Comparison of the Efficacy of Systemic Versus Local Steroid Treatment in Idiopathic Granulomatous Mastitis: A Cohort Study.

INTRODUCTION: Steroid therapy is known to be effective against granulomatous mastitis. We aimed to compare the efficacy of local versus systemic steroid administration in patients with idiopathic granulomatous mastitis. MATERIALS AND METHODS: This prospective cohort study included 58 patients who had either local (n = 42) or systemic (n = 16) treatment due to granulomatous mastitis between 2015 and 2019. Recurrence rates were determined as per ultrasound and magnetic resonance imaging examinations and the rate of side effects was evaluated as per patient complaints and physical examinations at the end of a 2-year follow-up period. RESULTS: Median doses of 140 mg and 3810 mg were administered to the local and systemic group, respectively. Six (14.3%) patients in the local treatment group and 13 (81.3%) in the systemic treatment group had steroid-related side effects. The local treatment group had significantly fewer side effects than the systemic treatment group (P < 0.001). The recurrence rates were similar in both groups (P > 0.05). CONCLUSIONS: Local steroid injection was as effective as systemic steroid therapy. Compared to systemic therapy, local steroid administration can be considered as a new therapeutic protocol with a lower dose and side effect rate.

When and how important is anti-fibrotic therapy in the post-COVID-19 period?

PURPOSE: In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various post-acute signs and symptoms. In our study, we aimed to examine the efficacy of anti-fibrotic therapy in patients who developed pulmonary fibrosis after COVID-19. METHODS: In total, 15 patients who applied to the Post-Covid Outpatient Clinic between May 2021 and August 2021 and were diagnosed with COVID-19 pneumonia, and whose cough, dyspnea, exertional dyspnea and low saturation continued to be present at least 12 weeks after the diagnosis, were included in the study. Off-label pirfenidone treatment was started according to the radiological findings, pulmonary function test parameters (PFT) and 6-minute walking test (6MWT) results. The patients were followed up for 12 weeks. RESULTS: While all of the FVC, FVC%, FEV1, FEV1%, DLCO%, DLCO/VA%, 6MWT, and room air saturation levels were observed to increase statistically significantly in the patients at the 12th week, it was determined that there was a statistically significant decrease in the pulse level in room air (p = 0.01, 0.01, 0.01, 0.01, 0.004, 0.001, 0.002, 0.001, and 0.002, respectively). In regression analysis based on radiological scoring, it was observed that the DLCO and room air saturation levels at the 12th week of the treatment were statistically significantly higher in patients with lower scores at the beginning (p = 0.04, 0.03). In addition, it was observed that anti-fibrotic treatment, which was started in the earliest period, i.e., 12 weeks after the diagnosis, resulted in an improvement in radiological, PFT and 6MWT parameters. CONCLUSION: Patients who still had dyspnea and low saturation 12 weeks after the diagnosis, defined as chronic COVID-19, should be evaluated for anti-fibrotic therapy after the necessary radiological and PFT evaluation. Early treatment commencement brings about, besides radiological improvement, a better response obtained in PFT and 6MWT (Tab. 2, Fig. 2, Ref. 21).

Hemorrhagic lesions associated with anticoagulant therapy: a pictorial review.

Anticoagulant therapy is a treatment that can cause bleeding complications in many anatomical structures. Intracranial, intramuscular and intraabdominal bleeding are internal bleeding that can be secondary to anticoagulated therapy. The prognosis of these hemorrhages can be very good, depending on the anatomical region involved, or they can be fatal. Early recognition of especially intracranial and renal hemorrhages is important for prognosis. For diagnosis, CT and / or MRI should be evaluated according to the region. Internal bleeding should be kept in mind in cases such as sudden hemoglobin decrease or change in consciousness during anticoagulant therapy.

