Background. A fast and well-organized complex diagnostic process is important for better success in the treatment of lung cancer patients. The aim of our study was to reveal the gaps and inefficiencies in the diagnostic process and to suggest improvement strategies in a single tertiary centre in Slovenia. Patients and methods. We employed a comprehensive approach to carefully dissect all the steps in the diagnostic journey for individuals suspected of having lung cancer. We gathered and analysed information from employees and patients involved in the process by dedicated questionnaires. Further, we analysed the patients' data and calculated the diagnostic intervals for patients in two different periods. Results. The major concerns among employees were stress and excessive administrative work. The important result of the visual journey and staff reports was the design of electronic diagnostic clinical pathway (eDCP), which could substantially increase safety and efficacy by diminishing the administrative burden of the employees. The patients were generally highly satisfied with diagnostic journey, but reported too long waiting times. By analysing two time periods, we revealed that diagnostic intervals exceeded the recommended timelines and got importantly shorter after two interventions - strengthening the diagnostic team and specially by purchase of additional PET-CT machine (the average time from general practitioner (GP) referral to the multidisciplinary treatment board (MDTB) decision was 50.8 [+/- 3.0] prior and 37.1 [+/- 2.3] days after the interventions). Conclusions. The study illuminated opportunities for refining the diagnostic journey for lung cancer patients, underscoring the importance of both administrative and capacity-related enhancements.

In 2019, the Recommendations for the management of patients with lung cancer were published bringing much-needed standardisation of diagnosis and treatment to improve survival of patients with lung cancer. Three years after the original Recommendations were published, the update of the Recommendations brings the most innovations in the chapter on systemic treatment of patients with lung cancer. This reflects the remarkable progress made in the field of understanding the oncogenesis and biology of lung cancer and thus the development of new drugs. The burden of lung cancer remains high, as lung cancer is still the most common cause of cancer related death in our country and worldwide. Lung cancer is responsible for one of five cancer-related deaths. Almost one third of patients with lung cancer do not receive any oncological treatment, either because of poor performance status, comorbidities or the extent of the disease. Half of the patients have metastatic disease at diagnosis, resulting in only small improvements in survival despite advances in the treatment of lung cancer patients. These data remind us that if we are to make major shifts in the management of lung cancer patients, we will need to take different approaches. The most promising seems to be the detection of early stages of lung cancer which offers the best treatment results. The Recommendations written here are guidelines for the management of patients with lung cancer. Only with comprehensive multidisciplinary treatment approach, the best outcome from the prognostically unfavourable disease can be offered.

Izhodišča: Bolniki s plevralnim izlivom pogosto potrebujejo razbremenilno plevralno punkcijo (RPP), po kateri navajajo bolj ali manj izrazito olajšanje dispneje. Zaradi varnosti se priporoča, da se med RPP odstrani do 1.500 mL tekočine. Metode: V raziskavo smo vključili 96 bolnikov, pri katerih je bila potrebna RPP. Zbirali smo ocene stopnje dispneje na lestvici VAS pred, takoj po in 2 uri po RPP, pri 73 bolnikih pa še 24 ur po RPP ter beležili količino odstranjene tekočine. Med RPP smo z vodnim manometrom merili plevralne tlake, iz katerih smo izračunali elastanco plevralnega prostora in na podlagi meritev bolnike razdelili v skupine z različnimi elastančnimi krivuljami. Rezultati: Med začetnim plevralnim tlakom in količino odstranjene tekočine ter olajšanjem dispneje po opravljeni RPP smo ugotovili statistično značilno povezanost. Pri največjem deležu bolnikov smo RPP zaključili zaradi pojava simptomov, zaradi meritev plevralnega tlaka pa smo RPP prekinili pri 16 bolnikih (16,7 %). V skupino z normalno elastančno krivuljo smo uvrstili 74 bolnikov, nezmožnost razpenjanja pljuč pa smo ugotovili pri 22 bolnikih. Med RPP ni bilo pomembnih zapletov, kljub temu da smo več kot 1.500 mL izliva odstranili pri 32 (33 %) bolnikih. Zaključek: Višji začetni plevralni tlak je šibko povezan z višjo začetno stopnjo dispneje in večjim olajšanjem dispneje po opravljeni RPP. Najbolj uporabna je dinamika sprememb plevralnega tlaka, s katero lahko že med RPP prepoznamo nezmožnost razpenjanja pljuč. Med RPP s plevralno manometrijo lahko varno odstranimo tudi več kot 1.500 mL tekočine.

