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Atherosclerosis is a condition that is associated with lipid accumulation in the arterial intima. Consequently, the enlarging lesion, which is also known as an atherosclerotic plaque, may close the blood vessel lumen, thus leading to organ ischaemia. Furthermore, the plaque may rupture and initiate the formation of a thrombus, which can cause acute ischaemia. Atherosclerosis is a background pathological condition that can eventually lead to major cardiovascular diseases such as acute coronary syndrome or ischaemic stroke. The disorder is associated with an altered profile of alarmins, stress response molecules that are secreted due to cell injury or death and that induce inflammatory responses. High-mobility group box 1 (HMGB1), S100 proteins, interleukin-33, and heat shock proteins (HSPs) also affect the behaviour of endothelial cells and vascular smooth muscle cells (VSMCs). Thus, alarmins control the inflammatory responses of endothelial cells and proliferation of VSMCs, two important processes implicated in the pathogenesis of atherosclerosis. In this review, we will discuss the role of alarmins in the pathophysiology of atherosclerosis and myocardial infarction.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and aggressive subtype of inflammatory myofibroblastic tumor. The disease is associated with rearrangements of the anaplastic lymphoma kinase (ALK). In this paper, we present the clinicopathological features and treatment of a female patient diagnosed with EIMS. In 2019, an 18-year-old female patient was admitted to the hospital with abdominal pain. Radiological examinations confirmed a large pelvic mass which was subsequently resected. After re-evaluation of the initial histologic diagnosis, the final diagnosis of EIMS was established. Consequently, due to the lack of response to chemotherapy and deteriorating clinical condition, she began the therapy with ALK inhibitors. In total, the patient was treated with crizotinib, alectinib, and lorlatinib. As a result, after over 4 years since the initial diagnosis, she is still alive with significantly improved clinical condition and quality of life. This paper demonstrates the clinical benefits of sequential therapy of ALK inhibitors and an exceptionally long response to lorlatinib, a third-generation tyrosine kinase inhibitor.

Alarmins are immune-activating factors released after cellular injury or death. By secreting alarmins, cells can interact with immune cells and induce a variety of inflammatory responses. The broad family of alarmins involves several members, such as high-mobility group box 1, S100 proteins, interleukin-33, and heat shock proteins, among others. Studies have found that the concentrations and expression profiles of alarmins are altered in immune-mediated diseases. Furthermore, they are involved in the pathogenesis of inflammatory conditions. The aim of this narrative review is to present the current evidence on the role of alarmins in rheumatoid arthritis, osteoarthritis, and psoriasis. We discuss their potential involvement in mechanisms underlying the progression of these diseases and whether they could become therapeutic targets. Moreover, we summarize the impact of pharmacological agents used in the treatment of these diseases on the expression of alarmins.

Membrane transporters are expressed in a wide range of tissues in the human organism. These proteins regulate the penetration of various substances such as simple ions, xenobiotics, and an extensive number of therapeutics. ABC and SLC drug transporters play a crucial role in drug absorption, distribution, and elimination. Recent decades have shown their contribution to the systemic exposure and tissue penetration of numerous drugs, thereby having an impact on pharmacokinetic and pharmacodynamic parameters. Importantly, the activity and expression of these transporters depend on numerous conditions, including intestinal microbiome profiles or health conditions. Moreover, the combined intake of other drugs or natural agents further affects the functionality of these proteins. In this review, we will discuss the involvement of ABC and SLC transporters in drug disposition. Moreover, we will present current evidence of the potential role of drug transporters as therapeutic targets.

Acute kidney injury (AKI) describes a condition associated with elevated serum creatinine levels and decreased glomerular filtration rate. AKI can develop as a result of sepsis, the nephrotoxic properties of several drugs, and ischemia/reperfusion injury. Renal damage can be associated with metabolic acidosis, fluid overload, and ionic disorders. As the molecular background of the pathogenesis of AKI is insufficiently understood, more studies are needed to identify the key signaling pathways and molecules involved in the progression of AKI. Consequently, future treatment methods may be able to restore organ function more rapidly and prevent progression to chronic kidney disease. MicroRNAs (miRNAs) are small molecules that belong to the non-coding RNA family. Recently, numerous studies have demonstrated the altered expression profile of miRNAs in various diseases, including inflammatory and neoplastic conditions. As miRNAs are major regulators of gene expression, their dysregulation is associated with impaired homeostasis and cellular behavior. The aim of this article is to discuss current evidence on the involvement of miRNAs in the pathogenesis of AKI.

