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Objective: Challenging differential diagnosis Background: Right ventricular (RV) failure can result from acute or chronic cardiac or pulmonary conditions, or both, resulting in increased afterload, reduced contractility, changes in preload, ventricular interdependence, or dysrhythmias. Notably, increased afterload, particularly among previously healthy individuals, is often the primary cause of RV failure in cases of pulmonary and cardiac origin. Massive pulmonary thromboembolism is a common cause of impending RV failure, and chronic conditions like atrial septal defects can also contribute to pulmonary hypertension. Case Report: A 72-year-old patient, with no known past medical history, presented to the emergency department in profound shock, rapidly progressing to cardiorespiratory arrest. Bedside ultrasound revealed marked right chambers dilatation, severe mitral and tricuspid insufficiency, a large atrial septal defect, mild pericardial effusion, and global hypokinesia. This case illustrates how multiple mechanisms of RV dysfunction can converge, leading to fulminant RV failure and subsequent cardiac arrest, including increased afterload, decreased contractility, dysrhythmias, and ventricular interdependence. Conclusions: This article emphasizes the usefulness of bedside ultrasound in diagnosing and elucidating the causes of circulatory collapse. In this patient, ultrasound played an important role in identifying 3 contributing factors: chronic RV overload from an extensive atrial septal defect, left ventricular impact due to ventricular interdependence, and acute pulmonary thromboembolism. Being aware of these factors, along with the practicality of bedside ultrasound, allowing emergency physicians to make prompt diagnoses and effectively manage RV failure-related emergencies. [ABSTRACT FROM AUTHOR]

Background: IgG4-related disease (IgG4RD) is a rare fibroinflammatory disease with multiorgan involvement. It presents insidiously over several years and can be a diagnostic enigma. Delays in diagnosis occur due to failure to consider IgG4 as a differential diagnosis, atypical presentations, and an insidious clinical course. Case presentation: We report the case of a 70-year-old Sri Lankan man with pulmonary, renal, and neurological involvement of IgG4-related disease. Clinical manifestations evolved over a 4-year period and included exertional shortness of breath and dysesthesia of extremities. The diagnosis was established with clinical, radiological, and pathological criteria laid down by The American College of Rheumatology/European League Against Rheumatism in 2019. Following diagnosis, the patient was started on oral steroids, with rapid improvement of his respiratory and neurological symptoms. He is currently under follow-up and will be monitored with clinical and radiological parameters, complement levels, and lung function tests. Conclusion: This case outlines the presentation of a patient with IgG4-related disease with concurrent involvement of three uncommon sites. It highlights methods of diagnostic deduction by considering the clinical course of illness, imaging, and histopathology. It also describes evolving associations of IgG4-related disease with tuberculosis and lymphomas, which bear important diagnostic and therapeutic considerations. [ABSTRACT FROM AUTHOR]

It is unclear how the immune system controls the transition from latent tuberculosis (TB) infection (LTBI) to active pulmonary infection (PTB). Here, we applied mass spectrometry cytometry time-of-flight (CyTOF) analysis of peripheral blood mononuclear cells to compare the immunological landscapes in patients with high tuberculous bacillary load PTB infections and LTBI. A total of 32 subjects (PTB [n = 12], LTBI [n = 17], healthy volunteers [n = 3]) were included. Participants with active PTBs were phlebotomized before administering antituberculosis treatment, whereas participants with LTBI progressed to PTB at the time of household screening. In the present study, CyTOF analysis identified significantly higher percentages of mucosal-associated invariant natural killer T (MAIT NKT) cells in subjects with LTBI than in those with active PTB and healthy controls. Moreover, 6 of 17 (35%) subjects with LTBI progressed to active PTB (LTBI progression) and had higher proportions of MAIT NKT cells and early NKT cells than those without progression (LTBI non-progression). Subjects with LTBI progression also showed a tendency toward low B cell levels relative to other subject groups. In conclusion, MAIT NKT cells were substantially more prevalent in subjects with LTBI, particularly those with progression to active PTB. [ABSTRACT FROM AUTHOR]

Sarcoidosis is the classic multisystem granulomatous disease. First reported as a disorder of the skin, it is now clear that, in the overwhelming majority of patients with sarcoidosis, the lungs will bear the brunt of the disease. This review explores some of the key concepts in the imaging of pulmonary sarcoidosis: the wide array of typical (and some of the less common) findings on high-resolution computed tomography (HRCT) are reviewed and, with this, the concept of morphologic/HRCT phenotypes is discussed. The pathophysiologic insights provided by HRCT through studies where morphologic abnormalities and pulmonary function tests are compared are evaluated. Finally, this review outlines the important contribution of HRCT to disease monitoring and prognostication. [ABSTRACT FROM AUTHOR]

Pulmonary accelerated rheumatoid nodules (ARN) represent a rare occurrence within the context of rheumatoid arthritis (RA), with conventional treatment typically involving corticosteroids. In this report, we present a unique case of pulmonary ARN managed with baricitinib, a Janus kinase inhibitor. The patient, a 46-year-old woman diagnosed with RA, initially displayed no evident pulmonary nodules upon pulmonary imaging. Her treatment regimen encompassed corticosteroids, methotrexate, and leflunomide. Nevertheless, a chest computed tomography (CT) scan conducted after a year unveiled the presence of multiple bilateral pulmonary nodules. A thoracoscopic biopsy of these nodules confirmed the presence of rheumatoid nodules. Treatment with baricitinib, a Janus kinase inhibitor or synthetic disease-modifying antirheumatic drug (DMARD), effectively reduced the size of the nodules. Our review of 45 articles on ARN published since 1986 found that nine of them reported 13 cases of pulmonary ARN. These nodules may be caused by certain synthetic and biological DMARDs and often present with respiratory symptoms. CT scans typically reveal multiple solid nodules or ground-glass opacities, some of which may have cavities. Treatment customarily involves discontinuing the suspected drugs and administering corticosteroids. This case suggests that Janus kinase inhibitors may be an effective treatment option for ARN. [ABSTRACT FROM AUTHOR]

