Treatment of Patients After Lung Transplantation With Covid Infection During Long-Term Follow-Up.

BACKGROUND: Patients undergoing lung transplantation are routinely managed with lifelong immunosuppression, which is associated with a heightened risk for infections. This study delves into the therapeutic challenges and strategies for managing lung transplant recipients (LTRs) infected with COVID-19 during long-term follow-up. METHODS: The was a case series analysis, among which nonstandard therapies consisting of targeted antibody treatment, antiviral drugs, or anti-interleukin-6 drugs were applied in patients after lung transplantation. Additional analysis of laboratory test results for systemic inflammation and imaging studies was also carried out. The study was limited to a dedicated COVID-19 center, commonly known as a temporary hospital, and included patients infected with COVID-19 in the late post-lung transplant period (home-related infection). RESULTS: Fifteen post-lung transplantation patients with current COVID-19 infection were treated with antibodies such as tocilizumab, casirivimab, imdevimab, and regdanvimab. Of these patients, 1 was given tocilizumab (7%), 8 casirivimab and imdevimab (53%), and 2 regdanvimab (13%). Of the 15 lung transplant recipients studied, 8 presented COVID-19-associated lung changes in computed tomography scans (53%). Common clinical manifestations included dyspnea, fever, and fatigue. Antiviral agents, like remdesivir, were employed in the remaining 4 cases (27%), and adjunctive therapies, such as corticosteroids and anticoagulants, were used selectively. All treated patients survived the infection without complications; the treatment proved effective and safe.

Anti-HLA Immunization in Patients After Lung Transplantation: A Comparative Study Before and During the Pandemic.

Anti-human leukocyte antigen (anti-HLA) sensitization in lung transplant recipients (LTRs) can significantly impact graft survival and patient outcomes. The global pandemic, induced by the SARS-CoV-2 virus, brought about numerous challenges in the medical sphere, including potential alterations in HLA immunization patterns among LTRs. A retrospective analysis of LTRs group transplanted from July 2018 to 1 March 2020 (pre-pandemic) was compared with patients transplanted from 1 March 2020 to December 2022 (during the pandemic). Totally 92 patients were controlled. Patients were also divided into 2 groups: vaccinated and non-vaccinated. The results of cytotoxic crossmatch, results of anti-HLA antibody testing, presence of DSA before and after transplantation, and early and late graft function were compared between groups. In the pandemic and vaccinated groups, an increase was observed in the number of positive crossmatch tests performed with a pool of B lymphocytes. However, the presence of dithiothreitol abolished the positive reaction in 90% of cases. We also observed an increased percentage of patients immunized based on the results of solid phase tests both in the pandemic group and in the group of patients who received vaccination against the SARS-CoV-2 virus. It might be that the pandemic/vaccination has influenced the prevalence of anti-HLA immunization in LTRs. Further studies are essential to establish causative factors and develop targeted interventions for this population of patients.

Antibody-mediated rejection with detection of de novo donor-specific anti-human leukocyte antigen Class II antibodies after lung transplantation: Problems in diagnosis, treatment and monitoring on a case report basis.

Lung transplantation, like other transplants, carries a risk of graft rejection due to genetic differences between the donor and the recipient. In this paper, we focus on antibody-mediated rejection, which can cause acute and more importantly chronic graft dysfunction and subsequently shortened allograft survival. We present the case of a 46-year-old patient who, two months after lung transplantation (LTx), developed AMR manifested by the deterioration of graft function and de novo production of donor-specific antibodies (DSA): DQ3 (DQ7, DQ8, DQ9). As the patient was after left single LTx and heavily oxygen dependent a transbronchial biopsy was deemed to be high risk and it was decided to determine the clinical significance of the detected antibodies by their ability to bind complement. The test confirmed that the detected DSAs have the ability cause cytotoxicity of the transplanted organ. After treatment with methotrexate, intravenous immunoglobulin G (IVIg) and alemtuzumab, the patient's condition improved and a complete decrease in DSA was obtained. However, after a year, the production of antibodies increased sharply. Treatment with IVIg, cyclophosphamide and plasmapheresis slightly improved the patient's condition, reducing the MFI DSA values by half, but leaving them at high levels. Based on this clinical case, we discuss problems with making a diagnosis, choosing the right AMR treatment and monitoring the patient's condition during treatment. We also indicate a poor prognosis in the case of the production of DSA antibodies at the DQ locus.

