Associations Between Vitamin K and Suicide Attempts in Patients with Depression: A Case-Control Study.

Background: Hypovitaminosis K has been linked to depression and suicide, but epidemiological research is scarce. This study aimed to explore the association among vitamin K with depression and suicidal attempts. Methods: This was a retrospective cross-sectional study involving 146 cases with a history of suicidal attempts and 149 subjects without a lifetime history of suicidal attempts. The levels of thyroid hormones, lipid profile, inflammatory cytokines, and vitamins were measured. Results: Subjects who had suicidal attempts presented with a significant decrease in FT4, TC, vitamin D, and vitamin K but increased CRP levels. In these variables, vitamin K has a better diagnostic value for suicidal attempts in depressed patients, with a sensitivity of 0.842 and a specificity of 0.715. Correlation analysis suggested that vitamin K was significantly and positively related to FT4, TC, LDL, and sdLDL. Multivariate analysis showed that serum vitamin K level predicts suicidal attempts in depressive patients (OR = 0.614, P = 0.004, 95% CI 0.153-0.904). Moreover, a negative correlation between vitamin K and suicidal attempts was also noted for partial FT4, CRP, and vitamin D strata analysis. Conclusion: Our study suggests that low vitamin K levels were correlated with suicidal attempts in patients with depression, indicating that vitamin K deficiency might be a biological risk factor for depression.

Risk factors associated with severe adverse events in patients with relapsing polychondritis undergoing flexible bronchoscopy.

BACKGROUND: Patients with relapsing polychondritis (RP) sometimes experience upper airway collapse or lower airway stenosis, and bronchoscopy may provide a valuable typical image to confirm the diagnosis. This study aimed to identify potential risk factors associated with severe adverse effects during bronchoscopy. METHODS: We performed a retrospective cohort study of 82 consecutive patients with RP hospitalized at Peking Union Medical College Hospital between January 1, 2012 and December 31, 2022. Clinical features and disease patterns were compared among patients with RP undergoing bronchoscopy with or without severe adverse effects. Binary logistic regression analysis was performed to identify the associated risk factors. RESULTS: For patients with RP undergoing bronchoscopy with severe adverse effects, the forced vital capacity (FVC), forced vital capacity percent predicted values (FVC%), and peak expiratory flow were significantly lower (P = 0.001, P = 0.001, and P = 0.021, respectively) than those in the non-severe adverse effect subgroup. Binary logistic regression analysis revealed that low FVC% (odds ratio, 0.930; 95% confidence interval, 0.880-0.982; P = 0.009) was an independent risk factor for severe adverse events in patients undergoing bronchoscopy. CONCLUSIONS: Low FVC or FVC% suggests a high risk of severe adverse effects in patients with RP undergoing bronchoscopy. Patients with such risk factors should be carefully evaluated before bronchoscopy and adequately prepared for emergency tracheal intubation or tracheostomy.

Rapid LC-MS/MS detection of 25-hydroxyvitamin D in dried blood spots.

BACKGROUND: The detection of 25-hydroxyvitamin D (25OHD) from dried blood spots (DBS) has been widely studied. However, the existing pretreatment methods suffer from limitations in terms of throughput (usually exceeding 2 h), complexity (involving liquid-liquid extraction or solid-phase extraction), and contamination (including multiple steps of organic solvent evaporation). RESULTS: We first released 25OHD from DBS samples by 50% acetonitrile solution through ultrasonication. Subsequently, the cold-induced phase separation technique was introduced for in-situ concentration and purification. Afterward, the PTAD derivatization of 25OHD was performed directly, profiting from the high acetonitrile content in the concentrated solution. In the end, the resulting solution was submitted to LC-MS/MS for quantification. The established LC-MS/MS methodology possessed favorable analytical performance, possessing lower limit of quantification of 1 ng/mL pointing to plasma, accuracy of 86.8-110.1% and imprecision of 5.4-16.8%. Method comparison with plasma samples demonstrated that over 93% of the detections met the acceptance limit for cross-validation of ±20%. SIGNIFICANCE AND NOVELTY: The novel sample preparation can be finished within 15 min and eliminated the traditional steps of extraction and organic solvent evaporation. Based on this high-throughput, reliable and applicable LC-MS/MS method, the detection of 25OHD in DBS samples can be better achieved for clinical patients and researchers with relevant demands.

