Efficacy of mTOR Inhibitors and Intravenous Immunoglobulin for Treatment of Polyoma BK Nephropathy in Kidney Transplant Recipients: A Biopsy-Proven Study.

OBJECTIVES: We investigated the efficacy of a predetermined protocol that consisted of immunosuppressive drug reduction/withdrawal and intravenous immunoglobulin administration for the treatment of polyoma BK virus nephropathy. MATERIALS AND METHODS: Patients with biopsy-proven polyoma BK virus nephropathy received a treatment regimen based on discontinuation of both calcineurin inhibitors and antiproliferative agents and switching to mTOR inhibitors accompanied by intravenous immunoglobulin administration. RESULTS: Our study included 508 patients, with polyoma BK viremia detected in 80 patients. The mean age was 45.3 ± 9.5 years (range, 18-71 y), 64% were male, and mean follow-up was 37 ± 21 months (6-94 mo). All 16 patients who developed polyoma BK virus nephropathy and 9 patients who had highgrade polyoma BK viremia without nephropathy received intravenous immunoglobulin treatment. Compared with patients with viremia, patients with polyoma BK virus nephropathy had significantly higher rates of graft loss due to rejection (18.8% vs 1.6%; P = .024) and all-cause graft loss (31.2% vs 6.3%; P = .014). Histopathologically, viral inclusion bodies disappeared and SV40 became negative after treatment in all 13 patients who underwent protocol biopsies. Unfortunately, histopathologically complete recovery without chronic tubular and interstitial tissue damage was achieved in only 4 patients after treatment. In addition, 3 patients lost their grafts due to acute antibody-mediated or mixed-type rejection (18.8%). CONCLUSIONS: In patients with polyoma BK virus nephropathy, clearance of viremia and SV40 should not be the sole outcomes to obtain. Aggressive reductions in maintenance immunosuppression and switching to double-drug therapy combined with high-dose intravenous immunoglobulin leads to high rates of graft loss/rejection and sequalae of chronic histological changes.

The Immunopathology of Pulmonary Rejection after Murine Lung Transplantation.

To improve outcomes following lung transplantation, it is essential to understand the immunological mechanisms that result in chronic graft failure. The associated clinical syndrome is termed chronic lung allograft dysfunction (CLAD), which is known to be induced by alloimmune-dependent (i.e., rejection) and alloimmune-independent factors (e.g., infections, reflux and environmental factors). We aimed to explore the alloimmune-related mechanism, i.e., pulmonary rejection. In this study, we use a murine orthotopic left lung transplant model using isografts and allografts (C57BL/6 or BALB/c as donors to C57BL/6 recipients), with daily immunosuppression (10 mg/kg cyclosporin A and 1.6 mg/kg methylprednisolone). Serial sacrifice was performed at days 1, 7 and 35 post-transplantation (n = 6 at each time point for each group). Left transplanted lungs were harvested, a single-cell suspension was made and absolute numbers of immune cells were quantified using multicolor flow cytometry. The rejection process followed the principles of a classic immune response, including innate but mainly adaptive immune cells. At day 7 following transplantation, the numbers of interstitial macrophages, monocytes, dendritic cells, NK cells, NKT cells, CD4+ T cells and CD8+ T and B cells were increased in allografts compared with isografts. Only dendritic cells and CD4+ T cells remained elevated at day 35 in allografts. Our study provides insights into the immunological mechanisms of true pulmonary rejection after murine lung transplantation. These results might be important in further research on diagnostic evaluation and treatment for CLAD.

Stimuli-specific senescence of primary human lung fibroblasts modulates alveolar stem cell function.

