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Lysosomal acid sphingomyelinase (ASM; SMPD1) deficiency causes Niemann-Pick Disease (NPD) that, in Type B, manifests with interstitial lung disease and susceptibility to infections. Constitutional Smpd1 ( Smpd1 -/- mice) deletion causes lung inflammation with foamy dysfunctional macrophages, but is protective against acute lung injury. It is unknown whether these manifestations are from progressive accumulation of sphingomyelin, decreased ceramide, or compensatory alterations in sphingolipid metabolism. We developed a conditional knockout mouse, Smpd1 fl/fl xCAGG-CreERTM, induced by tamoxifen (5 weeks), with decreased Smpd1 expression (by 75%) and ASM activity (by up to 40%). We investigated how brief post-developmental ASM insufficiency affects lung sphingolipids and pathology including following lipopolysaccharide (LPS)-induced injury. Compared to controls, Smpd1 fl/fl mice exhibited modest sphingomyelin elevation with lower palmitoyl/lignoceroyl ceramide (C16/C24) ratios, increased de novo sphingolipid synthesis and sphingosine-1 phosphate levels. At 3 days following LPS instillation (20μg) control mice had increased lung (neutrophilic and monocytic) inflammation and apoptosis; Smpd1 fl/fl mice showed more exuberant inflammation with reduced apoptosis, particularly in endothelial cells. During repair (6-9 days), Smpd1 fl/fl lungs had increased cell proliferation with reduced autophagosome-tagging p62/SQSTM1. These results indicate that prior to significant lysosomal lipid storage, ASM insufficiency inhibits stress-induced lung apoptosis and promotes compensatory sphingolipid changes that favor exuberant inflammatory responses to LPS. Overall, ASM inhibition limits lung vascular injury and stimulates repair following inflammatory insults. These results provide novel insights into the function of ASM in the lung, which are relevant to understanding the pathogenesis and complications of NPD and the role of distinct sphingolipid metabolites in lung injury and repair.

Background: Unilateral chronic thromboembolism pulmonary disease (CTEPD) is very rare. There is limited information on the safety and efficacy of pulmonary endarterectomy (PEA) in this population. This study investigated the effectiveness of PEA in this unique disease., Methods: This multicentre study included patients with unilateral CTEPD from three referral centres in the United States, Turkey, and Iran. The patients' demographic information, 6-minute walk test distance (6MWD), New York Heart Association (NYHA) functional class, and haemodynamics were evaluated., Result: Of the 1,031 patients who had undergone PEA, 39 patients (3.7%) had pure unilateral involvement, of whom 28 were female (71.8%). There was a significant improvement in the mean pulmonary artery pressure (mPAP, 26 mmHg vs 21 mmHg; p=0.011) and pulmonary vascular resistance (PVR, 202 vs 136 dynes∗sec 1 ∗cm -5 ; p=0.014). There was also a significant improvement in NYHA functional class (p<0.001) and 6MWD (360 vs 409 m; p<0.001). In the nine patients with normal haemodynamic parameters at rest, there was no significant change in median 6MWD (448.5 vs 449 m; p=0.208), mPAP (19 mmHg vs 16.5 mmHg; p=0.397), and PVR (129 vs 84.5 dynes∗sec 1 ∗cm -5 ; p=0.128). The most common postoperative complication was ipsilateral pleural effusion. One patient needed extracorporeal membrane oxygenation support. No patient died within the 1-year follow up., Conclusion: Pulmonary endarterectomy is a safe and effective procedure for improving the symptoms and haemodynamic parameters of patients with unilateral CTEPH. Symptomatic patients with unilateral chronic thromboembolic disease are suitable for PEA., Competing Interests: Conflicts of Interest The authors declare no conflict of interest regarding this study., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Pulmonary artery sarcomas (PAS) are rare tumours causing an insidiously progressive obstruction of the pulmonary circulation. The clinical presentation is often indistinguishable from chronic thromboembolic pulmonary hypertension (CTEPH). However, the atypical appearance of a heterogeneous filling defect in CT pulmonary angiography (CTPA) should prompt further investigation., Case Presentation: A previously healthy young man presented with massive haemoptysis, acute respiratory distress, and progressive exertional dyspnea since the year before. Echocardiography demonstrated severe right ventricular dysfunction and highly probable pulmonary hypertension. CTPA revealed an extensive filling defect with an appearance concerning PAS. Due to syncopal episodes at rest, the patient underwent urgent pulmonary artery endarterectomy (PEA). A massive tree-like tumour was excised as a result. Post-operatively, reperfusion injury and refractory pulmonary oedema mandated extracorporeal membrane oxygenation (ECMO). Unfortunately, ECMO was complicated with massive haemolysis and acute kidney injury. The patient succumbed to multi-organ failure. Through tissue analysis established a diagnosis of embryonal rhabdomyosarcoma., Discussion: Unfortunately, the patient had not reached out for his worsening dyspnea. PASs should not be mistaken for a thrombus and anticoagulation should be avoided. The urgent condition precluded biopsy and tissue diagnosis. Similarly, neoadjuvant chemotherapy was not feasible. Post-operatively, reperfusion injury and pulmonary oedema ensued, which mandated ECMO. This complication should be anticipated preoperatively. There is a need for more data on PASs to establish a consensus for management., (© 2024 Farid Rashidi et al., published by Sciendo.)

