Pulmonary Pathology Research Articles

Hemodynamical Approach to Pulmonary Hypertension

Pulmonary hypertension (PH) is a pathophysiological disorder characterized by a vascular obstruction leading to increased right ventricular overload. It can be caused by multiple conditions that we classify into 5 clinical groups. PH is defined hemodynamically and the role and indications of cardiac catheterization are increasingly important. The subject includes a panoply of pathologies with great complexity at the same time physio-pathological, histo-etiopathogenic, genetic... which are gathered under one chapter: the pulmonary vascular pathology. Right heart catheterization (RHC) is crucial and allows to measure and calculate variables to determine patients hemodynamics that are necessary for positive, etiological and severity diagnosis. It can also have therapeutic purpose: vasoreactivity test (APVT), pre-gesture assessment. Materiel and Methods: retrospective cross-sectional study of 143 patients with suspicion of pulmonary hypertension whom underwent RHC (left heart) performed between January 2017 and December 2021 in cardiology A department within Ibn Sina university hospital center. Results: In terms of the results of our study, we have a very diverse review in which PH is assessed at different levels for all groups and subgroups using a multitude of hemodynamic parameters. Our population is characterized by a clear predominance of women The average age of all 143 cases is 38 years. In terms of hemodynamic classification, isolated pre-capillary PH is the most common (52%). 64% of our cases had PVRs >2 Wu indicating the prevalence of pulmonary vasculopathy. Group 3 represents the population with the most preserved hemodynamical severity parameters. The main vasoreactivity test performed was the NO test.

A hybrid model- and deep learning-based framework for functional lung image synthesis from multi-inflation CT and hyperpolarized gas MRI.

Hyperpolarized gas MRI is a functional lung imaging modality capable of visualizing regional lung ventilation with exceptional detail within a single breath. However, this modality requires specialized equipment and exogenous contrast, which limits widespread clinical adoption. CT ventilation imaging employs various metrics to model regional ventilation from non-contrast CT scans acquired at multiple inflation levels and has demonstrated moderate spatial correlation with hyperpolarized gas MRI. Recently, deep learning (DL)-based methods, utilizing convolutional neural networks (CNNs), have been leveraged for image synthesis applications. Hybrid approaches integrating computational modeling and data-driven methods have been utilized in cases where datasets are limited with the added benefit of maintaining physiological plausibility. To develop and evaluate a multi-channel DL-based method that combines modeling and data-driven approaches to synthesize hyperpolarized gas MRI lung ventilation scans from multi-inflation, non-contrast CT and quantitatively compare these synthetic ventilation scans to conventional CT ventilation modeling. In this study, we propose a hybrid DL configuration that integrates model- and data-driven methods to synthesize hyperpolarized gas MRI lung ventilation scans from a combination of non-contrast, multi-inflation CT and CT ventilation modeling. We used a diverse dataset comprising paired inspiratory and expiratory CT and helium-3 hyperpolarized gas MRI for 47 participants with a range of pulmonary pathologies. We performed six-fold cross-validation on the dataset and evaluated the spatial correlation between the synthetic ventilation and real hyperpolarized gas MRI scans; the proposed hybrid framework was compared to conventional CT ventilation modeling and other non-hybrid DL configurations. Synthetic ventilation scans were evaluated using voxel-wise evaluation metrics such as Spearman's correlation and mean square error (MSE), in addition to clinical biomarkers of lung function such as the ventilated lung percentage (VLP). Furthermore, regional localization of ventilated and defect lung regions was assessed via the Dice similarity coefficient (DSC). We showed that the proposed hybrid framework is capable of accurately replicating ventilation defects seen in the real hyperpolarized gas MRI scans, achieving a voxel-wise Spearman's correlation of 0.57±0.17 and an MSE of 0.017±0.01. The hybrid framework significantly outperformed CT ventilation modeling alone and all other DL configurations using Spearman's correlation. The proposed framework was capable of generating clinically relevant metrics such as the VLP without manual intervention, resulting in a Bland-Altman bias of 3.04%, significantly outperforming CT ventilation modeling. Relative to CT ventilation modeling, the hybrid framework yielded significantly more accurate delineations of ventilated and defect lung regions, achieving a DSC of 0.95 and 0.48 for ventilated and defect regions, respectively. The ability to generate realistic synthetic ventilation scans from CT has implications for several clinical applications, including functional lung avoidance radiotherapy and treatment response mapping. CT is an integral part of almost every clinical lung imaging workflow and hence is readily available for most patients; therefore, synthetic ventilation from non-contrast CT can provide patients with wider access to ventilation imaging worldwide.