Effects of COVID-19 infection in patients with autoimmune pulmonary alveolar proteinosis: a single-center study.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare interstitial lung disease. COVID-19 is associated with worse prognosis in previous lung diseases patients. But the prognosis of aPAP patients after infection with COVID-19 is unclear. In December 2022, China experienced a large-scale outbreak of Omicron variant of the SARS-CoV-2. In this study, we aim to explore the clinical outcomes of aPAP patients infected with COVID-19. RESULTS: A total of 39 aPAP patients were included in this study. 30.77% patients had a decrease in oxygen saturation after COVID-19 infection. We compared the two groups of patients with or without decreased oxygen saturation after COVID-19 infection and found that patients who had previous oxygen therapy (decreased oxygen saturation vs. non decreased oxygen saturation: 6/12 vs. 4/27, P = 0.043), with lower baseline arterial oxygen partial pressure (74.50 ± 13.61 mmHg vs. 86.49 ± 11.92 mmHg, P = 0.009), lower baseline DLCO/VA% [77.0 (74.3, 93.6) % vs. 89.5 (78.2, 97.4) %, P = 0.036], shorter baseline 6MWD [464 (406, 538) m vs. 532 (470, 575) m, P = 0.028], higher disease severity score (P = 0.017), were more likely to have decreased oxygen saturation after COVID-19 infection. CONCLUSION: aPAP patients with poor baseline respiration have a higher probability of hypoxia after COVID-19 infection, but fatal events were rare.

Evaluation of Vitamin D Status and the Analysis of Risk Factors of Vitamin D Deficiency in Twin Pregnancies.

OBJECTIVE: Optimization of maternal vitamin D (VD) status has beneficial effects on pregnancies, but little is known about it of twin pregnancies (TP). Our aim was to promote the current understanding of VD status and its associated factors in TP. METHODS: We performed liquid chromatography-tandem mass spectrometry to quantify 25-hydroxyvitamin D [25(OH)D] and used the enzyme-linked immunosorbent assay method to detect vitamin D binding protein (VDBP) in 218 singleton pregnancies (SP) and 236 TP. RESULTS: Levels of 25(OH)D and VDBP were higher in TP than SP. The 25(OH)D, free 25(OH)D, C-3 epimer of 25-hydroxyvitamin D [epi-25(OH)D], and VDBP all increased with gestational progress. Age, body mass index, and hemoglobin level were associated with VD deficiency (VDD). Analysis of covariance demonstrated that the 25(OH)D and VDBP of TP and SP still showed differences after adjusting for the above associated factors. CONCLUSION: Differences in VD status were found in SP and TP, suggesting that the assessment of VD status in TP should be treated with caution. High VDD prevalence is observed among pregnant Chinese women, and it is recommended to promote evaluation for VDD.

Determinants of Progression and Mortality in Lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis is a progressive diffuse cystic lung disease with approximately 85% survival at 10 years. The determinants of disease progression and mortality after the introduction of sirolimus therapy and vascular endothelial growth factor D (VEGF-D) as a biomarker have not been well defined. RESEARCH QUESTION: Which factors, including VEGF-D and sirolimus therapy, influence disease progression and survival prognosis in patients with lymphangioleiomyomatosis? STUDY DESIGN AND METHODS: The progression dataset and the survival dataset included 282 and 574 patients, respectively, from Peking Union Medical College Hospital, Beijing, China. A mixed-effects model was used to compute the rate of decline in FEV1, and generalized linear models were used to identify variables affecting FEV1 decline. A Cox proportional hazards model was used to explore the association between clinical variables and the outcomes of death or lung transplantation in patients with lymphangioleiomyomatosis. RESULTS: VEGF-D levels and sirolimus treatment were associated with FEV1 changes and survival prognosis. Compared with patients with VEGF-D of < 800 pg/mL at baseline, patients with VEGF-D of ≥ 800 pg/mL lost FEV1 faster (SE, -38.86 mL/y; 95% CI, -73.90 to -3.82 mL/y; P = .031). The 8-year cumulative survival rates of patients with VEGF-D of ≥ 2,000 pg/mL and < 2,000 pg/mL were 82.9% and 95.1%, respectively (P = .014). The generalized linear regression model also demonstrated the benefit of delaying the decline of FEV1 by 65.56 mL/y (95% CI, 29.06-102.06 mL/y) in patients treated with sirolimus compared with those without sirolimus (P < .001). The 8-year risk of death was reduced by 85.1% (hazard ratio, 0.149; 95% CI, 0.075-0.299) after sirolimus treatment. After inverse treatment probability weighting, the risks of death in the sirolimus group were reduced by 85.6%. CT scan results of grade III severity were associated with worse progression than results of grades I or II severity. Patients with baseline FEV1 of 70% predicted or St. George's Respiratory Questionnaire Symptoms domain 50 or higher predicted a higher risk of worse survival. INTERPRETATION: Serum VEGF-D levels, a biomarker of lymphangioleiomyomatosis, are associated with disease progression and survival. Sirolimus therapy is associated with slower disease progression and better survival in patients with lymphangioleiomyomatosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03193892; URL: www. CLINICALTRIALS: gov.

