Explore the vast range of titles available.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease process in which pulmonary hypertension (PH) develops in the setting of malignancy. The purpose of this study is to present a detailed analysis of cases of PTTM reported in literature in the hopes of achieving more ante-mortem diagnoses. We conducted a systematic review of currently published and available cases of PTTM by searching the term “pulmonary tumor thrombotic microangiopathy” on the Pubmed.gov database. Seventy-nine publications were included consisting of 160 unique cases of PTTM. The most commonly reported malignancy was gastric adenocarcinoma (94 cases, 59%). Cough and dyspnea were reported in 61 (85%) and 102 (94%) cases, respectively. Hypoxemia was reported in 96 cases (95%). Elevation in D-dimer was noted in 36 cases (95%), presence of anemia in 32 cases (84%), and thrombocytopenia in 30 cases (77%). Common findings on chest computed tomography (CT) included ground-glass opacities (GGO) in 28 cases (82%) and nodules in 24 cases (86%). PH on echocardiography was noted in 59 cases (89%) with an average right ventricular systolic pressure of 71 mmHg. Common features of PTTM that are reported across the published literature include presence of dyspnea and cough, hypoxemia, with abnormal CT findings of GGO, nodules, and mediastinal/hilar lymphadenopathy, and PH. PTTM is a universally fatal disease process and this analysis provides a detailed examination of all the available published data that may help clinicians establish an earlier diagnosis of PTTM.

Background Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35–52% of patients and accounting for 20–40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD. Methods A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from − 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤  − 2.5 or ≥  + 2.5 with a standard deviation not crossing zero. Results Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants. Conclusions This modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need.

Right heart catheterization (RHC)–determined pulmonary hemodynamics are mandatory for the diagnosis and classification of pulmonary hypertension (PH) and can be used to assess response to PH-specific therapy and inform clinical decision-making. PH is diagnosed in patients with a mean pulmonary arterial pressure of ≥25 mm Hg at rest, with a further classification of pulmonary arterial hypertension (PAH) in patients with a pulmonary artery wedge pressure of ≤15 mm Hg and, often, reduced cardiac output. In addition, a number of hemodynamic variables, either measured directly with RHC or subsequently derived, have been shown to have prognostic significance in PAH, with different variables having more prognostic significance in specific patient populations. Although there is no hemodynamic definition of exercise-induced PAH, measurement of certain hemodynamic variables during exercise may identify an intermediary phenotype between healthy individuals and overt PAH at rest and may have prognostic implications. However, although exercise hemodynamics may be a closer reflection of the true resistive component of the pulmonary vasculature and its ability to respond to therapy, the lack of standardized protocols limits application in routine clinical practice.

ABSTRACT Pulmonary emboli (PE) are a common clinical problem seen when a peripheral deep vein thrombosis (DVT) migrates to the pulmonary arteries. However, emerging literature suggests that not all filling defects in the pulmonary arteries are the result of embolism, and that in situ pulmonary arterial thrombus (ISPAT) or low‐flow stasis artifact (LFSA) within the pulmonary arteries can mimic acute PE. The proposed mechanism for ISPAT is chronic stasis due to abnormal perfusion in areas of parenchymal lung disease leading to in situ thrombosis. Similarly, LFSA occurs when stasis leads to persistent visualization of intravenous contrast which is then mistaken for thrombus. The clinical scenarios in which ISPAT and LFSA develop are not yet fully defined. We report here a series of patients with parenchymal lung disease leading to ventilation–perfusion mismatch who likely had ISPAT or LFSA and not acute PE. Our aim is to further define parenchymal lung disease as a subgroup of patients who are at high risk for ISPAT. Cases initially diagnosed as acute PE leading to activation of the UCLA pulmonary embolism response team (PERT) were reviewed. Inclusion criteria were all cases of PE that led to PERT activation. Inclusion criteria included absence of DVT, previously diagnosed pulmonary disease, and presence of thrombus only in areas of abnormal parenchyma. Cases were reviewed with radiology to identify cases in which ISPAT was the likely diagnosis, and five representative cases were selected to be discussed. These cases were then analyzed qualitatively for commonalities which are described below. The five representative cases described represent patients with known chronic lung disease who were diagnosed and initially managed as acute PE but, on review, met criteria for either ISPAT or stasis artifact. These cases, which were all rediagnosed as ISPAT or LFSA, were all seen in the absence of DVT, with thrombus specifically located in areas of significant parenchymal lung disease with suspected decrease in ventilation and perfusion in these areas. ISPAT or LFSA have been described in the literature, though its presence specifically in parenchymal lung disease has yet to be described. The authors recommend considering this diagnosis in patient's diagnosed with acute PE when the following are present: significant parenchymal lung disease, absence of DVT, absence of thrombus in the areas of the lung relatively spared of parenchymal lung disease, and suspected baseline decrease in both ventilation and perfusion to the affected areas of the lung. As this phenomenon may be physiologically beneficial, the authors suggest that not all cases of ISPAT or LFSA need anticoagulation, and that treatment should be considered on a case‐by‐case basis.