Necrotising soft tissue infection of chest wall secondary to rib fractures

Necrotising soft tissue infection (NSTI) is a surgical emergency. We hereby present a rare case with NSTI of the chest wall secondary to rib fractures without any intra pulmonary pathology leading to a life-threatening surgical condition.

Protective effects of Qing-Re-Huo-Xue formula on bleomycin-induced pulmonary fibrosis through the p53/IGFBP3 pathway

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing lung disease with high mortality. Inflammation and epithelial mesenchymal transformation (EMT) may play an important role in the occurrence and development of IPF. Qing-Re-Huo-Xue formula (QRHXF) has been used clinically by our team for half a century and has obvious therapeutic effects on lung disease. Nevertheless, the role and mechanism of QRHXF in the treatment of IPF have never been studied.MethodsA mouse pulmonary fibrosis model was established by intratracheal injection of BLM. The effects of QRHXF on the treatment of pulmonary fibrosis were studied by pulmonary function testing, imaging examination, pathological staining, transmission electron microscopy (TEM) observation and mRNA expression. Tandem mass tag (TMT)-based quantitative proteomics was carried out to analyse the lung protein expression profiles between the control (CTL), bleomycin (BLM) and QRHXF (BLM + QRHXF) groups. Immunohistochemistry and qRT-PCR were used to verify the possible existence of drug target proteins and signalling pathways.ResultsThe results of pulmonary function, lung pathology and imaging examinations showed that QRHXF could significantly alleviate BLM-induced pulmonary fibrosis in vivo. Additionally, inflammatory cell infiltration and EMT were markedly reduced in BLM-induced PF mice administered QRHXF. Proteomics detected a total of 35 proteins, of which 17 were upregulated and 18 were downregulated. A total of 19 differentially expressed proteins (DEPs) overlapped between the BLM versus CTL groups and the BLM + QRHXF versus BLM groups. The expression of p53 and IGFBP3 was reversed in the QRHXF intervention group, which was verified by immunohistochemistry and qRT-PCR.ConclusionsQRHXF attenuated BLM-induced pulmonary fibrosis, and regulation of the p53/IGFBP3 pathway might be associated with its efficacy, which holds promise as a novel treatment strategy for pulmonary fibrosis patients.Graphical

Syndrome of Inappropriate Antidiuresis: From Pathophysiology to Management.

Hyponatremia is the most common electrolyte disorder, affecting more than 15% of patients in the hospital. Syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hypotonic hyponatremia, mediated by nonosmotic release of arginine vasopressin (AVP, previously known as antidiuretic hormone), which acts on the renal V2 receptors to promote water retention. There are a variety of underlying causes of SIAD, including malignancy, pulmonary pathology, and central nervous system pathology. In clinical practice, the etiology of hyponatremia is frequently multifactorial and the management approach may need to evolve during treatment of a single episode. It is therefore important to regularly reassess clinical status and biochemistry, while remaining alert to potential underlying etiological factors that may become more apparent during the course of treatment. In the absence of severe symptoms requiring urgent intervention, fluid restriction (FR) is widely endorsed as the first-line treatment for SIAD in current guidelines, but there is considerable controversy regarding second-line therapy in instances where FR is unsuccessful, which occurs in around half of cases. We review the epidemiology, pathophysiology, and differential diagnosis of SIAD, and summarize recent evidence for therapeutic options beyond FR, with a focus on tolvaptan, urea, and sodium-glucose cotransporter 2 inhibitors.

