Idiopathic Fibrosis Research Articles

Nintedanib alleviates polypropylene mesh-induced adhesion in rabbit ventral herniorrhaphy

Abstract BACKGROUND: Nintedanib (previously known as BBIF 1120) was approved by the United States Food and Drug Administration and European Medical Agency to treat idiopathic lung fibrosis in the year 2014 and 2015, respectively. It is now gaining interest for its anti-fibrotic activity in other organs and disease conditions. Although a surgical mesh is used as a mainstay therapy for herniorrhaphy, postoperative peritoneal adhesion with a polypropylene mesh is a significant drawback. This study aims to assess the efficacy of nintedanib in preventing postoperative adhesion incited with a polypropylene mesh in a rabbit model of ventral hernia. MATERIALS AND METHODS: Ventral hernia was induced surgically in ten adult healthy New Zealand White rabbits of either sex. Hernioplasty was performed with a polypropylene mesh, and the rabbits were randomly allocated into two groups to receive either oral 1 ml sterile water or 100 mg nintedanib in 1 ml of sterile water for 7 days. The adhesion of the implanted mesh with the intra-abdominal organs was assessed clinically, by histological and ultrastructural studies with scanning electron microscopy (SEM) at 30 days postoperatively. RESULTS: All rabbits were clinically healthy for 30 days post-surgery with no complication at the site of surgery. The incidence of peritoneal adhesion and tenacity was less in the nintedanib group versus the control group (P = 0.00105). Histopathological and SEM evaluations also indicated less fibrosis and adhesion in the nintedanib-treated group versus control. CONCLUSION: Our results show successful prevention of mesh-associated adhesion with nintedanib, but further studies on the mechanistic pathway, pharmacokinetics, dose standardization, and evaluation of systemic side effects are warranted.

Long-term experience with AMS-700 CXR inflatable penile prosthesis in high-risk patients with corporal fibrosis.

Despite the widespread use of narrow diameter inflatable penile prosthesis (IPP) cylinders in patients with corporal fibrosis, outcomes data is sparse. We evaluated patients who underwent IPP placement with AMS™ 700 Controlled Expansion Restricted (CXR) cylinders from 2007-2021. Patient characteristics, device details, and surgical outcomes were assessed. A non-validated questionnaire was also distributed to patients to assess satisfaction. Among 982 IPPs placed over the study period at our institution, 49 (5.0%) used CXR cylinders. Indications for narrow cylinders: prior explant for infection (67.3%), ischemic priapism (16.3%), and idiopathic fibrosis (16.3%). Median corporal length was 19 cm (IQR 17-21 cm). Discordant intraoperative corporal measurements (24.5%) and RTE lengths (26.5%) were common. Post-operative complications occurred in 8 patients (16.3%) and included 3 infections (6.1%), 2 cylinder herniations (4.1%), 2 mechanical failures (4.1%), and one case of glans necrosis (2.0%). Five of these (10.2%) required explantation, while 4 (8.2%) were managed with revision. Over the follow-up period, 73.5% of patients reported satisfaction with rigidity. Primary drivers of dissatisfaction were perceived loss of penile length and girth. The AMS™ 700 CXR is a useful tool for challenging corporal fibrosis cases and shows acceptable surgical outcomes with moderate patient acceptability.

Assessing Lung Fibrosis with ML-Assisted Minimally Invasive OCT Imaging.

This paper presents a combined optical coherence tomography (OCT) imaging/machine learning (ML) technique for real-time analysis of lung tissue morphology to determine the presence and level of invasiveness of idiopathic lung fibrosis (ILF). This is an important clinical problem as misdiagnosis is common, resulting in patient exposure to costly and invasive procedures and substantial use of healthcare resources. Therefore, biopsy is needed to confirm or rule out radiological findings. Videoscopic-assisted thoracoscopic wedge biopsy (VATS) under general anesthesia is typically necessary to obtain enough tissue to make an accurate diagnosis. This kind of biopsy involves the placement of several tubes through the chest wall, one of which is used to cut off a piece of lung to send for evaluation. The removed tissue is examined histopathologically by microscopy to confirm the presence and the pattern of fibrosis. However, VATS pulmonary biopsy can have multiple side effects, including inflammation, tissue morbidity, and severe bleeding, which further degrade the quality of life for the patient. Furthermore, the results are not immediately available, requiring tissue processing and analysis. Here, we report an initial attempt of using ML-assisted polarization sensitive OCT (PS-OCT) imaging for lung fibrosis assessment. This approach has been preliminarily tested on a rat model of lung fibrosis. Our preliminary results show that ML-assisted PS-OCT imaging can detect the presence of ILF with an average of 77% accuracy and 89% specificity.

