Nintedanib treatment for bleomycin-induced lung injury - First report.

Although the antineoplastic agent bleomycin is known for more than 50 years, its exact pharmacological and side-effect mechanisms remain incompletely understood. The major limitation of bleomycin therapy is the risk of pulmonary toxicity which can be diverse, and potentially fatal in 10% of patients. The optimal treatment for bleomycin lung toxicity has not been established and no clinical trials have been performed. Here we present first successful case report of nintedanib therapy in a patient with bleomycin-induced lung injury (BILI). The prevention, early diagnosis, and management of bleomycin pulmonary toxicities are essential, clinical trials are needed in this area.

Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. METHODS: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 µM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. RESULTS: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).

Compassionate mesenchymal stem cell treatment in a severe COVID-19 patient: a case report.

COVID-19 presentations range from cold-like symptoms to severe symptoms with the development of acute respiratory distress syndrome (ARDS). We report on a severe COVID-19 patient who was mechanically ventilated and who developed ARDS and bacterial infection. Because of rapid clinical deterioration and the exhaustion of other treatment options, the family and attending physicians requested a compassionate use of adult allogeneic bone marrow-derived mesenchymal stem cells (MSC) in addition to commonly used immunosuppressive, antiviral, and supportive therapy. The clinical course is discussed thoroughly, with a special emphasis on the safety and effect of MSC therapy. Compassionate MSC treatment, given in three rounds, affected ARDS regression. The patient was discharged from the intensive care unit after 31 days and from hospital after 49 days in a good general condition. MSC treatment was not associated with any side effects and was well tolerated in a three-week period; therefore, it should be studied in larger trials and considered for compassionate use.

B regulatory cells and monocyte subpopulations in patients with chronic graft-vs-host disease.

AIM: To assess the correlations of B regulatory cells (Bregs) and monocyte subsets in peripheral blood with the National Institutes of Health (NIH)-consensus-defined clinical manifestations of chronic graft-vs-host disease (cGvHD), in an attempt to establish their role as cellular biomarkers. METHODS: This multidisciplinary prospective study enrolled adult cGVHD patients treated in the University Hospital Center Zagreb and University of Zagreb School of Medicine. Immunophenotypic subpopulations of CD24highCD38high Bregs (CD27-, CD27+, and total) and monocyte (classical, intermediate, and non-classical) counts were correlated with demographic, transplant, and cGVHD-related data. Bivariate correlation analysis was performed to evaluate the correlations between Bregs and monocytes subsets and cGVHD organ involvement, as well as cGVHD severity and immunosuppression intensity. RESULTS: Twenty-two adult patients (54.5% female) with cGVHD were enrolled. The median (range) age was 44.5 years (24-65). All patients were transplanted for hematologic malignancies and 40.9% had severe NIH cGVHD global score. The median time from cGVHD diagnosis to the analysis was 16.6 months (0-176). The organ most frequently affected with cGVHD were the eyes (68.2%), skin (45.5%), lungs (45.5%), and liver (40.9%). Lower total and CD27-Bregs counts were correlated with worse cGVHD severity, higher immunosuppression intensity, and lung cGVHD, in terms of cell count, but also with skin cGVHD, in terms of percentages. Patients with liver and joint/fascia cGVHD had a lower percentage of non-classical monocytes and patients with more severe global NIH score had a higher classical monocytes count. CONCLUSION: Different organs affected by cGVHD are differently associated with different subpopulations of Bregs and monocytes.

Treatment of EGFR positive lung adenocarcinoma in a heart transplanted patient.

Lung cancer incidence in heart transplant patients is higher than in general population and correlates with smoking history. EGFR-mutations are more frequent in adenocarcinoma and among non-smoking women but incidence in solid organ transplanted patients is still not known. We present case of a 65-year-old ex-smoker male with history of heart transplantation and EGFR positive metastatic lung adenocarcinoma. At admission he was in a severe clinical condition and treatment with erlotinib was started. Initially he had good clinical and radiologic response to treatment with only grade 1 side effects.  Data about drug interactions between cyclosporine and erlotinib are insufficient but we have to take this interaction into consideration during treatment because both drugs are substrates and inhibitors of CYP34A. In our case erlotinib was safe and well tolerated drug, there were no relevant toxicity, but close monitoring and dose reduction of cyclosporine was needed.

Metastatic cancer mimics interstitial lung disease. Cases when we need fast diagnosis and treatment.

Interstitial lung diseases (ILD) are a heterogeneous group of diseases and one of the differential diagnosis which have to be excluded during diagnostic procedures are malignancies. We will present four patients who were referred to our Department because of suspicion of interstitial lung diseases according to radiology finding. In one case only, one of the radiologist's differential diagnosis was pulmonary lymphangitic carcinomatosis. All four patients had exertional dyspnea and dry cough which are nonspecific and can be first manifestation of ILD or obstructive lung diseases. After diagnostic evaluation in three cases, diagnosis was pulmonary lymphangitic carcinomatosis due to metastatic lung adenocarcinoma and in one due to metastatic adenocarcinoma of unknown primary origin. Patients with lymphangitic carcinomatosis have poor prognosis without treatment and usually die because of respiratory failure. With these four cases we want to highlight importance of thinking about malignancies when we have patients with suspicion of interstitial lung disease especially when reticular pattern is present on chest X ray. We also wanted to show how important is radiology finding and multidisciplinary approach, and how radiologist's differential diagnosis can be very helpful in making decisions in further investigations and way of clinicians thinking.

