affected. Patients in the age group 30-39 have had the most lung lesions at almost 69% of both lungs affected. Compared to vaccinated patients with comorbidities, unvaccinated patients with comorbidities had developed increased lung lesions by 5%. CONCLUSION: The study revealed a higher percentage of lung lesions among unvaccinated SARS-CoV-2-positive patients admitted to The National Institute of Pulmonology "Marius Nasta" in Bucharest, Romania, underlining the importance of vaccination and also the usefulness of artificial intelligence in CT interpretation.

Parameterisation of Respiratory Impedance in Lung Cancer Patients From Forced Oscillation Lung Function Test.

OBJECTIVE: This study aims to analyze the contribution and application of forced oscillation technique (FOT) devices in lung cancer assessment. Two devices and corresponding methods can be feasible to distinguish among various degrees of lung tissue heterogeneity. METHODS: The outcome respiratory impedance Zrs (in terms of resistance Rrs and reactance Xrs) is calculated for FOT and is interpreted in physiological terms by being fitted with a fractional-order impedance mathematical model (FOIM). The non-parametric data obtained from the measured signals of pressure and flow is correlated with an analogous electrical model to the respiratory system resistance, compliance, and elastance. The mechanical properties of the lung can be captured through Gr to define the damping properties and Hr to describe the elastance of the lung tissue, their ratio representing tissue heterogeneity ηr. RESULTS: We validated our hypotheses and methods in 17 lung cancer patients where we showed that FOT is suitable for non-invasively measuring their respiratory impedance. FOIM models are efficient in capturing frequency-dependent impedance value variations. Increased heterogeneity and structural changes in the lungs have been observed. The results present inter- and intra-patient variability for the performed measurements. CONCLUSION: The proposed methods and assessment of the respiratory impedance with FOT have been demonstrated useful for characterizing mechanical properties in lung cancer patients. SIGNIFICANCE: This correlation analysis between the measured clinical data motivates the use of the FOT devices in lung cancer patients for diagnosis of lung properties and follow-up of the respiratory function modified due to the applied radiotherapy treatment.

Lumped Parametric Model for Skin Impedance Data in Patients with Postoperative Pain.

The societal and economic burden of unassessed and unmodeled postoperative pain is high and predicted to rise over the next decade, leading to over-dosing as a result of subjective (NRS-based) over-estimation by the patient. This study identifies how post-surgical trauma alters the parameters of impedance models, to detect and examine acute pain variability. Model identification is performed on clinical data captured from post-anesthetized patients, using Anspec-PRO prototype apriori validated for clinical pain assessment. The multisine excitation of this in-house developed device enables utilizing the complex skin impedance frequency response in data-driven electrical models. The single-dispersion Cole model is proposed to fit the clinical curve in the given frequency range. Changes in identified parameters are analyzed for correlation with the patient's reported pain for the same time moment. The results suggest a significant correlation for the capacitor component. Clinical Relevance- Individual model parameters validated on patients in the post-anesthesia care unit extend the knowledge for objective pain detection to positively influence the outcome of clinical analgesia management.

Occupations and their impact on the spreading of COVID-19 in urban communities.

The current pandemic has disproportionally affected the workforce. To improve our understanding of the role that occupations play in the transmission of COVID-19, we analyse real-world network data that were collected in Bucharest between August 1st and October 31st 2020. The data record sex, age, and occupation of 6895 patients and the 13,272 people they have interacted with, thus providing a social network from an urban setting through which COVID-19 has spread. Quite remarkably, we find that medical occupations have no significant effect on the spread of the virus. Instead, we find common transmission chains to start with infected individuals who hold jobs in the private sector and are connected with non-active alters, such as spouses, siblings, or elderly relatives. We use relational hyperevent models to assess the most likely homophily and network effects in the community transmission. We detect homophily with respect to age and anti-homophily with respect to sex and employability. We note that, although additional data would be welcomed to perform more in-depth network analyses, our findings may help public authorities better target under-performing vaccination campaigns.

Model Calibration of Pharmacokinetic-Pharmacodynamic Lung Tumour Dynamics for Anticancer Therapies.

Individual curves for tumor growth can be expressed as mathematical models. Herein we exploited a pharmacokinetic-pharmacodynamic (PKPD) model to accurately predict the lung growth curves when using data from a clinical study. Our analysis included 19 patients with non-small cell lung cancer treated with specific hypofractionated regimens, defined as stereotactic body radiation therapy (SBRT). The results exhibited the utility of the PKPD model for testing growth hypotheses of the lung tumor against clinical data. The model fitted the observed progression behavior of the lung tumors expressed by measuring the tumor volume of the patients before and after treatment from CT screening. The changes in dynamics were best captured by the parameter identified as the patients' response to treatment. Median follow-up times for the tumor volume after SBRT were 126 days. These results have proven the use of mathematical modeling in preclinical anticancer investigations as a potential prognostic tool.

The role of age in the spreading of COVID-19 across a social network in Bucharest.

We analyse officially procured data detailing the COVID-19 transmission in Romania's capital Bucharest between 1st August and 31st October 2020. We apply relational hyperevent models on 19,713 individuals with 13,377 infection ties to determine to what degree the disease spread is affected by age whilst controlling for other covariate and human-to-human transmission network effects. We find that positive cases are more likely to nominate alters of similar age as their sources of infection, thus providing evidence for age homophily. We also show that the relative infection risk is negatively associated with the age of peers, such that the risk of infection increases as the average age of contacts decreases. Additionally, we find that adults between the ages 35 and 44 are pivotal in the transmission of the disease to other age groups. Our results may contribute to better controlling future COVID-19 waves, and they also point to the key age groups which may be essential for vaccination given their prominent role in the transmission of the virus.

Lung cancer dynamics using fractional order impedance modeling on a mimicked lung tumor setup.

Introduction: As pulmonary dysfunctions are prospective factors for developing cancer, efforts are needed to solve the limitations regarding applications in lung cancer. Fractional order respiratory impedance models can be indicative of lung cancer dynamics and tissue heterogeneity. Objective: The purpose of this study is to investigate how the existence of a tumorous tissue in the lung modifies the parameters of the proposed models. The first use of a prototype forced oscillations technique (FOT) device in a mimicked lung tumor setup is investigated by comparing and interpreting the experimental findings. Methods: The fractional order model parameters are determined for the mechanical properties of the healthy and tumorous lung. Two protocols have been performed for a mimicked lung tumor setup in a laboratory environment. A low frequency evaluation of respiratory impedance model and nonlinearity index were assessed using the forced oscillations technique. Results: The viscoelastic properties of the lung tissue change, results being mirrored in the respiratory impedance assessment via FOT. The results demonstrate significant differences among the mimicked healthy and tumor measurements, (p-values <0.05) for impedance values and also for heterogeneity index. However, there was no significant difference in lung function before and after immersing the mimicked lung in water or saline solution, denoting no structural changes. Conclusion: Simulation tests comparing the changes in impedance support the research hypothesis. The impedance frequency response is effective in non-invasive identification of respiratory tissue abnormalities in tumorous lung, analyzed with appropriate fractional models.

A Minimal PKPD Interaction Model for Evaluating Synergy Effects of Combined NSCLC Therapies.

This paper introduces a mathematical compartmental formulation of dose-effect synergy modelling for multiple therapies in non small cell lung cancer (NSCLC): antiangiogenic, immuno- and radiotherapy. The model formulates the dose-effect relationship in a unified context, with tumor proliferating rates and necrotic tissue volume progression as a function of therapy management profiles. The model accounts for inter- and intra-response variability by using surface model response terms. Slow acting peripheral compartments such as fat and muscle for drug distribution are not modelled. This minimal pharmacokinetic-pharmacodynamic (PKPD) model is evaluated with reported data in mice from literature. A systematic analysis is performed by varying only radiotherapy profiles, while antiangiogenesis and immunotherapy are fixed to their initial profiles. Three radiotherapy protocols are selected from literature: (1) a single dose 5 Gy once weekly; (2) a dose of 5 Gy × 3 days followed by a 2 Gy × 3 days after two weeks and (3) a dose of 5 Gy + 2 × 0.075 Gy followed after two weeks by a 2 Gy + 2 × 0.075 Gy dose. A reduction of 28% in tumor end-volume after 30 days was observed in Protocol 2 when compared to Protocol 1. No changes in end-volume were observed between Protocol 2 and Protocol 3, this in agreement with other literature studies. Additional analysis on drug interaction suggested that higher synergy among drugs affects up to three-fold the tumor volume (increased synergy leads to significantly lower growth ratio and lower total tumor volume). Similarly, changes in patient response indicated that increased drug resistance leads to lower reduction rates of tumor volumes, with end-volume increased up to 25-30%. In conclusion, the proposed minimal PKPD model has physiological value and can be used to study therapy management protocols and is an aiding tool in the clinical decision making process. Although developed with data from mice studies, the model is scalable to NSCLC patients.

Pain Detection with Bioimpedance Methodology from 3-Dimensional Exploration of Nociception in a Postoperative Observational Trial.