Atherosclerosis is a highly prevalent condition associated with lipid accumulation in the intima layer of arterial blood vessels. The development of atherosclerotic plaques is associated with the incidence of major cardiovascular events, such as acute coronary syndrome or ischemic stroke. Due to the significant prevalence of atherosclerosis and its subclinical progression, it is associated with severe and potentially lethal complications. The pathogenesis of atherosclerosis is complex and not entirely known. The identification of novel non-invasive diagnostic markers and treatment methods that could suppress the progression of this condition is highly required. Non-coding RNA (ncRNA) involves several subclasses of RNA molecules. microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) differently regulate gene expression. Importantly, these molecules are frequently dysregulated under pathological conditions, which is associated with enhanced or suppressed expression of their target genes. In this review, we aim to discuss the involvement of ncRNA in crucial mechanisms implicated in the pathogenesis of atherosclerosis. We summarize current evidence on the potential use of these molecules as diagnostic and therapeutic targets.

Hepatitis C virus (HCV) is a hepatotropic virus that can be transmitted through unsafe medical procedures, such as injections, transfusions, and dental treatment. The infection may be self-limiting or manifest as a chronic form that induces liver fibrosis, cirrhosis, or progression into hepatocellular carcinoma (HCC). Epigenetic mechanisms are major regulators of gene expression. These mechanisms involve DNA methylation, histone modifications, and the activity of non-coding RNAs, which can enhance or suppress gene expression. Abnormal activity or the dysregulated expression of epigenetic molecules plays an important role in the pathogenesis of various pathological disorders, including inflammatory diseases and malignancies. In this review, we summarise the current evidence on epigenetic mechanisms involved in HCV infection and progression to HCC.

Lung cancer is a leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is a predominant subtype and treatment may include immunotherapy, radiotherapy, chemotherapy, and surgery. Tumors of bigger size infiltrating large bronchi and vessels require more invasive resection such as pneumonectomy. To save lung parenchyma, sleeve lobectomy can be performed in certain patients.We report the case of a patient with NSCLC infiltrating the chest wall who underwent arterial sleeve lobectomy with rib resection. Furthermore, we discuss other surgical treatment strategies.A 58-year-old female patient was admitted to the hospital in 2020 with pain in her left posterolateral chest. Radiological imaging revealed a tumor (5.0×3.5×4.8 cm) in the top of the left lung, infiltrating pulmonary artery and ribs. Therefore, left upper sleeve lobectomy together with resection of rib blocks II to V was performed. The surgery was uncomplicated, but a few weeks postoperatively, the patient experienced repeated episodes of consciousness disturbances. Contrast CT revealed a cerebral malformation in the patient who died 3.5 months after surgery.Sleeve lobectomy can be safely performed in patients with lung tumors infiltrating larger bronchi and vessels who would not tolerate pneumonectomy.

Primary pulmonary lymphoma is a rare neoplasm characterized by the proliferation of lymphoid tissue affecting the lungs. The most common subtype is marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). Rarely, a MALT lymphoma transforms into a diffuse large B-cell lymphoma (DLBCL). Treatment options include chemotherapy, radiotherapy, immunotherapy, and surgery. Here, we describe a patient with a primary pulmonary MALT lymphoma transforming into DLBCL. The purpose of this case report is to raise awareness of the relevant clinical and imaging features and to emphasize the need for a multidisciplinary approach to optimal management. In addition, we screened the PubMed and Embase databases for similar reports with a confirmed presence of transforming lymphoma within the lungs.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The pathogenesis of RA is complex and involves broad interactions between various cells present in the inflamed synovium, including fibroblast-like synoviocytes (FLSs), macrophages, and T cells, among others. Under inflammatory conditions, these cells are activated, further enhancing inflammatory responses and angiogenesis and promoting bone and cartilage degradation. Novel treatment methods for RA are greatly needed, and mesenchymal stromal cells (MSCs) have been suggested as a promising new regenerative and immunomodulatory treatment. In this paper, we present the interactions between MSCs and RA-FLSs, and macrophages and T cells, and summarise studies examining the use of MSCs in preclinical and clinical RA studies.