Ultrasound Scanning in Lung Procurement. Protocol for Decision-Making With the Purpose of Increasing Transplant Eligible Lungs

BackgroundThe main obstacle to obtaining lungs for transplantation is the shortage of donors. Once potential donors have been offered to transplant programs, the acceptance rate is highly variable, ranging from 5% to 20%. Minimizing donor leakage by converting potential lung donors into real donors is one of the key elements to improve results, and it is essential to have tools that facilitate decision-making in this scenario. The selection and rejection of transplantation-eligible lungs are usually made with chest x-rays; however, lung ultrasound scanning has shown better sensitivity and specificity for diagnosing pulmonary pathologies. Lung ultrasound scanning allows us to identify the reversible causes of low PaO2/fraction of inspired oxygen (FIO2) ratio, thus enabling the establishment of specific interventions, which, if proved successful, could turn lungs into transplant-eligible lungs. The available literature on its use in managing brain death donors and lung procurement is extremely scarce. MethodsA simple protocol aimed at identifying and treating the main reversible causes of low PaO2/FIO2 ratio to aid in decision-making is presented in this paper. ConclusionLung ultrasound is a powerful, useful, and cheap technique available at the donor's bedside. It is conspicuously underused, despite being potentially helpful in decision-making by minimizing the discarding of donors, thus probably increasing the number of lungs sui for transplantation.

Fractionated FLASH radiation in xenografted lung tumors induced FLASH effect at a split dose of 2 Gy

Purpose To explore the minimum split dose of FLASH radiotherapy (FLASH). Material and Methods Lungs of nude mice were used to verify the capacity of normal tissue sparing of FLASH, while tumor-bearing nude mice were used to evaluate the curative power. Xenografted tumor models were established in Balb/c-nu mice using A549 cells at a concentration of 5 × 106/100μL. With the same total dose (20 Gy), the dose rate of FLASH was 200 Gy/s when conventional radiotherapy(CONV) was 0.033 Gy/s. Two schemes of FLASH irradiations were applied: single pulse (FLASH1) and ten pulses (FLASH10). Then, according to the different tissue types and irradiation schemes, mice were divided into eight groups: Control-T, CONV-T, FLASH1-T, FLASH10-T (T for tumor) and Control-L, CONV-L, FLASH1-L, FLASH10-L (L for lung). Evaluation of FLASH effect was based on the changes in tumor volume and pathological analysis of tumor and lung tissues before and after irradiation. Results Compared to control group, the mean volume of tumors in nude mice increased slowly or decreased after irradiation with both FLASH and CONV (Control-T: 233.6 ± 55.19 mm3, CONV-T: 146.1 ± 50.62 mm3, FLASH1-T: 148 ± 18.83 mm3, FLASH10-T: 119.1 ± 50.62 mm3, p ≤ 0.05) . Tumor cells of irradiated groups had similar degrees of dissolution damage and inflammation, while the acute radiation pneumonia induced by FLASH was less severe. The pulmonary pathology of FLASH1-L and FLASH10-L were similar, and only a few neutrophils were observed. In addition to inflammatory cells, slight thickening of alveolar septum and obvious interstitial hemorrhage were also observed in the CONV-L group. Conclusion The FLASH effect was successfully reproduced in both single and fractionated irradiation, with 2 Gy being the minimum split dose to achieve the FLASH effect in existing experiments. It is suggested that the transient oxygen depletion might not be the only mechanism behind the FLASH effect.

Regulation of Epithelial Sodium Transport by SARS-CoV-2 Is Closely Related with Fibrinolytic System-Associated Proteins.