Introduction: Computed tomography (CT) is often utilized for both diagnostic and pre-operative planning purposes in shoulder arthroplasty. Our study reports on the incidence of pulmonary findings in our pre-operative shoulder arthroplasty population over 14 years at our institution. Methods: We conducted a retrospective review of all "shoulder CT" exams ordered by two orthopedic upper extremity surgeons between the years of 2008 and 2021. These exams were then further analyzed to include only those ordered for the purpose of pre-operative "shoulder arthroplasty" planning. All incidental findings were documented and those with pulmonary findings were then further analyzed. A detailed chart review was then performed on these patients to determine the impact on their planned shoulder arthroplasty. Results: A total of 363 shoulder pre-operative CTs were ordered by our two upper extremity orthopedic surgeons at our institution between the years of 2008 and 2021. Primary lung cancer in the form of adenocarcinoma (n = 3) had an incidence of 0.8% of all CT scans and 1.4% of all pulmonary incidental findings. Fifteen patients (4% of all CT scans and 7% of all pulmonary incidental findings) had no concern for malignancy and were appropriately evaluated with further imaging based on their initial shoulder CT. Conclusion: While shoulder arthroplasty and pre-operative planning with CT imaging continue to become more common, so too is the incidence of reported pulmonary findings. From a patient care standpoint, it is important that these findings are accurately identified, appropriately triaged, and communicated clearly to our patients. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) is a disease that causes severe mortality and morbidity worldwide, including India. Endobronchial Tuberculosis (EBTB) is an uncommon form of TB, which is often underdiagnosed due to the difficulty in diagnosis. This form of TB often has a poor prognosis and long-lasting sequelae. Aim: To study the proportion of EBTB in clinically diagnosed pulmonary TB and to study the clinicoradiological and bronchoscopic profile of EBTB. Materials and Methods: This study was a hospital-based recordbased cross-sectional study that included patients with sputum smear negative for Acid-Fast Bacilli (AFB) and Mycobacterium tuberculosis (M. tuberculosis) not detected on Nucleic Acid Amplification Test (NAAT), who were clinically diagnosed with TB. Bronchoscopy was performed on such patients, and samples were sent for investigations, including histopathology and NAAT. Demographic characteristics, bronchoscopy and radiology findings, and microbiology results were documented. Quantitative variables were summarised as means, and categorical variables were presented as percentages. Results: A total of 198 underwent bronchoscopy, of which 20 (10%) were diagnosed with EBTB. The mean age was 22 years, and 65% were females. The most common clinical feature in these patients was fever, the most common radiological presentation was lobar collapse, and the most common bronchoscopy feature was a tumorous lesion. NAAT detected M. tuberculosis in the bronchial wash in 50% of patients diagnosed with EBTB. A total of 45% of patients had TB which was diagnosed on histopathology. Conclusion: EBTB was diagnosed in 10% of smear-negative, NAAT-negative cases. The use of NAAT on bronchoscopy wash samples resulted in a high yield in diagnosis. [ABSTRACT FROM AUTHOR]

The Western Diet commonly consists of high-fat meals (HFMs) with saturated fats (SF) and increased omega-6 polyunsaturated fatty acids (O6FA) to omega-3 polyunsaturated fatty acids (O3FA) ratios. Even a single high-fat meal (HFM) may increase airway inflammation assessed via exhaled nitric oxide (eNO). When HFMs are consumed chronically, persistent airway inflammation may lead to deleterious structural changes in the airways, decrease pulmonary function, and increase the risk of respiratory disease development. To examine the effect of varying fatty acid composition in a HFM on eNO, pulmonary function, and airway resistance. Fifteen individuals [6 M/9 F; 21.9 ± 1.5 years old] each completed three HFM conditions {SF, O6FA, and O3FA; 12 kcal/kg body weight, 63% total fat, and 0.72 g/kg sugar smoothies} in random order separated by at least 48 h. Airway inflammation assessed via eNO, pulmonary function measured using the maximum flow volume loop (MFVL) and airway resistance measured using impulse oscillometry (iOS) were taken at baseline, 2h and 4h postprandially. There was no difference in eNO or iOS across time in any condition or between conditions (p > 0.05). There was a significant time by condition effect for FEV1 post-HFM in the SF and O6FA conditions (p < 0.05). Different fatty acid compositions do not increase eNO or iOS in healthy, college-aged participants after consumption of a HFM, though the minimally processed meals with fruit added may contribute to these findings. [ABSTRACT FROM AUTHOR]

BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1β and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up. [ABSTRACT FROM AUTHOR]

Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy for treatment of lung diseases. In this work, we have demonstrated successful development of an mRNA-lipid nanoparticle (LNP) dry powder product (DPP), wherein the LNPs were spray dried using hydroalcoholic solvent along with mannitol and leucine as excipients. The desired critical attributes for the DPP were accomplished by varying the excipients, lipid composition, concentration of LNPs, and weight percentage of mRNA. Leucine alone or in combination with mannitol improved the formulation by increasing the mRNA yield as well as decreasing the particle size. Intratracheal administration of the DPP in mice resulted in luciferase expression in the trachea and lungs indicating successful delivery of functional mRNA. Our results show formulation optimization of mRNA LNPs administered in the form of DPP results in an efficacious functional delivery with great promise for future development of mRNA therapeutics for lung diseases. [ABSTRACT FROM AUTHOR]

Objectives: Pulmonary papillomatosis is a rare but severe manifestation of recurrent respiratory papillomatosis (RRP). Efficacy data of systemic bevacizumab for pulmonary RRP are limited. This study's objective was to characterize disease response of pulmonary RRP to systemic bevacizumab. Methods: A retrospective review was performed to identify patients with pulmonary RRP seen at three medical institutions. Clinical symptoms, CT findings, and disease response were compared before and after initiation of systemic bevacizumab therapy. Disease response was categorized as complete response, partial response, stabilization, or progression for each subsite involved by papilloma. Results: Of the 12 pulmonary RRP patients treated with systemic bevacizumab, 4 (33.3%) were male, and 11 (91.7%) were juvenile‐onset RRP patients. All presented with laryngeal, tracheal, and pulmonary RRP. The median (range) age at first bevacizumab infusion was 48.1 (19.5–70.2) years. Progression to pulmonary malignancy was identified in 3 (25.0%) patients, 2 before initiation of and 1 after complete cessation of bevacizumab therapy. Clinical symptoms such as dyspnea (75.0% vs. 25.0%; p = 0.01) and dysphagia and/or odynophagia (33.3 vs. 0.0%; p = 0.03) were significantly decreased following bevacizumab therapy. Compared with pre‐treatment baseline, 9 (75.0%) patients experienced a stable‐to‐partial response in the lungs to systemic bevacizumab, and 10 (83.3%) experienced partial‐to‐complete responses in the larynx and trachea. Conclusion: Systemic bevacizumab is effective in stabilizing progression in even the most severe cases of RRP, with both a dramatic reduction in laryngeal and tracheal disease as well as a stable‐to‐partial response of pulmonary involvement in a majority of patients. Level of Evidence: 4 Laryngoscope, 134:577–581, 2024 [ABSTRACT FROM AUTHOR]

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor, with particularly low incidence in the lungs, and a correspondingly poor prognosis. To determine the clinicopathological characteristics, outcomes, and prognostic factors of primary pulmonary NMC, a case was reported and a systematic review was performed. Twenty-nine records, including ours, involving 62 cases, were finally included. The median age at diagnosis was 29.5 years. At presentation, the most common symptoms at presentation were cough (47.50%) and chest/back pain (37.50%). In terms of diagnosis, 32.14% of NMC cases were identified through immunohistochemistry (IHC); However, a greater number of cases may be misdiagnosed initially, and ultimately, the diagnosis of NMC was confirmed through a combination of IHC and fluorescence in situ hybridization (FISH). Despite the clinical application of various chemotherapy-based treatments, the actual effectiveness remains unsatisfactory. Furthermore, Cox regression analysis of multiple factors identified male gender and concurrent presence of pleural effusion as indicators of shorter survival time in patients. These results emphasize the importance of increased diagnostic awareness among clinical and pathology practitioners concerning NMC. While there is currently no established standard for treating NMC, a treatment approach combining multiple methods shows promise for future research. Concurrently, clinical and foundational investigations addressing variables such as gender and the presence of pleural effusion may yield valuable insights into the diagnosis and treatment of NMC. [ABSTRACT FROM AUTHOR]

