Acute Exacerbation of Idiopathic Pulmonary Fibrosis With Concurrent Cardiac Amyloidosis: A Technetium Pyrophosphate Study.

Amyloidosis presents a diagnostic challenge, particularly when concomitant with severe conditions like acute exacerbations of idiopathic pulmonary fibrosis (IPF). In this report, we detail the case of a 73-year-old patient with acute exacerbation of IPF and simultaneous emergence of cardiac amyloidosis. The patient's clinical journey began with persistent exertional dyspnea, progressing to hypoxemia on admission. Chest CT scans showed extensive ground-glass opacities, consolidations, and pre-existing honeycombing-like cysts and reticular shadows, accompanied by a right-sided pleural effusion. The therapeutic strategy for acute exacerbation of IPF encompassed methylprednisolone pulse therapy, tacrolimus, and nintedanib, augmented with intravenous immunoglobulin and recombinant thrombomodulin. Concurrently, heart failure with preserved ejection fraction was managed with a pharmacological trio: empagliflozin, diuretics, and eplerenone. A hypertrophied heart and low limb voltage prompted an investigation for cardiac amyloidosis, which 99mTechnetium pyrophosphate (99mTc-PYP) scintigraphy confirmed, yielding a probable diagnosis. Following steroid tapering, the patient was discharged home. This case prompted an investigation into the potential role of amyloidosis in pulmonary pathology. Our retrospective review of 10 patients, including four with cardiac amyloidosis, who underwent 99mTc-PYP scintigraphy, revealed a nonsignificant yet notable trend of increased pulmonary accumulation in cardiac amyloidosis cases (median (interquartile range): 5.4×104 (5.3-13.1×104) vs. 3.6×104 (2.4-5.1×104), p=0.0667). Notably, the pulmonary counts in this patient exceeded the negative cohort's mean values, hinting at a possible contribution of amyloid deposition to pulmonary pathology. This study, pioneering in evaluating lung field accumulation of 99mTc-PYP in cardiac amyloidosis, may provide novel insights into the influence of amyloidosis on pulmonary conditions.

Amikacin Liposome Inhalation Suspension in the Real-World Management of Refractory Mycobacterium avium Complex Pulmonary Disease.

The increasing prevalence of Mycobacterium avium complex (MAC) pulmonary disease poses a significant therapeutic challenge, particularly due to the limited efficacy and systemic toxicity associated with conventional guideline-based therapy. Amikacin liposome inhalation suspension (ALIS) has been developed, yet its real-world application remains underreported. This retrospective analysis, conducted from March 2021 to February 2024, examined ALIS's clinical use in patients aged 20 years or older with refractory MAC pulmonary disease at our institution. The primary objective of this study is to describe the patient characteristics and clinical trajectories associated with the initiation of ALIS therapy in real-world settings for individuals diagnosed with MAC pulmonary disease. Of 11 patients initiated on ALIS, one was excluded due to financial constraints impacting continuation. The analysis proceeded with the remaining 10 subjects. The mean age of participants was 70.2 years, with a predominance of female patients (n = 7, 70%) and a higher incidence of M. avium infections (n = 6, 60%). Forty percent of the cohort (n = 4) had a history of ethambutol-induced optic neuritis leading to the cessation of the drug. The average interval from the initiation of guideline-based therapy to the start of ALIS was 8.5 ± 6.9 years (mean ± standard deviation). The majority (80%) presented with positive Gaffky scores at ALIS initiation, and a significant proportion exhibited resistance to clarithromycin and ethambutol. Comorbid conditions, including diabetes and previous cancer, were noted. The study also observed elevated anti-MAC antibody levels. Treatment duration varied, with fatigue leading to discontinuation in two cases. Treatment-emergent adverse events were documented in individual patients, each presenting with grade 1 severity: hemoptysis (n = 1, 10%), elevated creatinine levels (n = 1, 10%), and dysphonia (n = 2, 20%) were observed, respectively. Correlation analysis revealed a significant inverse relationship between body mass index (BMI) and ALIS discontinuation due to fatigue, and a positive correlation between Gaffky scores and C-reactive protein (CRP) levels. These results underscore the potential benefits and limitations of ALIS, suggesting that timely intervention and comprehensive healthcare support are crucial for optimal outcomes in the treatment of advanced MAC pulmonary disease.