The association of OSAS and uvula: the role of MRI in this egg-chicken problem in OSAS.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) is a condition resulting from repetitive partial or complete upper airway obstruction, and its etiology remains uncertain. Polysomnography is the gold standard diagnostic test for OSAS. However, there are long wait times for this evaluation, so questionnaires or ancillary diagnostic methods are used to select appropriate patients. One of these is magnetic resonance imaging (MRI). The present study aimed to investigate the association between clinical features of OSAS and uvular changes on MRI. MATERIALS AND METHODS: A total of 102 participants, 80 with OSAS and 22 controls, were included in the study. All participants underwent full-night polysomnography, MRI, and anthropometric measurements. RESULTS: In comparisons of MRI measurements of the uvula, statistically significant differences in uvular length, thickness, and angle were observed between the OSAS and control groups. MRI measurement significantly associated with apnea-hypopnea index was uvular thickness. Evaluation of anthropometric and MRI measurements revealed statistically significant associations between waist circumference and uvular thickness, uvular width, and oropharyngeal space among the OSAS patients. CONCLUSION: Thickened uvula on MRI is associated with the presence of OSAS, and its thickness is well correlated with the severity of the diseases. Thus, it may be a reliable indicator of OSAS and could be used as a supportive finding to identify patients suitable for referral for diagnostic polysomnography.

A Rare Neurologic Disease that Mimics Cranial Hydatid Cyst: Leukoencephalopathy, Cerebral Calcifications, and Cysts.

A 33-year-old male patient was admitted to the clinic with seizures and progressive neurologic symptoms. In the family history of the patient, a first degree relative had a history of hydatid cyst surgery. Cranial computed tomography images showed intracranial cysts and calcifications. Thus, it was suspected that it might be hydatid cyst. However, the patient was diagnosed with leukoencephalopathy with intracranial calcifications and cysts, a rare neurologic entity by advanced radiologic imaging, serologic and pathologic evaluation.

Is it better to include necrosis in apparent diffusion coefficient (ADC) measurements? The necrosis/wall ADC ratio to differentiate malignant and benign necrotic lung lesions: Preliminary results.

PURPOSE: To determine whether the use of necrosis/wall apparent diffusion coefficient (ADC) ratios in the differentiation of necrotic lung lesions is more reliable than measuring the wall alone. MATERIALS AND METHODS: In this retrospective study, a total of 76 patients (54 males and 22 females, 71% vs. 29%, with a mean age of 53 ± 18 years, range, 18-84) were enrolled, 33 of whom had lung carcinoma and 43 had a benign necrotic lung lesion. A 3T scanner was used. The calculation of the necrosis/wall ADC ratio was based on ADC values measured from necrosis and the wall of the lesions by diffusion-weighted imaging (DWI). Statistical analyses were performed with the independent samples t-test and receiver operating characteristic analysis. Intraobserver and interobserver reliability were calculated for ADC values of wall and necrosis. RESULTS: The mean necrosis/wall ADC ratio was 1.67 ± 0.23 for malignant lesions and 0.75 ± 0.19 for benign lung lesions (P < 0.001). To estimate malignancy the area under the curve (AUC) values for necrosis ADC, wall ADC, and the necrosis/wall ADC ratio were 0.720, 0.073, and 0.997, respectively. A wall/necrosis ADC ratio cutoff value of 1.12 demonstrated a 100% sensitivity and 98% specificity in the estimation of malignancy. Positive predictive value was 100%, and negative predictive value 98% and diagnostic accuracy 99%. There was a good intraobserver and interobserver reliability for wall and necrosis. CONCLUSION: The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating lung carcinoma from benign necrotic lung lesions than measuring the wall alone. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1001-1006.

Added value of DCE-MRI in the management of cystic-cavitary lung lesions.

BACKGROUND AND OBJECTIVE: We evaluated the added value of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to CT in the evaluation of cystic-cavitary lung lesions. We aimed to compare morphological parameters, including wall thickness and inner wall irregularity, and to determine whether DCE-MRI with morphological and dynamic parameters was useful in indeterminate lesions. We also aimed to investigate the added value of DCE-MRI in terms of whether to biopsy, and if so the site of biopsy. METHODS: This prospective study included 39 consecutive patients with cystic and/or cavitary lung lesions detected by CT who then underwent additional DCE-MRI. After initial evaluation, the lesions were classified as benign, indeterminate or malignant and the findings of CT and DCE-MRI compared with each other by considering the final diagnosis that was determined by histopathological findings and clinical evaluation and follow up. RESULTS: The mean values for wall thickness obtained by DCE-MRI were lower and the range of wall thickness for indeterminate lesions was narrower than those obtained by CT (5.50-11.50 mm and 5.75-13.50 mm for DCE-MRI and CT), and inner wall irregularity on DCE-MRI was more sensitive in malignant lesions. Also, DCE-MRI obviated biopsy in three benign patients and changed the biopsy site in two patients. CONCLUSION: Our study suggests that DCE-MRI is helpful in indeterminate cystic-cavitary lung lesions, with morphological and dynamic features. It narrowed the range of wall thickness used for indeterminate lesions, was more sensitive than CT in determining malignant inner wall irregularity, and was also useful in determining the need for and appropriate site of biopsy. See article, page 576.