Early and Midterm Results of Orthotopic Heart Transplantation in Poland (2015-2019).

Orthotopic heart transplantation (OHT) has become one of the most expensive and resource-consuming treatment options for patients with end-stage heart failure. It is therefore useful to review clinical data, such as treatment duration after surgery and midterm follow-up in this group of patients. Contemporary epidemiologic data on early and midterm OHT follow-ups including patient demographics, hospitalization rates and related post-OHT morbidity, and mortality are scarce in Poland. The aim of the study was to determine early survival, hospitalization rates related to OHT and related morbidity, and mortality in Poland in the recent decade.

Demographic and Psychosocial Characteristics of Lung Transplant Candidates: Single-Center Analysis.

BACKGROUND: Lung transplantation has changed the course of treatment of lung diseases for the better; however, there are various factors that should be considered to increase the probability of a better outcome. Factors such as the patient's background, level of education, and income could affect their perception and eventually the results of the procedure. METHODS: The present study involved patients who underwent the qualification process for lung transplant along with psychological and sociologic assessment at the Lung Transplant Unit in the Department of Cardiac Surgery and Vascular Surgery, Medical University of Gdansk. The following data were identified in the patients' medical history: marital status, size of the city, source of income, profession, voivodeship, and their Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) score for psychosocial prediction of the outcome. RESULTS: A group of 121 patients were included in the study: 77 (63.64%) men and 44 (36.36%) women. The average age of the patients was 55.4 ± 9.81 years. Eighty (66.12%) lived in the city, and 26 (21.49%) of patients were professionally active with a fixed salary as their source of income. One hundred two patients were married. The median SIPAT score was 10.0 ± 3.0 for men and 10.0 ± 2.75 for women (P = .0974). CONCLUSION: For optimum care and results of the lung transplant procedure, it is important to consider these background patient factors because they play a crucial role in determining the course of the surgery. The analysis of demographic data is undoubtedly one of the elements helpful in the further fate of the whole process.

Routine Coronary Angiography is Still the Key Test for Patients Eligible for Lung Transplantation Also for Those With No Symptoms and With High Risk of Coronary Artery Disease.

BACKGROUND: Coronary artery disease (CAD) has a considerable morbidity and mortality effect on the outcomes of a lung transplant. Currently, coronary angiography is performed as part of the pretransplant evaluation process. Unfortunately, there are no clear guidelines about performing cardiac angiography in lung transplant candidates. BACKGROUND: The aim of our work is to find a correlation between cardiovascular risk and coronary arterial status to optimize the selection of patients for coronary angiography prior transplantation. METHODS: We retrospectively analyzed 48 patients in whom coronary angiography and cardiac catheterization was performed during assessment for bilateral lung transplantation at the Medical University of Gdansk from 2018 to 2021. The coronary artery disease status was classified into 2 categories: without any stenosis and with stenosis. For each patient, the 10-year cardiovascular risk was estimated by using a Systematic COronary Risk Evaluation calculator modified for the Polish population. RESULTS: Coronary stenosis was detected in 15 patients during angiography (31%). The group with coronary stenosis had a median SCORE risk of 8%, which is considered as high risk, and in patients without stenosis it was 5%, which is also considered a high risk. Median mean pulmonary artery pressure in patients with stenosis was the same as that in patients without stenosis (23 mm Hg). CONCLUSIONS: CAD among lung transplant candidates cannot be predicted by risk factors, so coronary angiography is very important as a part of the evaluation process. Because pulmonary hypertension has a big impact on surveillance after transplantation, performing heart catheterization during the qualification process is crucial.