Effect of aspirin on cardiovascular events in patients undergoing hemodialysis with hyperphosphatemia: A post hoc analysis of the LANDMARK trial.

INTRODUCTION: The clinical benefits of aspirin in patients undergoing hemodialysis remain unclear. METHODS: The secondary analysis of the LANDMARK trial investigated whether aspirin use was associated with cardiovascular events (CVEs) and all-cause mortality was performed. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity score matching. RESULTS: The risk of CVEs was comparable between participants with aspirin use at baseline and those without at baseline, between participants with aspirin use during the study period and those without during the study period, and between participants with new aspirin prescription and those without aspirin use during the study period. CONCLUSION: Aspirin use was not significantly associated with a lower risk of CVEs in participants undergoing hemodialysis patients at risk of vascular calcification.

Relapsing eosinophilic pneumonia in a patient with recurrent breast cancer receiving abemaciclib plus endocrine therapy.

This report presents the case of a 42-year-old Japanese woman with recurrent hormone receptor-positive breast cancer who developed eosinophilic pneumonia (EP) during treatment with abemaciclib combined with endocrine therapy. Seven years after a radical surgery and definite diagnosis of Stage I breast cancer, her cancer recurred with metastases to multiple organs. Initially treated with abemaciclib plus letrozole and goserelin for 3 months, she developed EP, which improved after the discontinuation of anti-cancer treatment and the administration of prednisolone. However, EP occurred again upon the reintroduction of endocrine therapy (i.e., letrozole and goserelin). It improved gradually with the suspension of endocrine therapy and the re-administration of prednisolone. This case underscores the need for further research into the prevention and management of EP in patients receiving abemaciclib with endocrine therapy for advanced breast cancer.

A Case of Pneumocystis Pneumonia Developed During Rheumatoid Arthritis Treatment With Methotrexate and Golimumab.

Here, we report a case of an 87-year-old female patient with rheumatoid arthritis (RA) treated with methotrexate (MTX) and golimumab who developed severe pneumocystis pneumonia (PCP), also known as Pneumocystis jirovecii pneumonia. The patient presented with chief complaints of dyspnea on exertion, dry cough, and fatigue. A high-resolution chest CT scan revealed diffuse, unevenly distributed ground-glass opacities throughout both lungs. The patient was clinically diagnosed with PCP based on the clinical settings, imaging, and a high level of serum ß-D-glucan. While the patient required high-flow oxygen therapy, low-dose trimethoprim/sulfamethoxazole and corticosteroid therapy improved her condition, and the patient was discharged on day 25. Although to our knowledge no case report has been published regarding PCP in patients with RA treated with golimumab, this case emphasizes the importance of attention to opportunistic infections in elderly patients receiving immunosuppressive therapy. MTX use alongside tumor necrosis factor inhibitors like golimumab may increase the risk of serious infections such as PCP. The case underscores the necessity of prophylactic measures and early intervention for PCP, highlighting the delicate balance between immunosuppression benefits and infection risks in RA management.

Effective treatment of inhaled corticosteroid and bronchodilator for "lymphocytic interstitial pneumonia" in primary Sjögren's syndrome.