Background: Immunosuppressive agents represent a broad group of drugs, such as calcineurin inhibitors, mTOR inhibitors, and glucocorticosteroids, among others. These drugs are widely used in a number of conditions, but lifelong therapy is crucial in the case of organ recipients to prevent rejection. To further increase the safety and efficacy of these agents, their off-target mechanisms of action, as well as processes underlying the pathogenesis of adverse effects, need to be thoroughly investigated. The aim of this study was to examine the impact of various combinations of cyclosporine/tacrolimus/mycophenolate with rapamycin and steroids (CRG, TRG, MRG), on the morphology and morphometry of rats’ cardiomyocytes, together with the presence of cardiac collagen and the immunoexpression of MMPs and TIMPs. Methods: Twenty-four rats were divided into four groups receiving different immunosuppressive regiments. After six months of treatment, the hearts were collected and analyzed. Results: Cardiomyocytes from the CRG cohorts demonstrated the most pronounced morphological alterations. In addition, chronic immunosuppression reduced the width and length of cardiac cells. However, immunosuppressive therapy did not alter the presence of cardiac collagen fibers. Nevertheless, we observed significant alterations regarding MMP/TIMP homeostasis. Conclusions: Chronic immunosuppression seems to disturb the MMP/TIMP balance in aspects of immunolocalization in the hearts of rats. Further studies are required to analyze other mechanisms and pathways affected by the use of immunosuppressants.

Fusions and mutations of anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, have been identified in several neoplastic diseases. Rearranged ALK is a driver of tumorigenesis, which activates various signaling pathway associated with proliferation and survival. To date, several agents that target and inhibit ALK have been developed. The most studied ALK-positive disease is non-small cell lung cancer, and three generations of ALK tyrosine kinase inhibitors (TKIs) have been approved for the treatment of metastatic disease. Nevertheless, the use of ALK-TKIs is associated with acquired resistance (resistance mutations, bypass signaling), which leads to disease progression and may require a substitution or introduction of other treatment agents. Understanding of the complex nature and network of resistance mutations may allow to introduce sequential and targeted therapies. In this review, we aim to summarize the efficacy and safety profile of ALK inhibitors, describe off-target anticancer effects, and discuss resistance mechanisms in the context of personalized oncology.

Small cell cancer (SCC) is a neuroendocrine neoplasm, which is most frequently found in the lungs. Extrapulmonary location of SCC is rare and may involve 2.5-5% of SCCs. We present a case of a 31-year-old male patient with an extremely uncommon subglottic SCC. The patient was qualified for a radical sequential chemoradiotherapy. After treatment, patient’s condition suggested complete remission. Recurrence was detected one year later, and the disease rapidly progressed, despite a second line chemotherapy. The patient died 29 months after initial diagnosis. This case aims to raise awareness on the aggressive laryngeal SCC and its good response to first line chemotherapy composed of cisplatin and etoposide, followed by radiotherapy.

Background: One of the most uncommon manifestations of perioperative Covid-19 infection is impaired wound healing. The aim of this study is to present previously unreported observation of thoracotomy and esophageal anastomosis dehiscence in the course of Covid-19 infection after uncomplicated thoracic surgeries. Methods: This is a single-center study describing unusual wound and anastomosis complications in COVID-19 patients after uncomplicated thoracic surgeries. Medical data was prospectively collected and retrospectively reviewed. All patients admitted to the hospital were symptom free and tested negative for COVID-19 infection preoperatively. Clinical courses were compared to a non-infected control group from historical data. Results: The total of 14 patients were included. Study group involved 7 patients with major wound and anastomosis complications concurrent with COVID-19 infection. Control group was composed of 7 patients matched with the type of surgeries and treated before Coronavirus pandemic. Surgeries included lung transplantations, lung cancer surgeries and esophagectomies. The mean age of the study group was 65.7 years. Major wound and anastomosis complications occurred 13.6 days postoperatively while the mean time of Covid-19 detection was 21 days. The course of infection varied from mild to very severe which resulted in 3 deaths due to COVID-19 induced ARDS. The mean time of hospital stay was 40,9 days. There were no differences between both groups in baseline characteristics while hospitalization time was significantly longer in the study group. Conclusions: COVID-19 infection should be included in differential diagnosis in postoperative patients with major wound or anastomosis complications.

