Intravenous Immunoglobulins Alone for the Desensitization of Lung Transplant Recipients with Preformed Donor Specific Antibodies and Negative Flow Cytometry Crossmatch.

BACKGROUND: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach. METHODS: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models. RESULTS: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups. CONCLUSION: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.

Small cell lung cancer stem cells display mesenchymal properties and exploit immune checkpoint pathways in activated cytotoxic T lymphocytes.

Small cell lung cancer (SCLC) is an aggressive tumor type with early dissemination and distant metastasis capacity. Even though optimal chemotherapy responses are observed initially in many patients, therapy resistance is almost inevitable. Accordingly, SCLC has been regarded as an archetype for cancer stem cell (CSC) dynamics. To determine the immune-modulatory influence of CSC in SCLC, this study focused on the characterization of CD44+CD90+ CSC-like subpopulations in SCLC. These cells displayed mesenchymal properties, differentiated into different lineages and further contributed to CD8+ cytotoxic T lymphocytes (CTL) responses. The interaction between CD44+CD90+ CSC-like cells and T cells led to the upregulation of checkpoint molecules PD-1, CTLA-4, TIM-3, and LAG3. In the patient-derived lymph nodes, CD44+ SCLC metastases were also observed with T cells expressing PD-1, TIM-3, or LAG3. Proliferation and IFN-γ expression capacity of TIM-3 and LAG3 co-expressing CTLs are adversely affected over long-time co-culture with CD44+CD90+ CSC-like cells. Moreover, especially through IFN-γ secreted by the T cells, the CSC-like SCLC cells highly expressed PD-L1 and PD-L2. Upon a second encounter with immune-experienced, IFN-γ-stimulated CSC-like SCLC cells, both cytotoxic and proliferation capacities of T cells were hampered. In conclusion, our data provide evidence for the superior potential of the SCLC cells with stem-like and mesenchymal properties to gain immune regulatory capacities and cope with cytotoxic T cell responses. With their high metastatic and immune-modulatory assets, the CSC subpopulation in SCLC may serve as a preferential target for checkpoint blockade immunotherapy .

Evaluation of Exudative Pleural Effusions: A Multicenter, Prospective, Observational Study.

PURPOSE: The aim of this study is to determine the diagnostic performances of pleural procedures in undiagnosed exudative pleural effusions and to evaluate factors suggestive of benign or malignant pleural effusions in tertiary care centers. METHODS: This was a multicenter prospective observational study conducted between January 1 and December 31, 2018. A total of 777 patients with undiagnosed exudative pleural effusion after the initial work-up were evaluated. The results of diagnostic procedures and the patients' diagnoses were prospectively recorded. Sensitivity, specificity, and accuracy estimates with 95% confidence intervals were used to examine the performance of pleural procedures to detect malignancy. RESULTS: The mean age ± SD of the 777 patients was 62.0 ± 16.0 years, and 68.3% of them were male. The most common cause was malignancy (38.3%). Lung cancer was the leading cause of malignant pleural effusions (20.2%). The diagnostic sensitivity and accuracy of cytology were 59.5% and 84.3%, respectively. The diagnostic sensitivity of image-guided pleural biopsy was 86.4%. The addition of image-guided pleural biopsy to cytology increased diagnostic sensitivity to more than 90%. Thoracoscopic biopsy provided the highest diagnostic sensitivity (94.3%). The highest diagnostic sensitivity of cytology was determined in metastatic pleural effusion from breast cancer (86.7%). CONCLUSION: The diagnostic performance increases considerably when cytology is combined with image-guided pleural biopsy in malignant pleural effusions. However, to avoid unnecessary interventions and complications, the development of criteria to distinguish patients with benign pleural effusions is as important as the identification of patients with malignant pleural effusions.

Has the pandemic changed the test quality of the pulmonary function test laboratory?