We present a case of an 86-year-old woman who visited our hospital with a one-year history of exertional dyspnea (modified medical research council dyspnea scale; mMRC grade 2). Despite the absence of any smoking or dust exposure history, multiple cystic lesions were apparent in both lungs on her CT scan. We suspected Sjögren's syndrome-associated lymphocytic interstitial pneumonia (LIP) due to her additional symptoms of dry mouth and eyes. Her respiratory function test showed a restrictive disorder with a forced vital capacity (FVC) of 1.23 L (70.3 % predicted), forced expiratory volume in 1 s (FEV1) of 0.88 L, and FEV1/FVC of 71.5 %. The flow-volume curve showed a downward convex, suggesting peripheral airway obstruction. We initiated a daily inhalation treatment regimen comprising vilanterol 25 µg and fluticasone furoate 200 µg. One month later, at the follow-up visit, the clinical diagnosis of Sjögren's syndrome with LIP was made by positive SS-A and SS-B antibodies in the initial blood work, a Saxon test that confirmed decreased salivary secretion, and a confirmed diagnosis of dry eyes by her ophthalmologist. We noted improvement in FVC of 1.45 L (+17.8 %) and FEV1 to 0.99 L (+12.5 %) in the subsequent respiratory function test, along with alleviation of her symptoms. The present case represents the first report of LIP treated exclusively with inhaled corticosteroids and bronchodilators, highlighting a potential therapeutic approach, particularly for elderly patients vulnerable to immunosuppressive therapies.

Phosphate and Coronary Artery Disease in Patients with Chronic Kidney Disease.

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Both traditional and CKD-related factors are associated with CVD in CKD patients. Traditional factors that play an important role in the atherosclerotic process directly contribute to a higher risk of coronary artery disease in patients with early-stage CKD. Among CKD-related factors, CKD-mineral and bone disorder plays a critical role in the pathomechanism of nonatherosclerotic diseases, which increases the risk of cardiovascular morbidity and mortality in patients with advanced CKD. Higher serum phosphate levels were significantly associated with cardiovascular events and all-cause mortality in patients with or without CKD. An increased phosphate load, directly and indirectly, promotes arterial medial calcification and left ventricular hypertrophy, both of which predispose patients to coronary artery disease. Calciprotein particles that form in a hyperphosphatemic state promote the transformation of vascular smooth muscle cells (VSMCs) into osteoblastic cells, thereby providing a scaffold for medial calcification in the artery. Increases in fibroblast growth factor-23 and disturbed vitamin D metabolism induced by an excessive phosphate load play a significant role in the development of cardiomyocyte hypertrophy and cardiac fibrosis. Recently, hyperphosphatemia was reported to promote de novo cholesterol synthesis in VSMCs and macrophages, which is likely to contribute to statin resistance in patients with end-stage kidney disease. This review outlines the association between increased phosphate load and coronary artery disease in patients with CKD.

Effect of renin-angiotensin system inhibitors on cardiovascular events in hemodialysis patients with hyperphosphatemia: A post hoc analysis of the LANDMARK trial.

INTRODUCTION: The clinical benefits of renin-angiotensin system inhibitors (RASi) in patients undergoing hemodialysis remain obscure. METHODS: This is a post hoc cohort analysis of the LANDMARK trial investigate whether RASi use was associated with cardiovascular events (CVEs) and all-cause mortality. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity-score matching. RESULTS: The risk of CVEs was similar between participants with RASi use at baseline and those without RASi use at baseline and between participants with RASi use during the study period and those without RASi use during the study period. No clinical benefits of RASi use on all-cause mortality were observed. Serum phosphate levels were significantly associated with the effect of RASi on CVEs. CONCLUSIONS: RASi use was not significantly associated with a lower risk of CVEs or all-cause mortality in hemodialysis patients at risk of vascular calcification.

Insights from the trends of omalizumab and mepolizumab utilization in patients with asthma: A population-based cohort study using the National Database in Japan.

BACKGROUND: Biologics are increasingly being used in patients with severe uncontrolled asthma. However, the trends in their use for treating severe asthma in Japan remain unclear. METHODS: The number of patients with asthma prescribed omalizumab or mepolizumab between April 2017 and March 2018 was estimated according to sex, age, and geographical region using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: Overall, 5,014, 3,449 and 7,977 patients were prescribed omalizumab, mepolizumab, or either combination, respectively. The total number of patients prescribed biologics displayed a bimodal distribution with peaks in their early teens and seventies. Biologics were most commonly used by male and female patients in their seventies. Prescription was 1.24 times higher in males than in females up to the teenage years, whereas it was 1.95 times higher in females than in males from their twenties onwards. Omalizumab was prescribed 1.45 times more frequently than mepolizumab, especially in pediatric patients, and was prescribed 1.96 times more often to female patients than to male patients. Regional differences were observed in the proportion of patients prescribed biologics. Correlation analysis suggested a weak relationship (r = 0.3226, p = 0.0270) between the proportion of patients prescribed biologics and board-certified allergists according to the geographic region. CONCLUSIONS: In Japan, biologics are prescribed more often to older patients with severe asthma compared to those in other countries. Thus, eliminating the regional disparities in asthma treatment by specialists is necessary to provide appropriate medical care to patients with severe asthma.