The Use of Breast Magnetic Resonance Imaging Parameters to Identify Possible Signaling Pathways of a Serum Biomarker, HE4.

OBJECTIVES: This study aimed to investigate the relationship between breast magnetic resonance imaging (MRI) parameters; clinical features such as age, tumor diameter, N, T, and TNM stages; and serum human epididymis protein 4 (HE4) levels in patients with breast carcinoma and use this as a means of estimating possible signaling pathways of the biomarker, HE4. METHODS: Thirty-seven patients with breast cancer were evaluated by breast MRI and serum HE4 levels before therapy. Correlations between parameters including age, tumor diameter T and N, dynamic curve type, enhancement ratio (ER), slope washin (S-WI), time to peak (TTP), slope washout (S-WO), and the serum level of HE4 were investigated statistically. Human epididymis protein 4 levels of early and advanced stage of disease were also compared statistically. RESULTS: Breast MRI parameters showed correlation to serum HE4 levels and correlations were statistically significant. Of these MRI parameters, S-WI had higher correlation coefficient than the others. Human epididymis protein 4 levels were not statistically different in early and advanced stage of disease. CONCLUSIONS: High correlation with MRI parameters related to neoangiogenesis may indicate signaling pathway of HE4.

Correlation of diffusion MRI with the Ki-67 index in non-small cell lung cancer.

BACKGROUND: The primary objective of the study was to evaluate the association between the minimum apparent diffusion coefficient (ADCmin) and Ki-67, an index for cellular proliferation, in non-small cell lung cancers. Also, we aimed to assess whether ADCmin values differ between tumour subtypes and tissue sampling method. METHODS: The patients who had diffusion weighted magnetic resonance imaging (DW-MRI) were enrolled retrospectively. The correlation between ADCmin and the Ki-67 index was evaluated. RESULTS: Ninety three patients, with a mean age 65 ± 11 years, with histopathologically proven adenocarcinoma and squamous cell carcinoma of the lungs and had technically successful DW-MRI were included in the study. The numbers of tumour subtypes were 47 for adenocarcinoma and 46 for squamous cell carcinoma. There was a good negative correlation between ADCmin values and the Ki-67 proliferation index (r = -0.837, p < 0.001). The mean ADCmin value was higher and the mean Ki-67 index was lower in adenocarcinomas compared to squamous cell carcinoma (p < 0.0001). There was no statistical difference between tissue sampling methods. CONCLUSIONS: Because ADCmin shows a good but negative correlation with Ki-67 index, it provides an opportunity to evaluate tumours and their aggressiveness and may be helpful in the differentiation of subtypes non-invasively.

[Diffusion magnetic resonance imaging of thorax]. / Toraks difüzyon manyetik rezonans görüntüleme.

Although magnetic resonance imaging (MRI) of Thorax is only useful for morphological evaluation, currently we can use it for functional evaluation such as diffusion weighted imaging. Currently, we can obtain higher quality images because of new technologies such as software that decrease motion artefact, use of multi-channel, parallel imaging and fast sequences. Many promising results of thorax MRI have been published. It may also be an alternative to thorax computed tomography in some indications without radiation exposure risk. In this review, we evaluated current literature on use of DWI MRI examination on the pathologies of lungs and mediastinum and aimed to present what kind of information is provided on recognition and characterization of thoracic pathologies.

Role of Neutrophils as Therapeutic Targets in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge.

Temporal Assessment of Gadolinium Deposition and T1 Signal Intensity Changes in Rat Kidney with Single and Multiple Doses of Injection: An Experimental Study.