Dyspnea and progressive hypoxemia are the main clinical features of patients with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pulmonary pathology shows diffuse alveolar damage with edema, hemorrhage, and the deposition of fibrinogens in the alveolar space, which are consistent with the Berlin Acute Respiratory Distress Syndrome Criteria. The epithelial sodium channel (ENaC) is a key channel protein in alveolar ion transport and the rate-limiting step for pulmonary edema fluid clearance, the dysregulation of which is associated with acute lung injury/acute respiratory distress syndrome. The main protein of the fibrinolysis system, plasmin, can bind to the furin site of γ-ENaC and induce it to an activation state, facilitating pulmonary fluid reabsorption. Intriguingly, the unique feature of SARS-CoV-2 from other β-coronaviruses is that the spike protein of the former has the same furin site (RRAR) with ENaC, suggesting that a potential competition exists between SARS-CoV-2 and ENaC for the cleavage by plasmin. Extensive pulmonary microthrombosis caused by disorders of the coagulation and fibrinolysis system has also been seen in COVID-19 patients. To some extent, high plasmin (ogen) is a common risk factor for SARS-CoV-2 infection since an increased cleavage by plasmin accelerates virus invasion. This review elaborates on the closely related relationship between SARS-CoV-2 and ENaC for fibrinolysis system-related proteins, aiming to clarify the regulation of ENaC under SARS-CoV-2 infection and provide a novel reference for the treatment of COVID-19 from the view of sodium transport regulation in the lung epithelium.

Persistent changes in expression of genes involved in inflammation and fibrosis in the lungs of rats exposed to airborne lunar dust

NASA is currently planning return missions to the Moon for further exploration and research. The Moon is covered by a layer of potentially reactive fine dust, which could pose a toxicological risk of exposure to explorers. To assess this risk, we exposed rats to lunar dust (LD) that was collected during the Apollo14 mission. Rats were exposed to respirable sizes of LD at concentrations of 0, 2.1, 6.8, 20.8, or 60.6 mg/m3 for 4 weeks. At thirteen weeks after exposure, we assessed 44,000 gene transcripts and found the expression of 614 genes with known functions were significantly altered in the rats exposed to the 2 higher concentrations of LD, whereas few changes in gene expression were detected in the group exposed to the lowest concentration of LD. Many of the significant changes in gene expression involved genes known to be associated with inflammation or fibrosis. Four genes encoding pro-inflammatory chemokines were analyzed further for all the sampling points at 1 day, and 1, 4, and 13 weeks after the 4-week dust exposure, using real-time polymerase chain reaction. The expression of these genes was altered in a dose- and time-dependent manner and persistently changed in the lungs of the rats exposed to the two higher concentrations of LD. Their expressions are consistent with changes we detected in pulmonary toxicity biomarkers and pathology in these animals during a previous study. Because Apollo-14 LD contains common mineral oxides similar to an Arizona volcanic ash, besides revealing the toxicity of LD, our findings could help elucidate the genomic and molecular mechanisms involved in pulmonary toxicity induced by terrestrial mineral dusts.

Development, refinement, and characterization of a nonhuman primate critical care environment.

Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated a critical care phase without the use of general anesthesia. We describe the development of a prolonged critical care environment with sedation and ventilation support, and also report corresponding NHP biologic and inflammatory markers. Eight adult male rhesus macaques underwent ventilation with sedation for 48-96 hours in a critical care setting. Three of these NHPs underwent "sham" procedures as part of trauma control model development. Blood counts, chemistries, coagulation studies, and cytokines/chemokines were collected throughout the study, and histopathologic analysis was conducted at necropsy. Eight NHPs were intentionally survived and extubated. Three NHPs were euthanized at 72-96 hours without extubation. Transaminitis occurred over the duration of ventilation, but renal function, acid-base status, and hematologic profile remained stable. Chemokine and cytokine analysis were notable for baseline fold-change for Il-6 and Il-1ra (9.7 and 42.7, respectively) that subsequently downtrended throughout the experiment unless clinical respiratory compromise was observed. A NHP critical care environment with ventilation support is feasible but requires robust resources. The inflammatory profile of NHPs is not profoundly altered by sedation and mechanical ventilation. NHPs are susceptible to the pulmonary effects of short-term ventilation and demonstrate a similar bioprofile response to ventilator-induced pulmonary pathology. This work has implications for further development of a prolonged care NHP model.

Determining Frequency of Common Pulmonary Gross and Histopathological Findings in Feedyard Fatalities.