Rapid Derivatization of Phenolic and Oxime Hydroxyl with Isonicotinoyl Chloride under Aqueous Conditions and Its Application in LC-MS/MS Profiling Multiclass Steroids.

Quantification of steroids possesses a crucial clinical value in early diagnosis and prognosis evaluation of various endocrine diseases. However, it is still challenging to realize feasible analysis of estrogens, androgens, progestogens, and corticoids within one single workflow. In this study, two derivatization reactions were newly designed for improvement: (1) acylation of phenolic hydroxyl on estrogens with isonicotinoyl chloride (INC) under the catalysis of 4-dimethylaminopyridine and (2) post-modification of oxime hydroxyl on hydroxylamine-pretreated ketosteroids with INC. Both reactions could conduct instantaneously at room temperature under aqueous conditions. Moreover, the resulting phenolic-INC and oxime-INC esters exhibited favorable MS responses. Through integrating these derivatization strategies with cold-induced phase separation technology, a feasible LC-MS/MS method was developed for simultaneous quantification of 15 multiclass steroids with proper sample consumption (50 µL serum), satisfying sensitivity (lower limit of quantitation at 0.01-5.00 ng/mL) and high throughput (40 min for sample-preparation). The practical applicability was tested by detecting 30 real samples from pregnant and non-pregnant women. The obtained results showed a good agreement with a previous validated methodology.

Quantification of immunosuppressants from one 3.2 mm dried blood spot by a novel cold-induced phase separation based LC-MS/MS method.

Dried blood spots (DBS) have been regarded as a promising alternative for therapeutic drug monitoring (TDM) of immunosuppressants (ISDs) for over fifteen years. Nonetheless, there are still three main issues impeding its preference: (i) the requirement of relatively large disc; (ii) the controversial and intricate desorption approaches; (iii) the lack of feasible extraction strategies. For improvement, this work described a new LC-MS/MS method realizing quantification of four ISDs from one piece of 3.2 mm DBS. During sample pretreatment, a modified approach (infiltrating the DBS in pure water before adding acetonitrile and zinc sulfate as protein-precipitators) was developed to completely dissociate the targets from filter paper. Afterward, effective enrichment and purification of the targets were achieved by using cold-induced phase separation technique. Benefiting from these novelties, the method exhibited satisfying throughput (15 min for sample preparation), applicability (consuming only one 3.2 mm disc), reliability (82.3-107.8% for accuracy and <14.3% for precision) and sensitivity (lower limit of quantification of 0.5, 7.6, 0.7 and 0.8 ng mL-1 for tacrolimus, cyclosporine A, everolimus and sirolimus, respectively). Without hematocrit correction, the method showed favorable interchangeability to the certified whole blood method through analyzing 120 paired clinical samples. By taking ±20% of the mean as the limit of acceptance for cross validation, over 90% of the detection met the criterion. It can be expected the developed method is able to further promote the popularization of DBS-based TDM for ISDs in practice.

Lung function and air pollution exposure in adults with asthma in Beijing: a 2-year longitudinal panel study.

The effect of air pollution on the lung function of adults with asthma remains unclear to date. This study followed 112 patients with asthma at 3-month intervals for 2 years. The pollutant exposure of the participants was estimated using the inverse distance weight method. The participants were divided into three groups according to their lung function level at every visit. A linear mixed-effect model was applied to predict the change in lung function with each unit change in pollution concentration. Exposure to carbon monoxide (CO) and particles less than 2.5 micrometers in diameter (PM2.5) was negatively associated with large airway function in participants. In the severe group, exposure to chronic sulfur dioxide (SO2) was negatively associated with post-bronchodilator forced expiratory flow at 50%, between 25% and 75% of vital capacity % predicted (change of 95% CI per unit: -0.34 (-0.55, -0.12), -0.24 (-0.44, -0.03), respectively). In the mild group, the effect of SO2 on the small airways was similar to that in the severe group, and it was negatively associated with large airway function. Exposure to CO and PM2.5 was negatively associated with the large airway function of adults with asthma. The negative effects of SO2 were more evident and widely observed in adults with severe and mild asthma than in adults with moderate asthma. Patients with asthma react differently to air pollutants as evidenced by their lung function levels.

Cold-induced phase separation for the simple and reliable extraction of sex hormones for subsequent LC-MS/MS analysis.