BACKGROUND:  Gadolinium deposition in biological tissues was first reported in patients with renal failure. We aimed to investigate gadolinium deposition in the rat kidney after exposure to single and multiple doses of gadolinium and evaluate deposition for 1- and 3-month periods. We also aimed to determine any correlation between the amount of deposition and T1-weighted image intensity. METHODS:  Seventy rats (5 animals per group) were included in the sample, and 9 groups received a single dose (0.3, 0.6, and 1.2 mmol/kg) of gadolinium, and 1 group for each dose was sacrificed at the end of the first day, week, and month. Four groups received weekly doses (0.3 and 0.6 mmol/kg) and were sacrificed at the end of 6 and 12 weeks. Measurement of T1 intensities was carried out with postinjection images before sacrifice, and deposition was determined using inductively coupled plasma mass spectrometry. RESULTS:  The number of injections was associated with increased gadolinium deposition (P <.001) in the kidney. After the weekly injections, the deposited gadolinium levels did not significantly difer between the low and medium doses at the end of the sixth week (P=.067). There was no agreement between the observers regarding the measurement of T1 signal intensity in both single-dose and multidose experiments (P=.263 and P=.307, respectively). CONCLUSION:  Deposition was dose dependent in the postinjection stage in contrast to the late stage in which deposition was not associated with dose or number of injections until the 12th week. T1 signal intensity measurement is unreliable for assessing deposition in the rat kidney.

Ultrasonography-based staging of inflammatory granulomatous mastitis and estimation of steroid response.

OBJECTIVES: The aim of this study is to present novel diagnostic ultrasonography (USG)-based classification of inflammatory granulomatous mastitis (IGM) and to assess and compare dosage responses of locoregional steroid therapy. METHODS: From January 2017 through March 2023, total of 230 biopsy-proven IGM patients were reclassified (grades I, II, and III) according to USG-based morphological features. The injection applications were grouped in Group1 (40 mg/mL between years 2017 and 2019) versus Group2 (80 mg/mL between years 2019 and 2023), and effectiveness was analysed for each grade in between groups. RESULTS: The mean age was 31 years old (range: 19-60) with median follow-up period of 7 months. The most common clinical presentation was breast mass accompanying draining skin sinuses of the affected skin and hypoechogenic mass with tubular extensions was the most prevalent feature on USG examination. As per USG-based features, 79 (34.3%) patients were redefined as grade I, 64 (27.8%) as grade II, and 87 (37.8%) as grade III. All patients underwent locoregional steroid injection only. The average number of treatments in the first group was 6 (±3 SD) with an effective dose of 40 mg/mL in the first group, and 4 (±2 SD) with an effective dose of 80 mg/mL in the second group. The generalized linear mixed model was used to investigate effects between groups (P < .05). CONCLUSIONS: High-dose steroid treatment was effective in burnout lesions (grades II and III), and it was found to be statistically significant in lowering number of treatments irrespective of grade. ADVANCES IN KNOWLEDGE: This novel classification could be a convenient tool in terms of common language between radiologists and clinicians. In addition, our study is a pioneer in comparing steroid dosage with no relapse in IGM patients.

The role of dynamic magnetic resonance imaging in the evaluation of pulmonary nodules and masses.

OBJECTIVE: The aim of our study was to determine whether or not dynamic magnetic resonance imaging (MRI) with kinetic and morphological parameters can reveal significant differences between malignant and benign pulmonary lesions, and thus to evaluate the use of dynamic MRI in the management of pulmonary nodules. PATIENTS AND METHODS: Thirty-one patients (4 women and 27 men) underwent 1.5 T MRI, where 10 consecutive dynamic series were performed every 30 s by using 3D fast low-angle shot sequences. The percentage increase in the signal intensity of the lesions was determined for each time point. Time-enhancement curves of the lesions were drawn and classified into four types: A, B, C and D. Early peak (EP) and maximum peak (MP) values of the curves were calculated and compared with the diagnoses of the patients. The usefulness of these parameters was tested statistically. In addition to the comparison of the parameters between the groups, receiver-operating characteristic analysis was used to assess sensitivity, specificity, and both positive and negative predictive values of EP and MP parameters. RESULTS: Of the 31 pulmonary lesions, 16 (52%) were malignant. These showed a stronger enhancement with higher median values of EP and MP (77.08 and 123.15, respectively) than those corresponding to the benign lesions (14.45 and 32.53, respectively). There were significant differences between the benign and malignant lesions (p < 0.001). Sensitivity, specificity, positive predictive value and negative predictive value were 75, 93, 92 and 78% for EP and 93, 86, 88 and 93% for MP, respectively. CONCLUSION: A combination of kinetic and morphological evaluation in dynamic MRI provided accurate differentiation between benign and malignant pulmonary lesions. It was a useful and noninvasive method of evaluating pulmonary nodules.