Background Sepsis is a common cause of death in patients with pulmonary arterial hypertension (PAH). Treatment requires careful fluid management and hemodynamic support. This study compares patients with or without PAH presenting with sepsis with a focus on initial fluid resuscitation. Methods This retrospective analysis compared adults with and without PAH admitted for sepsis at two academic hospitals between 2013 and 2022. Prior PAH diagnosis was verified by review of right heart catheterization data and sepsis present on admission was verified by chart review. Demographics, vital signs, laboratory values, imaging results, treatment approaches, and all-cause mortality data were obtained. Controls were propensity score weighted by age, sex, and Charlson Comorbidity index. Logistic regression models controlling for age and Charlson comorbidity indices were used to examine factors associated with survival. Results Thirty patients admitted for sepsis with pre-existing PAH were compared to 96 matched controls. Controls received significantly more fluids at 24 h compared to PAH patients (median 0 mL v. 1216 mL, p  < 0.001), while PAH patients were more likely to receive vasoactive medications (23.3% vs. 8.3%, p  = 0.037). At 30 days, 7 PAH patients (23.3%) and 13 control patients (13.5%) had died ( p  = 0.376). PAH patients that received more fluids had decreased mortality (OR 0.31, 95% CI 0.11–0.92, p  = 0.03) and patients who received fluids had shorter mean time to antibiotics (2.3 h v. 6.5 h, p  = 0.04), although decreased time to antibiotics was not associated with mortality. Patients who received no fluids more often had previously identified right ventricular systolic dysfunction (62.5% v. 28.6%, p  = 0.136). Conclusion Patients with PAH and sepsis have high mortality and receive different treatments than controls, with more reliance on vasopressors and less on fluid resuscitation. PAH patients who received less fluids had higher mortality and those who received no fluids had a longer time to receiving antibiotics, indicating a potential delay in recognizing sepsis. Timely recognition of sepsis and dynamic decision-making around fluid resuscitation remains critical in this high-risk population.

Dysregulation of Fractalkine (CX3CL1) and its receptor CX3CR1 has been linked to the pathobiology of chronic inflammatory conditions. We explored CX3CL1 in systemic sclerosis (SSc) related progressive interstitial lung disease (ILD) and pulmonary hypertension (PH) in two different but complementary sources of biomaterial. We collected lung tissue at the time of lung transplantation at UCLA from SSc-ILD patients (n = 12) and healthy donors (n = 12); and serum samples from the prospective Oslo University Hospital SSc cohort (n = 292) and healthy donors (n = 100). CX3CL1 was measured by ELISA. Cellular sources of CX3CL1/CX3CR1 in lung tissues were determined by immunohistochemistry and immunofluorescence. ILD progression and new onset PH endpoints were analysed. CX3CL1 concentrations were increased in SSc in lung tissue as well as in sera. In the UCLA cohort, CX3CL1 was highly correlated with DLCO. In the SSc-ILD lungs, CX3CL1 was identified in reactive type II pneumocytes and airway epithelial cells. CX3CR1 stained infiltrating interstitial mononuclear cells, especially plasma cells. In the Oslo cohort, CX3CL1 correlated with anti-Topoisomerase-I-antibody and lung fibrosis. CX3CL1 was associated with ILD progression in multivariable regression analysis but not PH. CX3CL1 is associated with progressive SSc-ILD but not SSc-PH. The CX3CR1/CX3CL1-biological axis may be involved in recruiting antibody secreting plasma cells to SSc lungs, thereby contributing to the immune-mediated pathobiology of SSc-ILD.