Copper homeostasis dysregulation in respiratory diseases: a review of current knowledge.

Cu is an essential micronutrient for various physiological processes in almost all human cell types. Given the critical role of Cu in a wide range of cellular processes, the local concentrations of Cu and the cellular distribution of Cu transporter proteins in the lung are essential for maintaining a steady-state internal environment. Dysfunctional Cu metabolism or regulatory pathways can lead to an imbalance in Cu homeostasis in the lungs, affecting both acute and chronic pathological processes. Recent studies have identified a new form of Cu-dependent cell death called cuproptosis, which has generated renewed interest in the role of Cu homeostasis in diseases. Cuproptosis differs from other known cell death pathways. This occurs through the direct binding of Cu ions to lipoylated components of the tricarboxylic acid cycle during mitochondrial respiration, leading to the aggregation of lipoylated proteins and the subsequent downregulation of Fe-S cluster proteins, which causes toxic stress to the proteins and ultimately leads to cell death. Here, we discuss the impact of dysregulated Cu homeostasis on the pathogenesis of various respiratory diseases, including asthma, chronic obstructive pulmonary disease, idiopathic interstitial fibrosis, and lung cancer. We also discuss the therapeutic potential of targeting Cu. This study highlights the intricate interplay between copper, cellular processes, and respiratory health. Copper, while essential, must be carefully regulated to maintain the delicate balance between necessity and toxicity in living organisms. This review highlights the need to further investigate the precise mechanisms of copper interactions with infections and immune inflammation in the context of respiratory diseases and explore the potential of therapeutic strategies for copper, cuproptosis, and other related effects.

COVID-19 PBMCs are doubly harmful, through LDN-mediated lung epithelial damage and monocytic impaired responsiveness to live Pseudomonas aeruginosa exposure.

Although many studies have underscored the importance of T cells, phenotypically and functionally, fewer have studied the functions of myeloid cells in COVID disease. In particular, the potential role of myeloid cells such as monocytes and low-density neutrophils (LDNs) in innate responses and particular in the defense against secondary bacterial infections has been much less documented. Here, we compared, in a longitudinal study, healthy subjects, idiopathic fibrosis patients, COVID patients who were either hospitalized/moderate (M-) or admitted to ICU (COV-ICU) and patients in ICU hospitalized for other reasons (non-COV-ICU). We show that COVID patients have an increased proportion of low-density neutrophils (LDNs), which produce high levels of proteases (particularly, NE, MMP-8 and MMP-9) (unlike non-COV-ICU patients), which are partly responsible for causing type II alveolar cell damage in co-culture experiments. In addition, we showed that M- and ICU-COVID monocytes had reduced responsiveness towards further live Pseudomonas aeruginosa (PAO1 strain) infection, an important pathogen colonizing COVID patients in ICU, as assessed by an impaired secretion of myeloid cytokines (IL-1, TNF, IL-8,…). By contrast, lymphoid cytokines (in particular type 2/type 3) levels remained high, both basally and post PAO1 infection, as reflected by the unimpaired capacity of T cells to proliferate, when stimulated with anti-CD3/CD28 beads. Overall, our results demonstrate that COVID circulatory T cells have a biased type 2/3 phenotype, unconducive to proper anti-viral responses and that myeloid cells have a dual deleterious phenotype, through their LDN-mediated damaging effect on alveolar cells and their impaired responsiveness (monocyte-mediated) towards bacterial pathogens such as P. aeruginosa.

