Aggregates in apheresis-derived platelet concentrates: A 5-year single-centre experience.

BACKGROUND AND OBJECTIVES: The phenomenon of aggregates in apheresis-derived platelet concentrates (APCs) has not yet been fully elucidated. Initially, visible aggregates (IVA) usually dissolve within 24 h after collection, but some persist till the end of the shelf life (persistent aggregates, PA). A study conducted at the Croatian Institute of Transfusion Medicine aimed to identify factors that influence the aggregate occurrence in APCs. MATERIALS AND METHODS: We conducted a cross-sectional study for the 2018-2022 period and collected data on APCs with IVA. We analysed APCs discarded due to PA separately for two apheresis technologies and compared them to the control group. RESULTS: Significantly more donations were discarded in the IVA group compared with the control group and total number of discarded APCs. A total of 205 APCs were discarded due to PA (14.7% of IVA APCs and 1.27% of all APCs collected). Amicus APCs with PA had a significantly lower platelet count and mean platelet volume. They were obtained by procedures with less anticoagulant used. In contrast to Amicus APCs, Haemonetics APCs with PA had a significantly higher platelet count. None of the donor-related factors examined was predictive of PA. CONCLUSION: APCs with IVA are more often discarded, not only due to aggregates, but also for impairment of other quality control parameters. Type of apheresis technology, being one of the most common risk factors for IVA, was not confirmed as the main risk factor for PA. There seem to be some donor-related causal factors.

IMPACT OF AIR TRANSPORT ON BLOOD SAMPLE QUALITY.

The aim of this study was to establish the impact of air transport on blood samples packaged with and without cooling elements and effect of outdoor temperature on sample quality. Venous samples from 38 blood donors in winter and 36 in summer were tested for hemolysis and complete blood count. One tube per subject was kept in controlled conditions at +4 °C. Two sets of tubes were sent by plane from Zagreb to Brussels, one with and one without cooling elements, and another two sets were sent to London following the same principle. Packages with cooling elements were stored in controlled warehousing conditions at airports (+2 °C to +8 °C), whereas packages without cooling elements were stored in ambient warehouse conditions. Data loggers were used for temperature monitoring. Our research revealed statistically significant differences in several hematologic parameters when comparing the samples stored in controlled laboratory conditions and those transported by plane. These differences were more pronounced in the samples transported during the summer. Transport conditions without cooling elements had additional negative impact on the sample quality. Transport of samples using cooling elements and controlled warehousing conditions at airports are sometimes not sufficient to maintain laboratory storage conditions.

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).

International Society of Blood Transfusion survey of experiences of blood banks and transfusion services during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has impacted blood systems worldwide. Challenges included maintaining blood supplies and initiating the collection and use of COVID-19 convalescent plasma (CCP). Sharing information on the challenges can help improve blood collection and utilization. MATERIALS AND METHODS: A survey questionnaire was distributed to International Society of Blood Transfusion members in 95 countries. We recorded respondents' demographic information, impacts on the blood supply, CCP collection and use, transfusion demands and operational challenges. RESULTS: Eighty-two responses from 42 countries, including 24 low- and middle-income countries, were analysed. Participants worked in national (26.8%) and regional (26.8%) blood establishments and hospital-based (42.7%) institutions. CCP collection and transfusion were reported by 63% and 36.6% of respondents, respectively. Decreases in blood donations occurred in 70.6% of collecting facilities. Despite safety measures and recruitment strategies, donor fear and refusal of institutions to host blood drives were major contributing factors. Almost half of respondents working at transfusion medicine services were from large hospitals with over 10,000 red cell transfusions per year, and 76.8% of those hospitals experienced blood shortages. Practices varied in accepting donors for blood or CCP donations after a history of COVID-19 infection, CCP transfusion, or vaccination. Operational challenges included loss of staff, increased workloads and delays in reagent supplies. Almost half of the institutions modified their disaster plans during the pandemic. CONCLUSION: The challenges faced by blood systems during the COVID-19 pandemic highlight the need for guidance, harmonization, and strengthening of the preparedness and the capacity of blood systems against future infectious threats.

External quality assessment providers' services appear to more impact the immunohaematology performance of laboratories than national regulatory and economic conditions.

