Parenchymal Fibrosis Research Articles

Bufei huoxue capsule alleviates bleomycin-induced pulmonary fibrosis in mice via TGF-β1/Smad2/3 signaling

Ethnopharmacological relevanceBufei huoxue (BFHX) is a Traditional Chinese Medicine formulation that consists of Astragalus Exscapus L, Paeonia Lactiflora Pall, and Psoralea Aphylla L. It can ameliorate collagen deposition and inhibit EMT. However, it remains unknown whether and how BFHX alleviates IPF. Aim of the studyOur work aimed to explore the therapeutic efficacy of BFHX on IPF and dissect the mechanisms involved. Materials and methodsA mouse model of IPF was induced by bleomycin. BFHX was administered on the first day of modeling and maintained for 21 days. Pulmonary fibrosis and inflammation were evaluated by micro-CT, lung histopathology, pulmonary function assessment, and cytokines in BALF. In addition, we examined the signaling molecules involved in EMT and ECM by immunofluorescence, western Blot, EdU, and MMP (Δψm) assays. ResultsBFHX alleviated lung parenchyma fibrosis as evidenced by Hematoxylin-eosin (H&E), Masson's trichrome staining, and micro-CT, and it improved lung function. In addition, BFHX treatment not only decreased the levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), but also upregulated E-cadherin (E-Cad) and downregulated α-smooth muscle actin (α-SMA), collagen Ӏ (Col Ӏ), vimentin, and fibronectin (FN). Mechanistically, BFHX repressed TGF-β1–driven Smad2/3 phosphorylation, which, in turn, suppressed EMT and transition of fibroblasts to myofibroblasts in vivo and in vitro. ConclusionBFHX effectively reduces the occurrence of EMT and inhibits the production of ECM by inhibiting the TGF-β1/Smad2/3 signaling pathway, which provides a potential novel therapeutic strategy for IPF.

A Prospective Observational Study Among Patients on Long Term Hemodialysis for Changes in Serum Electrolytes with Varying Urine Outputs and Impact of Patient Counselling on their Quality of Life- A Pilot Study

Chronic kidney disease (CKD) is defined as a progressive loss of function occurring over several months to years and is characterized by the gradual replacement of normal kidney architecture with parenchymal fibrosis. End stage renal disease (ESRD) is defined as irreversible decline in a person's own kidney function, which is severe enough to be fatal in the absence of dialysis or transplantation. Since hemodialytic patients with greater urine output have a greater ability to excrete electrolytes, acids, and fluid compared to patients low urine output, they are likely to have less body accumulation of these elements. Health-related quality of life (HRQOL) is a critically important outcome for patients with ESRD.

RETRACTED ARTICLE: Qilongtian ameliorate bleomycin-induced pulmonary fibrosis in mice via inhibiting IL-17 signal pathway

Pulmonary fibrosis (PF) is a special type of pulmonary parenchymal disease, with chronic, progressive, fibrosis, and high mortality. There is a lack of safe, effective, and affordable treatment methods. Qilongtian (QLT) is a traditional Chinese prescription that is composed of Panax notoginseng, Earthworm, and Rhodiola, and shows the remarkable clinical curative effect of PF. However, the mechanism of QLT remains to be clarified. Therefore, we studied the effectivity of QLT in treating Bleomycin (BLM) induced PF mice. 36 C57BL/6 J mice were randomized into the control group, the model group, the low-, medium- and high-dose QLT group, and Pirfenidone group. After establishing a model of pulmonary fibrosis in mice, the control and model groups were infused with a normal saline solution, and the delivery group was infused with QLT. Pulmonary function in the mice from each group was detected. Pulmonary tissue morphologies and collagen deposition were stained by HE and Masson. The content of hydroxyproline (HYP) was detected by alkaline hydrolysis and the mRNA and protein expression of related genes in pulmonary tissues were detected by using q-PCR, ELISA, and Western blot. Our studies have shown that QLT significantly reduced the inflammatory injury, hydroxy-proline content, and collagen deposition of pulmonary tissue in BLM-induced PF mice and down-regulated the cytokine related to inflammation and fibrosis and PF expression on the mRNA and protein level in PF mice. To identify the mechanism of QLT, the Transcriptome was measured and the IL-17 signal pathway was screened out for further research. Further studies indicated that QLT reduced the mRNAs and protein levels of interleukin 17 (IL-17), c–c motif chemokine ligand 12 (CCL12), c-x-c motif chemokine ligand 5 (CXCL5), fos-like antigen 1 (FOSL1), matrix metalloproteinase-9 (MMP9), and amphiregulin (AREG), which are inflammation and fibrosis-related genes in the IL-17 signal pathway. The results indicated that the potential mechanism for QLT in the prevention of PF progression was by inhibiting inflammation resulting in the IL-17 signal pathway. Our study provides the novel scientific basis of QLT and represents new therapeutics for PF in clinical.