Abstract PO2-02-13: A Mechanical Conditioning gene expression (MeCo) score detects the patients that benefit from neoadjuvant anti-fibrotic therapy in early HER2-negative breast cancer (HER2negBC)

Abstract Background: Extracellular matrix (ECM) stiffness in the tumor microenvironment is associated with aggressive features that lead to adverse clinical outcomes, including metastasis. Mechanical conditioning (MC) is the phenomenon whereby cancer cells that have grown in a fibrotic-like stiff ECM acquire aggressive features which can be maintained after metastasis in distant sites (Cell Rep.; 35:109293). MeCo Score is a gene expression signature that measures the response to ECM stiffness in early tumors which is associated with subsequent metastasis. We sought to study whether MeCo Score is associated with pathologic complete response (pCR) in early HER2negBC, and whether anti-fibrotic treatment with nintedanib (a multikinase VEGFR1-3, FGFR1-3 and PDGFRA/B inhibitor approved for idiopathic lung fibrosis) is able to mitigate the impact of MC. Methods: Baseline tumor samples from patients (N=130) from a randomized phase II clinical trial (Clin Cancer Res 23: 1432-42) in early HER2negBC trial comparing weekly paclitaxel monotherapy (85 mg/m2 x 12 courses; N=65; Arm A) versus the same treatment plus nintedanib (150 mg p.o. bid, continuous schedule; Arm B) were analyzed by RNAseq. MeCo Score was computed as previous described (Cell Rep.; 35:109293), and intrinsic PAM50 subtypes were determined using the R package genefu. Clinical, demographic and pathologic variables were gathered for all patients; pCR was graded according to the Residual Cancer Burden (RCB) score, RCB=0. Regression models were built using the variables RCB, T, N, G, age, intrinsic subtype, Ki67, MeCo Score and treatment arm. Bi-variate correlations were analyzed with the Pearson coefficient. All statistic tests were two-sided. Results: MeCo Score was successfully determined in 76 women (50% from each arm); the average score was 0.34 (range: 0.052 – 0.617). Of them, 48.6% were Luminal A, 34.2% Luminal B, 14.5% Basal-like, and 2.7% Normal according to PAM50. Median age was 49 y.o. (range: 30.6 – 79.2); tumor size distribution was T1:3.0%; T2:68.2%; T3:24.3%; T4: 4.5%; 47% of the patients were N0, 47% were N1 and 6% were N2. Most patients (85%) were ER and/or PR positive; 15% were “triple-negative”. Histological grade distribution was G1/G2/G3: 15%/62%/23%. The average Ki67 was 28.7% (range: 1%-98%). pCR was 10.8% and 4.5% in arms A and B. The average MeCo Score by intrinsic subtype was 0.26 (LumA); 0.43 (LumB) and 0.38 (Basal), LumB vs LumA P< 0.001; LumB vs Basal: P=0.037. We did not find correlation between MeCo Score and G, T, N, age or Ki67, neither in the Luminal subgroup or the whole cohort. In Arm A, patients with high MeCo Score (i.e., above median) had a 0% pCR rate compared to 10.5% pCR rate for those with low MeCo Score (P=0.035); however, in the nintedanib arm (Arm B) no differences were found: 10.5% versus 11.1% pCR rate in high versus low MeCo Score (P=0.4). Conclusions: Among early HER2negBC, Luminal B cases display the highest MeCo Scores. MeCo Score was independent of all classic prognostic variables. High MeCo Score is associated with lack of pCR to neoadjuvant paclitaxel monotherapy, but concurrent administration of the anti-fibrotic agent nintedanib rescues this association. Citation Format: Miguel Quintela-Fandino, Adam Watson, Adam Grant, Gus Mouneimne, Maria J. Bueno, Silvana Mouron. A Mechanical Conditioning gene expression (MeCo) score detects the patients that benefit from neoadjuvant anti-fibrotic therapy in early HER2-negative breast cancer (HER2negBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-13.