Pulmonary disease is often associated with feedlot cattle mortality, and the most common syndromes include bronchopneumonia, acute interstitial pneumonia, and bronchopneumonia with an interstitial pneumonia. The study objective was to utilize gross necropsy and histopathology to determine the frequency of pulmonary lesions from three major syndromes and agreement between gross and histopathological diagnosis. A cross sectional, observational study was performed at six U.S. feedyards using a full systematic necropsy to assess mortalities during summer 2022. A subset of mortalities had four lung samples submitted for histopathological diagnosis. Gross necropsy was performed on 417 mortalities, 402 received a gross diagnosis and 189 had a histopathological diagnosis. Descriptive statistics were used to evaluate pulmonary diagnosis frequency based on method (gross/histopathology), and generalized linear mixed models were used to evaluate agreement between histopathological and gross diagnoses. Using gross diagnosis, bronchopneumonia represented 36.6% of cases with acute interstitial pneumonia and bronchopneumonia with an interstitial pneumonia representing 10.0% and 35.8%, respectively. Results identified bronchopneumonia with an interstitial pneumonia as a frequent syndrome which has only been recently reported. Histopathological diagnosis had similar findings; bronchopneumonia represented 32.3% of cases, with acute interstitial pneumonia and bronchopneumonia with an interstitial pneumonia representing 12.2% and 36.0%, respectively. Histopathological diagnosis tended (p-VALUE = 0.06) to be associated with gross diagnosis. Pulmonary disease was common and both diagnostic modalities illustrated three primary syndromes: bronchopneumonia, acute interstitial pneumonia, and bronchopneumonia with an interstitial pneumonia with similar frequencies. Improved understanding of pulmonary pathology can be valuable for evaluating and adjusting therapeutic interventions.

SARS-CoV-2 Disease Severity in the Golden Syrian Hamster Model of Infection Is Related to the Volume of Intranasal Inoculum.

The golden Syrian hamster (Mesocricetus auratus) is now commonly used in preclinical research for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the assessment of vaccines, drugs and therapeutics. Here, we show that hamsters inoculated via the intranasal route with the same infectious virus dose of prototypical SARS-CoV-2 administered in a different volume present with different clinical signs, weight loss and viral shedding, with a reduced volume resulting in reduced severity of disease similar to that obtained by a 500-fold reduction in the challenge dose. The tissue burden of the virus and the severity of pulmonary pathology were also significantly affected by different challenge inoculum volumes. These findings suggest that a direct comparison between the severity of SARS-CoV-2 variants or studies assessing the efficacy of treatments determined by hamster studies cannot be made unless both the challenge dose and inoculation volume are matched when using the intranasal route. Additionally, analysis of sub-genomic and total genomic RNA PCR data demonstrated no link between sub-genomic and live viral titres and that sub-genomic analyses do not provide any information beyond that provided by more sensitive total genomic PCR.

Videolaparoscopic surgical treatment of strangulated paraesophageal hiatal hernia (clinical observation)

Relevance. Paraesophageal hiatal hernias are much less common than other types of diaphragmatic hernias. The risk of strangulation in this pathology is about 21 %. It is often very difficult to establish the correct diagnosis in time, because patients are admitted with an atypical clinic of acute cardiological or pulmonary pathology. Usually, the correct diagnosis is established only on the 4th day. Due to late diagnosis, necrosis and perforation of the strangulated organ occur, which causes high mortality; sometimes the correct diagnosis is established only at autopsy.Clinical observation. The patient was admitted to the surgical department on an emergency basis with complaints of intense pain in the lower chest and epigastric region, vomiting of eaten food. From the anamnesis it is known that about a year ago, periodic nausea and vomiting of food eaten began to bother. The last 12 hours before admission to the hospital, pain in the chest and epigastrium intensified, all eaten food came out with vomiting. X-ray diagnosed strangulated paraesophageal hernia of the esophageal opening of the diaphragm. During esophagogastroduodenoscopy it was impossible to pass into the distal parts of the stomach; hyperemia and petechial hemorrhages were detected in the zone of strangulation. Video-laparoscopic reduction of the hernial contents, resection of the hernial sac and anterior diaphragm crurorrhaphy were urgently performed. The early postoperative period was uneventful. The presented clinical observation indicates the promise of using video-endoscopic technologies for diagnosis and treatment of strangulated diaphragmatic hernias. The key to success is the timely establishment of the correct diagnosis. We consider it impractical to perform an antireflux intervention simultaneously in conditions of an acute inflammatory process.