Anti-HBc prevalence among Croatian blood donors in a 14-year period (2004-2017): Assessment of trends, risks and need for implementing routine testing.

OBJECTIVES: The anti-HBc prevalence over a 14-years period (2004-2017), trends, infectivity, residual risk, and need for testing in blood donors (BD) of the Croatian Institute of Transfusion Medicine were assessed. MATERIAL AND METHODS: Anti-HBc was tested in 19,969 BD serum samples collected in 2004 (N=7561), 2013 (N=7318) and 2017 (N=5090). All serums were initially screened for HBsAg, anti-HCV, HIV Ag/Ab, and anti-TP. 2013 and 2017 samples were also tested by ID-NAT. RESULTS: Over a 14-years period, the anti-HBc prevalence significantly decreased among Croatian BD (5.24% in 2004, 2.56% in 2013, and 1.32% in 2017). Similarly, the prevalence of anti-HBc-only profiles decreased from 0.62% in 2004, 0.25% in 2013, and 0.21% in 2017. The 4-time decreasing trend was observed in all age groups of BD from 2017 but mostly among repeat donors (5.90% to 1.38%). First-time donors showed no significant difference in anti-HBc prevalence probably due to their younger age (<29 years) and HBV vaccine status. However, similar anti-HBs carriage rates (80.56%, 87.57%, and 82.09%) were reported in anti-HBc positive donors over the study period. HBsAg and HBV DNA were not detected. No OBI infection was found in the study despite an OBI frequency of 1:10,900 donations previously reported in Croatia. A HBV decreasing residual risks of 68, 88, and 12 per million donations were estimated for years 2004, 2013, and 2017, respectively. CONCLUSION: Anti-HBc testing is an additional measure of preventing HBV infection by transfusion. Implementation of anti-HBc testing will result in the deferral of 1.3% BD and should be supported by cost-benefit analyses.

[Combined pulmonary fibrosis and emphysema syndrome]. / Sindrom plucne fibroze udruzene s emfizemom.

CPFE-combined pulmonary fibrosis and emphysema is a new term for a syndrome whose main characteristic is fibrosis in lower pulmonary lobes with simultaneous emphysema in upper pulmonary lobes. CPFE patients have well preserved pulmonary test values for unexpectedly long period, but extremely lowered carbon monoxide diffusion capacity and significant arterial hypertension. All CPFE studies indicate that CPFE occurs predominately in older male population. Smoking is considered main cause in developing CPFE. Reduced survival rate is linked with arterial hypertension extent, and mortality rate is greater than that for patients with isolated pulmonary fibrosis or emphysema. This study is focused on characteristics of twelve CPFE patients. This paper describes cases of 12 patients with the syndrome of pulmonary fibrosis associated with emphysema. All patients were male, mean age of 68 years. At the certain period of life they all were smokers, but most of them were also exposed to air pollution due to their profession. Shortness of breath on exertion was present in all patients. All patients had neat pulmonary function tests with significantly reduced diffusing capacity for carbon mon- oxide (average 39%). Pulmonary arterial hypertension (PAH) averaged 56 mmHg (range 25-75 mmHg) was present in 75% of patients. Four patients died during the period of four months, of which three patients had PAH greater than 70 mmHg. The fourth patient died of lung cancer.

WHOQOL-bREF questionnaire as a measure of quality of life in sarcoidosis.

The aim of this study was to evaluate the usefulness of a short form of the WHOQOL questionnaire, the WHOQOL-BREF, which consists of 24 questions, in evaluating quality of life (QOL) in sarcoidosis patients. A group of 97 sarcoidosis patients and a matched group of 97 healthy controls took part in the study. Their QOL was examined by means of the WHOQOL-BREF, and the respiratory functions were measured in sarcoidosis patients. The WHOQOL-BREF revealed significantly poorer QOL of sarcoidosis patients in the domains of Physical and Psychological Health in comparison to healthy controls. In contrast, sarcoidosis patients perceived their QOL significantly better than healthy controls in the domains of Social Relations and Environment. Differences between sarcoidosis patients and healthy controls were found in several items from the WHOQOL-BREF and some of them were modified by gender. However, the WHOQOL-BREF did not prove to be a sensitive measure of fatigue, which is the most common symptom in sarcoidosis patients.

Lymphomatoid granulomatosis in a 23-year-old man--cytological and histological typing and rapid response to steroid and cyclophosphamide combination therapy.

Lymphomatoid granulomatosis (LG) is currently called as extranodal angiocentric and angiodestructive immunoproliferative disorder with various degrees of histological differentiation and disease severity. Histological grading and clinical manifestations are due to number of atypical large EBV + B-lymphatic cells. We report the case of a 23-year-old man clinically presented with fever, sweating, and physical intolerance, and bilateral pulmonary infiltrates of nodular type and destructive changes on the chest X-ray, previously treated with antituberculotics for 1.5 month. As the disease showed progression, diagnostic procedures extended to transbronchial lung biopsy and percutaneous fine needle aspiration with cytological and histological analysis of collected specimens, all being not conclusive enough. LG was confirmed by open lung biopsy, followed by induction of corticosteroids and cyclophosphamide therapy. Very good clinical, functional and radiomorphologic improvement was achieved in a few weeks, and remission of disease maintained in long term follow-up.