Evaluation of the value of exhaled carbon monoxide in the differentiation of viral and bacterial pneumonia.

Aim: This study compared exhaled carbon monoxide (CO) levels in patients hospitalized for bacterial and COVID-19-related viral community-acquired pneumonia. Materials & methods: The study included a total of 150 patients: 50 patients hospitalized for COVID-19 between February 2021 and March 2022, 50 patients with bacterial community-acquired pneumonia and 50 healthy controls. Results: In comparisons of exhaled CO levels among the groups, there was no significant difference between patients with bacterial pneumonia and controls, whereas patients with COVID-19 pneumonia had significantly higher exhaled CO levels compared with both the bacterial pneumonia and control groups (p < 0.001). Conclusion: Viral agents can directly affect the heme oxygenase system of the lower respiratory tract, leading to greater increases in ferritin and exhaled CO levels compared with bacterial pneumonia.

Infections in the lung tissue cause stress in the body. Several mechanisms are activated in the body to balance this stress. The heme oxygenase system plays a role in suppressing inflammation, and its overactivation can cause an increase in the amount of carbon monoxide (CO) we exhale. This study examined exhaled CO levels in patients with bacterial lung infection and COVID-19 viral lung infection in comparison with the healthy population. We found that patients with COVID-19 lung infection had higher levels of CO in their breath than patients with bacterial lung infection and healthy control subjects. These findings suggest that measurements of exhaled CO levels in people with signs and symptoms of lung infection might be used to differentiate patients with viral and bacterial lung infections.

Comparison of two antifibrotic treatments for lung fibrosis in post-COVID-19 syndrome: A randomized, prospective study.

Background: Although pulmonary fibrosis secondary to COVID-19 infection is uncommon, it can lead to problems if not treated effectively in the early period. This study aimed to compare the effects of treatment with nintedanib and pirfenidone in patients with COVID-19-related fibrosis. Methods: Thirty patients who presented to the post-COVID outpatient clinic between May 2021 and April 2022 with a history of COVID-19 pneumonia and exhibited persistent cough, dyspnea, exertional dyspnea, and low oxygen saturation at least 12 weeks after diagnosis were included. The patients were randomized to receive off-label treatment with nintedanib or pirfenidone and were followed up for 12 weeks. Results: After 12 weeks of treatment, all pulmonary function test (PFT) parameters, 6MWT distance, and oxygen saturation were increased compared to baseline in both the pirfenidone group and nintedanib groups, while heart rate and radiological score levels were decreased (p < 0.05 for all). The changes in 6MWT distance and oxygen saturation were significantly greater in the nintedanib group than in the pirfenidone group (p = 0.02 and 0.005, respectively). Adverse drug effects were more frequent with nintedanib than pirfenidone, with the most common being diarrhea, nausea, and vomiting. Conclusion: In patients with interstitial fibrosis after COVID-19 pneumonia, both nintedanib and pirfenidone were observed to be effective in improving radiological score and PFT parameters. Nintedanib was more effective than pirfenidone in increasing exercise capacity and saturation values but caused more adverse drug effects.

Introducción: Aunque la fibrosis pulmonar secundaria a la infección por COVID-19 es poco común, puede generar problemas si no se trata de manera efectiva en el período inicial. Este estudio tuvo como objetivo comparar los efectos del tratamiento con nintedanib y pirfenidona en pacientes con fibrosis relacionada con COVID-19. Métodos: Se incluyeron 30 pacientes que acudieron a la consulta externa post-COVID entre mayo de 2021 y abril de 2022 con antecedentes de neumonía por COVID-19 y presentaron tos persistente, disnea, disnea de esfuerzo y baja saturación de oxígeno al menos 12 semanas después del diagnóstico. Los pacientes fueron aleatorizados para recibir un tratamiento no aprobado con nintedanib o pirfenidona y fueron seguidos durante 12 semanas. Resultados: Después de 12 semanas de tratamiento, todos los parámetros de la prueba de función pulmonar (PFT), la distancia de la PM6M y la saturación de oxígeno aumentaron en comparación con los valores basales tanto en el grupo de pirfenidona como en el de nintedanib, mientras que la frecuencia cardíaca y los niveles de puntuación radiológica disminuyeron (p < 0,05 para todos). Los cambios en la distancia de la PM6M y la saturación de oxígeno fueron significativamente mayores en el grupo de nintedanib que en el grupo de pirfenidona (p = 0,02 y p = 0,005, respectivamente). Los efectos adversos del fármaco fueron más frecuentes con nintedanib que con pirfenidona, siendo los más comunes diarrea, náuseas y vómitos. Conclusión: En pacientes con fibrosis intersticial después de neumonía por COVID-19 se observó que tanto nintedanib como pirfenidona son efectivos para mejorar la puntuación radiológica y los parámetros de la PFT. Nintedanib fue más eficaz que pirfenidona para aumentar la capacidad de ejercicio y los valores de saturación, pero provocó más efectos adversos del fármaco.