A synergistic mechanism of Liquiritin and Licochalcone B from Glycyrrhiza uralensis against COPD

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a refractory respiratory disease mainly attributed to multiple pathological factors such as oxidative stress, infectious inflammation, and idiopathic fibrosis for decades. The medicinal plant Glycyrrhiza uralensis extract (ULE) was widely used to control respiratory diseases in China. However, the regulatory mechanism of scientific evidence to support the therapeutic benefits of ULE in the management of COPD is greatly limited. PurposeThis study aims to discover the potential protection mechanism of ULE on COPD via a muti-targets strategy. Study design and methodsThe present study set out to determine the potential protective effects of ULE on COPD through a multi-target strategy. In vivo and in vitro models of COPD were established using cigarette smoke and lipopolysaccharide to assess the protective effects of ULE. It was evaluated by measuring inflammatory cytokines and assessing pulmonary pathological changes. HPLC was used to verify the active compounds of the potential compounds that were collected and screened using HERB, works of literature, and ADME tools. The mechanisms of ULE in the treatment of COPD were explored using transcriptomics, connectivity-map, and network pharmacology approaches. The relevant targets were further investigated using RT-PCR, western blot, and immunohistochemistry. The HCK inhibitor (iHCK-37) was used to evaluate the potential mechanism of ULE's active compounds in the prevention of COPD. ResultsULE effectively protected the lungs of COPD mice from oxidative stress, inflammation, and fibrosis damage. After screening and verification using ADME properties and HPLC, 4 active compounds were identified in ULE: liquiritin (LQ), licochalcone B (LCB), licochalcone A (LCA), and echinatin (ET). Network pharmacology integrated with transcriptomics analysis showed that ULE mitigated oxidative stress, inflammation, and fibrosis in COPD by suppressing HCK. The combination of LCB and LQ was optimized for anti-inflammation, antioxidation, and anti-fibrosis activities. The iHCK-37 further validated the preventive treatment of LCB and LQ on COPD by inhibiting HCK to exert antioxidant, anti-inflammatory, and anti-fibrotic effects. The combination of LCB and LQ, in a 1:1 ratio, exerted synergistic antioxidative, anti-inflammatory, and anti-fibrotic effects in the treatment of COPD by downregulating HCK. ConclusionThe combination of LCB and LQ performed a significant anti-COPD effect via downregulating HCK.

Bioinformatics-based dynamics of cuproptosis -related indicators in experimental silicosis

Pneumoconiosis is one of the most serious occupational diseases worldwide. Silicosis due to prolonged inhalation of free silica dust during occupational activities is one of the main types. Cuproptosis is a newly discovered mode of programmed cell death characterized by the accumulation of free copper in the cell, which ultimately leads to cell death. Increased copper in the serum of silicosis patients, suggests that the development of silicosis is accompanied by changes in copper metabolism, but whether cuproptosis is involved in the progression of silicosis is actually to be determined. To test this hypothesis, we screened the genetic changes in patients with idiopathic fibrosis by bioinformatics methods and predicted and functionally annotated the cuproptosis-related genes among them. Subsequently, we established a mouse silicosis model and detected the concentration of copper ions and the activity of ceruloplasmin (CP) in serum, as well as changes of the concentration of copper and cuproptosis related genes in mouse lung tissues. We identified 9 cuproptosis-related genes among the differential genes in patients with IPF at different times and the tissue-specific expression levels of ferredoxin 1 (FDX1) and Lipoyl synthase (LIAS) proteins. Furthermore, serum CP activity and copper ion levels in silicosis mice were elevated on days 7th and 56th after silica exposure. The expression of CP in mouse lung tissue elevated at all stages after silica exposure. The mRNA level of FDX1 decreased on days 7th and 56th, and the protein level remained in accordance with the mRNA level on day 56th. LIAS and Dihydrolipoamide dehydrogenase (DLD) levels were downregulated at all times after silica exposure. In addition, Heatshockprotein70 (HSP70) expression was increased on day 56. In brief, our results demonstrate that there may be cellular cuproptosis during the development of experimental silicosis in mice and show synchronization with enhanced copper loading in mice.