The alternative approach: genomic classifiers for prognostication in interstitial lung disease

Interstitial lung disease (ILD) reflects a large group of entities characterised by pulmonary parenchymal inflammation and fibrosis, with many patients suffering from functional limitation, progressive symptoms and accelerated mortality [1]. Idiopathic pulmonary fibrosis (IPF), which is characterised by a usual interstitial pneumonia (UIP) pattern on imaging and histology, is the most common and deadly form of ILD [2, 3]. Prognosis and treatment approaches differ between ILD subtypes, making an accurate diagnosis crucial; however, this can be challenging due to overlapping clinical and morphological presentations of some ILDs. The potential of genomic classifiers for ILD prognostication has not been exhausted yet <http://bit.ly/3ZMMdjx>

Cytokine imbalance and progression of changes in the liver parenchyma in patients with non-alcoholic fatty liver disease and essential hypertension

Objective — to determine the relationship between the activity of pro‑ and anti‑inflammatory cytokines and liver functional parameters in patients with non‑alcoholic fatty liver disease (NAFLD) and hypertension (HTN), depending on the degree of liver parenchyma damage. Materials and methods. The study included 120 people, divided into 3 groups: 49 patients (67.3% women) with NAFLD and concomitant HTN (main group); 51 patients (58.5% women) with isolated NAFLD (comparison group) and 20 relatively healthy individuals (55.0% women and 45.0% men) of the control group. In the main group, 55.1% of patients had steatosis, 44.9% had steatohepatitis. In the comparison group, 58.8% had steatosis, 41.2% had steatohepatitis (χ2=0.141, p=0.707). The assessments included body mass index (BMI), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), γ‑glutamine transpeptidase, interleukin 8 and 10 (IL‑8, IL‑10), alkaline phosphatase (ALP), De Ritis index (AST/ALT ratio). The diagnosis of NAFLD and HTN was established in accordance with the local and international recommendations. Ultrasound examination of the liver was performed according to the standard method in fasting condition. Results. Body mass index corresponded to the normal or increased body weight: in the main group — 27.8 [26.6; 28.5] kg/m2 and 27.3 [24.2; 28.3] kg/m2 in the comparison group, in the control group — 24.3 [21.9; 26.0] kg/m2 (p&lt;0.001 and p=0.004 respectively). The results of the biochemical analysis showed a significant (p&lt;0.001) predominance of AST and ALT in patients with steatohepatitis compared to patients with steatosis, both in the main/group (AST=56.5 [54.0, 57.0] U/l and ALT=47.0 [44.5; 49.0] U/L, respectively), and in the comparison group (AST=45.0 [43.0; 48.0] U/l and ALT 39.0 [35.0; 42.0] U/L, respectively). The analysis of correlational relationships in patients with steatohepatitis, stronger relationships were found, both between the systemic increase in blood pressure, and between the cytokine’s levels and liver functional parameters. Thus, in patients of the main group with steatohepatitis, an inverse relationship was determined between the levels of AST and anti‑inflammatory IL‑10 (r=–0.588, p=0.004), the levels of GGTP (r=–0.407 p=0.060) and the levels of albumin (r=– 0.466, p=0.069). In patients of the comparison group and steatohepatitis, an inverse correlation was determined between the levels of diastolic blood pressure and GGTP (r=0.490, p=0.024). GGTP levels were also inversely correlated with AST levels (r=–0.508, p=0.019) and directly with IL‑8 and IL‑10 levels (r=0.438, p=0.049 and r=0.373, p=0.096). IL 10 demonstrated a strong negative correlation with albumin levels (r=–0.604, p=0.004). IL‑8 levels showed a direct correlation with IL‑10 (r=0.431, p=0.051) in this subgroup of patients. Conclusions. The presence of concomitant hypertension in patients with NAFLD was associated with more active progression compared to patients with isolated NAFLD. Correlation analysis showed gradual exhaustion of anti‑inflammatory protection and increase of pro‑inflammatory activity as changes in liver parenchyma progressed, especially in patients with comorbid NAFLD and HTN course. That allows us to consider HTN as a prognostically unfavorable risk factor for the development and progression of the liver parenchyma fibrosis.