Introduction: Pulmonary function tests are used in the evaluation of the respiratory system. Maneuvers during spirometry can create aerosols and spread viruses such as SARS-CoV-2. Measures due to the pandemic can negatively affect both the number and the quality of the spirometry tests. There are no comparative studies on this subject. Materials and Methods: The tests conducted in the spirometry laboratory between November 2019 and November 2021 were evaluated. Result: Four hundred forty patients were included in the study. 50.5% of the patients were male and the mean age was 61.8 ± 16.5 years. The age, gender, height, and weight of the patients were similar. 75.2% (331) of the tests were evaluated as successful. The most common errors in tests were early termination (84.1%), uncooperative patients (29%), and poor effort (22.4%). The types of errors were not different between the two periods. The median number of tests performed for each patient was six. The total number of spirometry tests performed were 262 and 178 for 2019 and 2021 (p= 0.011), but test success remained unchanged over the years (p= 0.513). There was no significant difference between the three operators and the test success (p= 0.909), which was similar for both periods. However, the number of tests performed until the successful maneuver varied significantly (p= 0.009), and fewer maneuvers were required before the pandemic. Conclusions: According to this study, the measures taken during the pandemic did not affect the quality of spirometry, but they did lead to more tests being done up until the successful maneuver was performed.

Post-COVID syndrome: pulmonary complications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worlwide and caused a pandemic that is still ongoing. The virus can cause a disease named as COVID-19, which is composed of multi systemic manifestations with a pulmonary system predominance. As the time passes, we are dealing more and more with a wide variety of effects and complications of the disease in survivors as far as with concerns about the clinical outcome and the timeline of symptoms in different patients. Since the lungs are the most involved organs and the post-COVID prolonged and persistent effects are mainly related to the pulmonary system, it is crucial to define and predict the outcome and to determine the individuals that can progress to fibrosis and loss of function of lungs. This review summarizes the current literature regarding the pulmonary complications in post-COVID syndrome and the management of these conditions.

Nowadays COVID underestimates the other suspects.

The whole world has been facing the pandemic of SARS-CoV-2 infection and every day we still find out new knowledge regarding the disease. COVID-19 which is the name given to the clinical syndrome related to this infection has been shown to own a wide diversity of clinical presentations which challenges the healthcare workers and makes difficult the diagnosis and management of patients. Pulmonary embolism is also an entity that accompanies this type of infection and sometimes it is difficult to differentiate between the two. Here we present a patient who was admitted inward with typical lesions on chest tomography for COVID-19, but that turned out to be a submassive pulmonary embolism case without any infection. This case is remarkable because it shows that patients suspected for COVID-19 should be carefully examined and that pulmonary embolism can per se mimick the parenchymal lesions caused by viral infections.

Humidification therapy; long-term effects in COPD and OSAS patients.

Humidification therapy is widely used in patients during invasive ventilation and the importance of heating and humidifying the inhaled air is well defined in both the acute and long term setting. On the other hand the continuous usage of humidification in noninvasive ventilation is controversial and the long term effects are still not well defined. The usage of noninvasive ventilation is especially important in hypercapnic Chronic obstructive pulmonary disease (COPD) and also the obstructive sleep apnea syndrome (OSAS) patients and compliance to this treatment is essential in long term. Limited number of studies have shown that heated humidification is preferred by COPD patients and might help in mucus clearance, reduce mucus viscosity and help in expectoration, but there was shown no priority as far as concerns the lung function or blood gas parameters. Humidification might also be important in long term oxygen treatment since the inhalation of dry air can lead to ciliary dysfunction, alterations in mucus properties and mucociliary clearance impairment. Studies concerning OSAS patients showed that humidification helps to reduce the nasal symptoms but plays no role in increasing the compliance of patients in long term. Multi-center studies with large number of patients are needed to identify patients' groups who are likely to benefit from the addition of humidification to noninvasive therapy.

Spheroid formation and invasion capacity are differentially influenced by co-cultures of fibroblast and macrophage cells in breast cancer.