Aging is the main risk factor for chronic lung diseases (CLDs) including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging such as cellular senescence are present in different lung cell types such as fibroblasts in these patients. However, whether the senescent phenotype of fibroblasts derived from IPF or COPD patients differs is still unknown. Therefore, we characterized senescence at baseline and after exposure to disease-relevant insults (H 2 O 2 , bleomycin, and TGF-ß1) in cultured primary human lung fibroblasts (phLF) from control donors, IPF, or COPD patients. We found that phLF from different disease-origins have a low baseline senescence. H 2 O 2 and bleomycin treatment induced a senescent phenotype in phLF, whereas TGF-ß1 had primarily a pro-fibrotic effect. Notably, we did not observe any differences in susceptibility to senescence induction in phLF based on disease origin, while exposure to different stimuli resulted in distinct senescence programs in phLF. Moreover, senescent phLF reduced colony formation efficiency of distal alveolar epithelial progenitor cells in a stimuli-dependent manner. In conclusion, the senescent phenotype of phLF is mainly determined by the senescence inducer and impairs alveolar epithelial progenitor capacity in vitro .

Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.

BACKGROUND: Fibroblast-to-myofibroblast conversion is a major driver of tissue remodelling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet their specific activation states and phenotypic trajectories during injury and repair have remained unclear. METHODS: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-sequencing and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. Our findings were validated in idiopathic pulmonary fibrosis patient tissues in situ as well as in cell differentiation and invasion assays using patient lung fibroblasts. Cell differentiation and invasion assays established a function of SFRP1 in regulating human lung fibroblast invasion in response to transforming growth factor (TGF)ß1. MEASUREMENTS AND MAIN RESULTS: We discovered a transitional fibroblast state characterised by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1 + cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage-specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1 + transitional fibroblasts and Cthrc1 + myofibroblasts. TGFß1 downregulated SFRP1 in noninvasive transitional cells and induced their switch to an invasive CTHRC1+ myofibroblast identity. Finally, using loss-of-function studies we showed that SFRP1 modulates TGFß1-induced fibroblast invasion and RHOA pathway activity. CONCLUSIONS: Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies SFRP1 as a modulator of TGFß1-driven fibroblast phenotypes in fibrogenesis. These findings are relevant in the context of therapeutic interventions that aim at limiting or reversing fibroblast foci formation.

Small Airway Disease in Pre-Chronic Obstructive Pulmonary Disease with Emphysema: A Cross-Sectional Study.

Rationale: Small airway disease is an important pathophysiological feature of chronic obstructive pulmonary disease (COPD). Recently, "pre-COPD" has been put forward as a potential precursor stage of COPD that is defined by abnormal spirometry findings or significant emphysema on computed tomography (CT) in the absence of airflow obstruction. Objective: To determine the degree and nature of (small) airway disease in pre-COPD using microCT in a cohort of explant lobes/lungs. Methods: We collected whole lungs/lung lobes from patients with emphysematous pre-COPD (n = 10); Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (n = 6), II (n = 6), and III/IV (n = 7) COPD; and controls (n = 10), which were analyzed using CT and microCT. The degree of emphysema and the number and morphology of small airways were compared between groups, and further correlations were investigated with physiologic measures. Airway and parenchymal pathology was also validated with histopathology. Measurements and Main Results: The numbers of transitional bronchioles and terminal bronchioles per milliliter of lung were significantly lower in pre-COPD and GOLD stages I, II, and III/IV COPD compared with controls. In addition, the number of alveolar attachments of the transitional bronchioles and terminal bronchioles was also lower in pre-COPD and all COPD groups compared with controls. We did not find any differences between the pre-COPD and COPD groups in CT or microCT measures. The percentage of emphysema on CT showed the strongest correlation with the number of small airways in the COPD groups. Histopathology showed an increase in the mean chord length and a decrease in alveolar surface density in pre-COPD and all GOLD COPD stages compared with controls. Conclusions: Lungs of patients with emphysematous pre-COPD already show fewer small airways and airway remodeling even in the absence of physiologic airway obstruction.

Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multilineage cell circuit dynamics in human lung fibrogenesis.

Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques. In this work, we coupled ex vivo cytokine and drug perturbations of human precision-cut lung slices (hPCLS) with single-cell RNA sequencing and induced a multilineage circuit of fibrogenic cell states in hPCLS. We showed that these cell states were highly similar to the in vivo cell circuit in a multicohort lung cell atlas from patients with pulmonary fibrosis. Using micro-CT-staged patient tissues, we characterized the appearance and interaction of myofibroblasts, an ectopic endothelial cell state, and basaloid epithelial cells in the thickened alveolar septum of early-stage lung fibrosis. Induction of these states in the hPCLS model provided evidence that the basaloid cell state was derived from alveolar type 2 cells, whereas the ectopic endothelial cell state emerged from capillary cell plasticity. Cell-cell communication routes in patients were largely conserved in hPCLS, and antifibrotic drug treatments showed highly cell type-specific effects. Our work provides an experimental framework for perturbational single-cell genomics directly in human lung tissue that enables analysis of tissue homeostasis, regeneration, and pathology. We further demonstrate that hPCLS offer an avenue for scalable, high-resolution drug testing to accelerate antifibrotic drug development and translation.

The effect of multiple outgrowths from bronchial tissue explants on progenitor/stem cell number in primary bronchial epithelial cell cultures from smokers and patients with COPD.

Background: Although studies suggest a deficiency in stem cell numbers in chronic airway diseases such as chronic obstructive pulmonary disease (COPD), the role of bronchial epithelial progenitor/stem (P/S) cells is not clear. The objectives of this study were to investigate expression of progenitor/stem (P/S) cell markers, cytokeratin (CK) 5, CK14 and p63 in bronchial epithelial explants and cell cultures obtained from smokers with and without COPD following multiple outgrowths, and to study this effect on bronchial epithelial cell (BEC) proliferation. Methods: Bronchial epithelial explants were dissected from lung explants and cultured on coverslips. Confluent cultures were obtained after 3-4 weeks' (transfer, Tr1), explants were then transferred and cultured for a second (Tr2) and third (Tr3) time, respectively. At each stage, expression of CK5, CK14 and p63 in explants and BEC were determined by immunostaining. In parallel experiments, outgrowing cells from explants were counted after 4wks, and explants subsequently transferred to obtain new cultures for a further 3 times. Results: As the transfer number advanced, CK5, CK14 and p63 expression was decreased in both explants and BEC from both smokers without COPD and patients with COPD, with a more pronounced decrease in BEC numbers in the COPD group. Total cell numbers cultured from explants were decreased with advancing outgrowth number in both groups. Smoking status and lung function parameters were correlated with reduced P/S marker expression and cell numbers. Conclusion: Our findings suggest that the number of P/S cells in airway epithelium may play a role in the pathogenesis of COPD, as well as a role in the proliferation of airway epithelial cells, in vitro.

Effect of Mesoappendix Volume on Preoperative Pain of Acute Appendicitis.

OBJECTIVE: To investigate the relationship between preoperative pain scores and the mesoappendix volume and the presence of complications in patients with acute appendicitis. STUDY DESIGN: Cross-sectional observational study. Place and Duration of the Study: Department of General Surgery at Kutahya Health Sciences University, Kutahya, Turkey, from January to December 2021. METHODOLOGY: Pain degrees in patients with acute appendicitis were measured by Numerical Rating Scale (NRS) and Wong-Baker Scale (WBS). Mesoappendix volume was calculated using the formula: mesoappendix length x width x height. Appendicitis type (as complicated or uncomplicated) was grouped. RESULTS: There was a positive and statistically significant correlation (17%) between the NRS and mesoappendix volume (p=0.065). In addition, there was a positive and statistically significant correlation (17%) between the WBS and mesoappendix volume (p=0.057). Additionally, there was a statistically significant relationship between the NRS, WBS, and complicated appendicitis (p=0.022, p=0.022, respectively). CONCLUSION: The mesoappendix volume might contribute to preoperative pain process in acute appendicitis patients. Specifically, there is a statistically significant correlation between complicated appendicitis and preoperative pain scores. KEY WORDS: Appendicitis, Pain, Mesentery, Complicated appendicitis.

Nanoparticle-Exposure-Triggered Virus Reactivation Induces Lung Emphysema in Mice.