Cardiac contraction and relaxation require a substantial amount of energy provided by the mitochondria. The failing heart is adenosine triphosphate (ATP)- and creatine-depleted. Studies have found iron is involved in almost every aspect of mitochondrial function, and previous studies have shown myocardial iron deficiency in heart failure (HF). Many clinicians advocated intravenous iron repletion for HF patients meeting the conventional criteria for systemic iron deficiency. While clinical trials showed improved quality of life, iron repletion failed to significantly impact survival or significant cardiovascular adverse events. There is evidence that in HF, labile iron is trapped inside the mitochondria causing oxidative stress and lipid peroxidation. There is also compelling preclinical evidence demonstrating the detrimental effects of both iron overload and depletion on cardiomyocyte function. We reviewed the mechanisms governing myocardial and mitochondrial iron content. Mitochondrial dynamics (i.e., fusion, fission, mitophagy) and the role of iron were also investigated. Ferroptosis, as an important regulated cell death mechanism involved in cardiomyocyte loss, was reviewed along with agents used to manipulate it. The membrane stability and iron content of mitochondria can be altered by many agents. Some studies are showing promising improvement in the cardiomyocyte function after iron chelation by deferiprone; however, whether the in vitro and in vivo findings will be reflected on on clinical grounds is still unclear. Finally, we briefly reviewed the clinical trials on intravenous iron repletion. There is a need for more well-simulated animal studies to shed light on the safety and efficacy of chelation agents and pave the road for clinical studies., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: A small percentage of acute pulmonary thromboembolisms (PTE) persist as chronic fibrin clots, potentially leading to chronic thromboembolic pulmonary hypertension (CTEPH). A scoring system for evaluating the burden of acute PTE based on computed tomography pulmonary angiogram (CTPA) findings was tested for its association with CTEPH within one year., Material and Methods: In this retrospective cohort of 475 patients with a definitive diagnosis of acute PTE, the Qanadli score (QS) was calculated on the initial CTPA. Through regular follow-up over 1 year, symptomatic patients underwent extensive evaluation., Results: Of the 475 patients enrolled in the study [age 58.3 ± 16.6, 195 (41.1%) female, QS: 13.01 ± 7.37/40], 321 patients completed the study. A total of 22 (6.8%) patients were definitively diagnosed with CTEPH. In univariate analysis, the initial QS was significantly higher in patients with subsequent CTEPH than in patients without (17 ± 5.6 vs. 13 ± 7.6, P = .009). QS was directly associated with CTEPH (odds ratio: 1.08, 95% confidence interval: 1.0-1.16, P = .042). The evolution of CTEPH in men could be predicted with a sensitivity of 100% and a specificity of 54% when a cut-off point of 14.5 (43.5%) was set for QS. The area under the receiver operating characteristic curve in this setting was 0.74 with a P-value of .032. Qanadli score failed to predict CTEPH in women., Conclusion: Scoring the clot burden in the pulmonary arteries through the Qanadli method can predict the evolution of CTEPH only in men 1 year after acute PTE. Women comprise most of the CTEPH patients. Thus, strict follow-up adherence seems to be even more important in women.

The coronavirus disease 2019 (COVID-19) is characterized by viral pneumonia with mild to moderate symptoms. Emerging studies suggest that some patients may experience uncommon complications, such as thrombotic or hemorrhagic episodes. Here we present a 59-year-old male patient who had a hemorrhage episode from a branch of the pulmonary arteries and was treated by interventional embolization. Our case report demonstrates the importance of early diagnosis of hemorrhagic complications of COVID-19 and the possible benefits of early vascular intervention., (© 2021 Published by Elsevier Inc. on behalf of University of Washington.)

The coronavirus disease 2019 (COVID-19) pandemic has affected the daily lives of millions of people worldwide and had caused significant mortality; hence, the assessment of therapeutic options is of great interest. The leading cause of death among COVID-19 patients is acute respiratory distress syndrome caused by hyperinflammation secondary to cytokine release syndrome (CRS). Cytokines, such as tumor necrosis factor-α, interleukin-6, interferon-γ and interleukin-10, are the main mediators of CRS. Based on recent evidence, the angiotensin-converting enzyme (ACE) II is known to be the target of the COVID-19 spike protein, which enables the virus to penetrate human cells. ACE II also possesses an anti-inflammatory role in many pathologies such as cardiovascular disease, hypertension, diabetes mellitus and other conditions, which are the main risk factors of poor prognosis in COVID-19 infection. Changes in tissue ACE II levels are associated with many diseases and hyperinflammatory states, and it is assumed that elevated levels of ACE II could aggravate the course of COVID-19 infection. Therefore, the use of renin-angiotensin-aldosterone system inhibitors (RASis) in COVID-19 patients could be hypothetically considered, though sufficient evidence is not presented by the scientific community. In this work, based on the most recent pieces of evidence, the roles of RAS and RASi in immunologic interactions are addressed. Furthermore, the molecular and immunologic aspects of RASi and their potential significance in COVID-19 are discussed., (© 2020 Australian and New Zealand Society for Immunology Inc.)

Since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic, an increasing number of reports and studies have tried to warn the medical community about the thrombotic complications of coronavirus disease 2019 (COVID-19). It is suggested that the hyperinflammatory response and endothelial injury, especially in patients with severe disease, lead to a hypercoagulable state. Sudden deaths occurring in some patients also point to fulminant arrhythmias and massive pulmonary embolism (PE). Several expert panels have published recommendations regarding the prophylaxis and treatment of such complications. Nonetheless, there are limited high-quality studies for evidence-based decision-making, and most of these recommendations have arisen from descriptive studies, and optimal anticoagulant agents and dosages are yet to be designated. The coagulopathy persists after the acute phase of the illness, and some panels recommend the continuation of deep vein thrombosis prophylaxis for several days after regaining the normal daily activities by the patient. Here, we review the incidence and possible mechanisms of thrombotic complications, and present a summary of the considerations for the prophylaxis and treatment of such complications in the adult population., (Copyright: © Iranian Journal of Medical Sciences.)

Background: Numerous studies have evaluated the impact of Helicobacter pylori (H. pylori) eradication on the number, severity, and recurrence of migraine attacks. But the association of migraine, H. pylori, and gastrointestinal (GI) presentation is challenging. The aim of the current study was to investigate the correlation between migraine, H. pylori, and peptic ulcers among patients with dyspepsia undergoing upper GI endoscopy. Methods: 305 patients with dyspepsia referring to our endoscopy ward, Shahid Beheshti Hospital affiliated to Qom University of Medical Sciences, Qom, Iran, for upper GI endoscopy filled out the study questionnaire. If a patient was experiencing headaches and the migraine was confirmed by neurologists, he/she was asked to answer the questions related to migraine, which were prepared exactly from Migraine Disability Assessment (MIDAS) questionnaire. The relation between migraine and confirmed H. pylori contamination was investigated using statistical models. Results: Of all the 305 patients, 133 (43.6%) had confirmed episodic migraine headaches (MHs) and 177 patients (58.04%) had positive RUT for confirming H. pylori contamination, of which 123 (69.5%) had confirmed migraine. 52 (17.0%) had duodenal peptic ulcer(s), of which, 49 (94.2%) had a positive rapid urease test (RUT) (P < 0.001). 20 (6.5%) of all patients had the gastric peptic ulcer(s) which did not have a significant relation with H. pylori contamination. There was a significant relationship between the peptic ulcer site and migraine. In total, 177 patients (58.0%) had a positive RUT. History of migraine was significantly positive in those with positive H. Pylori contamination. Notably, multivariable analysis demonstrated a significant relation of H. pylori and migraine at younger ages. Conclusion: The prevalence of H. pylori and migraine in patients with dyspepsia seems to be high. Moreover, there is a meaningful association between migraine, duodenal peptic ulcers, and H. pylori infection, too.

Objective: Stroke is a common heterogeneous disease classified into two subtypes: ischemic and hemorrhagic. Many risk factors have been associated with stroke, and the most well-known is hypertension. Although the relation between stroke and these risk factors has been emphasized before, there is inconclusive evidence about the relation between the different risk factors and the subtypes of stroke. The present study aims to fill this gap., Materials and Methods: In the present retrospective, cross-sectional study, 827 patients with diagnosed stroke were included. Demographic data and the acquired risk factors were determined using pre-designed questionnaires. Statistical analysis was conducted using chi-square test, Student t-test, and Pearson correlation coefficient., Results: Among the included 827 patients, 432 (52.2%) were men and 395 (47.8%) were women. The mean±standard deviation of age was 68.41±12.46 y in men and 67.89±11.85 y in women, respectively, and the difference was not significant. Of all the patients, 672 had ischemic strokes and 155 had hemorrhagic strokes. The most common risk factor in the patients was hypertension with a prevalence of 66.7%. Of all the risk factors, only hypertension, atrial fibrillation (AF), age, and a positive family history were significantly related to a subtype of stroke., Conclusion: Knowing that the prevalence of hypertension, AF, age, and positive family history are significantly different between the two subtypes, the patients having these risk factors can be entered into more specified public health measures, which puts more emphasis on the subtype that they are more prone to., Competing Interests: Conflict of Interest: Authors have no conflict of interest to declare.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease resulting from mutation(s) in TSC1 or TSC2 genes. TSC is associated with the formation of hamartomas in the brain, heart, eyes, skin, kidneys, and lymphangioleiomyomatosis (LAM) of the lungs. LAM is almost restricted to women in reproductive age. Different mutations in TSC1 and TSC2 genes have been reported in the literature. Here, we present a female patient with TSC-LAM with a novel mutation in TSC2 gene. The patient also had multiple hepatic angiomyolipomas, which is a relatively less-reported manifestation of the disease. The impact of this mutation on the pattern of disease presentation and response to treatment is not clear yet.