Search the repository

A+ | A- | | SLO | ENG

Abstract: Background: Highly effective CFTR modulator therapy, such as elexacaftor/tezacaftor/ivacaftor (ETI), has been linked to significant clinical improvements in people with cystic fibrosis (pwCF). However, its effect on the presence of respiratory pathogens in the lower respiratory tract of younger, mainly non-expectorant children with CF remains poorly understood, especially using lower airway sampling methods. We aimed to investigate changes in lower airway microbiology and clinical outcomes in children with CF aged 6-12 years before and after starting ETI. Methods: We conducted a prospective observational single-centre study including children with CF commencing ETI who had no prior exposure to CFTR modulators, inhaled antibiotics, or prophylactic antibiotics. Lower airway microbiology was assessed longitudinally using sputum or induced sputum (IS). Pathogen prevalence, sweat chloride concentration, pulmonary function, nutritional status, and rate of exacerbations were evaluated before and up to 12 months after ETI initiation. Results: Sixteen pwCF were included (median age 8.4 years, 69 % boys, 75% were F508del homozygous). None of the children was expectorant at any point during the study. Following ETI initiation, we observed decreased growth of methicillin-sensitive Staphylococcus aureus and Aspergillus fumigatus, reduced variability in fungal populations, and an increase in negative bacterial and fungal culture results. Conclusions: In this exploratory study of young, modulator-naïve children with CF, ETI initiation was associated with changes in the lower airway microbiology composition assessed by IS. These findings highlight potential shifts in lower airway microbiology and the importance of age-appropriate lower airway sampling in future paediatric studies.
Keywords: children, cystic fibrosis, elexacaftor/tezacafot/ivacaftor, respiratory pathogens
Published in DiRROS: 24.04.2026; Views: 439; Downloads: 384
Full text (1,50 MB)
This document has many files! More...

Abstract: The striking similarity of disc edema without leakage on fluorescein angiography, which is pathognomonic of Leber hereditary optic neuropathy (LHON), was present in a patient with cystic fibrosis with antibiotic toxic optic neuropathy. This similarity suggested the common effect of oxidative stress on retinal ganglion cells in inherited mitochondrial and antibiotic optic neuropathies. We present the case of a patient with advanced cystic fibrosis on chronic antibiotic treatment who experienced a rapid painless bilateral visual decline over a course of a few weeks. At examination, his corrected visual acuity was reduced to 0.3 in both eyes, with dyschromatopsia and central scotoma. The appearance of the fundus resembled the typical clinical features of acute LHON with hyperemic optic discs and tortuous vessels with no dye leakage from the optic discs on fluorescein angiography. Ganglion cell layer loss was seen on optic coherence tomography, with all findings pointing to LHON. Genetic testing did not reveal any LHON-specific mutations. After extended genetic testing, a heterozygous variant c.209C>T in the OPA3 gene on chromosome 19, g.46032648G>A, classified as a variant of unknown significance, was also found. After discontinuing antibiotics and general improvements in his health, surprisingly, his visual function completely improved. Later, he also received a bilateral lung transplant that further improved his general condition, and his vision remained normal. Excluding LHON, the transient optic neuropathy in our patient could be mainly due to antibiotic toxicity of linezolid and ciprofloxacin, which have been linked to mitochondrial dysfunction and advanced cystic fibrosis with hypoxic status. We suggest the possibility that patients with cystic fibrosis may be more prone to developing mitochondrial optic neuropathy, especially with additional risk factors such as chronic antibiotic therapy, which affect mitochondrial function, and can perhaps serve as a model for LHON.
Keywords: mitochondrial optic neuropathy, OPA3, cystic fibrosis
Published in DiRROS: 12.02.2026; Views: 763; Downloads: 392
Full text (4,45 MB)
This document has many files! More...

Abstract: Background. Sclerosing melanocytic lesions, which are characterized by either focal or diffuse sclerosis in the dermal component and atypical proliferation of predominantly nevoid melanocytes, remain poorly defined. Our aim was to analyze systematically their morphologic spectrum, especially the distinction between sclerosing melanocytic nevus and sclerosing melanoma, which has not been well documented. Patients and methods. We collected 90 sclerosing melanocytic lesions, occurring in 82 patients (49 male, 33 female; age range from 21 to 89 years). A four probe fluorescent in situ hybridization (FISH) assay was performed in 41 lesions to substantiate the diagnosis of sclerosing melanomas. Results. A prominent full-thickness pagetoid spread of melanocytes was identified in 44 (48%) lesions, and a melanoma in situ adjacent to the sclerosis in 55 (61%) lesions. In the intrasclerotic component, maturation was absent in 40 (44%) and mitotic figures were identified in 18 (20%) lesions. Of the 90 lesions, 26 (29%) were diagnosed morphologically as nevi and 64 (71%) as melanomas (Breslow thickness from 0.4 to 1.8 mm), including 45 (50%) melanomas with an adjacent nevus. A four-probe FISH assay was positive in the sclerotic component in 14 of 25 lesions diagnosed morphologically as melanomas and none of 16 nevi. A sentinel lymph node biopsy was performed for 17 lesions and was negative in all cases. Conclusions. Sclerosing melanocytic lesions form a morphologic spectrum and include both nevi and melanomas. The pathogenesis of sclerosis remains obscure but seems to be induced by melanocytes or an unusual host response in at least a subset of lesions.
Keywords: sclerosing melanoma, sclerosing nevus, fibrosis
Published in DiRROS: 02.07.2024; Views: 1413; Downloads: 616
Full text (1,34 MB)

Abstract: Background. The outcomes of patients with both lung cancer and idiopathic pulmonary fibrosis (IPF) are unfavorable. Therapeutic interventions for lung cancer such as surgery can cause acute exacerbation of IPF (aeIPF). This study aimed to assess the frequency of IPF in a group of patients with early-stage non-small-cell lung cancer (NSCLC) and to report clinical characteristics and outcomes of this cohort of patients. Patients and methods. This observational cohort retrospective study analyzed 641 pathological records of patients after surgical resection of early-stage non-small-cell lung cancer (NSCLC) at University Clinic Golnik from May 2010 to April 2017. Pathological records of NSCLC with coexisting IPF were reviewed. CT scans and biopsy specimens for this group of patients were analyzed by a thoracic radiologist and pathologist, independently. We searched radiological and pathological features of usual interstitial pneumonia (UIP) pattern in this group of patients. We report the clinical characteristics and outcome of this cohort of patients. Results. Out of 641 patients with early-stage NSCLC, only 13 (2.0%) had histologically and radiologically proven coexisting UIP/IPF. Squamous cell carcinoma was the most common type of lung cancer (7/13 patients). The majority of tumors were small size (all being pT1 or pT2), stage I–II (11/13 patients), located in the lower lung lobes (11/13 patients). Almost all patients were current or ex-smokers (11/13 patients). There were two pathologically confirmed fatal cases (15.4%) due to aeIPF in the first two months after radical treatment, one after adjuvant radiotherapy and the other after surgery. Out of 13 patients, one patient had a lung cancer relapse. Conclusions. Frequency of UIP/IPF in surgically treated early stage NSCLC is rather low. Our observational study shows that radical treatment of lung cancer can cause aeIPF with dismal outcome in this group of patients. The standard of care in these mostly elderly patients still remains unresolved.
Keywords: non-small-cell lung cancer, early-stage cancer, idiopathic pulmonary fibrosis, surgery, radiotherapy
Published in DiRROS: 07.10.2020; Views: 3551; Downloads: 1469
Full text (969,72 KB)