Nanoparticles (NPs) released from engineered materials or combustion processes as well as persistent herpesvirus infection are omnipresent and are associated with chronic lung diseases. Previously, we showed that pulmonary exposure of a single dose of soot-like carbonaceous NPs (CNPs) or fiber-shaped double-walled carbon nanotubes (DWCNTs) induced an increase of lytic virus protein expression in mouse lungs latently infected with murine γ-herpesvirus 68 (MHV-68), with a similar pattern to acute infection suggesting virus reactivation. Here we investigate the effects of a more relevant repeated NP exposure on lung disease development as well as herpesvirus reactivation mechanistically and suggest an avenue for therapeutic prevention. In the MHV-68 mouse model, progressive lung inflammation and emphysema-like injury were detected 1 week after repetitive CNP and DWCNT exposure. NPs reactivated the latent herpesvirus mainly in CD11b+ macrophages in the lungs. In vitro, in persistently MHV-68 infected bone marrow-derived macrophages, ERK1/2, JNK, and p38 MAPK were rapidly activated after CNP and DWCNT exposure, followed by viral gene expression and increased viral titer but without generating a pro-inflammatory signature. Pharmacological inhibition of p38 activation abrogated CNP- but not DWCNT-triggered virus reactivation in vitro, and inhibitor pretreatment of latently infected mice attenuated CNP-exposure-induced pulmonary MHV-68 reactivation. Our findings suggest a crucial contribution of particle-exposure-triggered herpesvirus reactivation for nanomaterial exposure or air pollution related lung emphysema development, and pharmacological p38 inhibition might serve as a protective target to alleviate air pollution related chronic lung disease exacerbations. Because of the required precondition of latent infection described here, the use of single hit models might have severe limitations when assessing the respiratory toxicity of nanoparticle exposure.

Systems toxicology of complex wood combustion aerosol reveals gaseous carbonyl compounds as critical constituents.

Epidemiological studies identified air pollution as one of the prime causes for human morbidity and mortality, due to harmful effects mainly on the cardiovascular and respiratory systems. Damage to the lung leads to several severe diseases such as fibrosis, chronic obstructive pulmonary disease and cancer. Noxious environmental aerosols are comprised of a gas and particulate phase representing highly complex chemical mixtures composed of myriads of compounds. Although some critical pollutants, foremost particulate matter (PM), could be linked to adverse health effects, a comprehensive understanding of relevant biological mechanisms and detrimental aerosol constituents is still lacking. Here, we employed a systems toxicology approach focusing on wood combustion, an important source for air pollution, and demonstrate a key role of the gas phase, specifically carbonyls, in driving adverse effects. Transcriptional profiling and biochemical analysis of human lung cells exposed at the air-liquid-interface determined DNA damage and stress response, as well as perturbation of cellular metabolism, as major key events. Connectivity mapping revealed a high similarity of gene expression signatures induced by wood smoke and agents prompting DNA-protein crosslinks (DPCs). Indeed, various gaseous aldehydes were detected in wood smoke, which promote DPCs, initiate similar genomic responses and are responsible for DNA damage provoked by wood smoke. Hence, systems toxicology enables the discovery of critical constituents of complex mixtures i.e. aerosols and highlights the role of carbonyls on top of particulate matter as an important health hazard.

The predictive value of computerized tomography-assessed sarcopenia for complicated appendicitis in geriatric patients.

Objective: Geriatric patients have more complicated appendicitis, which leads to higher morbidity and mortality rates. Sarcopenia has been shown to have a negative impact on patients undergoing surgery. This study aims to reveal the predictive value of computerized tomography-assessed (CT-assessed) sarcopenia for complicated appendicitis in geriatric patients. Methods: One-hundred fifty-four patients' with acute appendicitis age, gender, co-morbidities, appendicitis status, and body mass index (BMI) values were analyzed. The skeletal muscle index (SMI) and related measurements were evaluated. Results: Fifty-two percent of the patients had complicated, and 48% had uncomplicated appendicitis. There was a statistically significant difference between uncomplicated and complicated cases regarding BMI, SMI, and muscle area values (P < 0.05). The cutoff point by Receiver Operating Characteristic Curve analysis was conducted for SMI and showed 71% sensitivity and 52% specificity (P = 0.042). Multivariate analysis has shown that comorbidities are significantly more associated with complicated appendicitis than sarcopenia. Conclusion: Geriatric patients with lower BMI, decreased muscle area, and CT-detected sarcopenia have an increased risk of complicated appendicitis. Comorbidities are also important risk factors. Surgeons should be aware of factors leading to complicated appendicitis, which may cause higher morbidity and mortality rates in elderly patients.