Primary pulmonary salivary gland‐type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland‐type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial‐myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland‐type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland‐type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type‐tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high‐grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland‐type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland‐type tumours of the lung and those primary to other sites. [ABSTRACT FROM AUTHOR]

Background: While the development of CT imaging technique has brought cognition of in vivo organs, the resolution of CT images and their static characteristics have gradually become barriers of microscopic tissue research. Purpose: Previous research used the finite element method to study the airflow and gas exchange in the alveolus and acinar to show the fate of inhaled aerosols and studied the diffusive, convective, and sedimentation mechanisms. Our study combines these techniques with CT scan simulation to study the mechanisms of respiratory movement and its imaging appearance. Methods: We use 3D fluid‐structure interaction simulation to study the movement of an ideal alveolus under regular and forced breathing situations and ill alveoli with different tissue elasticities. Additionally, we use the Monte Carlo algorithm within the OpenGATE platform to simulate the computational CT images of the dynamic process with different designated resolutions. The resolutions show the relationship between the kinematic model of the human alveolus and its imaging appearance. Results: The results show that the alveolus and the wall thickness can be seen with an image resolution smaller than 15.6 μm. With ordinary CT resolution, the alveolus is expressed with four voxels. Conclusions: This is a preliminary study concerning the imaging appearance of the dynamic alveolus model. This technique will be used to study the imaging appearance of the dynamic bronchial tree and the lung lobe models in the future. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis, a critical outcome of chronic inflammatory diseases, has gained prominence in the context of post-coronavirus (post-COVID-19) complications. This review delves into the multifaceted landscape of post-COVID-19 pulmonary fibrosis, elucidating the intricate molecular mechanisms underlying its pathogenesis and highlighting promising therapeutic avenues. Examining the aftermath of severe acute respiratory syndrome-2 (SARS-CoV-2) infection, the review reveals key signaling pathways implicated in the fibrotic cascade. Drawing parallels with previous coronavirus outbreaks enhances our understanding of the distinctive features of post-COVID-19 fibrosis. Antifibrotic drugs, like pirfenidone and nintedanib, take center stage; their mechanisms of action and potential applications in post-COVID-19 cases are thoroughly explored. Beyond the established treatments, this review investigates emerging therapeutic modalities, including anti-interleukin agents, immunosuppressants, and experimental compounds, like buloxybutide, saracatinib, sirolimus, and resveratrol. Emphasizing the critical importance of early intervention, this review highlights the dynamic nature of post-COVID-19 pulmonary fibrosis research. In conclusion, the synthesis of current knowledge offers a foundation for advancing our approaches to the prevention and treatment of these consequential sequelae of COVID-19. [ABSTRACT FROM AUTHOR]

While rare, the likelihood of encountering a case of a pulmonary endemic mycosis (PEM) in the UK is increasing. Diagnosis may be challenging, often leading to considerable delay to appropriate treatment. Clinical suspicion must be present for respiratory disease, particularly in the immunocompromised or in those not responding to empiric treatment approaches, and an extended travel history should be obtained. This article summarises the epidemiology of PEM, key clinical features, diagnostic strategies and management. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of pediatric tuberculosis (TB) still remains a challenge due to the paucibacillary nature of the disease. Objectives: To assess the role of CB-NAAT in diagnosing pulmonary and extrapulmonary tuberculosis as compared to AFB smear and Mycobacterium tuberculosis culture in clinically diagnosed pediatric tuberculosis cases. Study design: Hospital-based prospective study. Methods: A total of142 patients with strong clinical suspicion of pulmonary or extra-pulmonary tuberculosiswere enrolled over a period of two yearsand then results of CB-NAAT were compared to conventional methods (culture/ AFB smear) on follow-up. Results: In subjects who had clinically diagnosed tuberculosis, culture was positive in 18.9% of cases, AFB smear was positive in only 12.1% whereas CB-NAAT was positive in 55.4% of subjects. The sensitivity, specificity, PPV, and NPV of CB-NAAT in patients with culture proven tuberculosis were100%, 83.3%, 47.5%, and 100% respectively with a diagnostic accuracy of 93.3%. and 60%, 100%, 100%, and 65.8% respectively with a diagnostic accuracy of 80.2% in clinically diagnosed pulmonary cases. Conclusion:CB-NAAT has true diagnostic potential with good sensitivity in confirmed cases and significantly better sensitivity than conventional methods in clinically diagnosed cases. [ABSTRACT FROM AUTHOR]

The early immune response to bacterial pneumonia requires a careful balance between pathogen clearance and tissue damage. The anti-inflammatory cytokine interleukin (IL)-10 is critical for restraining otherwise lethal pulmonary inflammation. However, pathogen-induced IL-10 is associated with bacterial persistence in the lungs. In this study, we used mice with myeloid cell specific deletion of IL-10R to investigate the cellular targets of IL-10 immune suppression during infection with Streptococcus pneumoniae , the most common bacterial cause of pneumonia. Our findings suggest that IL-10 restricts the neutrophil response to S. pneumoniae , as neutrophil recruitment to the lungs was elevated in myeloid IL-10 receptor (IL-10R)–deficient mice and neutrophils in the lungs of these mice were more effective at killing S. pneumoniae. Improved killing of S. pneumoniae was associated with increased production of reactive oxygen species and serine protease activity in IL-10R–deficient neutrophils. Similarly, IL-10 suppressed the ability of human neutrophils to kill S. pneumoniae. Burdens of S. pneumoniae were lower in myeloid IL-10R–deficient mice compared with wild-type mice, and adoptive transfer of IL-10R–deficient neutrophils into wild-type mice significantly improved pathogen clearance. Despite the potential for neutrophils to contribute to tissue damage, lung pathology scores were similar between genotypes. This contrasts with total IL-10 deficiency, which is associated with increased immunopathology during S. pneumoniae infection. Together, these findings identify neutrophils as a critical target of S. pneumoniae -induced immune suppression and highlight myeloid IL-10R abrogation as a mechanism to selectively reduce pathogen burdens without exacerbating pulmonary damage. [ABSTRACT FROM AUTHOR]

"Translational medicine" has been a buzzword for over two decades. The concept was intended to be lofty, to reflect a new "bench-to-bedside" approach to basic and clinical research that would bridge fields, close gaps, accelerate innovation, and shorten the time and effort it takes to bring novel technologies from basic discovery to clinical application. Has this approach been successful and lived up to its promise? Despite incredible scientific advances and innovations developed within academia, successful clinical translation into real-world solutions has been difficult. This has been particularly challenging within the pulmonary field, because there have been fewer U.S. Food and Drug Administration-approved drugs and higher failure rates for pulmonary therapies than with other common disease areas. The American Thoracic Society convened a working group with the goal of identifying major challenges related to the commercialization of technologies within the pulmonary space and opportunities to enhance this process. A survey was developed and administered to 164 participants within the pulmonary arena. This report provides a summary of these survey results. Importantly, this report identifies a number of poorly recognized challenges that exist in pulmonary academic settings, which likely contribute to diminished efficiency of commercialization efforts, ultimately hindering the rate of successful clinical translation. Because many innovations are initially developed in academic settings, this is a global public health issue that impacts the entire American Thoracic Society community. This report also summarizes key resources and opportunities and provides recommendations to enhance successful commercialization of pulmonary technologies. [ABSTRACT FROM AUTHOR]