Interactions with stromal components influence the growth, survival, spread, and colonization capacities of tumor cells. Fibroblasts and macrophages which are responsible for the stroma production and maintenance are of the basic elements found in tumor microenvironment. Cellular density and ratio of stromal cells to tumor cells can also have modulatory effects in cancer. Here, the contribution of fibroblast and/or macrophage cells on the malignant behavior of breast cancer cells was modeled in co-culture systems. Co-cultures were established at different cell densities and ratios with 4T1 breast cancer, NIH/3T3 or 3T3-L1 fibroblast, and J774A.1 monocyte/macrophage cell lines. Flow cytometry-based proliferation, 3D growth on alginate matrix, and matrigel invasion assays were performed to determine the change in the malignant assets of tumor cells. The data were also supported by immunocytochemical and morphological analyses. Co-culturing with fibroblasts (especially, NIH/3T3 cells) significantly supported the proliferation, scattering, and invasiveness of 4T1 cells whereas inclusion of macrophages disrupted this positive influence. On the other hand, the invasion capacity of 4T1 cells was not enhanced in the co-cultures with fibroblasts whose motility were inhibited with pertussis toxin pretreatment. Particularly at low-density seeding in 3D cultures, 4T1 cells could form substantially more spheroids than that of in the co-cultures with fibroblasts. Only, increasing the amount of fibroblasts could restore the 3D-growth. Intriguingly, co-existence of macrophage, fibroblast, and tumor cells in 3D cultures provided a convenient stroma sustaining the spheroid formation and growth. In conclusion, fibroblasts can form a favorable environment for tumor cells' spread and motility whereas restricting their 3D-growth capacity. On the other hand, presence of macrophages may disrupt the influence of fibroblasts and enhance the spheroid formation by the tumor cells.

ERS International Congress 2023: highlights from the Thoracic Surgery and Lung Transplantation Assembly.

Five sessions presented at the European Respiratory Society Congress 2023 were selected by Assembly 8, consisting of thoracic surgeons and lung transplant professionals. Highlights covering management of adult spontaneous pneumothorax, malignant pleural effusion, infectious and immune-mediated complications after lung transplantation, as well as the pro and con debate on age limit in lung transplantation and results of the ScanCLAD study were summarised by early career members, supervised by the assembly faculty.

Pulmonary Physician Consultancy in Emergency Services in Turkiye (PuPCEST) - a cross-sectional multicenter study.

Pulmonology is one of the branches that frequently receive consultation requests from the emergency department. Pulmonology consultation (PC) is requested from almost all clinical branches due to the diagnosis and treatment of any respiratory condition, preoperative evaluation, or postoperative pulmonary problems. The aim of our study was to describe the profile of the pulmonology consultations received from emergency departments in Turkiye. A total of 32 centers from Turkiye (the PuPCEST Study Group) were included to the study. The demographic, clinical, laboratory and radiological data of the consulted cases were examined. The final result of the consultation and the justification of the consultation by the consulting pulmonologist were recorded. We identified 1712 patients, 64% of which applied to the emergency department by themselves and 41.4% were women. Eighty-five percent of the patients had a previously diagnosed disease. Dyspnea was the reason for consultation in 34.7% of the cases. The leading radiological finding was consolidation (13%). Exacerbation of preexisting lung disease was present in 39% of patients. The most commonly established diagnoses by pulmonologists were chronic obstructive pulmonary disease (19%) and pneumonia (12%). While 35% of the patients were discharged, 35% were interned into the chest diseases ward. The majority of patients were hospitalized and treated conservatively. It may be suggested that most of the applications would be evaluated in the pulmonology outpatient clinic which may result in a decrease in emergency department visits/consultations. Thus, improvements in the reorganization of the pulmonology outpatient clinics and follow-up visits may positively contribute emergency admission rates.

Pulmonary Embolism in a Liver Donor: A Case Report and Review of the Literature.

Liver transplant is an important treatment option for end-stage liver disease, and living related donation is an option to shorten or eliminate the waiting period for the patients, especially when shortage of organs is of concern. It is crucial to provide optimal safety for the donors and to thoroughly examine them preoperatively in order to decrease perioperative and postoperative complications. Here, we report the case of a living donor who had undergone a left liver lobectomy and on postoperative day 2 presented with a radiologically severe pulmonary embolism, despite the absence of any risk factor for venous thromboembolism or pulmonary embolism. The patient was treated with tissue plasminogen activator and heparin infusions and was discharged 1 week later.

Can adipokines predict clinical prognosis and post-COVID lung sequelae?