Relationships Between Systemic Inflammatory Markers and 18F-FDG PET/CT Imaging and Clinical Findings in Pulmonary Sarcoidosis.

Background and aim Sarcoidosis is a multisystem inflammatory disease of unknown aetiology. This study aimed to evaluate the relationship between systemic inflammatory parameters, the systemic immune-inflammation index (SII) and the lymphocyte-to-monocyte ratio (LMR), and disease stage, clinical findings, and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) tomography/computed tomography (PET/CT) uptake. Materials and methods Our study included 73 patients. The general characteristics, radiological features, spirometric tests, PET/CT findings, and laboratory parameters of the patients were recorded. Results Relapse and parenchymal fibrosis were not associated with metabolic parameters, such as LMR and SII. Serum angiotensin-converting enzyme (ACE) levels were lower in the relapsed group than in the non-relapse group. However, the patients' PET/CT images indicated that 18F-FDG parenchym maximum standard uptake value (SUV max), lymph node SUV max, lymph node short axis dimension, SII, and LMR were similar between all patients, relapsed or not. Conclusion Although found to be significant in other inflammatory diseases, we found that SII and LMR alone did not indicate disease prognosis in sarcoidosis due to the small number of patients and the lack of homogeneity between the groups in our study. The usefulness of these markers for clinical use should be investigated by studies that include those with extrapulmonary sarcoidosis, and that calculate these markers at the time of disease diagnosis and during the post-treatment period.

МУЛЬТИМОДАЛЬНАЯ ДИАГНОСТИКА У ПАЦИЕНТОВ С КОМПОНЕНТАМИ МЕТАБОЛИЧЕСКОГО СИНДРОМА, ПЕРЕНЕСШИХ ИНТЕРСТИЦИАЛЬНУЮ ПНЕВМОНИЮ, АССОЦИИРОВАННУЮ С COVID-19

Introduction. Coronavirus infectious disease caused by SARS-CoV-2 characterized by vast clinical variability. Extrapulmonary complications associated with endothelial damage, thrombosis and impaired regulation of immune responses provide unfavorable impact on the outcome of the disease and rehabilitation opportunities. Also, infection inflict damage to the gastrointestinal tract, hepatobiliary system. A key - roles to avoid aforementioned conditions are proper diagnosis and treatment plan, which should be make as soon as possible among the patients with elements of metabolic syndrome. The aim of the study - analyze the possibilities of multimodal diagnostics in patients with elements of the metabolic syndrome who get infected by SARS-CoV-2. Material and methods. In 41 patients with positive SARS-CoV-2, according to a nasopharyngeal smear study, the elements of the metabolic syndrome such as an increase in body mass index, serum triglycerides, and blood pressure were determined. Dynamic ultrasound of the abdominal cavity organs, CT scan of the chest in the near and distant periods were performed. Results and discussion. In the period 2020 - 2021. in patients with elements of the metabolic syndrome who have suffered of interstitial pneumonia caused by COVID-19, the predominant patterns was diffuse mosaic changes in lung tissue lesions with the spread of changes in lung parenchyma to more than one segment were identified. In a comparative aspect, dynamic multimodal diagnostics of abdominal organs was performed, confirming extrapulmonary complications from the liver: hepatosplenomegaly (p ≤ 0.01), changes of hemodynamics in hepatic vessels in patients with MS (p ≤ 0.05), increased stiffness and formation of liver parenchyma fibrosis in almost 15% (F2- F3). Conclusion. Study confirm the need for careful and long-term monitoring of patients, who are a in group of risk to develop metabolic syndrome with multimodal noninvasive ultrasound control of the condition of target organs.