A Teaching Case: Persistent COVID-19 Pneumonia Resembling Cryptogenic Organizing Pneumonia in a Patient With Remitted Lymphoma.

We report a case of a female patient in her 50s, previously diagnosed with follicular lymphoma (now in complete remission), who was admitted to our hospital due to antibiotic-resistant pneumonia lasting a month. The patient had contracted coronavirus disease 2019 (COVID-19) pneumonia a year earlier and exhibited persistent hypogammaglobulinemia. Chest CT scans revealed wondering ground-glass opacities and consolidations initially suggestive of cryptogenic organizing pneumonia (COP). Despite repeatedly negative nasopharyngeal SARS-CoV-2 tests, the virus was detected in the bronchoalveolar lavage fluid (BALF) using the BioFire FilmArray Respiratory Panel 2.1. She was subsequently diagnosed with COVID-19 pneumonia and responded well to treatment with remdesivir (RDV) and intravenous immunoglobulin. The SARS-CoV-2 variant in the BALF was suspected as the Omicron variant (XBB.1.16), prevalent in the area at the admission, indicating a re-infection rather than a recurrence. This case underscores the protracted nature of COVID-19 pneumonia in immunocompromised patients and the risks of false negatives in nasopharyngeal SARS-CoV-2 tests. Direct SARS-CoV-2 measurement from BALF can be crucial in such cases. A COP diagnosis based solely on imaging and administering corticosteroids without antiviral treatment might exacerbate the situation by reactivating SARS-CoV-2. Given the current pandemic, clinicians should be aware of the potential for persistent or recurrent COVID-19, particularly in immunocompromised patients.

Acute Pneumonitis Associated With the Inhalation of Pyrethroid-Based Domestic Insecticides.

We report a 72-year-old female who presented to our hospital with a worsening cough and dyspnea that had emerged a week earlier following the accidental inhalation of a significant quantity of spray-type imiprothrin (a synthetic pyrethroid)-based insecticide in her bathroom. She exhibited acute respiratory failure necessitating 4 L/minute of nasal oxygen at maximum. Chest CT images showed diffuse centrilobular ground-glass opacities with mosaic attenuation and consolidation areas in the lower lobes of both lungs. The patient was diagnosed with acute pneumonitis due to insecticide inhalation, and her symptoms improved following methylprednisolone pulse and alpha-tocopherol therapy. Generally, the accidental inhalation of aerosolized pyrethroids does not induce significant respiratory symptoms, and case reports on pulmonary toxicity related to pyrethroid inhalation are scarce. This case report underscores the need to include inhaled pyrethroid insecticides in the differential diagnosis of patients with acute pneumonitis and suggests that methylprednisolone and alpha-tocopherol therapy can be beneficial for treating this condition.

An Unusual Case of Bilateral Lower Extremity Edema in the Elderly: Immunoglobulin A (IgA) Vasculitis.

We report a case of a 74-year-old male who exhibited bilateral lower extremity edema over three days. Examination revealed no signs of heart, renal, or hepatic failure, and hypothyroidism was also ruled out. An outpatient regimen of 40 mg furosemide was initiated. At a 12-day follow-up, although the edema had improved, the patient had developed pain in both lower limbs, especially ankles, accompanied by numerous petechiae and erythemas, some of which had formed papules. Skin biopsy of the rash displayed leukocytoclastic vasculitis with immunoglobulin A (IgA) deposition within the vascular walls, leading to a diagnosis of IgA vasculitis. Given the rarity of IgA vasculitis in elderly patients and the broad spectrum of potential diagnoses related to bilateral lower extremity edema in this population, IgA vasculitis can be easily overlooked. While this case did not present with glomerulonephritis, regular renal function monitoring is recommended due to the prognostic implications of renal involvement in adult-onset IgA vasculitis.