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Study Design.: Retrospective database cohort study. Objective.: To evaluate U.S. treatment trends and inpatient outcomes for children undergoing posterior spinal fusion (PSF) for Rett syndrome (RTT)–associated scoliosis (RAS). Summary of Background Data.: RTT is a rare, sporadic neurodevelopmental disorder presenting in childhood with developmental regression, ataxia, and seizures. RAS occurs in 50% to 80% of cases of RTT, but little is known about the case volume and perioperative experience for children undergoing PSF. Materials and Methods.: Using the International Classification of Diseases Ninth and 10th revision codes in the national Kids' Inpatient Database, we identified children with RTT who underwent PSF from 2000 to 2019. Annual case volumes were analyzed. Clinical characteristics and outcomes were compared with those of a cohort of patients with neuromuscular scoliosis (NMS). Results.: Among 220 patients with RAS, 216 (98.2%) were females (mean age at surgery: 12.3±3.3 yr). Surgical case incidence steadily increased over 19 years, with more RAS admissions in the South (31.4%). Overall, patients with RAS demonstrated a higher mean Elixhauser Comorbidity Index score (2 vs. 1, P < 0.001) and had more perioperative complications (41.4% vs. 18%, P < 0.001) than patients with NMS. RTT diagnosis independently predicted higher odds of any complications (odds ratio: 1.98, P < 0.001) and increased length of stay (odds ratio: 1.18, P = 0.009) for admissions for PSF. Conclusions.: Surgical treatment for RAS is rare but increased over a 19-year period. Cases appear to be clustering by region, with the highest proportion in the South. The higher Elixhauser Comorbidity Index in RAS patients predicted higher costs, longer hospital stays, more complications (particularly respiratory), and more nonroutine discharge disposition than in other patients with NMS. RTT was independently associated with higher odds of complications and longer length of stay. Because RAS cases appear to be increasing in number, future studies should emphasize methods to reduce morbidity and investigate deformity-specific metrics to help better understand this population. [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology. Background: Bartonella quintana is a slow-growing gram-negative bacterium that can cause severe culture-negative endocarditis. In many cases, its insidious onset can be difficult to diagnose given the variable symptoms in the early phases of the disease. This delay in detection and thus treatment can cause advanced consequences of the disease, including heart failure and severe pulmonary hypertension. Case Report: A 51-year-old man presented to the Emergency Department with signs and symptoms indicating an acute stroke. Further investigation showed that the source was cardioembolic, and despite negative blood cultures, endocarditis was suspected due to echocardiogram findings. Bartonella endocarditis was diagnosed based on serology results. Further testing indicated severe pulmonary hypertension, a sequelae of chronic heart failure in the setting of endocarditis. This caused a significant delay in valvular repair surgery. This case illustrates the progression from acute to chronic infection, the sequelae of this disease process, and the considerations involved in management. Conclusions: Bartonella is an under-appreciated cause of endocarditis and can evolve into chronic disease with clinical consequences requiring nuanced management. We described a case of chronic culture-negative endocarditis that presented with acute embolic stroke and the sequelae of severe multi-valvular disease in a patient with recent incarceration and unstable housing. This case provides clinicians with valuable insight into the recognition of Bartonella endocarditis, the variable clinical presentations of this pathology, the nuanced and multifactorial approaches to medical management, and the indications for surgery. [ABSTRACT FROM AUTHOR]

Rationale: Organ size matching is an important determinant of successful allocation and outcomes in lung transplantation. While computed tomography (CT) is the gold standard, it is rarely used in an organ‐donor context, and chest X‐ray (CXR) may offer a practical and accurate solution in estimating lung volumes for donor and recipient size matching. We compared CXR lung measurements to CT‐measured lung volumes and traditional estimates of lung volume in the same subjects. Methods: Our retrospective study analyzed clinically obtained CXR and CT lung images of 250 subjects without evidence of lung disease (mean age 9.9 ± 7.8 years; 129 M/121F). From CT, each lung was semi‐automatically segmented and total lung volumes were quantified. From anterior–posterior CXR view, each lung was manually segmented and areas were measured. Lung lengths from the apices to the mid‐basal regions of each lung were measured from CXR. Quantified CT lung volumes were compared to the corresponding CXR lung lengths, CXR lung areas, height, weight, and predicted total lung capacity (pTLC). Results: There are strong and significant correlations between CT volumes and CXR lung areas in the right lung (R2 =.89, p <.0001), left lung (R2 =.87, p <.0001), and combined lungs (R2 =.89, p <.0001). Similar correlations were seen between CT volumes and CXR measured lung lengths in the right lung (R2 =.79, p <.0001) and left lung (R2 =.81, p <.0001). This correlation between anatomical lung volume (CT) and CXR was stronger than lung‐volume correlation to height (R2 =.66, p <.0001), weight (R2 =.43, p <.0001), or pTLC (R2 =.66, p <.0001). Conclusion: CXR measures correlate much more strongly with true lung volumes than height, weight, or pTLC. The ability to obtain efficient and more accurate lung volume via CXR has the potential to change our current listing practices of using height as a surrogate for lung size, with a case example provided. [ABSTRACT FROM AUTHOR]