Periodontitis (PD) is a prevalent and chronic inflammatory disease with a complex pathogenesis, and it is associated with the presence of specific pathogens, such as Porphyromonas gingivalis. Dysbiosis and dysregulated immune responses ultimately lead to chronic inflammation as well as tooth and alveolar bone loss. Multiple studies have demonstrated that genetic polymorphisms may increase the susceptibility to PD. Furthermore, gene expression is modulated by various epigenetic mechanisms, such as DNA methylation, histone modifications, or the activity of non-coding RNA. These processes can also be induced by PD-associated pathogens. In this review, we try to summarize the genetic processes that are implicated in the pathogenesis of PD. Furthermore, we discuss the use of these mechanisms in diagnosis and therapeutic purposes. Importantly, novel treatment methods that could promote tissue regeneration are greatly needed in PD. In this paper, we also demonstrate current evidence on the potential use of stem cells and extracellular vesicles to stimulate tissue regeneration and suppress inflammation. The understanding of the molecular mechanisms involved in the pathogenesis of PD, as well as the impact of PD-associated bacteria and stem cells in these processes, may enhance future research and ultimately improve long-term treatment outcomes.

Cells can communicate with each other through extracellular vesicles (EVs), which are membrane-bound structures that transport proteins, lipids and nucleic acids. These structures have been found to mediate cellular differentiation and proliferation apoptosis, as well as inflammatory responses and senescence, among others. The cargo of these vesicles may include immunomodulatory molecules, which can then contribute to the pathogenesis of various diseases. By contrast, EVs secreted by mesenchymal stem cells (MSCs) have shown important immunosuppressive and regenerative properties. Moreover, EVs can be modified and used as drug carriers to precisely deliver therapeutic agents. In this review, we aim to summarize the current evidence on the roles of EVs in the progression and treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), which are important and prevalent joint diseases with a significant global burden.

Situs inversus totalis (SIT) is a congenital anomaly that involves the mirror rearrangement of the thoracic and abdominal internal organs. In this paper, we report a 56-year-old male patient with previously confirmed SIT, who was admitted to the hospital for the diagnosis and surgical treatment of non-small-cell lung cancer, located in the sixth right pulmonary segment. The patient underwent segmentectomy with mediastinal and hilar lymphadenectomy. Furthermore, we screened the PubMed and Embase databases for reports of the surgical treatment of patients with SIT and lung cancer. Articles describing inoperable and disseminated disease, as well as patients qualified for palliative treatment, were not included. Ultimately, we compared 21 articles (including the one described here). Data about the clinical condition, tumor characteristics, treatment, and histopathological examination were extracted and summarized.

