BACKGROUND: Pulmonary hernia is a rare condition characterized by the protrusion of lung tissue through a chest wall defect. Trauma and thoracic surgery are the most common causes of acquired lung hernias. We present an unusual case of (sequential) bilateral lung herniation with parenchymal infarction after bilateral lobar lung transplantation. CASE PRESENTATION: A 50-year-old female, wait-listed as high-urgency candidate, with a body mass index (BMI) of 29 kg/m2 underwent a bilateral lobar lung transplantation for pulmonary fibrosis through a clamshell thoracotomy approach. Due to a size mismatch, stapler resection of the segment 3 and the middle lobe of the right lung, as well as an upper left lobectomy was required. The chest was closed with 3 braided non-absorbable pericostal sutures on each side. Sternal osteosynthesis was performed with a titanium sternal splint along with 7 self-tapping screws with a length of 18 mm. On the posttransplant day (PTD) 18, patient's clinical condition deteriorated. Physical examination didn't reveal any palpable subcutaneous chest resistance. However, a computed tomography (CT) scan showed a herniation of the segment 6 of the right lung. During acute surgical revision, perioperative finding revealed posterior pericostal suture failure. Therefore, a stapler resection was performed due to the infarction of the herniated segment. On the PTD 36, herniation of the left lung parenchyma was detected by acute CT scan. The protruding vital parenchyma was surgically repositioned without necessity of resection. Two posterior pericostal sutures were broken, and distal part of sternal splint detached. Thoracotomy was closed using 5 braided non-absorbable sutures. Sternum was re-osteosynthesized with the STRATOS™ system. After 3 months of intensive postoperative care, the patient was transferred to the rehabilitation department. She was discharged on the PTD 99. After 20 months of follow-up, lung function remains stable without the need for oxygen support. CONCLUSION: Clamshell incision remains ultimate approach in thoracic surgery. However, pulmonary herniation after clamshell thoracotomy is a rare complication and may manifest as acute respiratory distress syndrome with an inflammatory response. In these cases, CT scan should be always considered, even if no palpable pathology of chest is present.

• Klíčová slova
• Clamshell thoracotomy, Lung hernia, Lung transplantation,
• MeSH
• hernie * etiologie   MeSH
• infarkt etiologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• operace kýly metody   škodlivé účinky   MeSH
• plíce diagnostické zobrazování   MeSH
• plicní nemoci chirurgie   etiologie   MeSH
• počítačová rentgenová tomografie MeSH
• pooperační komplikace chirurgie   MeSH
• torakotomie * metody   MeSH
• transplantace plic * škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Scoliotic deformity represents a serious spinal disorder that influences the locomotive and cardiopulmonary systems. Some patients with severe scoliosis and end-stage lung disease are therefore denied lung transplantation. In patients with scoliosis considering lung transplantation, size match, straight back syndrome, delayed chest closure and bronchial stenosis are key issues clinicians should evaluate. Therefore, it is vital to determine donor-recipient size matches very precisely. Chest opening is a routine intraoperative primary therapeutic procedure after lung transplantation in unstable patients with oversized transplanted lungs. Postoperative bronchial stenosis occurs predominantly on the right side and is usually handled through interventional bronchoscopy and the insertion of stents. This report describes the complex case of a patient with scoliosis who underwent lobar transplantation in our center.

• Klíčová slova
• Bronchial stenosis, Delayed chest closure, Lung transplantation, Scoliosis, Straight back syndrome,
• MeSH
• bronchiální nemoci * chirurgie   MeSH
• lidé MeSH
• skolióza * chirurgie   MeSH
• stenóza chirurgie   MeSH
• sternum chirurgie   MeSH
• transplantace plic * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Acute cellular rejection (ACR) frequently occurs following lung transplantation (LuTx) and represents a risk factor for the development of chronic lung allograft dysfunction (CLAD) as well as long-term survival. The histopathological diagnosis of ACR carries a burden of interobserver variability. The widespread utilization and cost-effectiveness of immunohistochemistry (IHC) was proven beneficial in diagnosing rejection in human kidney transplantations and LuTx rat models. However, its potential for ACR detection in patients remains unexplored. We analyzed surface markers (CD3, CD4, CD8, CD20, CD68, CD47, PD-1, PD-L1, and CD31/PECAM-1) on lung tissue cryobiopsy samples collected within 6 months post-LuTx from 60 LuTx recipients, 48 of whom were diagnosed with ACR. Additionally, serum samples from 51 patients were analyzed using a multiplex bead-based Luminex assay. The cytokines and markers included PD-L1, IL2, TNFα, IFNγ, and Granzyme B. We observed a significant increase in PD-L1 tissue expression within the rejection group, suggesting a concerted effort to suppress immune responses, especially those mediated by T-cells. Furthermore, we noted significant differences in PECAM-1 levels between ACR/non-ACR. Additionally, peripheral blood C-reactive-protein levels tended to be higher in the ACR group, while Luminex serum analyses did not reveal any significant differences between groups. In conclusion, our findings suggest the potential value of PECAM-1 and PD-L1 markers in diagnosing ACR.