OBJECTIVES: Medical laboratories may, at their own discretion, exceed but not undercut regulatory quality requirements. Available economic resources, however, may drive or hinder eagerness to exceed minimum requirements. Depending on the respective scopes of regulatory and economic framework conditions, differing levels of quality efforts to safeguard laboratory performance can be anticipated. However, this has not yet been investigated. METHODS: Immunohaematology external quality assessment (EQA) results collected by 26 EQA providers from their participant laboratories in 73 countries from 2004 to 2019 were evaluated. Error rates were aggregated in groups according to the respective national regulatory and economic framework conditions, to whether or not expert advice was provided in case of incorrect results, and the frequency of EQA samples. RESULTS: These representative data indicate no association between national regulatory (mandatory participation in EQA, monitoring of performance of individual laboratories by authorities, financial consequences of incorrect results) and economic (level of national income, share of national health expenditure) conditions to the quality performance of medical laboratories in immunohaematology. However, EQA providers' support for laboratories in the event of incorrect results appear to be associated with lower error rates, but a high EQA sample frequency with higher error rates. CONCLUSIONS: Further research into the impact of introducing or changing services of EQA providers is needed to confirm the results found in this first of its kind study.

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.

Weight Gain in Lung Transplantation Patients during the COVID-19 Pandemic in Croatia.

BACKGROUND: To determine the effect of lockdown measures on lung transplant patients during the COVID-19 pandemic. SUBJECTS AND METHODS: We collected data from Croatian lung transplant patients before and after the lockdown and analyzed changes in weight, BMI, lung function and blood lipid status. RESULTS: An average increase of 3.74 kg (+4.92%) body weight during the 4 month lockdown period was observed. Lung function values and blood lipid status remained stable. CONCLUSION: Such weight gain could have detrimental effects on the morbidity and mortality of lung transplant patients. Further follow up is needed to determine the long term impacts of this observation.

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.

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.

ADAPTATION AND VALIDATION OF THE CAMBRIDGE PULMONARY HYPERTENSION OUTCOME REVIEW (CAMPHOR) FOR CROATIA.

Pulmonary hypertension (PH) is a chronic disease which severely impairs quality of life (QoL). The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific tool to assess patient-reported symptoms, functioning and QoL in PH patients. The aim of this study was to adapt and validate the CAMPHOR for use in Croatia. The adaptation process involved three stages: translation (bilingual and lay panel), cognitive debriefing interviews with patients and psychometric validation. For the latter stage, a postal survey was conducted with 50 patients to examine the reliability and validity of the adapted scale. All three scales of the Croatian CAMPHOR demonstrated excellent internal consistency (Symptoms = 0.93; Activity limitations = 0.94; QoL = 0.92) and test-retest reliability correlations (Symptoms = 0.90; Activity limitations = 0.95; QoL = 0.90). Predicted correlations with the SF-36 scales provided evidence for construct validity of the CAMPHOR scales. Evidence for known group validity was shown by the ability of the scales to distinguish between participants based on patient-perceived general health and disease severity. The Croatian version of the CAMPHOR is a valid and reliable tool for use in clinical routine and clinical research.

Anemia, hypoalbuminemia, and elevated troponin levels as risk factors for respiratory failure in patients with severe exacerbations of chronic obstructive pulmonary disease requiring invasive mechanical ventilation.

AIM: To determine in-hospital and post-discharge mortality, readmission rates, and predictors of invasive mechanical ventilation (IMV) in patients treated at intensive care unit (ICU) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD). METHODS: A retrospective observational cohort study included all patients treated at a respiratory ICU for AECOPD during one year. A total of 62 patients (41 men) with mean age 68.4±10.4 years were analyzed for outcomes including in-hospital and post-discharge mortality, readmission rates, and IMV. Patients' demographic, hematologic, biochemical data and arterial blood gas (ABG) values were recorded on admission to hospital. Mean duration of follow-up time was 2.4 years. RESULTS: Of 62 patients, 7 (11.3%) died during incident hospitalization and 21 (33.9%) died during the follow-up. The overall 2.4-year mortality was 45.2%. Twenty nine (46.8%) patients were readmitted due to AECOPD. The average number of readmissions was 1.2. Multivariate analysis showed that blood pH, bicarbonate levels, low albumin, low serum chloride, and low hemoglobin were significant predictors of IMV during incident hospitalization (P<0.001 for the overall model fit). CONCLUSION: High in-hospital and post-discharge mortality and high readmission rates in our patients treated due to AECOPD at ICU indicate that these patients represent a high risk group in need of close monitoring. Our results suggested that anemia, hypoalbuminemia, and elevated troponin levels were risk factors for the need of IMV in severe AECOPD. Identification of such high-risk patients could provide the opportunity for administration of an appropriate and timely treatment.

[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.

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.