Структурные изменения слоев сетчатки при пилинге внутренней пограничной мембраны в хирургии идиопатического эпиретинального фиброза

Purpose. To study the structural changes in the retinal layers after peeling of the internal limiting membrane (ILM) during surgery for idiopathic epiretinal fibrosis (iERF). Material and methods. The study included 69 patients (69 eyes) with iERF. A retrospective study was conducted with the study of documentation on the basis of the Center of Ophthalmology of the N.I. Pirogov NMHC from the period from 2021 to 2023. Results. The average thickness of the retina in the inner ring decreased from 420.2 ± 55.7 to 361.5 ± 26.8 microns. The total thickness of the retina significantly decreased in both the nasal and temporal internal fields after surgery. Conclusions. In the present study, thickening of the nasal parafoveal zone and thinning of the temporal inner layers of the retina were observed, which is reflected by various anatomical changes caused by peeling of the ILM. Analysis of the thickness of each layer and sector of the retina revealed various changes in the structures. Keywords: internal limiting membrane, idiopathic epiretinal fibrosis, retina

Mesenchymal stem cells: application in chronic lung disease

Chronic lung diseases such as asthma, chronic obstructive lung disease and idiopathic lung fibrosis have limited treatment options and researchers are exploring new avenues to improve patient outcomes. Mesenchymal stem cell therapy has shown promising potential as a treatment option for chronic lung diseases, however, it is essential to note that it is still considered an experimental approach. Studies in animal models and some small-scale clinical trials have shown encouraging results. Mesenchymal stem cell therapy can reduce inflammation, promote tissue repair and potentially slow disease progression. However, it is crucial to understand that stem cell therapy is still in its early stages and many challenges and questions need to be addressed before widespread clinical application. Some of these challenges include determining optimal dose and delivery methods, ensuring the safety of the procedure, understanding long-term effects and addressing potential ethical concerns.

Advances in the Use of N-Acetylcysteine in Chronic Respiratory Diseases.

N-acetylcysteine (NAC) is widely used because of its mucolytic effects, taking part in the therapeutic protocols of cystic fibrosis. NAC is also administered as an antidote in acetaminophen (paracetamol) overdosing. Thanks to its wide antioxidative and anti-inflammatory effects, NAC may also be of benefit in other chronic inflammatory and fibrotizing respiratory diseases, such as chronic obstructive pulmonary disease, bronchial asthma, idiopathic lung fibrosis, or lung silicosis. In addition, NAC exerts low toxicity and rare adverse effects even in combination with other treatments, and it is cheap and easily accessible. This article brings a review of information on the mechanisms of inflammation and oxidative stress in selected chronic respiratory diseases and discusses the use of NAC in these disorders.

Thirteen Cases of Pulmonary Pneumocystis in HIV-Negative Patients.

We report 13 cases of pulmonary pneumocystis (PCP) in human immunodeficiency virus (HIV)-uninfected patients. Of eight males and five females, with a mean age of 55 years, one had breast neoplasia, two had common variable immunodeficiency (CVID), one had an autoimmune disease "Goodpasture's syndrome", and one had idiopathic fibrosis (nonspecific interstitial pneumonia/fibrosis(NIP)) undergoing prolonged corticosteroid therapy for two years, with no known immunosuppression in the remaining cases. The clinical picture was characterized by constant dyspnea and severe hypoxia in 11 cases. Lymphopenia was present in nine caseswith an average rate of 920.76 elements/mm3. The diagnosis was confirmed by isolation of Pneumocystis jirovecii(PCJ) from induced sputum, except in two cases where analysis of bronchoalveolar lavage (BAL) fluid was required. With trimethoprim/sulfamethoxazole (TMP/SMX) and corticosteroid therapy, the course was favorable in all cases. Prophylactic treatment was indicated in three cases.