Abstract Background Chronic obstructive pulmonary disease, cystic fibrosis and usual interstitial pneumonia are three most common indications for lung transplantation (LuTx) in Poland. As a result of irreversible destruction of pulmonary parenchyma and extended respiratory insufficiency that appear afterwards, it is crucial to estimate the reserve of gas exchange in each lung before and during surgery. Altering conditions of gas exchange require adaptation in circulatory system as well. In some of the cases the use of extracorporeal life support appears to be necessary to undergo the transplantation successfully. Cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) used during operation allow to replace the function of heart and lung, but they are also related to complications in the form of acute kidney failure, bleeding, heart arrhythmias or thromboembolic complications. Methods We reviewed 77 LuTx from 2009 to 2020 performed at the Department of Thoracic Surgery and Transplantation. 40/77 (51%) patients required intraoperative extracorporeal assistance: 8 required CBP and 32 required ECMO. In the ECMO group 14/32 (44%) patients had peripheral cannulation and 18/32 (56%) had central one. We have calculated the survival rates and reviewed postoperative complications after lung transplantations. Cumulative Kaplan–Meier survival curves were calculated. Differences between the groups were evaluated by the Chi- square analysis for discontinuous variables and t-test for continuous variables. Results The use of intraoperative central extracorporeal membrane oxygenator was associated with increased survival rates comparing to patients without external support (30-days, 1-year, 3-years, 5-years rates: 78%, 66%, 66%, 66% vs 83%, 65%, 59%, 44% respectively). Furthermore, survival was enhanced comparing to peripheral ECMO or cardiopulmonary bypass as well (50%, 41%, 41%, 33%; 75%, 50%, 50%, 38% respectively). Acute kidney injury and thromboembolic complications occurred statistically more often in case of patients that underwent lung transplantation with support devices (p = 0.005, p = 0.02 respectively). Frequency of other complications was comparable among groups. Conclusions The use of central extracorporeal membrane oxygenation should be favorized over peripheral cannulation or cardiopulmonary bypass. CPB should be no longer used during LuTx. Trial registration Not applicable.

Human echinococcosis is a zoonotic infection caused by the larvae of the tapeworm species Echinococcus. The liver is the most common location for a primary echinococcosis. However, the parasite may bypass or spread from the liver to the lungs, causing primary or secondary pulmonary echinococcosis, respectively. Pulmonary echinococcosis is a clinically challenging condition in which anthelminthic regiments are important, but surgery has the central role in removing the cysts and preventing recurrences. Surgical treatment may involve cystotomy, enucleation, capitonnage, or atypical resections, which occasionally are in combination with hepatic procedures. The utilization of modern devices is greatly underdescribed in surgery for thoracic infections, even though these facilitate much of the work. Therefore, this article aims to describe pulmonary echinococcosis and the role of modern surgical devices in the treatment process. Furthermore, we report surgical treatment of three different cases of pulmonary echinococcosis. Surgeries of uncomplicated and ruptured hepatic or pulmonary cysts are described. Simple small pulmonary echinococcal lesions can be excised by endostaplers both for diagnostic and curative reasons. Larger cysts can be removed by energy devices unless large bronchial air leaks occur. Complicated cysts require treatment by more extensive techniques. Inexperienced surgeons should not abstain but should carefully decide preoperatively how to proceed.

Background: Infections are one of the leading causes of death in the early postoperative period after lung transplantation (LuTx). Methods: We analyzed 59 transplantations and culture results of the donor bronchial aspirates (DBA), graft endobronchial swabs (GES), and recipient cultures (RC) before and after the procedure (RBA). We correlated the results with a cold ischemic time (CIT), recipient intubation time, and length of stay in the hospital and intensive care unit (ICU), among others. Results: CIT of the first and second lungs were 403 and 541 min, respectively. Forty-two and eighty-three percent of cultures were positive in DBA and GES, respectively. Furthermore, positive results were obtained in 79.7% of RC and in 33.9% of RBA. Longer donor hospitalization was correlated with Gram-negative bacteria isolation in DBA. Longer CIT was associated with Gram-positive bacteria other than Staphylococcus aureus in GES and it resulted in longer recipient stay in the ICU. Furthermore, longer CIT resulted in the development of the new pathogens in RBA. Conclusion: Results of GES brought more clinically relevant information than DBA. Donor hospitalization was associated with the occurrence of Gram-negative bacteria. Positive cultures of DBA, GES, and RBA were not associated with recipient death.

Basal cell carcinoma (BCC) is the most frequent human skin cancer, but metastasizing BCC (MBCC) is extremely rare, developing in approximately 0.0028% to 0.55% of BCC patients. Herein, we report two cases of pulmonary MBCC. The first one developed in a 72-year-old male who underwent surgical resection due to multiple recurrences and adjuvant radiotherapy. Immunohistochemistry showed that neoplastic cells expressed Ber-EP4, CK5/6, p63, EMA (focally), BCL-2, and CD10, but were negative for CK7, CK20, S100, estrogen and progesterone receptors, and TTF-1. The second case is a 64-year-old female treated with vismodegib. Clinicopathological features and differential diagnoses are described.