BACKGROUND: Adipokines play an important role in the regulation of inflammatory responses toward infections, including COVID-19. This study aimed to investigate the role of chemerin, adiponectin, and leptin in prognosis and post-COVID lung sequelae in hospitalized patients with COVID-19. METHODS: Serum levels of the three adipokines were measured upon admission of polymerase chain reaction-confirmed patients with COVID-19 who were followed up for 6 months for the clinical outcome and lung sequelae formation. RESULTS: A total of 77 patients were included in the study. Of the 77 patients, 58.4% were males, and the median age was 63.2 ± 18.3 years. Fifty-one patients (66.2%) had a good prognosis. Among adipokines, only chemerin was significantly lower in the bad prognosis group (P < 0.05), and the serum levels showed a negative correlation with age (rho = -0.238; P < 0.05). Leptin levels were negatively correlated with gamma glutamyl transferase levels, which were significantly higher in the bad prognostic group (rho = -0.240; P < 0.05). Twenty-four patients had no lung sequelae, and 20 developed sequelae within 6 months after infection. Chemerin/adiponectin ratio with a cut-off value of 0.96 and an area under the curve 0.679 (P < 0.05) might predict the sequelae formation. CONCLUSIONS: Chemerin levels are lower, especially in patients with a bad prognosis, and the chemerin/adiponectin ratio might predict the development of lung sequelae in patients with COVID-19.

Interview with the ECM Award winner 2022 and introducing the new ECM members.

This article presents the interview with the ERS Early Career Member Awardee 2022 (@MathioudakisAG) and provides a brief introduction to the new ECM members https://bit.ly/3BSRgV2.

ERS International Congress 2022: highlights from the Thoracic Surgery and Lung Transplantation Assembly.

The thoracic surgery and lung transplantation assembly (Assembly 8) of the European Respiratory Society (ERS) is delighted to present the highlights from the 2022 ERS International Congress that took place in a hybrid version in Barcelona, Spain. We have selected the four main sessions that discussed recent advances across a wide range of topics including the effects of coronavirus disease 2019 on thoracic surgery and the challenges regarding lung transplantation in connective tissue diseases and common variable immunodeficiency. The sessions are summarised by early career members in close collaboration with the assembly faculty. We aim to provide the reader with an update and enhanced insight into the highlights of the conference in the fields of thoracic surgery and lung transplantation.

Lung cancer from suspicion to treatment: An indicator of healthcare access in Turkey.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Before beginning lung cancer treatment, it is necessary to complete procedures such as suspecting lung cancer, obtaining a pathologic diagnosis, and staging. This study aimed to investigate the processes from suspicion of lung cancer to diagnosis, staging, and treatment initiation. METHODS: The study was designed as a multicenter and cross-sectional study. Patients with lung cancer from various health institutions located in all geographic regions of Turkey were included in the study. The sociodemographic and clinical characteristics of the patients, the characteristics of the health institutions and geographic regions, and other variables of the lung cancer process were recorded. The time from suspicion of lung cancer to pathologic diagnosis, radiologic staging, and treatment initiation, as well as influencing factors, were investigated. RESULTS: The study included 1410 patients from 29 different medical centers. The mean time from the initial suspicion of lung cancer to the pathologic diagnosis was 48.0 ± 52.6 days, 39.0 ± 52.7 days for radiologic staging, and 74.9 ± 65.5 days for treatment initiation. The residential areas with the most suspected lung cancer cases were highly developed socioeconomic zones. Primary healthcare services accounted for only 0.4% of patients with suspected lung cancer. The time to pathologic diagnosis was longer in the Marmara region, and the wait time for staging and treatment initiation was longer in Eastern and Southeastern Anatolia. Patients who presented to chest disease referral hospitals with peripheral lesions, those with early-stage disease, and those who were diagnosed surgically had significantly longer wait times. CONCLUSION: The time between pathologic diagnosis, staging, and treatment initiation in lung cancer was longer than expected. Increasing the role of primary healthcare services and distributing socioeconomic resources more equally will contribute to shortening the time to diagnosis and improve treatment processes for lung cancer.

Recurrence of primary disease following lung transplantation.