TOP6: Ambulatory Extra Corporeal Membrane Oxygenation as a Bridge to Lung Transplant

Background: Mechanical circulatory support, including both veno-venous (VV) and veno-arterial (VA) extra corporeal membrane oxygenation (ECMO), is being used more frequently to bridge critically ill patients to lung transplant (LTX). This study evaluates post LTX survival outcomes of patients bridged by ECMO. Methods: The United Network for Organ Sharing (UNOS) thoracic organ transplant database was queried for patients aged >/= 18 years between year 2016 and 2021 to identify pre-transplant patients supported by ECMO. Patients supported by both VA and VV-ECMO were excluded. The patients initially classified in VA-ECMO and VV-ECMO cohorts and further classified as ambulatory (AMB) and non-ambulatory (nAMB) within their respective ECMO cohorts. Each cohort was controlled against the non-ECMO patients. Univariate statistical tests as well as Kaplan-Meier survival curves were used for analysis. Results: Of total 14,369 LTX patients, 13,470 were non-ECMO, 702 were VV-ECMO (44% AMB, 56% nAMB) and 197 were VA-ECMO (47% AMB, 53% nAMB). Table 1A (non-ECMO v. AMB VV-ECMO v. nAMB VV-ECMO at time of LTX) and 1B (non-ECMO v. AMB VA-ECMO v. nAMB VA-ECMO at time of LTX) shows higher age (62 v. 52 v. 50) lower O2 requirement (4 v. 15 v. 10), LAS (44 v. 88 v. 89) and lesser likelihood of COVID etiology (1% v. 22% v. 6%) in non-ECMO group compared to VV-ECMO and VA-ECMO. Within the ECMO groups AMB and nAMB patients were comparable except idiopathic fibrosis was more common in nAMB. The 1-year post LTX survival between non-ECMO and AMB VV-ECMO was comparable (88% v. 88%, p=0.66) which was better than nAMB VV-ECMO patients (88% v. 88% v. 81% (nAMB VV-ECMO), p<.01, F1A). The 1-year (71% v. 78% v. 88%) survival was better for AMB VA-ECMO patients than nAMB VA-ECMO patients, and better for non-ECMO patients than AMB VA-ECMO patients (p<.01, F1B). A Cox proportional hazard model showed that compared to non-ECMO patients, the nAMB VV-ECMO patients (HR = 1.25, p=0.02) had higher risk of post LTX mortality whereas post LTX risk for AMB VV-ECMO patients (HR = 0.95, p=0.71) was similar. Conclusion: Although ambulatory VV-ECMO patients have higher LAS and O2 requirements at time of transplant, their post LTX survival is comparable to the non-ECMO patients. Survival amongst the VA-ECMO patients continued to be poor compared to the non-ECMO patients irrespective of their ambulatory status. Strategies to ambulate ECMO patients could be associated better post LTX outcomes. Figure 1. Survival by ECMO ambulationTable 1. Patient Characteristics at time of LTX

(346) Long Term Experience with AMS-700 CXR™ Prosthesis in High-Risk Patients with Corporal Fibrosis

Abstract Introduction Although commonly utilized for high-risk patients with corporal fibrosis, outcome data for narrow inflatable penile prosthesis (IPP) cylinders are relatively sparse. Objective The objective of this study is to assess the outcomes of a cohort of patients who underwent IPP placement with the AMS-700 CXR™ (CXR) cylinders at our tertiary referral center. Methods We retrospectively reviewed our institutional IPP database for patients who underwent CXR cylinder implantation between 2007 and 2021. Indications, clinical factors, and surgical outcomes were documented for all patients. Kaplan-Meier survival analysis was performed to illustrate implant survival. Patient satisfaction was assessed with a phone survey in which patients provided feedback on penile length, girth, rigidity, and overall satisfaction with the CXR implant. Results Among 1149 IPP surgeries reviewed during the study interval, 49 (4%) underwent CXR implantation with a mean (SD) age of 64 years (±11). Indications for CXR implantation included history of infected IPP (30/49, 62%), ischemic priapism 8/49 (16%), and idiopathic fibrosis (11/49, 22%). Postoperative complications occurred in 6/49 (12%) patients including infection 3/49 (6%), cylinder herniation 2/49 (4%), and glans necrosis 1/49 (2%). Discordant intraoperative corporal measurements were common (13/49, 27%), as were discordant rear tip extender lengths (16/49, 33%). The explantation and revision rates were 3/49 (6%) and 4/49 (8%), respectively. Forty percent (19/48) of patients were available for phone survey response (Figure). A total of 47% (9/19) of patients were dissatisfied with their implant, primarily due to perceived loss of penile length (12/19, 63%) and girth (10/19, 53%). Five (5/9, 55%) of these patients had a history of IPP explantation. Fifty-three percent (10/19) of those surveyed are still satisfied with their implant with 58% (11/19) pleased with the rigidity the CXR implant provides. Conclusions Narrow based inflatable penile implants have acceptable long-term survival. Cylinder lengths are often discordant in corporal fibrosis patients. Despite use in a high-risk group, patient satisfaction remains acceptable, although many complain of perceived loss of penile length and girth. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast.