To evaluate different approaches for the effective assessment of pulmonary perfusion with a pseudo-continuous arterial spin labeled (pCASL) MRI. Four different approaches were evaluated: 1) Cardiac-triggered inferior vena cava (IVC) labeling; 2) IVC labeling with cardiac-triggered acquisition; 3) Right pulmonary artery (RPA) labeling with cardiac-triggered acquisition; and 4) Cardiac-triggered RPA labeling with background suppression (BGS). Each approach was evaluated in 5 healthy volunteers (n = 20) using coefficient of variation (COV) across averages. Approach 4 was also compared against a flow alternating inversion recovery (FAIR). The IVC labeling (Approach 1) achieved perfusion-weighted images of both lungs, although this approach was more sensitive to variations in heart rate. Cardiac-triggered acquisitions using IVC (Approach 2) and RPA (Approach 3) labeling improved signal consistencies, but were incompatible with BGS. The cardiac-triggered RPA labeling with BGS (Approach 4) achieved a COV of 0.34 ± 0.03 (p < 0.05 compared to IVC labeling approaches) and resulted in perfusion value of 434 ± 64 mL/100 g/min, which was comparable to 451 ± 181 mL/100 g/min measured by FAIR (p = 0.82). Pulmonary perfusion imaging using pCASL-MRI is highly sensitive to cardiac phase, and requires approaches to minimize flow-induced signal variations. Cardiac-triggered RPA labeling with BGS achieves reduced COV and enables robust pulmonary perfusion imaging. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a common disease with pulmonary & extra-pulmonary symptoms. It is a leading cause of mortality & disability. In India, the crude estimate of COPD burden is over 30 million. Methods: Study was conducted over a period of 18 months in clinically diagnosed 70 cases (35 patients each in group I and II) of COPD of all ages and both gender. Results: Mean age of patients was 64.14±5.94 years in Group I and 65.05±5.58 in Group II. Majority of patients were males in our study, 30 (75.72%) patients were male in Group I and 28(80%) patients in Group II. In Group I (82.85%) & Group II (77.15%) patients were smoker. In Group I statistically significant decrease in mean mMRC after 6 weeks & 12 weeks of PR (baseline 2.57±0.50; 6 Wks 1.68±0.47; 12Wks 1.02±0.16) was observed. In group II, mean mMRC decrease was not statistically significant (baseline 2.54±0.50; at 6 weeks 2.51±0.50 & 2.48±0.50 at 12 weeks). In Group I statistically significant increase in mean 6MWD after 6 weeks & 12 weeks of PR (baseline 285.88±32.11 meter; 320.82±32.52 meter at 6 Wks; 345.48±32.10 meter at 12Wks) was found. In group II, mean 6MWD increase was not statistically significant (baseline 296.34±28.17 meter; 294.62±30.23 at 6 weeks & 297.02±28.89 at 12 weeks). In Group I statistically significant decrease in mean SGRQ after 6 weeks & 12 weeks of PR (baseline 68.05±5.54; at 6 Wks 53.74±5.79; at 12Wks 38.22±8.66). Decrease in SGRQ indicated improvement in quality of life whereas in group II, there was no significant decrease in mean SGRQ (baseline 66.28±3.97; at 6 weeks 65.2±3.88 & at 12 weeks 65.11±4.70). Conclusion: COPD patients had reduced exercise capacity (low 6 MWD), high dyspnea score and impaired quality of life as indicated by high SGRQ at baseline. Pulmonary rehabilitation results in statistically significant improvement in 6MWT, decrease in dyspnea score & improvement in quality of life at 6 & 12 weeks while no improvement was noted in the group not given pulmonary rehabilitation. Pulmonary rehabilitation found to be an effective non-pharmacological intervention for COPD patients. [ABSTRACT FROM AUTHOR]

With the recent increase in lung diseases, especially with the onset of the coronavirus pandemic, the design of a highly efficient and optimal targeted drug delivery system for the lungs is crucial in inhaler-based delivery systems. This study aimed to design a magnetic field-assisted targeted drug delivery system to the lungs using three types of metal–organic frameworks (MOFs) and nanoliposomes. The optimization of the system was based on three main parameters: the surface density of the nanocarriers' (NCs) adherence to each of the lung branches, the amount of drug transferred to each branch, and the toxicity based on the rate of nanocarrier delivery to the branches. The study investigated the effect of increasing the diameter of the drug carriers and the amount of drug loaded onto the NCs in improving drug delivery to targeted areas of the lung. Results showed that the presence of a magnetic field significantly increased the adhesion of NCs to the targeted branches. The application of a magnetic field and the type of drug carrier had a significant effect on drug delivery downstream of the lung and reduced drug toxicity. The study found that Fe3O4@UiO-66 (iron-oxide nanoparticle attached to the surface of UiO-66, a type of MOF) and Fe3O4@PAA/AuNCs/ZIF-8 carriers, (iron-oxide nanoparticle attached to a hybrid structure composed of three different materials: poly (acrylic acid) (PAA), gold nanoclusters (AuNCs), and zeolitic imidazolate framework-8 (ZIF-8)), had the greatest drug delivery rate in diameters above 200 nm and less than 200 nm, respectively. [ABSTRACT FROM AUTHOR]

Leptospirosis is a zoonotic disease caused by bacteria from the genus Leptospira. The infection occurs mainly in developing countries in the tropical zone and countries with lower hygiene standards. The highest incidence is observed especially in environments associated with the presence of rodents, mainly rats, which are a potential source of infection. The clinical manifestations and severity of leptospirosis are highly variable. This case report describes the a 53-year-old patient (male) without comorbidities, who was admitted to an infectious disease department in the east of Slovakia for jaundice, general fatigue, weakness, and fever (health difficulties for approximately 7 days at home). The clinical laboratory picture of the patient was dominated by significant hyperbilirubinemia, acute renal failure, hepatopathy, severe thrombocytopenia, and involvement of the lung parenchyma in the sense of bilateral interstitial pneumonia on chest X-ray. A double combination of antibiotics (ceftriaxone and clarithromycin) were added to the treatment. During hospitalization, a diagnosis of leptospirosis was suspected based on medical history and the results of laboratory tests and was subsequently confirmed serologically. The antibiotic regimen was de-escalated to cephalosporin (ceftriaxone) monotherapy with adequate laboratory and clinical effects (on the 4th day). The patient was discharged after a total of 18 days in good clinical condition. [ABSTRACT FROM AUTHOR]

Formaldehyde is the key chemical substance used by morticians to prevent known post-mortem changes. Hence, the objective of this paper is to evaluate some pulmonary functions among morticians in Teaching and General Hospitals exposed to formaldehyde in Benin City, Nigeria using appropriate standard methods. Results revealed significant increase in respiratory rate and significant decrease in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, peak expiratory flow rate (PEFR), and forced expiratory flow between 25 and 75 percent (FEF2575) among morticians of the Teaching hospital and General hospital when compared to the control while those of the General hospital morticians were found to be lower than those of the Teaching hospital morticians. It was therefore concluded that exposure to formaldehyde has deleterious effects on the respiratory health of morticians especially those in the General hospital hence, there is an urgent need to seek ways of reducing formaldehyde air levels in our mortuaries especially the General hospital mortuary in order to protect the respiratory health of the morticians. [ABSTRACT FROM AUTHOR]

This article emphasizes the importance of preventing common travel-related issues through common-sense measures, often overlooked by travelers. It provides recommendations backed by scientific evidence for travel health advisors to pass on to travelers. Additionally, it highlights the significance of addressing the health concerns of individuals with compromised immunity, such as those with severe immunosuppression. Furthermore, it underscores the need to consider the unique health challenges faced by elderly travelers when journeying to developing countries. The purpose of this study is to provide guidelines for an evidence-based approach to pre-travel counseling and medical considerations for the elderly in a travel clinic. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of Pulmonary Arterial Hypertension (PAH) therapies on the incidence of pericardial effusion and its prognostic implications for patient survival. Methods: This retrospective cohort study included 60 patients diagnosed with PAH at a high-volume tertiary care center, treated with intravenous or subcutaneous prostanoids. Data were collected from 2015 to 2019, including echocardiographic assessments, right heart catheterization, World Health Organization functional class evaluations, six-minute walk distance tests, and biomarkers such as brain natriuretic peptide and N-terminal prohormone of brain natriuretic peptide. Follow-up was conducted at least 90 days post-treatment initiation. Results: Pericardial effusion was observed in 31.7% of patients before therapy. Patients with moderate to large effusions had a significantly higher mortality risk (HR = 1.92; 95% CI 1.1–44.78; p =0.0044), while small effusions appeared protective (HR = 0.27; 95% CI 0.15–0.48; p =0.006). Survival rates declined from 89% at one year to 71% at three years post-therapy, with effusion presence correlating with more severe PAH manifestations. Conclusions: Initial pericardial effusion severity is a critical predictor of mortality in PAH patients. Early assessment and stratified management of pericardial effusion are essential for optimizing therapeutic outcomes in PAH management. Future research should explore targeted interventions for managing pericardial effusion to improve patient prognosis.