Clinical and radiological outcomes of longCOVID: Is the post-COVID fibrosis common?

COVID-19 survivors may take longer to regain full well-being. This study aimed to investigate clinical and functional evaluation and radiologic changes in the third month after COVID-19. A total of 126 patients were assessed in the third month for symptoms, pulmonary function, exercise capacity, radiologic imaging, and quality of life after being discharged following COVID-19 treatment. Two radiologists evaluated the initial and follow-up images. At the third month follow-up visit, the most common persisting symptoms were shortness of breath (32.5%), cough (12.7%), and muscle pain (12.7%). At the follow-up visit, oxygen saturations at rest and after a sixmin walking test were lower in patients with prior intensive care hospitalization compared to those without (p<0.001, p= 0.004). Computed tomography (CT) scans revealed persisting pulmonary pathologies in 64.6% of patients at the third month follow-up. The most common pathologies on follow-up thoracic CT were fibrotic-like changes in 44.2% and ground-glass opacities (GGO) in 33.3%. Regression analysis unveiled that age [95% confidence interval (CI), 1.01 to 1.15; p= 0.020], male sex (95% CI, 4.06 to 95.3, p<0.001), first CT severity score (95% CI, 1.02 to 1.41, p= 0.028), duration of hospitalization (95% CI, 1.02 to 1.18, p= 0.012), oxygen saturation (95% CI, 0.86 to 0.96, p<0.001) were independent predictors of fibrotic-like changes. In the third month following COVID-19, the most common symptom was dyspnea, and the most common radiological findings were fibrotic-like changes and GGO. Longer follow-up studies of COVID-19 survivors are needed to observe lasting changes.

Ultrahigh-Resolution Photon-Counting Detector CT of the Lungs: Association of Reconstruction Kernel and Slice Thickness With Image Quality.

BACKGROUND. Prior work has shown improved image quality for photon-counting detector (PCD) CT of the lungs compared with energy-integrating detector CT. A paucity of the literature has compared PCD CT of the lungs using different reconstruction parameters. OBJECTIVE. The purpose of this study is to the compare the image quality of ultra-high-resolution (UHR) PCD CT image sets of the lungs that were reconstructed using different kernels and slice thicknesses. METHODS. This retrospective study included 29 patients (17 women and 12 men; median age, 56 years) who underwent noncontrast chest CT from February 15, 2022, to March 15, 2022, by use of a commercially available PCD CT scanner. All acquisitions used UHR mode (1024 × 1024 matrix). Nine image sets were reconstructed for all combinations of three sharp kernels (BI56, BI60, and BI64) and three slice thicknesses (0.2, 0.4, and 1.0 mm). Three radiologists independently reviewed reconstructions for measures of visualization of pulmonary anatomic structures and pathologies; reader assessments were pooled. Reconstructions were compared with the clinical reference reconstruction (obtained using the BI64 kernel and a 1.0-mm slice thickness [BI641.0-mm]). RESULTS. The median difference in the number of bronchial divisions identified versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.5), BI600.4-mm (0.3), BI640.2-mm (0.5), and BI600.2-mm (0.2) (all p < .05). The median bronchial wall sharpness versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.3) and BI640.2-mm (0.3) and was lower for BI561.0-mm (-0.7) and BI560.4-mm (-0.3) (all p < .05). Median pulmonary fissure sharpness versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.3), BI600.4-mm (0.3), BI560.4-mm (0.5), BI640.2-mm (0.5), BI600.2-mm (0.5), and BI560.2-mm (0.3) (all p < .05). Median pulmonary vessel sharpness versus the clinical reference reconstruction was lower for reconstructions with BI561.0-mm (-0.3), BI600.4-mm (-0.3), BI560.4-mm (-0.7), BI640.2-mm (-0.7), BI600.2-mm (-0.7), and BI560.2-mm (-0.7). Median lung nodule conspicuity versus the clinical reference reconstruction was lower for reconstructions with BI561.0-mm (-0.3) and BI560.4-mm (-0.3) (both p < .05). Median conspicuity of all other pathologies versus the clinical reference reconstruction was lower for reconstructions with BI561.0 mm (-0.3), BI560.4-mm (-0.3), BI640.2-mm (-0.3), BI600.2-mm (-0.3), and BI560.2-mm (-0.3). Other comparisons among reconstructions were not significant (all p > .05). CONCLUSION. Only the reconstruction using BI640.4-mm yielded improved bronchial division identification and bronchial wall and pulmonary fissure sharpness without a loss in pulmonary vessel sharpness or conspicuity of nodules or other pathologies. CLINICAL IMPACT. The findings of this study may guide protocol optimization for UHR PCD CT of the lungs.