BACKGROUND:The European baseline series (EBS) of contact allergens is subject to change. An allergen is considered for inclusion when routine patch testing of patients with suspected contact dermatitis results in ≥0.5% prevalence rate.OBJECTIVES:We aimed to determine the frequency of sensitizations to 30 EBS allergens and 10 locally added allergens. Additionally, we assessed the strength and evolution of reactions to all tested allergens and co-reactivity of additional allergens.METHODS:Patch testing with our baseline series of 40 allergens was done in 748 consecutive adults. Tests were applied to the upper back and removed by patients after 48 h. Readings were done on Day 3 (D3) and D6 or D7 (D6/7). Positive reactions fulfilled the criteria of at least one plus (+) reaction. A retrospective analysis was done.RESULTS:Eight allergens not listed in the EBS had ≥0.5% prevalence rate (i.e., cocamidopropyl betaine, thiomersal, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, propylene glycol, Compositae mix II and dexamethasone-21-phosphate), and 16.6% of positive reactions would have been missed without D6/7 readings.CONCLUSION:We propose further studies to evaluate whether cocamidopropyl betaine, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea and Compositae mix II need to be added to the EBS.

Background The relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood. Methods A longitudinal prospective cohort of hospitalised patients with COVID-19 (n=254) was followed up to 35 days after admission (median, 8 days). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T-, B- and natural killer lymphocyte subsets and serum interleukin-6 (IL-6) response. We used machine learning to identify patterns of the immune response and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors. Results Overall, 45 (18%) patients died within 28 days after hospitalisation. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgG lowest T lowest B lowest NK mod IL-6 mod, and the anti-S1-IgG high T low B mod NK mod IL-6 highest had a high risk of fatal COVID-19 (HR 3.36–21.69; 95% CI 1.51–163.61 and HR 8.39–10.79; 95% CI 1.20–82.67; p≤0.03, respectively). The anti-S1-IgG highest T lowest B mod NK mod IL-6 mod and anti-S1-IgG low T highest B highest NK highest IL-6 low cluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1-IgG high T high B mod NK mod IL-6 low and anti-S1-IgG highest T highest B high NK high IL-6 lowest clusters were characterised by a very low risk of mortality. Conclusions By employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6-mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.

Background: Patients with pleural effusion often require therapeutic thoracentesis (TT), which results in more or less pronounced dyspnea relief. Due to safety concerns, it is recommended to remove up to a maximum of 1500 mL effusion in one session. Methods: 96 patients in whom TT was indicated were included in the study. VAS dyspnea score before, immediately after, two hours after TT, and in 73 patients additionally 24 hours after TT was collected. The amount of fluid removed was measured. During TT, water manometer was used to measure pleural pressures, from which pleural space elastance was calculated. Based on their elastance curves characteristics, the patients were divided into different groups. Results: We found a correlation between initial pleural pressure/volume of effusion removed and dyspnea relief after TT. TT was most often terminated due to the onset of symptoms, in 16 patients it was terminated due to pleural pressure measurement. 74 patients were classified in the group with a normal elastane curve, in 22 patients we detected unexpandable lungs. Although more than 1500 mL of effusion was removed in 32 (33%) patients, there were no important complications during TT. 1 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 2 Interventional Pulmonology Department, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia Correspondence / Korespondenca: Anita Meglič, e: anitameglic@gmail.com

Introduction: With prolonged life expectancy increasingly more patients with the lung cancer (LC) are found in the age group of over 80 years old. The main objective was to determine the safety of invasive diagnostic procedures for LC in the octogenarians. The secondary objective was to determine whether these patients receive specific oncologic treatment after the diagnosis and whether they have benefit from it. Methods: This retrospective study was done in patients over 80 years old with diagnosis of LC between January 2009 and December 2010. Results: 100 patients with age 80 years or more with lung cancer were included, which represented 7% of all patients with LC in that time period. 74 patients had bronchoscopy, 12 CT guided transthoracic needle aspiration and 14 other methods. Among 41 patients who were in stage I-III at the time of diagnosis 19 were treated with curative intent (3 surgery, 15 high dose radiotherapy, 1 radiofrequency ablation). Their median survival was significantly better (median 15 months) than survival in 22 non-radically treated patients from this group (median 5.5 months). 53 patients had stage IV disease at the time of diagnosis. 13 were treated with tyrosine kinase inhibitor (median survival 16 months), 8 with chemotherapy (median survival 6 months) and 32 received symptomatic treatment (median survival 3 months). A group of patients treated with TKI had statistically significant longer survival (p<0.05). Conclusion: Invasive diagnostic procedures are safe in octogenarians with LC and have low complication rate. Patients can benefit from these procedures, because alternative, treatable conditions are sometimes diagnosed.