• Klíčová slova
• acute cellular rejection, checkpoint inhibitors, immunohistochemistry, luminex, lung transplantation,
• MeSH
• akutní nemoc MeSH
• antigeny CD274 * metabolismus   krev   MeSH
• antigeny CD31 * metabolismus   MeSH
• biologické markery * krev   metabolismus   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• plíce patologie   MeSH
• rejekce štěpu * diagnóza   krev   MeSH
• senioři MeSH
• transplantace plic * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD274 * MeSH
• antigeny CD31 * MeSH
• biologické markery * MeSH
• CD274 protein, human MeSH Prohlížeč
• PECAM1 protein, human MeSH Prohlížeč

INTRODUCTION: Compared with traditional static ice storage, controlled hypothermic storage (CHS) at 4-10°C may attenuate cold-induced lung injury between procurement and implantation. In this study, we describe the first European lung transplant (LTx) experience with a portable CHS device. METHODS: A prospective observational study was conducted of all consecutively performed LTx following CHS (11 November 2022 and 31 January 2024) at two European high-volume centers. The LUNGguard device was used for CHS. The preservation details, total ischemic time, and early postoperative outcomes are described. The data are presented as median (range: minimum-maximum) values. RESULTS: A total of 36 patients underwent LTx (i.e., 33 bilateral, 2 single LTx, and 1 lobar). The median age was 61 (15-68) years; 58% of the patients were male; 28% of the transplantations had high-urgency status; and 22% were indicated as donation after circulatory death. In 47% of the patients, extracorporeal membrane oxygenation (ECMO) was used for perioperative support. The indications for using the CHS device were overnight bridging (n = 26), remote procurement (n = 4), rescue allocation (n = 2), logistics (n = 2), feasibility (n = 1), and extended-criteria donor (n = 1). The CHS temperature was 6.5°C (3.7°C-9.3°C). The preservation times were 11 h 18 (2 h 42-17 h 9) and 13 h 40 (4 h 5-19 h 36) for the first and second implanted lungs, respectively, whereas the total ischemic times were 13 h 38 (4 h 51-19 h 44) and 15 h 41 (5 h 54-22 h 48), respectively. The primary graft dysfunction grade 3 (PGD3) incidence rates were 33.3% within 72 h and 2.8% at 72 h. Intensive care unit stay was 8 (4-62) days, and the hospital stay was 28 (13-87) days. At the last follow-up [139 (7-446) days], three patients were still hospitalized. One patient died on postoperative day 7 due to ECMO failure. In-hospital Clavien-Dindo complications of 3b were observed in six (17%) patients, and 4a in seven (19%). CONCLUSION: CHS seems safe and feasible despite the high-risk recipient and donor profiles, as well as extended preservation times. PGD3 at 72 h was observed in 2.8% of the patients. This technology could postpone LTx to daytime working hours. Larger cohorts and longer-term outcomes are required to confirm these observations.

• Klíčová slova
• controlled hypothermic storage, lung preservation, overnight bridging, preservation temperature, preservation time, primary graft dysfunction, total ischemic time,
• Publikační typ
• časopisecké články MeSH

Static ice storage has long been the standard-of-care for lung preservation, although freezing injury limits ischemic time (IT). Controlled hypothermic storage (CHS) at elevated temperature could safely extend IT. This retrospective analysis assesses feasibility and safety of CHS with IT > 15 hours. Three lung transplant (LuTx) centers (April-October 2023) included demographics, storage details, IT, and short-term outcome from 13 LuTx recipients (8 male, 59 years old). Donor lungs were preserved in a portable CHS device at 7 (5-9.3)°C. Indication was overnight bridging and/or long-distance transport. IT of second-implanted lung was 17.3 (15.1-22) hours. LuTx were successful, 4/13 exhibited primary graft dysfunction grade 3 within 72 hours and 0/13 at 72 hours. Post-LuTx mechanical ventilation was 29 (7-442) hours. Intensive care unit stay was 9 (5-28) and hospital stay 30 (16-90) days. Four patients needed postoperative extracorporeal membrane oxygenation (ECMO). One patient died (day 7) following malpositioning of an ECMO cannula. This multicenter experience demonstrates the possibility of safely extending IT > 15 hours by CHS.