Fibroblast Activation Protein Activates Macrophages and Promotes Parenchymal Liver Inflammation and Fibrosis

Fibroblast activation protein (FAP) is expressed on activated fibroblast. Its role in fibrosis and desmoplasia is controversial, and data on pharmacological FAP inhibition are lacking. We aimed to better define the role of FAP in liver fibrosis invivo and invitro. FAP expression was analyzed in mice and patients with fibrotic liver diseases of various etiologies. Fibrotic mice received a specific FAP inhibitor (FAPi) at 2 doses orally for 2 weeks during parenchymal fibrosis progression (6 weeks of carbon tetrachloride) and regression (2 weeks off carbon tetrachloride), and with biliary fibrosis (Mdr2-/-). Recombinant FAP was added to (co-)cultures of hepatic stellate cells (HSC), fibroblasts, and macrophages. Fibrosis- and inflammation-related parameters were determined biochemically, by quantitative immunohistochemistry, polymerase chain reaction, and transcriptomics. FAP+ fibroblasts/HSCs were α-smooth muscle actin (α-SMA)-negative and located at interfaces of fibrotic septa next to macrophages in murine and human livers. In parenchymal fibrosis, FAPi reduced collagen area, liver collagen content, α-SMA+ myofibroblasts, M2-type macrophages, serum alanine transaminase and aspartate aminotransferase, key fibrogenesis-related transcripts, and increased hepatocyte proliferation 10-fold. During regression, FAP was suppressed, and FAPi was ineffective. FAPi less potently inhibited biliary fibrosis. Invitro, FAP small interfering RNA reduced HSC α-SMA expression and collagen production, and FAPi suppressed their activation and proliferation. Compared with untreated macrophages, FAPi regulated macrophage profibrogenic activation and transcriptome, and their conditioned medium attenuated HSC activation, which was increased with addition of recombinant FAP. Pharmacological FAP inhibition attenuates inflammation-predominant liver fibrosis. FAP is expressed on subsets of activated fibroblasts/HSC and promotes both macrophage and HSC profibrogenic activity in liver fibrosis.

Disruption of GCN2 Pathway Aggravates Vascular and Parenchymal Remodeling during Pulmonary Fibrosis.

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) are chronic diseases of the pulmonary parenchyma and circulation, respectively, which may coexist, but underlying mechanisms remain elusive. Mutations in the GCN2 (general control nonderepressible 2) gene (EIF2AK4 [eukaryotic translation initiation factor 2 alpha kinase 4]) were recently associated with pulmonary veno-occlusive disease. The aim of this study is to explore the involvement of the GCN2/eIF2α (eukaryotic initiation factor 2α) pathway in the development of PH during PF, in both human disease and in a laboratory animal model. Lung tissue from patients with PF with or without PH was collected at the time of lung transplantation, and control tissue was obtained from tumor resection surgery. Experimental lung disease was induced in either male wild-type or EIF2AK4-mutated Sprague-Dawley rats, randomly receiving a single intratracheal instillation of bleomycin or saline. Hemodynamic studies and organ collection were performed 3 weeks after instillation. Only significant results (P < 0.05) are presented. In PF lung tissue, GCN2 protein expression was decreased compared with control tissue. GCN2 expression was reduced in CD31+ endothelial cells. In line with human data, GCN2 protein expression was decreased in the lung of bleomycin rats compared with saline. EIF2AK4-mutated rats treated with bleomycin showed increased parenchymal fibrosis (hydroxyproline concentrations) and vascular remodeling (media wall thickness) as well as increased right ventricular systolic pressure compared with wild-type animals. Our data show that GCN2 is dysregulated in both humans and in an animal model of combined PF and PH. The possibility of a causative implication of GCN2 dysregulation in PF and/or PH development should be further studied.