Pharmacological potential of Withania somnifera (L.) Dunal and Tinospora cordifolia (Willd.) Miers on the experimental models of COVID-19, T cell differentiation, and neutrophil functions.

Cytokine release syndrome (CRS) due to severe acute respiratory coronavirus-2 (SARS-CoV-2) infection leads to life-threatening pneumonia which has been associated with coronavirus disease (COVID-19) pathologies. Centuries-old Asian traditional medicines such as Withania somnifera (L.) Dunal (WS) and Tinospora cordifolia (Willd.) Miers (TC) possess potent immunomodulatory effects and were used by the AYUSH ministry, in India during the COVID-19 pandemic. In the present study, we investigated WS and TC's anti-viral and immunomodulatory efficacy at the human equivalent doses using suitable in vitro and in vivo models. While both WS and TC showed immuno-modulatory potential, WS showed robust protection against loss in body weight, viral load, and pulmonary pathology in the hamster model of SARS-CoV2. In vitro pretreatment of mice and human neutrophils with WS and TC had no adverse effect on PMA, calcium ionophore, and TRLM-induced ROS generation, phagocytosis, bactericidal activity, and NETs formation. Interestingly, WS significantly suppressed the pro-inflammatory cytokines-induced Th1, Th2, and Th17 differentiation. We also used hACE2 transgenic mice to further investigate the efficacy of WS against acute SARS-CoV2 infection. Prophylactic treatment of WS in the hACE2 mice model showed significant protection against body weight loss, inflammation, and the lung viral load. The results obtained indicate that WS promoted the immunosuppressive environment in the hamster and hACE2 transgenic mice models and limited the worsening of the disease by reducing inflammation, suggesting that WS might be useful against other acute viral infections. The present study thus provides pre-clinical efficacy data to demonstrate a robust protective effect of WS against COVID-19 through its broader immunomodulatory activity.

Rib Plating Outcomes in Elderly Trauma Patients with Multiple Rib Fractures: A Community Hospital Experience

Rib plating has been shown to be beneficial among certain populations, such as patients with flail chest and failure to wean from the ventilator in patients without primary pulmonary pathology. Surgical intervention has been shown to decrease ventilatory requirements, decrease pain management modalities, and lower costs. A retrospective data analysis was done to determine the efficacy of rib plating in elderly trauma patients with rib fractures on a total of 244 patients, 63% male and 37% female, mean age is 64 ± 18.5 years, 76% had an associated comorbid condition, such as Diabetes Mellitus (DM), Chronic Obstructive Pulmonary Disease (COPD), Coronary Artery Disease (CAD), Chronic Kidney Disease (CKD), or any combination, with 111 (46%) on anticoagulant therapy. 95% patients presented to the emergency department (ED) with Mild GCS range (13-15). Moderate GCS (9-12) was 4% and 3% of patients Severe GCS (3-8). The overall mortality rate was 4.5%.