Pulmonary hypertension (PH) has been linked to worse outcomes in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, an increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is the first step in trying to define a roadmap to facilitate and encourage future research in this area. The aim of our working group is to strengthen the communities understanding of PH due to lung diseases and to improve the care and quality of life of affected patients. This introductory statement provides a broad overview and lays the foundation for further in‐depth papers on specific topics pertaining to PH‐ILD.

Pulmonary hypertension (PH) is a frequent complication of interstitial lung disease (ILD). Although PH has mostly been described in idiopathic pulmonary fibrosis, it can manifest in association with many other forms of ILD. Associated pathogenetic mechanisms are complex and incompletely understood but there is evidence of disruption of molecular and genetic pathways, with panvascular histopathologic changes, multiple pathophysiologic sequelae, and profound clinical ramifications. While there are some recognized clinical phenotypes such as combined pulmonary fibrosis and emphysema and some possible phenotypes such as connective tissue disease associated with ILD and PH, the identification of further phenotypes of PH in ILD has thus far proven elusive. This statement reviews the current evidence on the pathogenesis, recognized patterns, and useful diagnostic tools to detect phenotypes of PH in ILD. Distinct phenotypes warrant recognition if they are characterized through either a distinct presentation, clinical course, or treatment response. Furthermore, we propose a set of recommendations for future studies that might enable the recognition of new phenotypes.

Pulmonary hypertension secondary to pulmonary fibrosis (PF‐PH) is one of the most common causes of PH, and there is no approved therapy. The molecular signature of PF‐PH and underlying mechanism of why pulmonary hypertension (PH) develops in PF patients remains understudied and poorly understood. We observed significantly increased vascular wall thickness in both fibrotic and non‐fibrotic areas of PF‐PH patient lungs compared to PF patients. The increased vascular wall thickness in PF‐PH patients is concomitant with a significantly increased expression of the transcription factor Slug within the macrophages and its target prolactin‐induced protein (PIP), an extracellular matrix protein that induces pulmonary arterial smooth muscle cell proliferation. We developed a novel translational rat model of combined PF‐PH that is reproducible and shares similar histological features (fibrosis, pulmonary vascular remodeling) and molecular features (Slug and PIP upregulation) with human PF‐PH. We found Slug inhibition decreases PH severity in our animal model of PF‐PH. Our study highlights the role of Slug/PIP axis in PF‐PH. Synopsis Pulmonary hypertension (PH) is a major complication of pulmonary fibrosis (PF), yet it is poorly understood. This study highlights the Slug/PIP axis as a key driver of vascular remodeling in pulmonary hypertension secondary to pulmonary fibrosis (PF‐PH) patients. Vascular walls were thickened in both fibrotic and non‐fibrotic areas in the lungs of PF‐PH patients, but wall thickening was mainly restricted to fibrotic areas of PF patients. In PF‐PH patients, the transcriptional factor Slug was up‐regulated in macrophages and led to increased vascular wall thickness through its target PIP. Inhibition of Slug ameliorated PH in an animal model that recapitulates human histological and molecular characteristics of PF‐PH. Graphical Abstract Pulmonary hypertension (PH) is a major complication of pulmonary fibrosis (PF), yet it is poorly understood. This study highlights the Slug/PIP axis as a key driver of vascular remodeling in pulmonary hypertension secondary to pulmonary fibrosis (PF‐PH) patients.