Evaluation of the efficacy of several sclerosing agents for pleurodesis in rats

Objective: This study aims to evaluate the efficiencies and effects of different sclerosing agents. Materials and Methods: Thirty-five female Wistar-albino rats were included in this study and divided into five groups randomly. Isotonic saline (group 1), iodopovidone (group 2), rifamycin (group 3), autologous blood (group 4), talc (group 5) were given into intrapleural space. On postoperative 28th day, ipsilateral and contralateral pleural and parenchymal fibrosis and inflammation were evaluated. Results: There were statistically differences between control and other groups on macroscopically pleural fibrosis examination (p=0.004, p=0.001, p=0.001, p=0.000, respectively). Microscopically pleural fibrosis were determined in all groups when compared to control group (p=0.023, p=0.023, p=0.035, p=0.001, respectively). There were no significant differences between sclerosing agent groups (p&amp;gt;0.05). Significant differences were observed according to microscopic pleural inflammation evaluation between talc group and other groups. There was superiority in talc group according to intraparenchymal inflammation grade compared to other groups (p=0.010, p=0.042, p=0.030, respectively). Macroscopically, fibrosis and microscopically, inflammation were significantly observed between talc and other groups in the contralateral pleura (p = 0.037and p=0.009, respectively). Conclusion: Iodopovidone, autologous blood, talc, and rifamycin can be used as effective pleurodesis agents. However, we found that rifamycin and autologous blood are safer as effective pleurodesis agents. We think that these two agents can be used in patients with secondary lung diseases due to their less intraparenchymal inflammation rates. It may be advantageous to prefer other sclerosing agents which has lower costs and less side effects comparing to talc.

Post-COVID Pulmonary Function Test Evaluation.

Since the lung is the most affected organ by COVID-19 disease, we aimed to evaluate the pulmonary function test, presence of hypoxemia, and Post-COVID-19 Functional Status Scale in 3- to 6-month post-COVID period. Post-COVID-19 Functional Status Scale, pulse oxygen saturation, and pulmonary function test were evaluated in 67 outpatients/inpatients after 3-6 months following COVID-19 (positive reverse transcription-polymerase chain reaction on nasopharyngeal swab) disease. Pre-COVID pulmonary function test parameters were available in 33 patients, and these were compared with post-COVID pulmonary function test parameters. We found 20.9% (14 patients) restrictive and 11.9% (8 patients) obstructive patterns in pulmonary function test. Of those with forced vital capacity < 80%, 53.3% were patients without known lung diseases. When pulmonary function test values before and after COVID-19 were compared, only a loss of 130 mL in forced expiratory volume in 1 second was determined (P = .005). About 65.4% of the patients with dyspnea were in the group without a lung disease (P = .002) and 66.7% of patients with forced expiratory volume in 1 second and forced vital capacity of .05). Smoking, hospitalization, oxygen support, and the severity of computed tomography involvement did not impact pulmonary function test. In post-COVID patients, the major disorder in the respiratory function test was determined as a restriction. However, advanced tests such as lung volumes and carbon monoxide diffusing capacity (DLCO) measurement and high-resolution lung tomography are needed to differentiate in terms of physical functional limitation or parenchymal fibrosis.