Abstract Objective To assess the risk of developing pulmonary tuberculosis (TB) in accordance with prior history of COVID‐19 infection. Background Since the advent of the COVID‐19 pandemic much discussion has been had on the possible role it might play on global efforts to combat TB; most, focusing on the pandemic's impact on health care systems' capabilities to manage TB cases. Mechanisms have also been proposed by which the COVID‐19 infection may directly affect individuals' chance of developing TB infection. Cases have been reported with a history of COVID‐19 infection preceding a diagnosis of TB, evidencing its possible role as a risk factor for the disease. Methods A case‐control study was conducted enrolling patients diagnosed with pulmonary TB in the absence of major risk factors previous history of TB, (HIV) human immunodeficiency virus infection), end‐stage renal disease, organ transplants, and use of immunosuppressive agents) for developing TB. Each patient was age and sex matched with one healthy control. Data regarding prior COVID‐19 infection, diabetes, and smoking status as well as the use of corticosteroids and Tocilizumab for the treatment of COVID‐19 infection was obtained. Bivariate analysis was conducted and variables with a likely association with TB status were entered in a multivariate model. Results Bivariate analysis demonstrated a significant relationship between prior COVID‐19 infection and TB (95% confidence interval = 1.1−22.8, odds ratio [OR] = 5). Among other variables the severity of COVID‐19 infection was found to have a likely association with TB status (p = .125). In a multivariate model, prior COVID‐19 infection per se, was not found to be significantly associated with TB (p = .12, OR = 4.5). Conclusions There seems to be an association between prior history of COVID‐19 and a future diagnosis of TB partially linked to the severity of disease. The findings of the current study may serve as a basis for further studies to determine the need for and efficacy of measures to follow‐up COVID‐19 patients at an increased risk for developing TB.

Trehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for Cryptococcus neoformans and a promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion of host defenses during pulmonary and disseminated phases of infection. In the pulmonary infection model, TPS1-deleted (tps1Δ) Cryptococci are rapidly cleared by mouse lungs whereas TPS1-sufficent WT (H99) and revertant (tps1Δ:TPS1) strains expand in the lungs and disseminate, causing 100% mortality. Rapid pulmonary clearance of tps1Δ mutant is T-cell independent and relies on its susceptibility to lung resident factors and innate immune factors, exemplified by tps1Δ but not H99 inhibition in a coculture with dispersed lung cells and its rapid clearance coinciding with innate leukocyte infiltration. In the disseminated model of infection, which bypasses initial lung–fungus interactions, tps1Δ strain remains highly attenuated. Specifically, tps1Δ mutant is unable to colonize the lungs from the bloodstream or expand in spleens but is capable of crossing into the brain, where it remains controlled even in the absence of T cells. In contrast, strains H99 and tps1Δ:TPS1 rapidly expand in all studied organs, leading to rapid death of the infected mice. Since the rapid pulmonary clearance of tps1Δ mutant resembles a response to acapsular strains, the effect of tps1 deletion on capsule formation in vitro and in vivo was examined. Tps1Δ cryptococci form capsules but with a substantially reduced size. In conclusion, TPS1 is an important virulence factor, allowing C. neoformans evasion of resident pulmonary and innate defense mechanisms, most likely via its role in cryptococcal capsule formation.

In this case report, primary pulmonary mycobacteriosis in a domestic cat was assessed using histopathological and immunohistochemical methods. The cat was admitted to a private veterinary clinic and presented with hyporexia, lethargy, and dyspnea with an abdominal component. For diagnostic purposes, thorax radiography was performed. Radiographic lung imaging showed the presence of opaque foci that were widely distributed throughout the lung. The cat’s condition gradually deteriorated, and the cat died 2 hours after being brought to the clinic. Following owner consent, gross post-mortem examination was performed immediately after death at the same clinic. White foci measuring 2–10 mm in diameter covered the surface of the lungs and were present throughout the parenchyma, mostly multifocally and occasionally coalesc­ing. No other macroscopical pathological findings were observed in other organs or on the skin. Some of the lung tissue with macroscopic lesions underwent further histo­pathological and immunohistochemical examination. Multifocal to coalescing areas of caseous necrosis (without a fibrous capsule) with, karyorrhectic nuclei, and numerous macrophages were observed. Ziehl-Neelsen staining revealed many acid-fast bacteria. Immunohistochemical staining revealed positive immunostaining for Mycobacterium spp. This case study highlights the importance of considering zoonotic risks in cats diagnosed with primary pulmonary mycobacteriosis. Primarna pljučna mikobakterioza pri mački: imunohistokemična in histopatološka ocena Izvleček: V tem poročilu o primeru je bila ocenjena primarna pljučna mikobakterioza pri domači mački z uporabo histopatoloških in imunohistokemičnih metod. Mačka je bila sprejeta v zasebno veterinarsko kliniko zaradi simptomov hiporeksije, letargije in dispneje z abdominalno komponento. Za diagnostične namene je bila opravljena rentgenska preiskava prsnega koša, ki je pokazala prisotnost motnih žarišč, široko razporejenih po pljučih. Stanje mačke se je posto­poma slabšalo, umrla je dve uri po prihodu v kliniko. Po privolitvi lastnika je bila takoj po smrti opravljena raztelesba. Bela žarišča, premera od 2 do 10 mm, so prekrivala površino pljuč. Prisotna so bila po celotnem parenhimu večinoma multifokalno in mestoma zlivajoče. V drugih organih in na koži ni bilo opaznih drugih makroskopskih patoloških sprememb. Nekatere dele pljučnega tkiva z makroskopskimi spremembami smo dodatno histopatološko in imunohistokemično pregledali. Opazili smo multifokalna do zlivajoča se območja kazeozne nekroze (brez fibrozne kapsule) s karioznimi jedri in številnimi makrofagi. Ziehl-Neelsenovo barvanje je razkrilo številne acidofilne bakterije. Imunohistokemično barvanje je pokazalo pozitivno imunobarvanje za Mycobacterium spp. To poročilo o primeru poudarja pomen upoštevanja zoonotskih tveganj pri mačkah z diagnozo primarne pljučne mikobakterioze. Ključne besede: mikobakterioza mačk; imunohistokemija; histopatologija; pluča

Background: The most serious manifestation of pulmonary cryptococcosis is complicated with cryptococcal meningitis, while its clinical manifestations lack specificity with delayed diagnosis and high mortality. The early prediction of this complication can assist doctors to carry out clinical interventions in time, thus improving the cure rate. This study aimed to construct a nomogram to predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis through a scoring system. Methods: The clinical data of 525 patients with pulmonary cryptococcosis were retrospectively analyzed, including 317 cases (60.38 %) with cryptococcal meningitis and 208 cases (39.62 %) without cryptococcal meningitis. The risk factors of cryptococcal meningitis were screened by univariate analysis, LASSO regression analysis and multivariate logistic regression analysis. Then the risk factors were incorporated into the nomogram scoring system to establish a prediction model. The model was validated by receiver operating characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve. Results: Fourteen risk factors for cryptococcal meningitis in patients with pulmonary cryptococcosis were screened out by statistical method, including 6 clinical manifestations (fever, headache, nausea, psychiatric symptoms, tuberculosis, hematologic malignancy) and 8 clinical indicators (neutrophils, lymphocytes, glutamic oxaloacetic transaminase, T cells, helper T cells, killer T cells, NK cells and B cells). The AUC value was 0.978 (CI 96.2 %∼98.9 %), indicating the nomogram was well verified. Conclusion: The nomogram scoring system constructed in this study can accurately predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis, which may provide a reference for clinical diagnosis and treatment of patients with cryptococcal meningitis.