The impact of the immune system on lung injury and regeneration in COPD.

COPD is a devastating respiratory condition that manifests via persistent inflammation, emphysema development and small airway remodelling. Lung regeneration is defined as the ability of the lung to repair itself after injury by the proliferation and differentiation of progenitor cell populations, and becomes impaired in the COPD lung as a consequence of cell intrinsic epithelial stem cell defects and signals from the micro-environment. Although the loss of structural integrity and lung regenerative capacity are critical for disease progression, our understanding of the cellular players and molecular pathways that hamper regeneration in COPD remains limited. Intriguingly, despite being a key driver of COPD pathogenesis, the role of the immune system in regulating lung regenerative mechanisms is understudied. In this review, we summarise recent evidence on the contribution of immune cells to lung injury and regeneration. We focus on four main axes: 1) the mechanisms via which myeloid cells cause alveolar degradation; 2) the formation of tertiary lymphoid structures and the production of autoreactive antibodies; 3) the consequences of inefficient apoptotic cell removal; and 4) the effects of innate and adaptive immune cell signalling on alveolar epithelial proliferation and differentiation. We finally provide insight on how recent technological advances in omics technologies and human ex vivo lung models can delineate immune cell-epithelium cross-talk and expedite precision pro-regenerative approaches toward reprogramming the alveolar immune niche to treat COPD.

Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease.

Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.

Evaluation of machine learning algorithms for renin-angiotensin-aldosterone system inhibitors associated renal adverse event prediction.

BACKGROUND: Renin-angiotensin-aldosterone system inhibitors (RAASi) are commonly used medications. Renal adverse events associated with RAASi are hyperkalemia and acute kidney injury. We aimed to evaluate the performance of machine learning (ML) algorithms in order to define event associated features and predict RAASi associated renal adverse events. MATERIALS AND METHODS: Data of patients recruited from five internal medicine and cardiology outpatient clinics were evaluated retrospectively. Clinical, laboratory, and medication data were acquired via electronic medical records. Dataset balancing and feature selection for machine learning algorithms were performed. Random forest (RF), k-nearest neighbor (kNN), naïve Bayes (NB), extreme gradient boosting (xGB), support vector machine (SVM), neural network (NN), and logistic regression (LR) were used to create a prediction model. RESULTS: 409 patients were included, and 50 renal adverse events occurred. The most important features predicting the renal adverse events were the index K and glucose levels, as well as having uncontrolled diabetes mellitus. Thiazides reduced RAASi associated hyperkalemia. kNN, RF, xGB and NN algorithms have the highest and similar AUC (≥ 98%), recall (≥ 94%), specifity (≥ 97%), precision (≥ 92%), accuracy (≥ 96%) and F1 statistics (≥ 94%) performance metrics for prediction. CONCLUSION: RAASi associated renal adverse events can be predicted prior to medication initiation by machine learning algorithms. Further prospective studies with large patient numbers are needed to create scoring systems as well as for their validation.

Aqp5-/- mice exhibit reduced maximal body O2 consumption under cold exposure, normal pulmonary gas exchange, and impaired formation of brown adipose tissue.

The fundamental body functions that determine maximal O2 uptake (V̇o2max) have not been studied in Aqp5-/- mice (aquaporin 5, AQP5). We measured V̇o2max to globally assess these functions and then investigated why it was found altered in Aqp5-/- mice. V̇o2max was measured by the Helox technique, which elicits maximal metabolic rate by intense cold exposure of the animals. We found V̇o2max reduced in Aqp5-/- mice by 20%-30% compared with wild-type (WT) mice. As AQP5 has been implicated to act as a membrane channel for respiratory gases, we studied whether this is caused by the known lack of AQP5 in the alveolar epithelial membranes of Aqp5-/- mice. Lung function parameters as well as arterial O2 saturation were normal and identical between Aqp5-/- and WT mice, indicating that AQP5 does not contribute to pulmonary O2 exchange. The cause for the decreased V̇o2max thus might be found in decreased O2 consumption of an intensely O2-consuming peripheral organ such as activated brown adipose tissue (BAT). We found indeed that absence of AQP5 greatly reduces the amount of interscapular BAT formed in response to 4 wk of cold exposure, from 63% in WT to 25% in Aqp5-/- animals. We conclude that lack of AQP5 does not affect pulmonary O2 exchange, but greatly inhibits transformation of white to brown adipose tissue. As under cold exposure, BAT is a major source of the animals' heat production, reduction of BAT likely causes the decrease in V̇o2max under this condition.