• Klíčová slova
• controlled hypothermic storage, extended preservation, ischemic time, lung transplantation, primary graft dysfunction,
• MeSH
• časové faktory MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• senioři MeSH
• studená ischemie MeSH
• studie proveditelnosti MeSH
• transplantace plic * metody   MeSH
• uchovávání orgánů * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8+ effector T (TEFF) cells and TIM3+PD1+, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8+ T cells. Conversely, CD8+ T cells from immunologically hot tumors like non-small cell lung carcinoma (NSCLC) are enriched in ICI-responsive TCF1+ PD1+ T cells. Spatial B-cell profiling identifies patterns of in situ maturation and differentiation associated with mTLSs. Moreover, B-cell depletion promotes signs of a dysfunctional CD8+ T cell compartment among tumor-infiltrating lymphocytes from freshly isolated HGSOC and NSCLC biopsies. Taken together, our data demonstrate that - at odds with NSCLC - HGSOC is associated with a low density of follicular helper T cells and thus develops a limited number of mTLS that might be insufficient to preserve a ICI-sensitive TCF1+PD1+ CD8+ T cell phenotype. These findings point to key quantitative and qualitative differences between mTLSs in ICI-responsive vs ICI-irresponsive neoplasms that may guide the development of alternative immunotherapies for patients with HGSOC.

• MeSH
• CD8-pozitivní T-lymfocyty MeSH
• ektopické lymfoidní struktury * MeSH
• fenotyp MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory plic * MeSH
• nádory vaječníků * patologie   MeSH
• nemalobuněčný karcinom plic * MeSH
• tumor infiltrující lymfocyty MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Background: Extracorporeal membrane oxygenation (ECMO) is frequently used during lung transplantation. Unfractionated heparin (UFH) is mainly used as part of ECMO support for anticoagulation. One of the most common perioperative complications is bleeding, which high-dose UFH can aggravate. Methods: We retrospectively analyzed (n = 141) patients who underwent lung transplantation between 2020 and 2022. All subjects (n = 109) underwent central cannulated VA ECMO with successful intraoperative ECMO weaning. Patients on ECMO bridge, postoperative ECMO, heart-lung transplants and transplants without ECMO were excluded. The dose of UFH for the entire surgical procedure, blood loss and consumption of blood derivatives intraoperatively and 48 h after ICU admission were recorded. Surgical revision for postoperative bleeding were analyzed. Thrombotic complications, mortality and long-term survival were evaluated. Results: Lower doses of UFH administered for intraoperative ECMO anticoagulation contribute to a reduction in intraoperative blood derivates consumption and blood loss with no thrombotic complications related to the patient or the ECMO circuit. Lower doses of UFH may lead to a decreased incidence of surgical revision for hemothorax. Conclusion: Lower doses of UFH as part of intraoperative ECMO anticoagulation might reduce the incidence of complications and lead to better postoperative outcomes.

• Klíčová slova
• ECMO, UFH, anesthesiology, anticoagulation, lung transplantation,
• MeSH
• antikoagulancia terapeutické užití   MeSH
• heparin terapeutické užití   MeSH
• lidé MeSH
• mimotělní membránová oxygenace * škodlivé účinky   MeSH
• pooperační krvácení MeSH
• retrospektivní studie MeSH
• transplantace plic * metody   MeSH
• trombóza * etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• antikoagulancia MeSH
• heparin MeSH

BACKGROUND: Metastatic esophageal carcinoma (EC) has a poor prognosis and only limited treatment options. While immune checkpoint inhibitors (ICIs) have improved the treatment of a broad spectrum of cancers, patients with EC mostly fail to respond to this treatment. For that reason, it is crucial to understand the immune phenotype of each cancer patient and moreover, to understand how different therapies modulate the cancer microenvironment and sensitize the tumors to the treatment with ICIs. SUMMARY: We have conducted a systematic review of the literature to evaluate the potential of ICI therapy in combination with chemotherapy, radiotherapy, and/or biologic therapy in EC patients. In our review, we have discussed the effects of diverse treatment approaches on the tumor microenvironment of EC. In addition, we have reviewed the current phase II and III clinical trials in EC patients to provide a rationale for immunotherapy application in combination settings with chemotherapy, radiotherapy, and/or biologic therapy. KEY MESSAGES: A great effort is already underway in clinical trials evaluating the combinatorial administration of ICIs and other treatment modalities in metastatic EC patients. PD-L1 expression status was shown to be higher in the squamous cell carcinoma (SCC) as compared to adenocarcinoma. Thus, ICIs plus chemotherapy are being discussed as a particularly feasible option for patients with SCC. Radiation was shown to induce the expression of immune checkpoint molecules and to promote the priming and activation of cytotoxic T cells which provides a rationale for ICI administration in a combination with radiotherapy. The combination of ICIs with biologic therapy was shown to be safe; however, the impact on the clinical outcomes of EC patients varied among studies.

