Modelling the dynamics of tuberculosis lesions in a virtual lung: Role of the bronchial tree in endogenous reinfection.

Tuberculosis (TB) is an infectious disease that still causes more than 1.5 million deaths annually. The World Health Organization estimates that around 30% of the world's population is latently infected. However, the mechanisms responsible for 10% of this reserve (i.e., of the latently infected population) developing an active disease are not fully understood, yet. The dynamic hypothesis suggests that endogenous reinfection has an important role in maintaining latent infection. In order to examine this hypothesis for falsifiability, an agent-based model of growth, merging, and proliferation of TB lesions was implemented in a computational bronchial tree, built with an iterative algorithm for the generation of bronchial bifurcations and tubes applied inside a virtual 3D pulmonary surface. The computational model was fed and parameterized with computed tomography (CT) experimental data from 5 latently infected minipigs. First, we used CT images to reconstruct the virtual pulmonary surfaces where bronchial trees are built. Then, CT data about TB lesion' size and location to each minipig were used in the parameterization process. The model's outcome provides spatial and size distributions of TB lesions that successfully reproduced experimental data, thus reinforcing the role of the bronchial tree as the spatial structure triggering endogenous reinfection. A sensitivity analysis of the model shows that the final number of lesions is strongly related with the endogenous reinfection frequency and maximum growth rate of the lesions, while their mean diameter mainly depends on the spatial spreading of new lesions and the maximum radius. Finally, the model was used as an in silico experimental platform to explore the transition from latent infection to active disease, identifying two main triggering factors: a high inflammatory response and the combination of a moderate inflammatory response with a small breathing amplitude.

Optimal Use of Transient Elastography and Acoustic Radiation Force Impulse to Stage Liver Fibrosis in HIV/HCV-Coinfected Patients in Clinical Practice.

OBJECTIVES: Liver fibrosis (LF) is crucial for the individualized management of patients with hepatitis C virus (HCV). We evaluated the concordance between two noninvasive methods for staging LF, transient elastography (TE) and acoustic radiation force impulse (ARFI), in patients coinfected with human immunodeficiency virus and HCV. We propose an algorithm for optimal use of both techniques in routine clinical practice. METHODS: A total of 89 human immunodeficiency virus/HCV-coinfected patients underwent TE and ARFI on the same day. The kappa index was used to assess concordance between the techniques. An algorithm combining ARFI and TE was proposed based on the independent factors associated with a kappa index greater than or equal to 0.70, obtained from a multiple regression analysis. We performed a cost-effectiveness analysis. The study was approved by our institutional review board and all patients signed the informed consent. RESULTS: Concordance between TE and ARFI for F2, F3, and F4 was 0.55, 0.59, and 0.69, respectively. Ultrasound normal spleen size (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.05-0.91) and high viral load (OR, 0.36; 95% CI, 0.17-0.77) reduced the probability of agreement between TE and ARFI, whereas ultrasound normal left liver lobe size (OR, 3.32; 95% CI, 1.21-9.10) increased this probability. The algorithm revealed that LF was adequately assessed in 74.16%, with 25.84% of patients misclassified. The incremental cost-effectiveness ratio of TE compared with ARFI to increase concordance by 1% was €8.86. CONCLUSIONS: Concordance between TE and ARFI was moderate. In the algorithm we proposed, ARFI was cost-effective as a first technique for the staging of LF in the study population.

Vagus nerve dysfunction in the post-COVID-19 condition: a pilot cross-sectional study.

OBJECTIVES: The post-COVID-19 condition (PCC) is a disabling syndrome affecting at least 5%-10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some PCC symptoms, such as dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances, or neurocognitive complaints. METHODS: We performed a cross-sectional pilot study in subjects with PCC with symptoms suggesting vagus nerve dysfunction (n = 30) and compared them with subjects fully recovered from acute COVID-19 (n = 14) and with individuals never infected (n = 16). We evaluated the structure and function of the vagus nerve and respiratory muscles. RESULTS: Participants were mostly women (24 of 30, 80%), and the median age was 44 years (interquartile range [IQR] 35-51 years). Their most prevalent symptoms were cognitive dysfunction 25 of 30 (83%), dyspnea 24 of 30 (80%), and tachycardia 24 of 30 (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (cross-sectional area [CSA] [mean ± standard deviation]: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2; p 0.08), reduced esophageal-gastric-intestinal peristalsis (34% vs. 0% vs. 21%; p 0.02), gastroesophageal reflux (34% vs. 19% vs. 7%; p 0.13), and hiatal hernia (25% vs. 0% vs. 7%; p 0.05). Subjects with PCC showed flattening hemidiaphragms (47% vs. 6% vs. 14%; p 0.007), and reductions in maximum inspiratory pressure (62% vs. 6% vs. 17%; p ≤ 0.001), indicating respiratory muscle weakness. The latter findings suggest additional involvement of the phrenic nerve. DISCUSSION: Vagus and phrenic nerve dysfunction contribute to the complex and multifactorial pathophysiology of PCC.

Corrigendum: Disseminated tuberculosis and diagnosis delay during the COVID-19 era in a Western European country: a case series analysis.

[This corrects the article DOI: 10.3389/fpubh.2023.1175482.].

Disseminated tuberculosis and diagnosis delay during the COVID-19 era in a Western European country: a case series analysis.

Background: Disseminated tuberculosis is frequently associated with delayed diagnosis and a poorer prognosis. Objectives: To describe case series of disseminated TB and diagnosis delay in a low TB burden country during the COVID-19 period. Methodology: We consecutively included all patients with of disseminated TB reported from 2019 to 2021 in the reference hospital of the Northern Crown of the Metropolitan Area of Barcelona. We collected socio-demographic information, clinical, laboratory and radiological findings. Results: We included all 30 patients reported during the study period-5, 9, and 16 in 2019, 2020, and 2021 respectively-20 (66.7%) of whom were male and whose mean age was 41 years. Twenty-five (83.3%) were of non-EU origin. The most frequent system involvement was central nervous system (N = 8; 26.7%) followed by visceral (N = 7; 23.3%), gastro-intestinal (N = 6, 20.0%), musculoskeletal (N = 5; 16.7%), and pulmonary (N = 4; 13.3%). Hypoalbuminemia and anemia were highly prevalent (72 and 77%). The median of diagnostic delay was 6.5 months (IQR 1.8-30), which was higher among women (36.0 vs. 3.5 months; p = 0.002). Central nervous system involvement and pulmonary involvement were associated with diagnostic delay among women. We recorded 24 cured patients, two deaths, three patients with post-treatment sequelae, and one lost-to-follow up. We observed a clustering effect of patients in low-income neighborhoods (p < 0.001). Conclusion: There was a substantial delay in the diagnosis of disseminated TB in our study region, which might impacted the prognosis with women affected more negatively. Our results suggest that an increase in the occurrence of disseminated TB set in motion by diagnosis delay may have been a secondary effect of the COVID-19 pandemic.

Single nucleotide polymorphisms in PNPLA3, ADAR-1 and IFIH1 are associated with advanced liver fibrosis in patients co-infected with HIV-1//hepatitis C virus.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), insulin resistance and liver fibrosis are prevalent in individuals co-infected with HIV type 1 (HIV-1)/hepatitis C virus (HCV), even after HCV eradication. Our aim was to evaluate single nucleotide polymorphisms (SNPs) associated with advanced liver fibrosis in HIV-1/HCV co-infected patients. DESIGN/METHODS: In a cohort of 102 participants, we genotyped 16 SNPs in 10 genes previously associated with NAFLD and the innate immune response and correlated the genotypes with liver fibrosis and fat accumulation. RESULTS: Multinomial logistic regression analysis identified three metabolic parameters that were significantly associated with advanced liver fibrosis (stage F3-F4): albumin [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69-0.91, P = 0.001], percentage of visceral fat area (PVFA) (OR 1.06, 95% CI 1.01-1.12, P = 0.03) and BMI (OR 1.47, 95% CI 1.22-1.77, P < 0.0001). After adjustment for sex, albumin, PVFA and BMI, we found that three SNPs were significantly associated with advanced fibrosis, one each in PNPLA3/rs738409 (P = 0.016), ADAR-1/rs1127313 (P = 0.029) and IFIH1/rs1990760 (P = 0.033). CONCLUSION: Our results indicate that genotyping for these SNPs can be a useful predictive tool for liver fibrosis progression and liver fat accumulation in patients co-infected with HIV-1/HCV.

Association Between Visceral Abdominal Fat Accumulation and Severity of Liver Fibrosis in Nondiabetic Individuals Coinfected by Human Immunodeficiency Virus and Hepatitis C Virus.

Our primary objective was to assess the independent association between liver fibrosis (LF) and abdominal fat accumulation (AFA) and fatty liver disease (FLD). We also aimed to determine the diagnostic accuracy of AFA and FLD for the prediction of cirrhosis measured using unenhanced low-dose computed tomography (CT). This is a cross-sectional study in stable human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with active HCV replication. CT was used to quantify fat content in segments III and VI of the liver and AFA. Transient elastometry was used to stage LF. Multivariate logistic regression, receiver operating characteristic curve analysis, and linear mixed model analysis were applied. One hundred fifteen HIV/HCV-coinfected patients were included. Cirrhosis was detected in 20.8% (24 patients). There was a high correlation between anthropometric characteristics and radiological variables. The factors independently associated with cirrhosis were albumin concentration [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.58-0.83; p < .0001] and visceral fat accumulation (OR, 1.02; 95% CI, 1.01-1.04; p = .0003). Multinomial analysis showed that visceral fat area (VFA) was the factor independently associated with stage F2 (OR, 1.02; 95% CI, 1.0-1.03; p < .005) and albumin concentration with stage F3 (OR, 0.75; 95% CI, 0.64-0.89; p < .001). VFA was the only radiological variable with an area under the curve >0.7 for the prediction of cirrhosis. There was no inter- or intraobserver variability in the measurement of AFA; however, high interobserver variability was recorded in the measurement of FLD. The association of VFA with cirrhosis, the high reproducibility of CT for the measurement of VFA, and the ability of VFA to predict cirrhosis make CT a suitable technique for identifying HIV/HCV-coinfected patients for closer surveillance.