Lung Transplant in a Patient With Multifocal Langerhans Cell Histiocytosis After Chemotherapy With Cladribine: A Case Report.

Langerhans cell histiocytosis (LCH) is a rare inflammatory disorder of myeloid dendritic cells with mutations involving KRAS, BRAF and/or NRAS, and MAP2K1 genes. We describe the case of a 58-year-old female previous smoker with multifocal LCH involving the lungs, pituitary gland and mandibular bone. Initial treatment with 6 cycles of cladribine showed improvement in her extrapulmonary lesions, however, her lung disease progressed and after qualification and assessment tests she underwent uncomplicated double lung transplant surgery and was discharged home. We highlight that in select patients with well managed and controlled extrapulmonary LCH, such an invasive procedure as lung transplant is possible.

Anti-HLA immunization of patients qualified for lung transplantation - Single center study.

For lung transplantation, the presence of donor-specific anti-HLA antibodies (DSA) is an important factor of antibody-mediated rejection (AMR) in its hyperacute, acute or chronic form during long-term follow up. The aim of the study was to assess the allosensitization of Polish patients qualified for a lung transplantation in our center. A retrospective study of 161 potential lung allograft recipients, also of 31 patients transplanted in the University Hospital of Gdansk, between June 2018 and December 2020 were performed. 121 potential recipients were thoroughly tested for immunization status before eventual lung transplantation. SAB-testing, PRA-CDC and vPRA assessment, and HLA typing were performed to guide donor-recipient matching and risk stratification. Then 73 patients were separated and qualified for the list of patients awaiting lung transplantation. Then 31 patients were transplanted based on a negative biological crossmatch result. The patients were generally not sensitized, as the median PRA-CDC was 0% (min 0; max 53), and the vPRA, calculated according to HLA ABDR (>2000 cut-off MFI), was 8% (min 0; max 99). If the cut-off was split into 2000 MFI for HLA ABDR, 10,000 MFI for HLAC, and 7000 MFI for HLA-DQ, the vPRA increased to 20% (min 0; max 99). The immunization status was assessed with single antigen-SAB assays. For class I, the number of any detectable alloantibodies was 14 (11.6%) 21 (17.35%) 16 (13.22%) for locus HLA-A/B/C, and 28 (23.14%) 30 (24.8%) 24 (19.8%) for locus HLA-DR/DQ/DP, respectively. The immunization of the transplanted patients was then analyzed in detail. Summarizing, the study is an analysis of the degree of anti-HLA immunization in the population of patients eligible for lung transplantation, which showed that this degree is of low intensity and can be effectively and safely and very precisely diagnosed before transplantation.

A Single-Center Experience with Lung Transplants During the COVID-19 Pandemic.

BACKGROUND This single-center study analyzed distinctions between lung transplants performed in the Department of Cardiac and Vascular surgery of the University Clinical Center in Gdansk, Poland before and during the COVID-19 pandemic. MATERIAL AND METHODS There were 189 patients who underwent the qualification procedure to lung transplantation in the Department of Cardiac and Vascular Surgery of the University Clinical Center in Gdansk, Poland in the years 2019 and 2020. The control group consisted of 12 patients transplanted in 2019, and the study group consisted of 16 patients transplanted in 2020. RESULTS During 2019, the qualification process was performed in 102 patients with pulmonary end-stage diseases. In 2020, despite the 3-month lockdown related to organizational changes in the hospital, 87 qualification processes were performed. The mortality rate of patients on the waiting list in 2020 was 14.3% (6 patients died), and during 2019 the rate was also 14.3% (4 patients died). Donor qualifications were according to ISHLT criteria. The distribution of donors in both years was similar. There was no relationship between the geographic area of residence and source of donors. In 2019, all 12 patients had double-lung transplant. In 2020, 11 patients had double-lung transplant and 5 patients had single-lung transplant. There was no difference in ventilation time and PGD aside from a shorter ICU stay in 2020. CONCLUSIONS Lung transplants were relatively well-conducted despite the continued obstacles of the COVID-19 pandemic.