Abstract Background. Ultrasound elastography is an imaging procedure that can assess the biomechanical characteristics of different tissues. The aim of this study was to define the diagnostic value of the endobronchial ultrasound (EBUS) elastography strain ratio of mediastinal lymph nodes in patients with a suspicion of lung cancer. The diagnostic values of the strain ratios were compared with the EBUS brightness mode (B-mode) features of selected mediastinal lymph nodes and with their cytological diagnoses. Patients and methods. This prospective, single-centre study enrolled patients with an indication for biopsy and mediastinal staging after a non-invasive diagnostic workup of a lung tumour. EBUS with standard B-mode evaluation and elastography with strain ratio measurement were performed before endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Results. Thirty-three patients with 80 suspicious mediastinal lymph nodes were included. Malignant infiltration was confirmed in 34 (42.5%) lymph nodes. The area under the receiver operating characteristic curve for the strain ratio was 0.87 (p < 0.0001). At a strain ratio ≥ 8, the accuracy for malignancy prediction was 86.25% (sensitivity 88.24%, specificity 84.78%, positive predictive value [PPV] 81.08%, negative predictive value [NPV] 90.70%). The strain ratio is more accurate than conventional B-mode EBUS modalities for differentiating between malignant and benign lymph nodes. Conclusions. EBUS-guided elastography with strain ratio assessment can distinguish malignant from benign mediastinal lymph nodes with greater accuracy than conventional EBUS modalities. This new method may reduce the number of mediastinal EBUS-TBNAs and thus reduce the invasiveness and expense of mediastinal staging in patients with non-small lung cancer (NSCLC).

Introduction: Chronic urticaria (CU) severely affects quality of life.If symptoms are not controlled by antihistamines, patients need immunomodulatory drugs.Recent studies show a tremendous effect of omalizumab, a monoclonal antibody against human IgE in refractory CU.Methods: We report on the use of omalizumab in four patients with CU.By reviewing medical files, we estimated the proportion of CU patients that are candidates for such treatment.We reviewed the literature to compare the dosing schedules and outcome measures used in different studies.Results: Up to 14% of CU patients referred to a tertiary center are candidates for omalizumab.Four of our CU were patients treated with doses of 150 mg/month or less, and all responded with nearly complete remission of symptoms.In the literature, 90% of patients respond to treatment, the response being obvious in days.Half of patients were able to stop all other medications, including antihistamines.More than half of patients responded well to doses of 150 mg of omalizumab every 4 to 8 weeks.In the majority of patients, the disease relapsed after discontinuation of omalizumab.Conclusions: Omalizumab should be offered to patients with refractory CU.The duration of treatment is not known.

Histamine intolerance (HIT) is characterized by an imbalance between histamine intake and the capacity for histamine degradation. The main enzyme for metabolizing ingested histamine is diamine oxidase (DAO). Determining DAO activity in serum may be useful in diagnosing HIT.

BACKGROUND Esophageal achalasia (EA) is a primary esophageal motility disorder of unclear aetiology. Standard treatments of EA are: pneumatic balloon dilation (PBD) of the lower esophageal sphyncter (LES) and surgical cleaving of the muscle by Heller myotomy. Although the treatment effectively cures dysphagia, the symptoms recur in about a half of the patients. Our point of interest was long-term effectiveness of EA treatment at our department. METHODSWe made a retrospective analysis of EA patients treated at our department of thoracic surgery during the 2000–2010 period.RESULTSIn 11 years we performed 187 PBD and 22 laparoscopic myotomies (LM) in 148 patients. Three years after the procedure 65 % of patients after PBD and 90 % of patients after LM showed no signs of disease. The risk of recurrence was 3.56-times greater (p = 0.03) after PBD (in comparison to LM), whereas patients older than 50 years bear 0.51-times lower risk (p = 0.02). The most significant complicatios were esophageal perforation in 3 patients (1.6 %) after PBD and gastroesophageal reflux in 3 patients (15 %) after LM.CONCLUSIONSPBD is a fast, simple, inexpensive and very efficient method of EA treatment, which can be safely performed in almost every patient. LM is far more expensive and a more complicated method that is more suitable for younger patients, in whom PBD is less effective.

BACKGROUND: Diagnosis of allergy to Hymenoptera venom is usually confirmed with skin testing and measurement of specific serum IgE antibody, tests which are sometimes inconclusive. In these cases, additional in vitro tests are necessary. The aim of this study was to show the applicability of the basophil activation test in detecting sensitization to Hymenoptera venom and to compare the test sensitivity and clinical positive-predictive value with skin prick tests and measurement of allergen-specific serum IgE. METHODS: This prospective study was conducted between June 2004 and December 2007 and included a large group of 204 patients. All patients had a history of at least one systemic allergic reaction of Müller grades II–IV after a Hymenoptera sting. We compared results of the basophil activation test, specific serum IgE and skin prick tests with patients' clinical history and data on culprit insects. RESULTS: The overall clinical sensitivities of the basophil activation test, specific serum IgE and skin prick tests were 90%, 76% and 64%, respectively; the clinical positive-predictive values of the three tests were 79%, 73% and 78% for bee venom, 86%, 59% and 43% for wasp venom; and 84%, 77% and 22% for both venoms. CONCLUSIONS: Our results revealed a higher clinical sensitivity and comparable or better clinical positive-predictive value of basophil activation tests than skin prick tests and allergen-specific serum IgE in the detection of allergy to Hymenoptera venom.