A Case of Allergic Bronchopulmonary Aspergillosis With Failure of Benralizumab and Response to Dupilumab.

We report a case of a 68-year-old woman who was being treated for bronchial asthma and developed allergic bronchopulmonary aspergillosis (ABPA) that was unresponsive to benralizumab therapy but went into remission with dupilumab therapy. The patient presented with an exacerbation of dry cough and was diagnosed with ABPA based on new diagnostic criteria. Despite the attempted therapeutic intervention, the patient declined to use systemic corticosteroids due to concerns about potential side effects. Subsequently, itraconazole and benralizumab were administered, with temporary relief before relapse. Given the patient's refusal to continue itraconazole and benralizumab, dupilumab was administered as an alternative therapy, which resulted in significant improvement of both symptoms and imaging. Although the use of biological agents for ABPA lacks clear evidence, our results suggest that dupilumab may provide an effective therapeutic strategy.

The Induction of Parathyroid Cell Differentiation from Human Induced Pluripotent Stem Cells Promoted Via TGF-α/EGFR Signaling.

The parathyroid gland plays an essential role in mineral and bone metabolism. Cultivation of physiological human parathyroid cells has yet to be established and the method by which parathyroid cells differentiate from pluripotent stem cells remains uncertain. Therefore, it has been hard to clarify the mechanisms underlying the onset of parathyroid disorders, such as hyperparathyroidism. In this study, we developed a new method of parathyroid cell differentiation from human induced pluripotent stem (iPS) cells. Parathyroid cell differentiation occurred in accordance with embryologic development. Differentiated cells, which expressed the parathyroid hormone, adopted unique cell aggregation similar to the parathyroid gland. In addition, these differentiated cells were identified as calcium-sensing receptor (CaSR)/epithelial cell adhesion molecule (EpCAM) double-positive cells. Interestingly, stimulation with transforming growth factor-α (TGF-α), which is considered a causative molecule of parathyroid hyperplasia, increased the CaSR/EpCAM double-positive cells, but this effect was suppressed by erlotinib, which is an epidermal growth factor receptor (EGFR) inhibitor. These results suggest that TGF-α/EGFR signaling promotes parathyroid cell differentiation from iPS cells in a similar manner to parathyroid hyperplasia.

Effects of evocalcet on parathyroid calcium-sensing receptor and vitamin D receptor expression in uremic rats.

Little is known about the effect of the recently developed calcimimetic evocalcet (Evo) on parathyroid calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) expression. We examined the effects of Evo and cinacalcet (Cina) on CaSR and VDR expression in 5/6 nephrectomized Sprague-Dawley rats fed a high-phosphorus diet for 4 weeks to develop secondary hyperparathyroidism (SHPT). These uremic rats were divided into 4 groups-baseline control (Nx4W) and groups with additional treatment with either the Vehicle, Evo, or Cina for 2 weeks; normal rats were used as normal controls (NC). Blood parameters and parathyroid tissue were analyzed. CaSR and VDR expression levels were determined using immunohistochemistry. The degree of kidney injury and hyperphosphatemia was similar in the uremic groups (Nx4W, Vehicle, Cina, and Evo). Serum parathyroid hormone levels were significantly higher in the Nx4W and Vehicle groups than in the NC group. This increase was significantly suppressed in the Cina and Evo groups compared with that in the Vehicle group. Serum calcium levels were significantly and equally lower in the Cina and Evo groups relative to those in the Vehicle group. CaSR expression was significantly lower in the Nx4W and Vehicle groups than in the NC group. This downregulation was of an equally lesser magnitude in the Cina and Evo groups. A similar trend was observed for VDR expression. These results indicate that Evo and Cina treatment can increase parathyroid CaSR and VDR expression in uremic rats with SHPT, which could provide better control of mineral and bone disorder markers.

Impact of increased plasma levels of calreticulin on prognosis of patients with advanced lung cancer undergoing combination treatment of chemotherapy and immune checkpoint inhibitors.

BACKGROUND: Damage-associated molecular pattern (DAMP)-related immunogenic cell death triggers secondary adaptive immune responses. The relationship between DAMP levels and prognosis in patients with non-small cell lung cancer (NSCLC) who undergo a combination therapy of immune checkpoint inhibitors (ICI) and chemotherapy remains unclear. METHODS: Serial plasma samples were prospectively collected from 45 patients treated with ICI combination therapy for advanced NSCLC. Plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), annexin A1, and heat shock protein 70 were measured. Associations between increases in plasma DAMP levels and the efficacy of the ICI combination therapy were evaluated. RESULTS: The maximum fold changes in plasma levels differed across individuals but demonstrated a marked increase, especially for CRT (mean ± SEM, 11.61 ± 46.15). Increased plasma DAMP levels were not clearly associated with clinical responses. There was a significant correlation between the maximum fold change in CRT levels and progression-free survival (PFS; r = 0.49, P < 0.001). Median PFS and overall survival (OS) rates were higher in patients with a ≥ 2-fold increase in plasma CRT levels than in those with a < 2-fold increase (PFS, 14.9 versus 6.0 months, hazard ratio (HR), 0.58; P = 0.17; OS, not reached versus 21.6 months, HR, 0.31, P = 0.02). CONCLUSIONS: Plasma CRT level monitoring has the potential to predict the efficacy of ICI combination therapy and shed light on the mechanisms underlying DAMP-related immunogenic cell death.

Tezepelumab treatment for allergic bronchopulmonary aspergillosis.

An 82-year-old man had been diagnosed with asthma. He experienced repeated exacerbations requiring treatment with a systemic corticosteroid despite being treated with medications including high-dose fluticasone furoate/umeclidinium/vilanterol, montelukast sodium, and theophylline; treatment with mepolizumab was then initiated. The patient had been free from exacerbations for 15 months; however, he suffered from post-obstructive pneumonia and atelectasis secondary to mucoid impaction in the right middle lobe of the lung, accompanied by a productive cough, wheezing, dyspnea, and right chest pain. In addition to the development of mucus plugs, the levels of serum IgE specific to Aspergillus spp. became positive; a definite diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was established. The patient underwent treatment with tezepelumab. Over 3 months, the mucus plugs and pulmonary opacities diminished gradually in parallel with the improvement in the control of asthmatic symptoms. Tezepelumab might provide a novel steroid-sparing strategy for the management of ABPA, although further studies are required.

Fibroblast Growth Factor 23 Exacerbates Cardiac Fibrosis in Deoxycorticosterone Acetate-Salt Mice With Hypertension.

Fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease; however, the mechanisms underlying the effect of FGF23 on cardiac function remain to be investigated. Herein, we studied the effect of continuous intravenous (CIV) FGF23 loading in a deoxycorticosterone acetate (DOCA)-salt mouse model with mild chronic kidney disease and hypertension as well as heart failure with a preserved ejection fraction. Wild-type male mice were randomly allocated to 4 groups: normal control, vehicle-treated DOCA-salt mice, FGF23-treated DOCA-salt mice, and FGF23- and calcitriol-treated DOCA-salt mice. The DOCA-salt mice received the agents via the CIV route for 10 days using an infusion minipump. DOCA-salt mice that received FGF23 showed a marked increase in the serum FGF23 level, and echocardiography in these mice revealed heart failure with a preserved ejection fraction. These mice also showed exacerbation of myocardial fibrosis, concomitant with an inverse and significant correlation with Cyp27b1 expression. Calcitriol treatment attenuated FGF23-induced cardiac fibrosis and improved diastolic function via inhibition of transforming growth factor-ß signaling. This effect was independent of the systemic and local levels of FGF23. These results suggest that CIV FGF23 loading exacerbates cardiac fibrosis and that locally abnormal vitamin D metabolism is involved in this mechanism. Calcitriol attenuates this exacerbation by mediating transforming growth factor-ß signaling independently of the FGF23 levels.