Terapeutic Remission of Community Acquired Pneumonia Caused by Rothia Mucilaginosa in an Adult Patient with Idiopathic Pulmonar Fibrosis

Rothia Mucilaginosa (RM) is part of the microbiota of the pharynx and upper respiratory tract. RM is a gram-positive, enveloped, coagulase-negative coccus of the family Micrococcaceae. Clinical manifestations range from mild bronchitis to recurrent pneumonia and lung abscess. It is difficult to determine the clinical significance of this organism in respiratory specimens, therefore, in the diagnosis of pneumonia caused by R. mucilaginosa, bronchoscopy specimens should be cultured. Risk factors associated with Rothia are hematologic malignancies and neutropenia. At present, the importance of Rothia in various pathologies remains unclear due to its difficulty in culture and high potential for contamination at the time of sampling. Although it is an oral microbiota, it has been implicated in pneumonia after being identified in sputum or bronchoalveolar lavage smears and in infectious lesions of the respiratory tract, such as lung abscess and empyema. The challenge of MRI infection in clinical practice is deciding whether it is a real infection or a product of sample contamination. We present the case of a 50-year-old adult patient, without neutropenia, without hematological malignancy, with progressive idiopathic pulmonary fibrosis (IPF) of 1 year of evolution. On admission to the hospital, this person presented signs of respiratory failure, tachycardia, upper rales. auscultation and 85% oxygen saturation, that's why he went through many different studies to diagnose Rothia Mucilaginosa pneumonia.

Role of Gut Microbiota and Oxidative Stress in the Progression of Transplant-Related Complications following Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplantation, has curative potential for various hematologic malignancies but is associated with risks such as graft-versus-host disease (GvHD), severe bloodstream infection, viral pneumonia, idiopathic pneumonia syndrome (IPS), lung fibrosis, and sinusoidal obstruction syndrome (SOS), which severely deteriorate clinical outcomes and limit the wide application of HSCT. Recent research has provided important insights into the effects of gut microbiota and oxidative stress (OS) on HSCT complications. Therefore, based on recent studies, we describe intestinal dysbiosis and OS in patients with HSCT and review recent molecular findings underlying the causal relationships of gut microbiota, OS, and transplant-related complications, focusing particularly on the involvement of gut microbiota-mediated OS in postengraftment complications. Also, we discuss the use of antioxidative and anti-inflammatory probiotics to manipulate gut microbiota and OS, which have been associated with promising effects in improving HSCT outcomes.

Impact of physical functional capacity on quality of life in patients with interstitial lung diseases

This study aimed to investigate the physical functioning predictors for health-related quality of life (HRQL) decline in patients with idiopathic interstitial fibrosis (IPF), sarcoidosis and other interstitial lung disease (ILD).The study enrolled 52 patients with ILD and 16 healthy individuals. Participants’ HRQL was assessed using the 36-item Short-Form Health Survey questionnaire. Spirometry, physical performance, and daily physical activity (PA) were monitored.Patients with IPF showed significantly lower PA compared to patients with other ILD (p = 0.002)and sarcoidosis (p = 0.01). The type of disease aetiology had no significant effect on aerobic capacity, HRQL and fatigue. Patients with ILD showed significant greater fatigue, lower physical functioning and greater physical aspects scores compared to the control group (F=6.0; p = 0.018; F=12.64; p = 0.001, respectively). A significant positive correlation was observed between 6-minute walking distance (6MWD) and the physical domain of HRQL (r = 0.35, p = 0.012) and PA and the physical aspects of HRQL (r = 0.37, p = 0.007).This study revealed that the key predictors for HRQL decline were lower lung function, lower PA and physical performance.