BackgroundThe prevalence of bronchiectasis among adult Aboriginal Australians is higher than that of non-Aboriginal Australians. However, despite evidence to suggest higher prevalence of bronchiectasis among Aboriginal people in Australia, there is sparce evidence in the literature assessing clinical parameters that may predict survival or mortality in this population.MethodsAboriginal Australians residing in the Top End Health Service region of the Northern Territory of Australia aged >18 years with chest computed tomography (CT) confirmed bronchiectasis between 2011 and 2020 were included. Demographics, body mass index (BMI), medical co-morbidities, lung function data, sputum microbiology, chest CT scan results, hospital admissions restricted to respiratory conditions and all-cause mortality were assessed.ResultsA total of 459 patients were included, of whom 146 were recorded deceased (median age at death 59 years). Among the deceased cohort, patients were older (median age 52 vs. 45 years, p = 0.023), had a higher prevalence of chronic obstructive pulmonary disease (91 vs. 79%, p = 0.126), lower lung function parameters (median percentage predicted forced expiratory volume in 1 s 29 vs. 40%, p = 0.149), a significantly greater proportion cultured non-Aspergillus fungi (65 vs. 46%, p = 0.007) and pseudomonas (46 vs. 28%, p = 0.007) on sputum microbiology and demonstrated bilateral involvement on radiology. In multivariate models advancing age, prior pseudomonas culture and Intensive care unit (ICU) visits were associated with increased odds of mortality. Higher BMI, better lung function on spirometry, prior positive sputum microbiology for Haemophilus and use of inhaled long-acting beta antagonist/muscarinic agents may have a favourable effect.ConclusionThe results of this study may be of use to stratify high risk adult Aboriginal patients with bronchiectasis and to develop strategies to prevent future mortality.

Abstract Introduction Ambrisentan is a selective type A endothelin receptor antagonist that has shown significant effectiveness and safety in the management of patients with pulmonary hypertension. Its use pattern with real‐world evidence in Colombia is unknown. Objective The objective of this study is to determine the prescription patterns of ambrisentan in some cities of Colombia. Methods A longitudinal descriptive study on the prescription patterns of ambrisentan in patients with pulmonary hypertension (all the groups) was conducted between January 2021 and December 2022 based on a population database of members of the Colombian Health System. Adherence at 1 year was determined using the Medication Possession Ratio (days the drug was dispensed/days from first dispensing to the end of the follow‐up period × 100). Descriptive analysis was carried out. Results Sixty‐seven patients taking ambrisentan were identified in 10 cities of the country. The individuals had a median age of 51.5 years (interquartile range‐IQR: 39.8–64.0 years), and 82.1% were women. The drug possession rate was 82.2% (IQR: 65.0–96.8%), and persistence at 1 year was present in 49.3% (n = 33) of the cases. The average dose was 8.8 ± 5.0 mg/day, and 76.1% (n = 51) received it in combination therapy, mainly with phosphodiesterase type 5 inhibitors (61.2%, n = 41). Conclusions Adherence to ambrisentan was good, but its persistence at 1 year was low. The dosages of the drug used were in accordance with the recommendations of the clinical practice guidelines, and it was used in combination therapy, especially with phosphodiesterase 5 inhibitors.

Key Clinical Message Although retroperitoneal bleeding and massive hematuria are potential complications of angiomyolipoma (AML), the pulmonary embolism as a presenting symptom is extremely rare. It is important to be aware that benign AMLs can present with pulmonary fat embolism.

After having traveled to California in 2017, a 26-year old Dutch man presented in 2020 with persisting cough and shortness of breath. Radiology showed cystic bronchiectasis with peri-bronchial consolidation in his right upper lobe. Laboratory studies in August 2021 showed an increased total IgE, specific Aspergillus IgE, eosinophilia and positive BAL culture for Coccidioides immitis/posadasii. After 6 weeks of itraconazole treatment for suspected allergic bronchopulmonary aspergillosis, symptoms persisted and respiratory cultures remained positive. The infection was cleared after a 6-month course of fluconazole. (max 75 words)

Electronic cigarettes (e-cigarettes) have rapidly gained popularity as alternatives to traditional combustible cigarettes. However, their long-term health impact remains uncertain. This study aimed to investigate the effects of chronic exposure to e-cigarette aerosol (ECA) in mice compared to conventional cigarette smoke (CS) exposure. The mice were exposed to air (control), low, medium, or high doses of ECA, or a reference CS dose orally and nasally for eight months. Various cardiovascular and pulmonary assessments have been conducted to determine the biological and prosthetic effects. Histopathological analysis was used to determine structural changes in the heart and lungs. Biological markers associated with fibrosis, inflammation, and oxidative stress were investigated. Cardiac proteomic analysis was applied to reveal the shared and unique protein expression changes in ECA and CS groups, which related to processes such as immune activation, lipid metabolism, and intracellular transport. Overall, chronic exposure to ECA led to adverse cardiovascular and pulmonary effects in mice, although they were less pronounced than those of CS exposure. This study provides evidence that e-cigarettes may be less harmful than combustible cigarettes for the long-term health of the cardiovascular and respiratory systems in mice. However, further human studies are needed to clarify the long-term health risks associated with e-cigarette use.

BackgroundCurrent TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB.ObjectivesTo determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB.MethodsWe quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions.ResultsIsoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions.ConclusionsDespite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid.

Sotatercept is an activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein that improves cardiopulmonary function in patients with pulmonary arterial hypertension (PAH) by selectively trapping activins and growth differentiation factors. However, the cellular and molecular mechanisms of ActRIIA-Fc action are incompletely understood. Here, we determined through genome-wide expression profiling that inflammatory and immune responses are prominently upregulated in the lungs of a Sugen-hypoxia rat model of severe angio-obliterative PAH, concordant with profiles observed in PAH patients. Therapeutic treatment with ActRIIA-Fc-but not with a vasodilator-strikingly reversed proinflammatory and proliferative gene expression profiles and normalized macrophage infiltration in diseased rodent lungs. Furthermore, ActRIIA-Fc normalized pulmonary macrophage infiltration and corrected cardiopulmonary structure and function in Bmpr2 haploinsufficient mice subjected to hypoxia, a model of heritable PAH. Three high-affinity ligands of ActRIIA-Fc each induced macrophage activation in vitro, and their combined immunoneutralization in PAH rats produced cardiopulmonary benefits comparable to those elicited by ActRIIA-Fc. Our results in complementary experimental and genetic models of PAH reveal therapeutic anti-inflammatory activities of ActRIIA-Fc that, together with its known anti-proliferative effects on vascular cell types, could underlie clinical activity of sotatercept as either monotherapy or add-on to current PAH therapies.