Cryobiopsy as a New Tool for Complications Diagnosis During Follow-up After Lung Transplantation: Single Institution Case Series.

BACKGROUND: The first description of performing a new diagnostic procedure, cryobiopsy, in lung transplant recipients in Poland. METHODS: Three cases of patients after lung transplantation were analyzed in context of the procedure of cryobiopsy, which was performed in a hybrid room with a bronchoscopic video track and C-arm radiograph. Patients were subjected to complete anesthesia and intubated. Two or three sections with an average diameter of 5 mm were collected. RESULTS: The sections were large and fully diagnostic. In all 3 described cases they brought a decisive element into diagnosis. CONCLUSIONS: Cryobiopsy is a useful tool in the differential diagnosis of lesions and complications that occur after lung transplantation.

Early Sirolimus-Based Immunosuppression is Safe for Lung Transplantation Patients: Retrospective, Single Arm, Exploratory Study.

BACKGROUND Sirolimus, a mechanistic target of sirolimus inhibitor, is an immunosuppression medication for patients undergoing heart and abdominal transplantation. Sirolimus-based immunosuppression administered de novo post-lung transplantation is associated with bronchial anastomosis healing-related complications. We hypothesized that sirolimus administration within the first postoperative month in selected lung transplant recipients is safe and may be associated with favorable short-term and long-term outcomes due to its anti-proliferative properties and minimal adverse side effects. MATERIAL AND METHODS Thirteen patients (13.3%; mean age, 46.8±11.9 years) received early sirolimus-based immunosuppression along with cyclosporine and prednisone; 10 patients received single-lung transplantation, 3 received double-lung transplantation, and all received induction immunosuppressants. Patients received early sirolimus-based immunosuppression after an uncomplicated postoperative course and detailed bronchoscopic assessment. RESULTS Sirolimus was begun on a mean of 20.6±4.7 days postoperatively (range, 14-32 days). The in-hospital and 30-day mortality rate was 0%. At long-term follow-up, 5 patients died (due to bacterial infection in 4 patients and pneumocystis jiroveci pneumonia in 1 patient). The mean overall survival was 4.4±2.53 (range, 0.8-10.0) years, 1-year survival was 92%, and 5-year survival was 62%. In 4 patients (30.8%), sirolimus was stopped due to infection in 3 patients and re-transplantation in 1 patient. Only one of the 13 patients developed bronchiolitis obliterans syndrome. In patients still taking sirolimus, renal function, systolic blood pressure, and lipid profile were within normal ranges; however, these patients required statin therapy. CONCLUSIONS In selected lung transplant recipients, early sirolimus-based immunosuppression is safe and associated with beneficial short-term and long-term outcomes.

Pulmonary hypertension in advanced lung diseases: Echocardiography as an important part of patient evaluation for lung transplantation.