SHRINKING LUNG SYNDROME IN SYSTEMIC LUPUS ERYTHEMATOSUS: DIAGNOSIS OF RARE ENTITY

SHRINKING LUNG SYNDROME IN SYSTEMIC LUPUS ERYTHEMATOSUS: DIAGNOSIS OF RARE ENTITY

Pancreatic Ducts Obliteration With Controlled Injection of Onyx®: A Proposal of New Onyx® Pancreatic Ducts Obliteration Scoring System.

The aim of this study was confirm the efficacy and feasibility of Onyx injection for pancreatic stump management after pancreaticoduodenectomy (PD) and investigate a new Onyx® Pancreatic Ducts Obliteration (OPDO) scoring system of pancreatic duct obliteration (PDOb) in patients with high risk of Post-Operative Pancreatic Fistula (POPF). We enrolled ten patients undergoing PDOb with Onyx® intraoperative controlled injection after elective PD. PDOb with Onyx® controlled injection was classified according to the OPDO scoring system in three degrees: complete 5/10 (50%), medium 2/10 (20%) and bad 3/10 (30%). Increased amylase in abdominal drainage was identified in two patients (20%) with a degree II and III, and resolved spontaneously within a week. A "clinically relevant" POPF (CR-POPF) was observed in one patient (10%) with a degree III and none in the patients with degree I and II. We confirm that intraoperative injection of Onyx® is a valid solution in high-risk POPF patients and our OPDO scoring system allows obtain an intraoperative classification of the degree of PDO to prevent the CR-POPOF; furthermore, it may be suggested that the viscosity of the injected product (Onyx®) reduce parenchymal fibrosis.

Quantification of parenchymal fibrosis in chronic pancreatitis: relation to atrophy and pancreatic function.

Non-invasive modalities for assessing chronic pancreatitis (CP) are needed in clinical practice. To investigate the correlation between magnetic resonance elastography (MRE)-derived stiffness and T1 relaxation times (as proxies of fibrosis) and explore their relationships to gland volume and pancreatic functions in patients with CP and healthy controls (HCs). In 49 patients with CP and 35 HCs, pancreatic stiffness, T1 relaxation times, and gland volume were assessed. Fecal elastase and the presence of diabetes were used to evaluate pancreatic exocrine and endocrine functions. Uni- and multivariable linear regression models were used to analyze correlations between imaging parameters. There was a positive correlation between MRE-derived stiffness and T1 relaxation times in patients with CP (R2 = 0.42; P < 0.001) and HCs (R2 = 0.14; P = 0.028). There was no correlation between MRE-derived stiffness and gland volume in patients (R2 = 0.007; P = 0.065) or HCs (R2 = 0.010; P = 0.57). T1 relaxation time was correlated to gland volume (R2 = 0.19; P = 0.002) in patients with CP but not in the HCs (P = 0.056). Severity of pancreatic functional impairment was reflected by increased fibrosis-related parameters in patients without functional impairment, followed by a further increase in fibrosis-related parameters and reduction in gland volume in patients with pancreatic functional impairments. Pancreatic MRE-derived stiffness and T1 relaxation times might reflect early pathophysiological changes in CP. The dynamic correlation with pancreatic function suggests that these parameters may be useful for the non-invasive and early identification of CP.

Lymphocytic Airway Inflammation in Lung Allografts.