Comparison of two antifibrotic treatments for lung fibrosis in post-COVID-19 syndrome: A randomized, prospective study.

BACKGROUND: Although pulmonary fibrosis secondary to COVID-19 infection is uncommon, it can lead to problems if not treated effectively in the early period. This study aimed to compare the effects of treatment with nintedanib and pirfenidone in patients with COVID-19-related fibrosis. METHODS: Thirty patients who presented to the post-COVID outpatient clinic between May 2021 and April 2022 with a history of COVID-19 pneumonia and exhibited persistent cough, dyspnea, exertional dyspnea, and low oxygen saturation at least 12 weeks after diagnosis were included. The patients were randomized to receive off-label treatment with nintedanib or pirfenidone and were followed up for 12 weeks. RESULTS: After 12 weeks of treatment, all pulmonary function test (PFT) parameters, 6MWT distance, and oxygen saturation were increased compared to baseline in both the pirfenidone group and nintedanib groups, while heart rate and radiological score levels were decreased (p<0.05 for all). The changes in 6MWT distance and oxygen saturation were significantly greater in the nintedanib group than in the pirfenidone group (p=0.02 and 0.005, respectively). Adverse drug effects were more frequent with nintedanib than pirfenidone, with the most common being diarrhea, nausea, and vomiting. CONCLUSION: In patients with interstitial fibrosis after COVID-19 pneumonia, both nintedanib and pirfenidone were observed to be effective in improving radiological score and PFT parameters. Nintedanib was more effective than pirfenidone in increasing exercise capacity and saturation values but caused more adverse drug effects.

The melatonin agonist ramelteon attenuates bleomycin-induced lung fibrosis by suppressing the NLRP3/TGF-Β1/HMGB1 signaling pathway.

PURPOSE: The possible effects of ramelteon, a melatonin receptor agonist on bleomycin-induced lung fibrosis were analyzed via transforming growth factor ß1 (TGF-ß1), the high mobility group box 1 (HMGB1) and Nod-like receptor pyrin domain-containing 3 (NLRP3) which are related to the fibrosis process. MATERIALS AND METHODS: Bleomycin (0.1 â€‹mL of 5 â€‹mg/kg) was administered by intratracheal instillation to induce pulmonary fibrosis (PF). Starting 24 â€‹h after bleomycin administration, a single dose of ramelteon was administered by oral gavage to the healthy groups, i.e. PF â€‹+ â€‹RM2 (pulmonary fibrosis model with bleomycin â€‹+ â€‹ramelteon at 2 â€‹mg/kg) and PF â€‹+ â€‹RM4 (pulmonary fibrosis model with bleomycin â€‹+ â€‹ramelteon at 4 â€‹mg/kg) at 2 and 4 â€‹mg/kg doses, respectively. Real-time polymerase chain reaction (real-time PCR) analyses, histopathological, and immunohistochemical staining were performed on lung tissues. Lung tomography images of the rats were also examined. RESULTS: The levels of TGF-ß1, HMGB1, NLRP3, and interleukin 1 beta (IL-1ß) mRNA expressions increased as a result of PF and subsequently decreased with both ramelteon doses (p â€‹< â€‹0.0001). Both doses of ramelteon partially ameliorated the reduction in the peribronchovascular thickening, ground-glass appearances, and reticulations, and the loss of lung volume. CONCLUSIONS: The severity of fibrosis decreased with ramelteon application. These effects of ramelteon may be associated with NLRP3 inflammation cascade.