Lung transplant has become definitive treatment for patients with several end-stage lung diseases. Since the first attempted lung transplantation in 1963, survival has significantly improved due to advancement in immunosuppression, organ procurement, ex vivo lung perfusion, surgical techniques, prevention of chronic lung allograft dysfunction and bridging to transplant using extracorporeal membrane oxygenation. Despite a steady increase in number of lung transplantations each year, there is still a huge gap between demand and supply of organs available, and work continues to select recipients with potential for best outcomes. According to review of the literature, there are some rare primary diseases that may recur following transplantation. As the number of lung transplants increase, we continue to identify disease processes at highest risk for recurrence, thus shaping our future approaches. While the aim of lung transplantation is improving survival and quality of life, choosing the best recipients is crucial due to a shortage of donated organs. Here we discuss the common disease processes that recur and highlight its impact on overall outcome following lung transplantation.

Frequency of Direct Oral Anticoagulants Usage in Acute Pulmonary Thromboembolism Treatment in Turkey (TUPEDO).

Background: Direct oral anticoagulants (DOACs) have been used in acute pulmonary thromboembolism as an alternative to warfarin due to drug interactions, narrow therapeutic range, and necessary close International Normalized Ratio (INR) monitoring. Phase 3 study results have reported that these drugs are at least as effective as warfarin and beneficial in terms of bleeding; however, studies that present up-to-date life data are necessary. Aims: To evaluate the frequency of using DOACs, which are prescribed with a limited number of indications in our country, and real-life data results. Study Design: Cross-sectional study. Methods: This cross-sectional survey collected the clinical data (history, current treatment, treatment duration, etc.) of patients with pulmonary thromboembolism and who applied to the physician for follow-up between October 15, 2019, and March 15, 2020. The researchers kept the patient records sequentially. Results: Data from 836 patients with acute pulmonary thromboembolism from 25 centers were collected, and DOAC was used in 320 (38.5%) of them. The most preferred DOAC was rivaroxaban (n = 294, 91.9%). DOAC was mostly preferred because it could not provide an effective INR level with warfarin (n=133, 41.6%). Bleeding was observed in 13 (4%) patients. Conclusion: The use of direct oral anticoagulants is becoming almost as widespread as conventional therapy. Real-life data results are important for their contribution to clinical practice.

New challenges for management of COVID-19 patients: Analysis of MDCT based "Automated pneumonia analysis program".

PURPOSE: The aim of this study is to define the role of an "Automated Multi Detector Computed Tomography (MDCT) Pneumonia Analysis Program'' as an early outcome predictor for COVID-19 pneumonia in hospitalized patients. MATERIALS AND METHODS: A total of 96 patients who had RT-PCR proven COVID-19 pneumonia diagnosed by non-contrast enhanced chest MDCT and hospitalized were enrolled in this retrospective study. An automated CT pneumonia analysis program was used for each patient to see the extent of disease. Patients were divided into two clinical subgroups upon their clinical status as good and bad clinical course. Total opacity scores (TOS), intensive care unit (ICU) entry, and mortality rates were measured for each clinical subgroups and also laboratory values were used to compare each subgroup. RESULTS: Left lower lobe was the mostly effected side with a percentage of 78.12 % and followed up by right lower lobe with 73.95 %. TOS, ICU entry, and mortality rates were higher in bad clinical course subgroup. TOS values were also higher in patients older than 60 years and in patients with comorbidities including, Hypertension (HT), Diabetes Mellitus (DM), Chronic Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and malignancy. CONCLUSION: Automated MDCT analysis programs for pneumonia are fast and an objective way to define the disease extent in COVID-19 pneumonia and it is highly correlated with the disease severity and clinical outcome thus providing physicians with valuable knowledge from the time of diagnosis.

ERS International Congress 2020: highlights from the Thoracic Surgery and Transplantation Assembly.

The Thoracic Surgery and Lung Transplantation Assembly of the European Respiratory Society is delighted to present the highlights from the 2020 Virtual International Congress. We have selected four sessions that discussed recent advances in a wide range of topics. From the use of robotic surgery in thoracic surgery and extracorporeal life support as a bridge to lung transplantation, to lung transplantation in the era of new drugs. The sessions are summarised by early career members in close collaboration with the assembly leadership. We aim to give the reader an update on the highlights of the conference in the fields of thoracic surgery and lung transplantation.