Lung transplant remains a key therapeutic option for patients with end stage lung disease but short- and long-term survival lag other solid organ transplants. Early ischemia-reperfusion injury in the form of primary graft dysfunction (PGD) and acute cellular rejection are risk factors for chronic lung allograft dysfunction (CLAD), a syndrome of airway and parenchymal fibrosis that is the major barrier to long term survival. An increasing body of research suggests lymphocytic airway inflammation plays a significant role in these important clinical syndromes. Cytotoxic T cells are observed in airway rejection, and transcriptional analysis of airways reveal common cytotoxic gene patterns across solid organ transplant rejection. Natural killer (NK) cells have also been implicated in the early allograft damage response to PGD, acute rejection, cytomegalovirus, and CLAD. This review will examine the roles of lymphocytic airway inflammation across the lifespan of the allograft, including: 1) The contribution of innate lymphocytes to PGD and the impact of PGD on the adaptive immune response. 2) Acute cellular rejection pathologies and the limitations in identifying airway inflammation by transbronchial biopsy. 3) Potentiators of airway inflammation and heterologous immunity, such as respiratory infections, aspiration, and the airway microbiome. 4) Airway contributions to CLAD pathogenesis, including epithelial to mesenchymal transition (EMT), club cell loss, and the evolution from constrictive bronchiolitis to parenchymal fibrosis. 5) Protective mechanisms of fibrosis involving regulatory T cells. In summary, this review will examine our current understanding of the complex interplay between the transplanted airway epithelium, lymphocytic airway infiltration, and rejection pathologies.

AN ASSESSMENT OF PLEUROPULMONARY POST-TUBERCULOSIS PATIENTS IN A TEACHING HOSPITAL IN EAST INDIA

Objectives: Quality of life of a patient may be impaired seriously in the aftermath of pleuropulmonary tuberculosis (TB) even after being cured or taking adequate treatment. Proper evaluation of post-TB sequelae is of extreme clinical importance. The study objective was to assess demographic, clinical, radiological, and spirometric pattern of pleuropulmonary post-TB patients in a teaching hospital. Methods: An observational cross-sectional study was carried out in a teaching hospital in India over a period of 14 months. A total of 300 patients of more than 12 years of age from both genders were included in the study. Detailed history, clinical, radiological, microbiological, and spirometric evaluation were being carried out. Results: It was a male predominant study with male: female ratio of 2.29:1 and mean age of patient was 52.97 ± 0.51 (mean±standard error of mean) years. History of pleural and pulmonary TB was present in 11% and 89% of cases, respectively. Cough was present in all patients. Shortness of breath (86.33%) and hemoptysis (58.33%) were among other common presenting symptoms. In majority of cases, pulmonary involvement was unilateral (57%). Pleural fibrosis/thickening was seen in 11% of cases, lung parenchymal fibrosis 38.67%, bronchiectasis in 12.67%, and aspergilloma found in 7% of cases. Bacteriological positivity was detected in 14.33% of cases. Spirometric evaluation revealed restrictive pattern (50.20%) in most of the cases followed by obstructive pattern in 38.13% of cases. Conclusion: Respiratory symptoms, radiological, and spirometric abnormalities can present among pleuropulmonary post-TB patients as a sequelae. It may be considered as an important cause of chronic lung disease, particularly in high TB burden countries.

Clinicopathological spectrum of xanthogranulomatous pyelonephritis; a single-center experience over 7 years

Background: Xanthogranulomatous pyelonephritis (XGP) is chronic pyelonephritis subtype where in renal parenchymal destruction occurs and therefore results in progressive loss of kidney functions. Although middle age group is the predominant age group affected but it can be seen at any age. There is accumulation of macrophages (lipid-laden) leading to renal parenchymal destruction and fibrosis. In this study, we present our data of 15 patients who had undergone nephrectomy and were biopsy proven XGP. Aims and Objectives: The aim of the study was to describe the clinical and radiological features of XGP in adults. Materials and Methods: XGP constituted 4.31% of the 348 nephrectomies done for infective causes over a period of 7 years. All our patients had undergone unilateral total nephrectomy. Demographic and clinical records were analyzed after consent from all the patients. Results: The age range in our study was 18–65 years with mean 42.93±15.66 years. Nine of our patients, that is, 60% were females. Diabetes was present in 53.3% of our patients. Three patients had imaging suggestive of pyonephrosis, three patients had perinephric collection and 9 patients (60%) had concomitant nephrolithiasis. All the kidneys were grossly enlarged and were non-functional on renal scintigraphy. Conclusion: XGP is a form of chronic pyelonephritis which although being less common but is devastating given the destruction of renal parenchyma it does and associated morbidity. Clinicoradiologic correlation cannot be overemphasized. The definitive diagnosis is established after histopathologic examination.