INTRODUCTION: Pulmonary hypertension (PH) is common complication in advanced lung disease. Echocardiography provides additional information and may be useful to assess PH probability. OBJECTIVES: The usefulness of combination of well-known echocardiographic parameters in detecting PH in patients with advanced lung disease referred for lung transplantation was evaluated. METHODS: The study population consisted of 37 consecutive patients with idiopathic pulmonary fibrosis (IPF), 20 patients with chronic obstructive pulmonary disease (COPD), and 8 patients with other interstitial lung diseases. PH was defined as mean pulmonary arterial pressure (mPAP) ≥25 mm Hg diagnosed by cardiac catheterization. RESULTS: PH was present in 67.6% of enrolled IPF patients, 30% of enrolled COPD patients, and 75% of patients with other interstitial lung diseases. The receiver operating characteristics (ROC) curve analysis demonstrated right ventricular systolic pressure (RVSP) ≥43 mm Hg to be the threshold for PH prediction (n = 37, sensitivity 92.3%, specificity 81.8%, area under curve (AUC) 0.84, 95% confidence interval (CI) 0.67-1.0; P = .019). Right ventricular outflow tract (RVOT) diameter ≥34 mm and tricuspid annular plane systolic excursion (TAPSE) ≤18 mm had acceptable sensitivity, specificity and AUC (n = 65, 62.2%, 89.3%, 0.77, 95% CI 0.66-0.89; P = .11 and n = 62, 77.1%, 66.7%, 0.74, CI 0.61-0.87; P = .27, respectively). Combination of RVSP, RVOT and TAPSE, obtained in 36 patients, increased the sensitivity and negative predictive value (NPV) to 100%. CONCLUSIONS: In patients with advanced lung diseases referred for lung transplantation the combination of RVSP, RVOT diameter, and TAPSE may be helpful in PH exclusion.

Entry of Human Coronavirus NL63 into the Cell.

The first steps of human coronavirus NL63 (HCoV-NL63) infection were previously described. The virus binds to target cells by use of heparan sulfate proteoglycans and interacts with the ACE2 protein. Subsequent events, including virus internalization and trafficking, remain to be elucidated. In this study, we mapped the process of HCoV-NL63 entry into the LLC-Mk2 cell line and ex vivo three-dimensional (3D) tracheobronchial tissue. Using a variety of techniques, we have shown that HCoV-NL63 virions require endocytosis for successful entry into the LLC-MK2 cells, and interaction between the virus and the ACE2 molecule triggers recruitment of clathrin. Subsequent vesicle scission by dynamin results in virus internalization, and the newly formed vesicle passes the actin cortex, which requires active cytoskeleton rearrangement. Finally, acidification of the endosomal microenvironment is required for successful fusion and release of the viral genome into the cytoplasm. For 3D tracheobronchial tissue cultures, we also observed that the virus enters the cell by clathrin-mediated endocytosis, but we obtained results suggesting that this pathway may be bypassed.IMPORTANCE Available data on coronavirus entry frequently originate from studies employing immortalized cell lines or undifferentiated cells. Here, using the most advanced 3D tissue culture system mimicking the epithelium of conductive airways, we systematically mapped HCoV-NL63 entry into susceptible cells. The data obtained allow for a better understanding of the infection process and may support development of novel treatment strategies.

Serum Levels of Visfatin, Omentin and Irisin in Patients with End-Stage Lung Disease Before and After Lung Transplantation.

BACKGROUND The aim of this study was to investigate serum concentrations of visfatin, irisin, and omentin in patients with end-stage lung diseases (ESLD) before and after lung transplantation (LTx) and to find relationship between adipokines levels and clinical outcomes. MATERIAL AND METHODS Fourteen consecutive lung transplant recipients (six males and seven females; age 32.0±14.2 years; body mass index (BMI) 21.8±5.3 kg/m²) who underwent lung transplantation with initial diagnosis of respiratory failure due to cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) were included. Visfatin, irisin, and omentin serum levels were assayed using commercially available ELISA kits at four time points: the day of LTx (day 0), 72 hours (day 3), one month (day 30) and three months (day 90) after LTx. RESULTS Omentin serum concentration decreased significantly within three days after LTx (350.5±302.0 to 200.0±0.90 ng/mL; p<0.05), while visfatin serum levels decreased later, 30 days after Ltx (4.81±3.78 to 0.78±0.35 [0.4-1.1] pg/mL; p<0.05). Downregulated serum levels of both adipokines remained stable for the next two months (256.0 [201.7-642.9] ng/mL and 0.77±0.76 pg/mL, respectively; p<0.05). Serum levels of irisin were unchanged before and after Ltx. Immunosuppressive regimen did not affect serum levels of the analyzed adipokines. CONCLUSIONS The study showed for the first time serum omentin and visfatin levels to be decreased after LTx in ESLD patients. Successful LTx contributes to the improvement of impaired lung function parameters and attenuation of ongoing inflammatory process, resulting in altered visfatin and omentin serum levels. Additional influence of immunosuppressive treatment on omentin and visfatin serum concentration cannot be excluded.