RIPK1 kinase-dependent inflammation and cell death contribute to the pathogenesis of COPD.

BACKGROUND: Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of regulated cell death (including apoptosis and necroptosis) and inflammation, both drivers of COPD pathogenesis. We aimed to define the contribution of RIPK1 kinase-dependent cell death and inflammation in the pathogenesis of COPD. METHODS: We assessed RIPK1 expression in single-cell RNA sequencing (RNA-seq) data from human and mouse lungs, and validated RIPK1 levels in lung tissue of COPD patients via immunohistochemistry. Next, we assessed the consequences of genetic and pharmacological inhibition of RIPK1 kinase activity in experimental COPD, using Ripk1 S25D/S25D kinase-deficient mice and the RIPK1 kinase inhibitor GSK'547. RESULTS: RIPK1 expression increased in alveolar type 1 (AT1), AT2, ciliated and neuroendocrine cells in human COPD. RIPK1 protein levels were significantly increased in airway epithelium of COPD patients compared with never-smokers and smokers without airflow limitation. In mice, exposure to cigarette smoke (CS) increased Ripk1 expression similarly in AT2 cells, and further in alveolar macrophages and T-cells. Genetic and/or pharmacological inhibition of RIPK1 kinase activity significantly attenuated airway inflammation upon acute and subacute CS exposure, as well as airway remodelling, emphysema, and apoptotic and necroptotic cell death upon chronic CS exposure. Similarly, pharmacological RIPK1 kinase inhibition significantly attenuated elastase-induced emphysema and lung function decline. Finally, RNA-seq on lung tissue of CS-exposed mice revealed downregulation of cell death and inflammatory pathways upon pharmacological RIPK1 kinase inhibition. CONCLUSIONS: RIPK1 kinase inhibition is protective in experimental models of COPD and may represent a novel promising therapeutic approach.

Endonasal endoscopic approach for sellar metastatic pathologies: a national observation.

PURPOSE: Sellar metastases are rare lesions. Recent improvements in diagnosis and treatment strategies have prolonged survival but increased the probability of metastatic tumors. Evaluation with clinical symptomatology and meticulous laboratory examination is crucial. We present our multicenter national study on sellar metastases to evaluate and underline the main clinical, endocrine, and radiological considerations regarding the diagnosis and endonasal endoscopic management of such rare lesions. METHODS: A medical literature-based retrospective study was planned across 13 neurosurgical centers in Turkey, where a data survey was conducted to collect information regarding sellar metastases surgically treated using the endoscopic endonasal approach, including clinical presentation, radiographic features, primary tumor origin, histopathological confirmation, time to metastasis, treatment, and patient outcomes. RESULTS: Between 2010 and 2020, 54 patients (22 women [40.7%] and 32 men [59.3%]) who underwent surgery with the endonasal endoscopic approach and had pathologically proven sellar metastases (overall incidence, 0.54%) were included. Of the patients, 59.3% had no known malignancy and presented with new-onset symptoms, 79.6% reported headache, 51.9% complained of some degree of visual deficits, and 50% had cranial nerve symptoms. Tissue biopsy was performed in 7.4% of the patients, whereas gross or subtotal resection was achieved in the remaining patients. CONCLUSION: To our knowledge, this is the largest series of patients surgically treated with the endonasal endoscopic approach for sellar metastases. For these patients, the treatment focus should be on management modalities for increasing quality of life instead radical treatment options with survival benefit.