BackgroundIn most eukaryotic cells, the mitochondrial DNA (mtDNA) is transmitted uniparentally and present in multiple copies derived from the clonal expansion of maternally inherited mtDNA. All copies are therefore near-identical, or homoplasmic. The presence of >1 mtDNA variant in the same cytoplasm can arise naturally or result from new medical technologies aimed at preventing mitochondrial genetic diseases and improving fertility. The latter is called divergent nonpathologic mtDNA heteroplasmy (DNPH). We hypothesized that DNPH is maladaptive and usually prevented by the cell.MethodsWe engineered and characterized DNPH mice throughout their lifespan using transcriptomic, metabolomic, biochemical, physiologic, and phenotyping techniques. We focused on in vivo imaging techniques for noninvasive assessment of cardiac and pulmonary energy metabolism.ResultsWe show that DNPH impairs mitochondrial function, with profound consequences in critical tissues that cannot resolve heteroplasmy, particularly cardiac and skeletal muscle. Progressive metabolic stress in these tissues leads to severe pathology in adulthood, including pulmonary hypertension and heart failure, skeletal muscle wasting, frailty, and premature death. Symptom severity is strongly modulated by the nuclear context.ConclusionsMedical interventions that may generate DNPH should address potential incompatibilities between donor and recipient mtDNA.

BackgroundThe WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population.MethodsIn this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895.FindingsWe identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

"Modern" vaping involving battery-operated electronic devices began approximately one dozen years and has quickly evolved into a multibillion dollar industry providing products to an estimated 50 million users worldwide. Originally developed as an alternative to traditional cigarette smoking, vaping now appeals to a diverse demographic including substantial involvement of young people who often have never used cigarettes. The rapid rise of vaping fueled by multiple factors has understandably outpaced understanding of biological effects, made even more challenging due to wide ranging individual user habits and preferences. Consequently while vaping-related research gathers momentum, vaping-associated pathological injury (VAPI) has been established by clinical case reports with severe cases manifesting as acute respiratory distress syndrome (ARDS) with examples of right ventricular cardiac failure. Therefore, basic scientific studies are desperately needed to understand the impact of vaping upon the lungs as well as cardiopulmonary structure and function. Experimental models that capture fundamental characteristics of vaping-induced ARDS are essential to study pathogenesis and formulate recommendations to mitigate harmful effects attributable to ingredients or equipment. So too, treatment strategies to promote recovery from vaping-associated damage require development and testing at the preclinical level. This review summarizes the back story of vaping leading to present day conundrums with particular emphasis upon VAPI-associated ARDS and prioritization of research goals.

RationaleThe MSTs (mammalian Ste20-like kinases) 1/2 are members of the HIPPO pathway that act as growth suppressors in adult proliferative diseases. Pulmonary arterial hypertension (PAH) manifests by increased proliferation and survival of pulmonary vascular cells in small PAs, pulmonary vascular remodeling, and the rise of pulmonary arterial pressure. The role of MST1/2 in PAH is currently unknown.ObjectiveTo investigate the roles and mechanisms of the action of MST1 and MST2 in PAH.Methods and resultsUsing early-passage pulmonary vascular cells from PAH and nondiseased lungs and mice with smooth muscle-specific tamoxifen-inducible Mst1/2 knockdown, we found that, in contrast to canonical antiproliferative/proapoptotic roles, MST1/2 act as proproliferative/prosurvival molecules in human PAH pulmonary arterial vascular smooth muscle cells and pulmonary arterial adventitial fibroblasts and support established pulmonary vascular remodeling and pulmonary hypertension in mice with SU5416/hypoxia-induced pulmonary hypertension. By using unbiased proteomic analysis, gain- and loss-of function approaches, and pharmacological inhibition of MST1/2 kinase activity by XMU-MP-1, we next evaluated mechanisms of regulation and function of MST1/2 in PAH pulmonary vascular cells. We found that, in PAH pulmonary arterial adventitial fibroblasts, the proproliferative function of MST1/2 is caused by IL-6-dependent MST1/2 overexpression, which induces PSMC6-dependent downregulation of forkhead homeobox type O 3 and hyperproliferation. In PAH pulmonary arterial vascular smooth muscle cells, MST1/2 acted via forming a disease-specific interaction with BUB3 and supported ECM (extracellular matrix)- and USP10-dependent BUB3 accumulation, upregulation of Akt-mTORC1, cell proliferation, and survival. Supporting our in vitro observations, smooth muscle-specific Mst1/2 knockdown halted upregulation of Akt-mTORC1 in small muscular PAs of mice with SU5416/hypoxia-induced pulmonary hypertension.ConclusionsTogether, this study describes a novel proproliferative/prosurvival role of MST1/2 in PAH pulmonary vasculature, provides a novel mechanistic link from MST1/2 via BUB3 and forkhead homeobox type O to the abnormal proliferation and survival of pulmonary arterial vascular smooth muscle cells and pulmonary arterial adventitial fibroblasts, remodeling and pulmonary hypertension, and suggests new target pathways for therapeutic intervention.

Abstract Background The pediatric pulmonary multisystem Langerhans cell histiocytosis (PPM LCH) is associated with either low risk or high risk organ(s). The nodulo-cystic lung lesions although pathognomonic, yet are very variable in severity and remain a source of controversy in certifying pulmonary LCH diagnosis. The study aimed to examine the prognostic value of clinical respiratory manifestations and radiological lung lesions severity. This is through associating a CT chest triad of bilateral, extensive and diffuse lesions. It is a retrospective study of 350 LCH patients who received systemic treatment at Children’s Cancer Hospital Egypt during the period from 2007 to 2020. Results Sixty-seven patients (67/350–19.1%) had PPM LCH at presentation. Severe lung lesions were present in 24 of them. The median follow-up period was 61 months (IQR: 3.4–8.3). The 5-year overall survival (OS) and event free survival (EFS) was 89% and 56.6% respectively. The EFS, for severe radiological lesions triad was 38% ± 20.7 versus 66% ± 16.2 for non-severe lesions triad p 0.002, while for presence of chest X-ray changes 27% ± 22.344 versus absence of chest X ray changes 66% ± 14.7 p 0.001, for clinical respiratory manifestations 13% ± 13.9 versus none 62% ± 22.9 p

PURPOSETo determine if mechanical thrombectomy (MT) for submassive pulmonary embolism (PE) positively impacts length of hospital stay (LOS), intensive care unit stay (ICU LOS), readmission rate, and in-hospital mortality compared with conservative therapy.METHODSThis was a retrospective review of all patients with submassive PE who either underwent MT or conservative therapy (systemic anticoagulation and/or inferior vena cava filter) between November 2019 and October 2021. Pediatric patients (age