Although the measurement of dielectric properties of the skin is a long-known tool for assessing the changes caused by nociception, the frequency modulated response has not been considered yet. However, for a rigorous characterization of the biological tissue during noxious stimulation, the bioimpedance needs to be analyzed over time as well as over frequency. The 3-dimensional analysis of nociception, including bioimpedance, time, and frequency changes, is provided by ANSPEC-PRO device. The objective of this observational trial is the validation of the new pain monitor, named as ANSPEC-PRO. After ethics committee approval and informed consent, 26 patients were monitored during the postoperative recovery period: 13 patients with the in-house developed prototype ANSPEC-PRO and 13 with the commercial device MEDSTORM. At every 7 min, the pain intensity was measured using the index of Anspec-pro or Medstorm and the 0-10 numeric rating scale (NRS), pre-surgery for 14 min and post-anesthesia for 140 min. Non-significant differences were reported for specificity-sensitivity analysis between ANSPEC-PRO (AUC = 0.49) and MEDSTORM (AUC = 0.52) measured indexes. A statistically significant positive linear relationship was observed between Anspec-pro index and NRS (r2 = 0.15, p < 0.01). Hence, we have obtained a validation of the prototype Anspec-pro which performs equally well as the commercial device under similar conditions.

Low Frequency Forced Oscillation Lung Function Test Can Distinguish Dynamic Tissue Non-linearity in COPD Patients.

This paper introduces the use of low frequencies forced oscillation technique (FOT) in the presence of breathing signal. The hypothesis tested is to evaluate the sensitivity of FOT to various degrees of obstruction in COPD patients. The measurements were performed in the frequency range 0-2 Hz. The use of FOT to evaluate respiratory impedance has been broadly recognized and its complementary use next to standardized method as spirometry and body plethysmography has been well-documented. Typical use of FOT uses frequencies between 4-32 Hz and above. However, interesting information at frequencies below 4 Hz is related to viscoelastic properties of parenchyma. Structural changes in COPD affect viscoelastic properties and we propose to investigate the use of FOT at low frequencies with a fourth generation fan-based FOT device. The generator non-linearity introduced by the device is separated from the linear approximation of the impedance before evaluating the results on patients. Three groups of COPD obstruction, GOLD II, III, and IV are evaluated. We found significant differences in mechanical parameters (tissue damping, tissue elasticity, hysteresivity) and increased degrees of non-linear dynamic contributions in the impedance data with increasing degree of obstruction (p < 0.01). The results obtained suggest that the non-linear index correlates better with degrees of heterogeneity linked to COPD GOLD stages, than the currently used hysteresivity index. The protocol and method may prove useful to improve current diagnosis percentages for various COPD phenotypes.

Diversity of Mosaic pbp2x Families in Penicillin-Resistant Streptococcus pneumoniae from Iran and Romania.

Penicillin-resistant Streptococcus pneumoniae strains are found at high rates in Romania and Iran. The mosaic structure of PBP2x was investigated in 9 strains from Iran and in 15 strains from Romania to understand their evolutionary history. Mutations potentially important for ß-lactam resistance were identified by comparison of the PBP2x sequences with the sequence of the related PBP2x of reference penicillin-sensitive S. mitis strains. Two main PBP2x mosaic gene families were recognized. Eight Iranian strains expressed PBP2x variants in group 1, which had a mosaic block highly related to PBP2x of the Spain23F-1 clone, which is widespread among international penicillin-resistant S. pneumoniae clones. A second unique PBP2x group was observed in Romanian strains; furthermore, three PBP2x single mosaic variants were found. Sequence blocks of penicillin-sensitive strain S. mitis 658 were common among PBP2x variants from strains from both countries. Each PBP2x group contained specific signature mutations within the transpeptidase domain, documenting the existence of distinct mutational pathways for the development of penicillin resistance.

[Study of Streptococcus pneumoniae strains resistant to antibiotics analyzed at "Cantacuzino" NIRDMI during 2006-2008]. / Studiul tulpinilor de Streptococcus pneumoniae rezistente la antibiotice analizate la INCDMI "Cantacuzino" în perioada 2006-2008.