BACKGROUND:Complement component 5a (C5a) might be involved in the formation of wheals in patients with chronic urticaria (CU). We sought to compare the in vitro responsiveness of basophils to C5a in patients with CU and in a control group.METHODS:Basophil surface expression of activation marker CD63 induced by C5a, anti-FcepsilonRI mAb or anti-IgE pAb was measured using flow cytometry in 17 patients with CU and in 10 healthy controls.RESULTS:Patients with CU showed significantly greater basophil CD63 surface expression induced by C5a (median [interquartile range]; 16.4% [13-25.1]; P = 0.011) than the group of healthy controls (10.7% [7.2-16.8]). In contrast, basophil CD63 response to anti-IgE and anti-FcepsilonRI was lower in the CU group (12.3% [6-36.3]; 25.9% [12.5-60.5]) than in the control group (51.7% [6.7-84.3]; 62.1% [9.7-89.2]), although not statistically significant.CONCLUSION:Results of this pilot study suggest that patients with CU might have an enhanced basophil response to stimulation with C5a, indicating that further studies in CU basophil responsiveness are needed.

BACKGROUND: Although immunotherapy is effective in allergic rhinitis, conjunctivitis, asthma and stinging insect hypersensitivity, it carries a risk of anaphylactic reactions. METHODS: In a 4-year retrospective survey, we investigated 1257 adult patients who had received venom or inhaled-allergen subcutaneous immunotherapy. The dose-increase phase was performed as the 2-day rush protocol for venom immunotherapy and the 6-week protocol for inhaled-allergen immunotherapy. RESULTS: A total of 904 patients received venom immunotherapy and 353 patients inhaled-allergen immunotherapy. The prevalence of systemic reactions was 13.6%. The frequency of systemic reactions was higher during the maintenance phase than in the dose-increase phase (9.6% vs. 5.9%) and was highest in both phases of treatment with honeybee venom (P < 0.001). The majority of systemic reactions were mild. Five (0.4%) patients had reaction with a fall of blood pressure and were treated with adrenaline. There was no fatal outcome. The systemic side-effects during the dose-increase phase of venom immunotherapy occurred at a median dose of 46 μg (range 2–100 μg). Large local reactions occurred in 13.9% of patients without any significant difference between the allergens. CONCLUSIONS: We have shown that systemic reactions are not rare even during maintenance phase in patients with a well tolerated dose-increase phase of treatment. The most prominent risk factor for systemic reactions was immunotherapy with honeybee extract.

Background: Cardiac tamponade can be associated with hyponatremia and/or acute renal failure. Case reports and a few case series describe conditions separately. The objective of this study was to determine the frequencies of the reversible hyponatremia and acute renal failure in patients with cardiac tamponade after pericardial drainage and to determine whether there is any association between them. Methods: In this retrospective study medical records of patients treated by pericardial drainage between years 2010 and 2016 were reviewed. Cardiac tamponade was confirmed by cardiac chamber compression proved by echocardiography. Sample means/medians of paired data were compared with paired t-test (sodium concentration before and after drainage) and Wilcoxon signed-rank test (creatinine concentration before and after drainage). Results: Median amount of evacuated pericardial fluid was 1100 ml (rang 250 ml to 2000 ml) in 23 included patients. The mean pre-drainage sodium level was 133.1 mEq/l ± 8.5 mEq/l and the mean post-drainage sodium level was 139.0 mEq/l ± 4.2 mEq/l (p<0.002). Among 23 patients 10 (43.5%) had hyponatremia before drainage and 3 (13.0%) after drainage. The median pre-drainage serum creatinine concentration was 87.5 μmol/l (range =47 283 μmol/l) and median post-drainage serum creatinine concentration was 70 μmol/l (range =42 186 μmol/l) (p=0.014). Sodium and creatinine concentrations were correlated in a way, that sodium concentration increases, and creatinine concentration decreases after cardiac decompression (p<0.001). Conclusion: Hyponatremia and acute renal failure are associated with cardiac tamponade and recover spontaneously after pericardial drainage. Sodium concentration increase and creatinine concentration decrease after cardiac decompression are in a correlation.