Двухпортовая витреомакулярная хирургия в лечении пациентов с эпиретинальным фиброзом

Perpose. To present a method of two-port vitrectomy in treatment of patients with epiretinal fibrosis. Material and methods. Two-port vitrectomy method was used to treat patients with idiopathic epiretinal fibrosis. The group included 25 patients (25 eyes) – 16 (64 %) women and 9 (36 %) men. The mean age of the patients was 61 ± 6.4 years. Exclusion criteria were glaucoma and concomitant retinal pathology. The mean value of best corrected visual acuity was 0.28 ± 0.07. The mean retinal thickness in the fovea was 417 ± 70 µm. Vitrectomy was performed with installation of two ports in the opposite quadrants – in the lower half for high-flow cannula (illuminator-chandelier built with infusion cannula), in the upper half for vitrectomy cutter and instruments. The High-Flow infusion cannula (Synergetics) integrated with the mercury vapor illuminator-chandelier is connected to the Photon II illumination system (Synergetics). Surgery was performed classically: central vitrectomy, separation of posterior hyaloid membrane, staining of membranes with vitral dye, membrane removal, tamponade ⅓ of vitreous cavity with sterile air. The average operation time was 18 minutes. Results. Six months after the operative treatment all patients noted reduction of visual discomfort and severity of metamorphopsies. Best corrected visual acuity was increased – 0.58 ± 0.1 (p ≤ 0,05 vs. preoperative values). Average retinal thickness in the fovea after surgical treatment decreased to 261 ± 25 µm according to macular OCT chart (p = 0.03). FCM readings were consistent with preoperative 5.1 ± 2.3 f/ms (p ≤ 0.01). Conclusion. The method of two-port vitrectomy with the use of mercury vapor chandeleur in the treatment of vitreomacular pathology allows safe and effective macular surgery. Keywords: retinophototoxicity, vitrectomy, epiretinal fibrosis

Recent insights into the role of antifibrotic drugs in the management of idiopathic pulmonary fibrosis (IPF)

Idiopathic aspiratory fibrosis (IPF) is the most well-known sort of idiopathic interstitial pneumonia (IIP). IIPs are precipitously shappening (idiopathic) diffuse parenchymal lung illnesses. IPF is characterized as a precipitouly happening (idiopathic) explicit type of persistent fibrosing interstitial pneumonia restricted to the lung and related with an example of Usual Interstitial Pneumonia (UIP) on imaging or histology. Pleasant rules for the analysis of Interstitial Lung Disease (ILD), preceding thought for against fibrotic treatment, specify that the conclusion of ILD has been made by a multidisciplinary group (MDT).

What is the need and why is it time for innovative models for understanding lung repair and regeneration?

Advances in tissue engineering continue at a rapid pace and have provided novel methodologies and insights into normal cell and tissue homeostasis, disease pathogenesis, and new potential therapeutic strategies. The evolution of new techniques has particularly invigorated the field and span a range from novel organ and organoid technologies to increasingly sophisticated imaging modalities. This is particularly relevant for the field of lung biology and diseases as many lung diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic fibrosis (IPF), among others, remain incurable with significant morbidity and mortality. Advances in lung regenerative medicine and engineering also offer new potential avenues for critical illnesses such as the acute respiratory distress syndrome (ARDS) which also continue to have significant morbidity and mortality. In this review, an overview of lung regenerative medicine with focus on current status of both structural and functional repair will be presented. This will serve as a platform for surveying innovative models and techniques for study, highlighting the need and timeliness for these approaches.