Superficial herpes simplex virus wound infection following lung transplantation.

Surgical site infections (SSIs) are infections of tissues, organs, or spaces exposed by surgeons during performance of an invasive procedure. SSIs are classified into superficial, which are limited to skin and subcutaneous tissues, and deep. The incidence of deep SSIs in lung transplant (LTx) patients is estimated at 5%. No reports have been published as to the incidence of superficial SSIs specifically in LTx patients. Common sense would dictate that the majority of superficial SSIs would be bacterial. Uncommonly, fungal SSIs may occur, and we believe that no reports exist as to the incidence of viral wound infections in LTx patients, or in any solid organ transplant patients. We report a de novo superficial wound infection with herpes simplex virus following lung transplantation, its possible source, treatment, and resolution.

HTCC: Broad Range Inhibitor of Coronavirus Entry.

To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobically-modified derivative (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses.

Novel Polyanions Inhibiting Replication of Influenza Viruses.

Novel sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) and N-sulfonated chitosan (NSCH) have been synthesized, and their activity against influenza A and B viruses has been studied and compared with that of a series of carrageenans, marine polysaccharides of well-documented anti-influenza activity. NSPAHs were found to be nontoxic and very soluble in water, in contrast to gel-forming and thus generally poorly soluble carrageenans.In vitroandex vivostudies using susceptible cells (Madin-Darby canine kidney epithelial cells and fully differentiated human airway epithelial cultures) demonstrated the antiviral effectiveness of NSPAHs. The activity of NSPAHs was proportional to the molecular mass of the chain and the degree of substitution of amino groups with sulfonate groups. Mechanistic studies showed that the NSPAHs and carrageenans inhibit influenza A and B virus assembly in the cell.

Minimally invasive aortic valve replacement - pros and cons of keyhole aortic surgery.

Over the last twenty years, minimally invasive aortic valve replacement (MIAVR) has evolved into a safe, well-tolerated and efficient surgical treatment option for aortic valve disease. It has been shown to reduce postoperative morbidity, providing faster recovery and rehabilitation, shorter hospital stay and better cosmetic results compared with conventional surgery. A variety of minimally invasive accesses have been developed and utilized to date. This concise review demonstrates and discusses surgical techniques used in contemporary approaches to MIAVR and presents the most important results of MIAVR procedures.

The nucleocapsid protein of human coronavirus NL63.

Human coronavirus (HCoV) NL63 was first described in 2004 and is associated with respiratory tract disease of varying severity. At the genetic and structural level, HCoV-NL63 is similar to other members of the Coronavirinae subfamily, especially human coronavirus 229E (HCoV-229E). Detailed analysis, however, reveals several unique features of the pathogen. The coronaviral nucleocapsid protein is abundantly present in infected cells. It is a multi-domain, multi-functional protein important for viral replication and a number of cellular processes. The aim of the present study was to characterize the HCoV-NL63 nucleocapsid protein. Biochemical analyses revealed that the protein shares characteristics with homologous proteins encoded in other coronaviral genomes, with the N-terminal domain responsible for nucleic acid binding and the C-terminal domain involved in protein oligomerization. Surprisingly, analysis of the subcellular localization of the N protein of HCoV-NL63 revealed that, differently than homologous proteins from other coronaviral species except for SARS-CoV, it is not present in the nucleus of infected or transfected cells. Furthermore, no significant alteration in cell cycle progression in cells expressing the protein was observed. This is in stark contrast with results obtained for other coronaviruses, except for the SARS-CoV.