OBJECTIVE: The aim of the this study was the analysis of the resistance to antibiotics of Streptococcus pneumoniae isolated in last years. METHODS: 328 S. pneumoniae strains, coming from blood, CSF tracheal aspirate (TA), or sputum, pleural fluid (PL) and other samples (ear and sinus fluid) isolated in 2006-2008, were analyzed at INCDMI "Cantacuzino", National Reference Center for Streptococcus pneumoniae. Strains were tested for susceptibility to by agar diution method (minimal inhibitory concentration-MIC) to the following antibiotics: penicillin (Pc), erythromycin (Em), cephalothin (Kf). cefuroxim (Cxm), cefotaxim (Ctx), trimethoprim/sulfamethoxazol (Sxt), ofloxacin (Ojx), amoxicillin (Amx). tetracycline (Te), cloramphenicol (Cm), vancomycin (Va). RESULTS: The analysis of the results was done according to CLSI 2009. Pneumococci strains isolated from blood, CSF, TA or sputum and PL showed lower resistance level to antibiotics (38.8% Pc, 9.3% Cxm. 4.1% Ctx, 2.7% Amx. 24% Em, 2.4% Ofx, 68% Sxt) against those isolated from ear ans sinus fluid which revealed high levels of resistance (70% Pc, 11.2 % Cxm, 5.9 % Ctx, 3.4% Amx, 58.4 % Em. 3.8% Ofx, 73% Sxt). Strains resistant to penicillin, isolated from blood and CSF revealed the following aspects: 17% low level of resistance and 11 % high level of resistance. CONCLUSIONS. The most efficient antibiotics were Ctx, Amx and Oft. A continuous surveillance of pneumococci strains resistant to antibiotics is needed, as well as the use of an pneumococcal efficient vaccine.

[Trends of antimicrobial resistance in microbial strains isolated from invasive infections in Romania. Experience of participation in EARSS (European Antimicrobial Resistance Surveillance System), 2002-2008]. / Tendintele rezistentei la antibiotice a izolatelor din infectii invazive în România. Experienta participarii în Sistemul European de Supraveghere a Rezistentei la Antibiotice (EARSS) în perioada 2002-2008.

EARSS (European Antimicrobial Resistance Surveillance System) is the biggest antimicrobial resistance surveillance project in the world financed from public finds, aiming to provide validated and comparable official data on antimicrobial resistance of invasive microbial strains (isolated from blood and CSF), belonging to 6 indicator bacterial species, i.e.: S. aureus, E. coli, E. faecium/faecalis, Str. pneumoniae, Ps. aeruginosa, K. pneumoniae. Romania reported data to EARSS since 2002 so far. Though the number of participating laboratories increased progressively from 12 to 35, the number of hospitals which reported for EARSS. as the number of strains included in the data base remained steady and relatively low. This issue is related to the particular position of Romania in the European context, in respect of the very low number of blood cultures performed in hospitals. Our paper is presenting the trends of antimicrobial resistance in the indicator strains in the 2002-2008 interval. During the 2002-2008 interval, Romania reported to EARSS a total number of 1276 bacterial strains, distributed by species as follows: 513 S aureus, 369 E. coli, 128 Streptococcus pneumoniae, 127 Enterococcus spp.. 71 Klebsiella pneumoniae, 68 Pseudomonas aeruginosa. Klebsiella pneumoniae and Pseudomonas aeruginosa were reported, according to the EARSS protocol, only for the 2005-2008 interval. It is difficult to describe trends, specially in Enterococcus, Streptococcus pneumonaie and the 2 species collected only since 2005, because of the low number of isolates, but there are several results that are supporting us to claim that antimicrobial resistance in invasive isolates is a real problem in Romanian hospitals, like in other Central, Southern and South Eastern European countries: more than 25% of S. aureus strains resistant to methicilline, with more than 50% in some years, high aminoglycozides resistance in more than 70-80% of Enterococcus faecium invasive strains, more than 80% of strains resistant to 3rd generation cephalosporines etc.

The in vitro susceptibility to 7 antibiotics of Neisseria meningitidis strains isolated last years in Romania.

Thirty-one strains of Neisseria meningitidis strains coming from CSF, collected at the National Reference Center for Meningococci between January 2007-March 2008 were serogrouped and analysed for the susceptibility to 7 antibiotics: penicillin (Pc), erythromycin (Em), ceftriaxone (Cro), cefotaxime (Ctx), ciprofloxacin (Cip), rifampin (Rif), sulfonamides (Sm). Results revealed that serogroup B accounted to the highest number of strains (51.7%), followed by serogroup C (35.5%), serogroup W 135 (6.4%) and serogroup X (6.4%). The data analysed according to EMGM revealed the following aspects: 100% susceptibility to Cro and Ctx., 96.7% susceptibility to Rif (MIC 50 and MIC 90 =0.03 mg/l) and 96.7% susceptibility to Cip (MIC 50 and MIC 90=0.0015 mg/l). Concerning Pc, it was revealed 58% susceptible strains, 38.7% intermediate and 3.3% resistant strains with MIC 50=0.06 mg/l and MIC 90=0.12 mg/l. A high proportion (100%) of isolates were fully resistant to Sm, while 22.6% of strains were resistant to Em. In conclusion, this study showed that Cro, Ctx, Cip and Rif were the most efficient drugs. Sulfonamides must be used neither for treatment nor for prophylaxis, as they would be ineffective. Serogroups B and C were predominant in this period in Romania. The need for new antimicrobial agents and vaccines is being felt in today's society.