Cerebrospinal Fluid Protein Markers Indicate Neuro-Damage in SARS-CoV-2-Infected Nonhuman Primates

Neurologic manifestations are among the most frequently reported complications of COVID-19. However, given the paucity of tissue samples and the highly infectious nature of the etiologic agent of COVID-19, we have limited information to understand the neuropathogenesis of COVID-19. Therefore, to better understand the impact of COVID-19 on the brain, we used mass-spectrometry–based proteomics with a data-independent acquisition mode to investigate cerebrospinal fluid (CSF) proteins collected from two different nonhuman primates, Rhesus Macaque and African Green Monkeys, for the neurologic effects of the infection. These monkeys exhibited minimal to mild pulmonary pathology but moderate to severe central nervous system (CNS) pathology. Our results indicated that CSF proteome changes after infection resolution corresponded with bronchial virus abundance during early infection and revealed substantial differences between the infected nonhuman primates and their age-matched uninfected controls, suggesting these differences could reflect altered secretion of CNS factors in response to SARS-CoV-2-induced neuropathology. We also observed the infected animals exhibited highly scattered data distributions compared to their corresponding controls indicating the heterogeneity of the CSF proteome change and the host response to the viral infection. Dysregulated CSF proteins were preferentially enriched in functional pathways associated with progressive neurodegenerative disorders, hemostasis, and innate immune responses that could influence neuroinflammatory responses following COVID-19. Mapping these dysregulated proteins to the Human Brain Protein Atlas found that they tended to be enriched in brain regions that exhibit more frequent injury following COVID-19. It, therefore, appears reasonable to speculate that such CSF protein changes could serve as signatures for neurologic injury, identify important regulatory pathways in this process, and potentially reveal therapeutic targets to prevent or attenuate the development of neurologic injuries following COVID-19.

Peak nasal inspiratory flow in chronic obstructive pulmonary disease.

The nasal airflow in chronic obstructive pulmonary disease (COPD) is poorly characterized. Peak nasal inspiratory flow (PNIF) is a valuable instrument for assessing nasal airflow and the effect of pulmonary pathology such as COPD on PNIF remains unknown. To test the hypothesis that nasal airflow is reduced in COPD, we assessed airflow using PNIF in COPD and a control group. We also explored whether there is an association between COPD, chronic rhinosinusitis without nasal polyps (CRSsNP), and other predefined covariates with PNIF. Ninety patients with COPD and 67 controls underwent PNIF and spirometry. The associations between PNIF and COPD and pre-bronchodilator forced expiratory volume in the first second (FEV1) (% predicted) were assessed by multivariable linear regression in two separate models. PNIF was significantly lower in the COPD group than in the control group. Multivariable linear regression showed that COPD and pre-bronchodilator FEV1 (% predicted) were significantly associated with lower PNIF after adjustment for age, sex, CRSsNP, weight and height. CRSsNP was not associated with PNIF in either of the adjusted regression analyses. PNIF is lower in COPD than in a control group. The finding of a low PNIF in the absence of disease in the upper airways may be due to obstructive lower airways diseases and special care should be taken when interpreting PNIF values in patients with COPD or reduced FEV1.

Repurposing Axl Kinase Inhibitors for the Treatment of Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) infection persists as a common pathogen of pulmonary infection in infants and in the elderly with high morbidity and mortality. However, no specific therapeutics are available. Axl, a member of the TAM (Tyro3, Axl, and Mertk) family receptor kinases, is a pleiotropic inhibitor of the innate immune response and functions as a negative regulator of interferon pathway activation. In this report, we investigated Axl inhibitors for their effects against RSV infection. Axl inhibition with kinase inhibitors, including BMS-777607, R428, and TP-0903, or Axl ablation resulted in a significant reduction of RSV infection in cell-based assays. In an animal model of pulmonary RSV infection, treatment with BMS-777607, R428, or TP-0903 ameliorated pulmonary pathology with a significant reduction of RSV titers in the lung tissues and, consequently, decreased the expression of proinflammatory genes. The host promotes ISG expression for the antiviral response and for viral clearance. We found that Axl inhibition led to more robust IFN-β expression and antiviral gene induction. Thus, the results of this study imply that Axl kinase inhibitors may possess a broad spectrum of antiviral effects by promoting ISG expression.