• Klíčová slova
• Anti-CTLA-4, Anti-PD-L1, Anti-PD1, Chemotherapy, Esophageal carcinoma, Immunotherapy, Targeted therapy,
• MeSH
• imunoterapie MeSH
• karcinom * MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory jícnu * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In melanoma and other cancers, invasion, epithelial-to-mesenchymal transition, metastasis and cancer stem cell maintenance are regulated by transcription factors including the Snail family. Slug (Snail2) protein generally supports migration and apoptosis resistance. However, its role in melanoma is not completely understood. The present study investigated the transcriptional regulation of the SLUG gene in melanoma. It demonstrated that SLUG is under the control of the Hedgehog/GLI signaling pathway and is activated predominantly by the transcription factor GLI2. The SLUG gene promoter contains a high number of GLI-binding sites. Slug expression is activated by GLI factors in reporter assays and inhibited by GANT61 (GLI inhibitor) and cyclopamine (SMO inhibitor). SLUG mRNA levels are lowered by GANT61 as assessed by reverse transcription-quantitative PCR. Chromatin immunoprecipitation revealed abundant binding of factors GLI1-3 in the four subregions of the proximal SLUG promoter. Notably, melanoma-associated transcription factor (MITF) is an imperfect activator of the SLUG promoter in reporter assays, and downregulation of MITF had no effect on endogenous Slug protein levels. Immunohistochemical analysis confirmed the above findings and showed MITF-negative regions in metastatic melanoma that were positive for GLI2 and Slug. Taken together, the results demonstrated a previously unrecognized transcriptional activation mechanism of the SLUG gene, which may represent its main regulation of expression in melanoma cells.

• Klíčová slova
• GLI family zinc finger, Hedgehog signaling, Slug, melanoma, melanoma-associated transcription factor,
• MeSH
• apoptóza MeSH
• lidé MeSH
• melanom * genetika   MeSH
• proteiny hedgehog * genetika   MeSH
• signální transdukce MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• proteiny hedgehog * MeSH
• transkripční faktory MeSH

BACKGROUND: Primary graft dysfunction (PGD) after lung transplantation (LuTx) contributes substantially to early postoperative morbidity. Both intraoperative transfusion of a large amount of blood products during the surgery and ischemia-reperfusion injury after allograft implantation play an important role in subsequent PGD development. METHODS: We have previously reported a randomized clinical trial of 67 patients where point of care (POC) targeted coagulopathy management and intraoperative administration of 5% albumin led to significant reduction of blood loss and blood product consumption during the lung transplantation surgery. A secondary analysis of the randomized clinical trial evaluating the effect of targeted coagulopathy management and intraoperative administration of 5% albumin on early lung allograft function after LuTx and 1-year survival was performed. RESULTS: Compared to the patients in the control (non-POC) group, those in study (POC) group showed significantly superior graft function, represented by the Horowitz index (at 72 h after transplantation 402.87 vs 308.03 with p < 0.001, difference between means: 94.84, 95% CI: 60.18-129.51). Furthermore, the maximum doses of norepinephrine administered during first 24 h were significantly lower in the POC group (0.193 vs 0.379 with p < 0.001, difference between the means: 0.186, 95% CI: 0.105-0.267). After dichotomization of PGD (0-1 vs 2-3), significant difference between the non-POC and POC group occurred only at time point 72, when PGD grade 2-3 developed in 25% (n = 9) and 3.2% (n = 1), respectively (p = 0.003). The difference in 1-year survival was not statistically significant (10 patients died in non-POC group vs. 4 patients died in POC group; p = 0.17). CONCLUSIONS: Utilization of a POC targeted coagulopathy management combined with Albumin 5% as primary resuscitative fluid may improve early lung allograft function, provide better circulatory stability during the early post-operative period, and have potential to decrease the incidence of PGD without negative effect on 1-year survival. TRIAL REGISTRATION: This clinical trial was registered at ClinicalTrials.gov (NCT03598907).

• Klíčová slova
• 5% albumin, Anesthetic management, Lung transplantation, Rotational thromboelastometry, Volume replacement therapy,
• MeSH
• alografty MeSH
• krvácení MeSH
• lidé MeSH
• primární dysfunkce štěpu * MeSH
• reperfuzní poškození * MeSH
• transplantace plic * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH