SFTPB in serum extracellular vesicles as a biomarker of progressive pulmonary fibrosis.

Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways. Among them, pulmonary surfactant-associated protein B (SFTPB) in serum EVs could predict ILD progression better than the known biomarkers, serum KL-6 and SP-D, and it was identified as an independent prognostic factor from ILD-gender-age-physiology index. Subsequently, the utility of SFTPB for predicting ILD progression was evaluated further in 2 cohorts using serum EVs and serum, respectively, suggesting that SFTPB in serum EVs but not in serum was helpful. Among SFTPB forms, pro-SFTPB levels were increased in both serum EVs and lungs of patients with PPF compared with those of the control. Consistently, in a mouse model, the levels of pro-SFTPB, primarily originating from alveolar epithelial type 2 cells, were increased similarly in serum EVs and lungs, reflecting pro-fibrotic changes in the lungs, as supported by single-cell RNA sequencing. SFTPB, especially its pro-form, in serum EVs could serve as a biomarker for predicting ILD progression.

Cryptogenic organizing pneumonia: clinical outcomes of 60 consecutive cases.

Background: Cryptogenic organizing pneumonia (COP) improves rapidly following corticosteroid treatment; however, relapse is common. Therefore, this retrospective observational study aimed to clarify the clinical outcomes of COP and identify the predictive factors for relapse. Methods: The laboratory findings, pulmonary function test results, computed tomography (CT) findings, and clinical outcomes of 60 consecutive COP patients treated at our institution between 2007 and 2013 were retrospectively reviewed. The clinical characteristics of COP patients who did and did not show improvement were compared to identify the predictive factors for relapse in patients showing improvement. Results: Forty-one patients showed improvement without relapsing (Group 1), whereas thirteen relapsed after showing improvement (Group 2). Six patients did not show any improvement (Group 3). The serum Krebs von den Lungen-6 (KL-6) levels in Group 3 were greater than those in Groups 1 and 2 (P=0.004). The incidence of traction bronchiectasis and reticular opacities in Group 3 was higher than that in Groups 1 and 2 (P=0.048 and P=0.006, respectively). The cut-off levels of C-reactive protein (CRP), blood neutrophil fraction (%neutrophils) and lymphocyte fraction (%lymphocytes) for predicting relapse were 6.84 mg/dL, 68.7% and 14.1% in Groups 1 and 2, respectively. The log-rank test revealed that high serum CRP levels (P<0.001), high %neutrophils (P=0.003) and low %lymphocytes (P=0.006) showed significant correlations with a shorter time to the first relapse episode. Conclusions: Chest CT findings depicting pulmonary fibrosis and high serum KL-6 levels were correlated with the non-improvement of COP. Blood test results indicating inflammatory reactions were correlated with relapse in patients with COP showing improvement.

Pulmonary Hypertension With Interstitial Pneumonia: Initial Treatment Effectiveness and Severity in a Japan Registry.

Background: Recent guidelines discourage the use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with pulmonary hypertension (PH) associated with respiratory diseases. Therefore, stratifications of the effectiveness of PAH-targeted therapies are important for this group. Objectives: The authors aimed to identify phenotypes that might benefit from initial PAH-targeted therapies in patients with PH associated with interstitial pneumonia and combined pulmonary fibrosis and emphysema. Methods: We categorized 270 patients with precapillary PH (192 interstitial pneumonia, 78 combined pulmonary fibrosis and emphysema) into severe and mild PH using a pulmonary vascular resistance of 5 WU. We investigated the prognostic factors and compared the prognoses of initial (within 2 months after diagnosis) and noninitial treatment groups, as well as responders (improvements in World Health Organization functional class, pulmonary vascular resistance, and 6-minute walk distance) and nonresponders. Results: Among 239 treatment-naive patients, 46.0% had severe PH, 51.8% had mild ventilatory impairment (VI), and 40.6% received initial treatment. In the severe PH with mild VI subgroup, the initial treatment group had a favorable prognosis compared with the noninitial treatment group. The response rate in this group was significantly higher than the others (48.2% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). In multivariate analysis, initial treatment was a better prognostic factor for severe PH but not for mild PH. Within the severe PH subgroup, responders had a favorable prognosis. Conclusions: This study demonstrated an increased number of responders to initial PAH-targeted therapy, with a favorable prognosis in severe PH cases with mild VI. A survival benefit was not observed in mild PH cases. (Multi-institutional Prospective Registry in Pulmonary Hypertension associated with Respiratory Disease; UMIN000011541).

Craniofacial Fracture with Superior Orbital Fissure Syndrome Resulting in Pupil-sparing Oculomotor Nerve Palsy.

Superior orbital fissure syndrome (SOFS) is a rare complication of craniofacial fracture, caused by damage to cranial nerves Ⅲ, Ⅳ, Ⅴ, and Ⅵ, which typically is associated with ophthalmoplegia, blepharoptosis, pupil dilatation and fixation, and upper eyelid and forehead hypesthesia. However, we here describe a very unusual case of craniofacial fracture with SOFS in the absence of pupil symptoms, involving a patient who was injured when he fell while riding his bicycle. Upon medical examination, we observed mild blepharoptosis and ophthalmoplegia of the right eye without pupillary symptoms. Computed tomography (CT) revealed basal skull and zygomatic fractures. After the patient had been treated conservatively for his skull base fracture, facial bone reduction was performed at our hospital. Because ophthalmoplegia and blepharoptosis remained after the surgery, we checked the preoperative CT images again and discovered stenosis of the superior orbital fissure. Postoperative CT revealed a widening of the superior orbital fissure after the facial bone reduction, and therefore, the patient was given steroid treatment without additional surgery. At 6 months postoperatively, the cranial nerves had completely recovered. Our finding emphasizes that, in contrast to common theory, trauma-induced SOFS can result in pupil-sparing oculomotor nerve palsy.

The effect of nintedanib on health-related quality of life in Japanese patients with progressive fibrosing interstitial lung diseases: A subset analysis of the INBUILD trial.

BACKGROUND: In previous Japanese subgroup/subset analyses of the global INBUILD trial, nintedanib reduced the annual rate of forced vital capacity (FVC) decline and the risk of disease progression in patients with progressive fibrosing interstitial lung diseases (PF-ILDs). This exploratory subset analysis assessed the effect of nintedanib on symptoms and impacts of pulmonary fibrosis in Japanese patients with PF-ILDs, including those with usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT). METHODS: This analysis included Japanese patients who received at least one dose of study treatment in the randomized, double-blind, placebo-controlled INBUILD trial. The Living with Pulmonary Fibrosis (L-PF) questionnaire was used to assess pulmonary fibrosis symptoms and impacts (higher scores indicated greater impairment) at baseline and weeks 12-52. RESULTS: In total, 108 Japanese patients (nintedanib: n = 52; placebo: n = 56) were included; 84 patients had UIP-like fibrotic pattern on HRCT. In the total Japanese subgroup and in those with UIP-like fibrotic pattern, numerically greater increases in L-PF total, symptoms total, symptoms fatigue domain, and impacts scores were observed in the placebo group than in the nintedanib group at all timepoints, starting from week 12. A numerically greater increase in the symptoms dyspnea domain score was observed with placebo versus nintedanib starting from week 36. Throughout the study, the symptoms cough domain score increased in the placebo group but decreased in the nintedanib group. CONCLUSIONS: Our findings demonstrate that nintedanib has the potential to reduce the worsening of symptoms and impacts of pulmonary fibrosis in Japanese patients with PF-ILDs.

Effect of mTOR inhibitors on the mortality and safety of patients with lymphangioleiomyomatosis on the lung transplantation waitlist: A retrospective cohort study.

BACKGROUND: Although lung transplantation (LTx) is the last resort for patients with end-stage lymphangioleiomyomatosis (LAM), the high waitlist mortality is a source of concern in Japan. Discontinuation of mechanistic target of rapamycin (mTOR) inhibitors prior to LTx is recommended due to the incidence of severe adverse events. Therefore, we hypothesized that mTOR inhibitors may affect the mortality of patients with LAM on the LTx waitlist. METHODS: We retrospectively compared the characteristics of consecutive patients with LAM on the LTx waitlist who were and were not receiving mTOR inhibitors. RESULTS: Twenty-nine consecutive patients with LAM who listed our center between January 2004 and December 2021 were selected from the database and enrolled in the present study. Seventeen patients (58.6%) were receiving a mTOR inhibitor, sirolimus (treatment group). During a median listing period of 1277 days, 12 patients (41.4%) were hospitalized, six patients (20.7%) died from disease before LTx, and 15 patients underwent LTx. Among the deceased patients, four patients (66.6%) had pneumothoraces. The waitlist mortality in the treatment group was significantly lower than that in the non-treatment group (p = 0.03). Among the six patients who discontinued sirolimus in the treatment group, four patients (66.6%) were hospitalized with respiratory complications after the discontinuation of sirolimus. No mTOR inhibitor-related complications arose in the treatment group undergoing LTx (n = 7), including those on a reduced sirolimus dose. CONCLUSIONS: Administration of an mTOR inhibitor until LTx may decrease waitlist mortality. Due to life-threatening events after discontinuing sirolimus pre-LTx, a reduced dose until LTx is permissible.

Towards the adoption of quantitative computed tomography in the management of interstitial lung disease.

The shortcomings of qualitative visual assessment have led to the development of computer-based tools to characterise and quantify disease on high-resolution computed tomography (HRCT) in patients with interstitial lung diseases (ILDs). Quantitative CT (QCT) software enables quantification of patterns on HRCT with results that are objective, reproducible, sensitive to change and predictive of disease progression. Applications developed to provide a diagnosis or pattern classification are mainly based on artificial intelligence. Deep learning, which identifies patterns in high-dimensional data and maps them to segmentations or outcomes, can be used to identify the imaging patterns that most accurately predict disease progression. Optimisation of QCT software will require the implementation of protocol standards to generate data of sufficient quality for use in computerised applications and the identification of diagnostic, imaging and physiological features that are robustly associated with mortality for use as anchors in the development of algorithms. Consortia such as the Open Source Imaging Consortium have a key role to play in the collation of imaging and clinical data that can be used to identify digital imaging biomarkers that inform diagnosis, prognosis and response to therapy.

Zinpentraxin Alfa for Idiopathic Pulmonary Fibrosis: The Randomized Phase III STARSCAPE Trial.

Rationale: A phase II trial reported clinical benefit over 28 weeks in patients with idiopathic pulmonary fibrosis (IPF) who received zinpentraxin alfa. Objectives: To investigate the efficacy and safety of zinpentraxin alfa in patients with IPF in a phase III trial. Methods: This 52-week phase III, double-blind, placebo-controlled, pivotal trial was conducted at 275 sites in 29 countries. Patients with IPF were randomized 1:1 to intravenous placebo or zinpentraxin alfa 10 mg/kg every 4 weeks. The primary endpoint was absolute change from baseline to Week 52 in FVC. Secondary endpoints included absolute change from baseline to Week 52 in percent predicted FVC and 6-minute walk distance. Safety was monitored via adverse events. Post hoc analysis of the phase II and phase III data explored changes in FVC and their impact on the efficacy results. Measurements and Main Results: Of 664 randomized patients, 333 were assigned to placebo and 331 to zinpentraxin alfa. Four of the 664 randomized patients were never administered study drug. The trial was terminated early after a prespecified futility analysis that demonstrated no treatment benefit of zinpentraxin alfa over placebo. In the final analysis, absolute change from baseline to Week 52 in FVC was similar between placebo and zinpentraxin alfa (-214.89 ml and -235.72 ml; P = 0.5420); there were no apparent treatment effects on secondary endpoints. Overall, 72.3% and 74.6% of patients receiving placebo and zinpentraxin alfa, respectively, experienced one or more adverse events. Post hoc analysis revealed that extreme FVC decline in two placebo-treated patients resulted in the clinical benefit of zinpentraxin alfa reported by phase II. Conclusions: Zinpentraxin alfa treatment did not benefit patients with IPF over placebo. Learnings from this program may help improve decision making around trials in IPF. Clinical trial registered with www.clinicaltrials.gov (NCT04552899).

What are the Factors That Induce Paradoxical Hypertrichosis After Laser Hair Removal?

BACKGROUND: Laser hair removal (LHR) is one of the most requested cosmetic procedures worldwide. A rare side effect is the appearance of excess hair around previously treated areas, known as paradoxical hypertrichosis. OBJECTIVES: The aim of this study was to retrospectively identify the cause of this side effect. METHODS: This study included all patients who underwent LHR at our center between November 2018 and November 2020. Alexandrite laser hair removal (HR) or diode laser super hair removal (SHR) was performed in 70% and 30% of cases, respectively. Clinical features and daily habits of patients with and without postlaser hypertrichosis were compared. RESULTS: Of the 7381 patients who received LHR, 25 patients (0.34%) demonstrated an increase in hair growth compared to baseline. Of these 25 patients, 24 had been treated with alexandrite laser HR (P < .01). The most common site was the upper arm, followed by the periareolar area. Daily sun protection was associated with a significantly lower incidence of hypertrichosis (P < .05), as was confirmed and shown to be independent of Fitzpatrick skin type by binary logistic regression analysis (odds ratio = 0.41, P < .05). CONCLUSIONS: In our clinic, we observed paradoxical hypertrichosis after laser hair removal in a small minority of cases, as described by others. We did not observe differences in incidence related to skin type, but daily sun protection and LHR with diode laser SHR were associated with significant reductions in incidence rates. In addition to previously reported common sites, we also identified the periareolar area as a high-risk region.

Japanese clinical practice guide 2022 for hypersensitivity pneumonitis.

Considering recently published two guidelines for the diagnosis of hypersensitivity pneumonitis (HP), the Japanese Respiratory Society (JRS) has now published its own Japanese clinical practice guide for HP. Major types of HP in Japan include summer-type, home-related, bird-related, farmer's lung, painter's lung, humidifier lung, and mushroom grower's lung. Identifying causative antigens is critical for increasing diagnostic confidence, as well as improving prognosis through appropriate antigen avoidance. This guide proposes a comprehensive antigen questionnaire including the outbreak sources reported in Japan. Drawing on the 2021 CHEST guideline, this guide highlights the antigen identification confidence level and adaptations for environmental surveys. The detection of specific antibodies against causative antigens is an important diagnostic predictor of HP. In Japan, the assessments of bird-specific IgG (pigeons, budgerigars) and the Trichosporon asahii antibody are covered by medical insurance. Although this guide adopts the 2020 ATS/JRS/ALAT guideline diagnostic criteria based on the combination of imaging findings, exposure assessment, bronchoalveolar lavage lymphocytosis, and histopathological findings, it added some annotations to facilitate the interpretation of the content and correlate the medical situation in Japan. It recommends checking biomarkers; seasonal changes in the KL-6 concentration (increase in winter for bird-related HP/humidifier lung and in summer for summer-type HP) and high KL-6 concentrations providing a basis for the suspicion of HP. Antigen avoidance is critical for disease management of HP. This guide also addresses the pharmacological management of HP, highlighting the treatment strategy for fibrotic HP including combination therapies with anti-inflammatory/immunosuppressive and antifibrotic drugs.

Effects of nintedanib on symptoms in patients with progressive pulmonary fibrosis.

BACKGROUND: Dyspnoea and cough can have a profound impact on the lives of patients with pulmonary fibrosis. We investigated the effects of nintedanib on the symptoms and impact of pulmonary fibrosis in patients with progressive pulmonary fibrosis (PPF) in the INBUILD trial using the Living with Pulmonary Fibrosis (L-PF) questionnaire. METHODS: Patients had a fibrosing interstitial lung disease (ILD) (other than idiopathic pulmonary fibrosis) of >10% extent on high-resolution computed tomography (HRCT) and met criteria for ILD progression within the prior 24 months. Patients were randomised 1:1 to receive nintedanib or placebo. Changes in L-PF questionnaire scores from baseline to week 52 were assessed using mixed models for repeated measures. RESULTS: In total, 663 patients were treated. Compared with placebo, there were significantly smaller increases (worsenings) in adjusted mean L-PF questionnaire total (0.5 versus 5.1), symptoms (1.3 versus 5.3), dyspnoea (4.3 versus 7.8) and fatigue (0.7 versus 4.0) scores in the nintedanib group at week 52. L-PF questionnaire cough score decreased in the nintedanib group and increased in the placebo group (-1.8 versus 4.3). L-PF questionnaire impacts score decreased slightly in the nintedanib group and increased in the placebo group (-0.2 versus 4.6). Similar findings were observed in patients with a usual interstitial pneumonia-like fibrotic pattern on HRCT and in patients with other fibrotic patterns on HRCT. CONCLUSION: Based on changes in L-PF questionnaire scores, nintedanib reduced worsening of dyspnoea, fatigue and cough and the impacts of ILD over 52 weeks in patients with PPF.

Neutrophil-to-Lymphocyte Ratio in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

BACKGROUND: This study aimed to clarify the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). METHODS: Eighty-six patients diagnosed with AE-IPF were included in this single-center retrospective study. The NLR was calculated by dividing the peripheral neutrophil count by the peripheral lymphocyte count. The cut-off values of the NLR for predicting 90-day survival were determined using receiver operating characteristic curve analysis. Oxygenation deterioration on days 4 and 8 relative to that on day 1 was clinically defined. The prognostic value of NLR was evaluated using Cox proportional hazard regression analysis. RESULTS: The cut-off value of day-1, day-4, and day-8 NLRs for predicting 90-day survival was 12.13, 14.90, and 10.56, respectively. A higher day-1 NLR was a significant predictor of a poor prognosis in univariate and multivariate analyses. Survival was significantly better in patients without oxygenation deterioration on days 4 and 8 than in those with deterioration. Day-4 and day-8 NLR could predict 90-day survival in patients without oxygenation deterioration. CONCLUSIONS: Day-1 NLR was a useful predictor of 90-day survival in AE-IPF. Further, monitoring day-4 and day-8 NLRs and evaluating oxygenation deterioration may be useful for managing AE-IPF.

A prospective cohort study of periostin as a serum biomarker in patients with idiopathic pulmonary fibrosis treated with nintedanib.

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (DLCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and DLCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased DLCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

A Case of Lymphangioleiomyomatosis Showing the Development of Mycobacterium abscessus subsp. massiliense Infection During Sirolimus Therapy.

Among nontuberculous mycobacterial pulmonary diseases (NTM-PDs), Mycobacterium abscessus species pulmonary disease (MABS-PD) is one of the most severe and intractable infections. We herein report a 45-year-old woman with advanced lymphangioleiomyomatosis (LAM) who developed MABS-PD while undergoing sirolimus therapy. MABS-PD was immediately controlled using antibiotic therapy, although the patient's lung transplant registration was significantly delayed. To our knowledge, this is the first case report on the development of NTM-PD in a patient with LAM before lung transplantation. This case suggests that the early diagnosis and optimal treatment of NTM-PD are crucial in patients with advanced LAM.

Autoimmune Pulmonary Alveolar Proteinosis Complicated by Myelodysplastic Syndrome: A Case Report.

Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal surfactant accumulation in peripheral air spaces. Autoimmune PAP (APAP) results from macrophage dysfunction caused by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, and the presence of antibodies more than the cutoff value is specific for APAP. In contrast, secondary PAP (SPAP) does not require anti-GM-CSF autoantibodies and is complicated by other diseases, including myelodysplastic syndrome (MDS). A 73-year-old man with anemia and thrombocytopenia was diagnosed with APAP and MDS simultaneously. The measurement of serum anti-GM-CSF autoantibodies is important for the correct diagnosis and management of PAP, even with an established diagnosis of underlying SPAP-suggestive disease.

COVID-19 in Patients with Pre-Existing Interstitial Lung Disease: Potential Value of a Steroid-Based Treatment Strategy.

The prognosis of patients with coronavirus disease 2019 (COVID-19) and pre-existing interstitial lung disease (preILD) is poor, and no effective treatment strategy has been determined. The aim of this study was to assess the effectiveness of a steroid-based treatment strategy for patients with COVID-19 and preILD. We retrospectively reviewed the medical records of 610 consecutive patients with COVID-19 treated at our institution between 1 March 2020 and 30 October 2021 and identified 7 patients with preILD, all of whom were treated with corticosteroids and remdesivir. All the patients were men with a median age of 63 years. Three of four patients with severe disease required invasive positive-pressure ventilation (n = 2) or nasal high-flow therapy (n = 1). All three patients could be weaned from respiratory support; however, one died in hospital. The remaining patient with severe COVID-19 had a do-not-resuscitate order in place and died while hospitalized. All three patients with moderate COVID-19 were discharged. The 30-day mortality was 0%, and the mortality rate during the entire observation period was 28.5%. The prognosis of our patients with COVID-19 and preILD has been better than in previous reports. Our management strategy using corticosteroids may have improved these patients' prognosis.

Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy.

While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately.Clinical Trial Registration: UMIN000009322.

Management of Rheumatoid Arthritis: Possibilities and Challenges of Mesenchymal Stromal/Stem Cell-Based Therapies.

Rheumatoid arthritis (RA) is a highly prevalent, chronic, and progressive autoimmune disorder primarily affecting joints and muscles. The associated inflammation, pain, and motor restriction negatively impact patient quality of life (QOL) and can even contribute to premature mortality. Further, conventional treatments such as antiinflammatory drugs are only symptomatic. Substantial progress has been made on elucidating the etiopathology of overt RA, in particular the contributions of innate and adaptive immune system dysfunction to chronic inflammation. Although the precise mechanisms underlying onset and progression remain elusive, the discovery of new drug targets, early diagnosis, and new targeted treatments have greatly improved the prognosis and QOL of patients with RA. However, a sizable proportion of patients develop severe adverse effects, exhibit poor responses, or cannot tolerate long-term use of these drugs, necessitating more effective and safer therapeutic alternatives. Mounting preclinical and clinical evidence suggests that the transplantation of multipotent adult stem cells such as mesenchymal stromal/stem cells is a safe and effective treatment strategy for controlling chronic inflammation and promoting tissue regeneration in patients with intractable diseases, including RA. This review describes the current status of MSC-based therapies for RA as well as the opportunities and challenges to broader clinical application.

Vocal cord paralysis associated with pleuroparenchymal fibroelastosis: A case report and literature review.

Here, we report a case of idiopathic pleuroparenchymal fibroelastosis (PPFE) that progressed to pulmonary aspergilloma, aspiration pneumonia, and left vocal cord paralysis (VCP). To date, five cases of PPFE with VCP have been reported, including the present case. Aspiration pneumonia occurred in three cases, leading to death in two cases. Four cases had left-sided paralysis, in two of which, the paralysis occurred on side opposite to the predominant side (right side) of PPFE. Structural mechanisms underlying the recurrent laryngeal nerve could be involved. This report may further highlight the existence of hoarseness and dysphagia in PPFE.