Driving Role of Interleukin-2-Related Regulatory CD4+ T Cell Deficiency in the Development of Lung Fibrosis and Vascular Remodeling in a Mouse Model of Systemic Sclerosis.

Systemic sclerosis (SSc) is a debilitating autoimmune disease characterized by severe lung outcomes resulting in reduced life expectancy. Fra-2-transgenic mice offer the opportunity to decipher the relationships between the immune system and lung fibrosis. This study was undertaken to investigate whether the Fra-2-transgenic mouse lung phenotype may result from an imbalance between the effector and regulatory arms in the CD4+ T cell compartment. We first used multicolor flow cytometry to extensively characterize homeostasis and the phenotype of peripheral CD4+ T cells from Fra-2-transgenic mice and control mice. We then tested different treatments for their effectiveness in restoring CD4+ Treg cell homeostasis, including adoptive transfer of Treg cells and treatment with low-dose interleukin-2 (IL-2). Fra-2-transgenic mice demonstrated a marked decrease in the proportion and absolute number of peripheral Treg cells that preceded accumulation of activated, T helper cell type 2-polarized, CD4+ T cells. This defect in Treg cell homeostasis was derived from a combination of mechanisms including impaired generation of these cells in both the thymus and the periphery. The impaired ability of peripheral conventional CD4+ T cells to produce IL-2 may greatly contribute to Treg cell deficiency in Fra-2-transgenic mice. Notably, adoptive transfer of Treg cells, low-dose IL-2 therapy, or combination therapy changed the phenotype of Fra-2-transgenic mice, resulting in a significant reduction in pulmonary parenchymal fibrosis and vascular remodeling in the lungs. Immunotherapies for restoring Treg cell homeostasis could be relevant in SSc. An intervention based on low-dose IL-2 injections, as is already proposed in other autoimmune diseases, could be the most suitable treatment modality for restoring Treg cell homeostasis for future research.

Antifibrotická terapie a její indikace u intersticiální plicní fibrózy

Idiopathic pulmonary fibrosis and chronic fibrotic interstitial lung disease with progressive phenotype are characterized by fibrotic lung parenchyma. Current antifibrotic treatment does not affect pre-existing lung parenchyma fibrosis, but prevents fibrosis progression and reduces mortality by reducing fibrotization. This work summarizes fibrotic lung processes and their treatment options.

Clinicopathologic Spectrum of Xanthogranulomatous Pyelonephritis: A Single Center Experience over 8 Years

Xanthogranulomatous pyelonephritis (XGP) is a chronic pyelonephritis subtype in which destruction of the renal parenchymal occurs, resulting in progressive loss of kidney functions. Although middle age is the predominant age group affected, but it can be spotted at any age. There is accumulation of macrophages (lipid-laden), leading to renal parenchymal destruction and fibrosis. In this study, we present our data of 15 patients who had undergone nephrectomy and had biopsy-proven XGP. XGP constituted 4.53% of the 331 nephrectomies performed for infective causes over a period of 8 years. All our patients had undergone unilateral total nephrectomy. Demographic and clinical data were analyzed after taking consent from all the patients. The age range of patients in our study was 18–65 years with a mean age of 43.93 ± 13.86 years. Ten (66.6%) of our patients were females. Diabetes was present in 40% of the patients. Three patients had imaging, suggestive of pyonephrosis, 3 had perinephric collection and 9 patients (60%) had concomitant nephrolithiasis. All the kidneys were grossly enlarged and were nonfunctional on renal scintigraphy. XGP is a form of chronic pyelonephritis, which, although less common, is devastating because of destruction of the renal parenchyma and associated morbidity. Clinicoradiologic correlation cannot be overemphasized. Definitive diagnosis is established through histopathologic examination.