Sex hormones, including androgens, estrogens, and progestogens, are important biomarkers for various diseases. Quantification of sex hormones is typically conducted by LC-MS/MS. At present, most methods require liquid-liquid extraction or solid phase extraction for sample preparation. However, these pretreatments are prone to compromise LC-MS/MS throughput. To improve on the current standard practices, we investigated cold-induced phase separation for sex hormone extraction. After protein precipitation with acetonitrile and adjusting the solution constitution with water, samples were stored at -30°C for 10 min to generate two distinct phases: an acetonitrile-rich layer on top of a water-rich layer. During this process, the hydrophobic sex hormones spontaneously separate into the upper layer. This simple and reliable cold-induced phase separation-based LC-MS/MS methodology was used here to simultaneously detect estrone, estradiol, estriol, testosterone, androstenedione, dehydroepiandrosterone, progesterone, and 17-hydroxyprogesterone in serum. Validation of this method indicated satisfactory performance, including acceptable linearity, accuracy, precision, and tractability. Compared with the mainstream liquid-liquid extraction-based method, this new method exhibits significant progress in throughput, which shortens the time cost of sample preparation from 90 to 40 min. We propose that this method can be an excellent alternative for sex hormone analysis in routine clinical laboratories.

Ga-68 EDTA aerosols in evaluation of inhaled-particle deposition and clearance of obstructive pulmonary diseases: A pilot prospective study compared with Galligas.

PURPOSE: 68-gallium (Ga-68) ethylenediaminetetraacetic acid (EDTA) aerosols and Galligas were compared in evaluation of inhaled-particle deposition and clearance in volunteers with or without obstructive pulmonary diseases. METHODS: Nonsmoking healthy volunteers, healthy smokers, asthma patients and patients with chronic obstructive pulmonary disease (COPD) were recruited to undergo the dynamic lung ventilation positron emission tomography/computerized tomography (PET/CT) scans within two consecutive days. The inhaled particles were Ga-68-labelled carbon nanoparticles (Galligas, 30-60 nm in size) and Ga-68-labelled EDTA aerosols (1-2 µm in size), respectively. The volunteers' lung function parameters were measured for comparison. RESULTS: Central deposition and inhomogeneity of both tracers were negatively correlated with lung function parameters, including the ratio of forced expiratory volume at 1 second to forced vital capacity (FEV1 /FVC). The central or hilum deposition of Galligas, but not 68-gallium (Ga-68) EDTA, was negatively correlated with the maximal expiratory flow at 25%, 50% and 75% of the forced vital capacity. Compared with Galligas, Ga-68 EDTA aerosols were more concentrated in the central region in all groups except for the healthy nonsmokers. Ventilation inhomogeneity was more evident when using Ga-68 EDTA aerosols, especially in patients with COPD and asthma patients. In the healthy smokers, the central region accumulated more Ga-68 EDTA at 30 minutes after inhalation than immediately after inhalation. Ga-68 EDTA cleared faster in lungs than Galligas. CONCLUSIONS: Both Galligas and Ga-68 EDTA aerosols can be used for PET/CT lung ventilation scan. However, Ga-68 EDTA aerosols showed more advantages in diagnosis and evaluation of obstructive airway diseases by revealing the inhaled-particle deposition and clearance.

Steroid profile analysis by liquid chromatography-tandem mass spectrometry in second-trimester pregnant women for trisomy 21 screening.

BACKGROUND: Trisomy 21 is a serious chromosome abnormality. The conventional Down's screening test is the most widely used for trisomy 21 screening. However, this method could lead to a higher false positive rate. Therefore, we aim to analyze steroid profile in second-trimester pregnant women and identify novel serum biomarkers of trisomy 21. METHODS: We employed an LC-MS/MS method to measure the steroid profile. The concentrations and product-to-substrate ratios in 71 second-trimester pregnant women were determined and statistically analyzed to identify novel biomarkers for trisomy 21 screening. RESULTS: We found that there were significant differences in levels of E3, 11-deoxycortisol, and 11-deoxycortisol /17-hydroxyprogesterone between two groups. The OPLS-DA plots revealed obvious separation between two groups. Combining VIP analysis (VIP > 1.0) with volcano plot (P < 0.05 and fold change >1.2 or < 0.83), 11-deoxycortisol was identified as a novel biomarker for trisomy 21. After controlling for confounders, we found 11-deoxycortisol was associated with trisomy 21 (adjusted P = 0.009), and the fully adjusted OR (95 % CI) was 0.098 (0.016-0.593) in highest quartile versus lowest quartile of 11-deoxycortisol (P = 0.011). CONCLUSIONS: Steroid profile analysis for the first time showed that steroid hormones perturbations occurred in pregnant women carrying a fetus affected by trisomy 21 and decreased 11-deoxycortisol levels were associated with trisomy 21.

Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a slow albeit progressive rare neoplastic disease featured with diffuse thin-walled cysts in lungs and angiomyolipomas in kidneys. LAM affects almost exclusively women and has one of the strongest gender predispositions of any extragenital human disease. Two forms of LAM present clinically, sporadic (S-LAM) and tuberous sclerosis complex-associated (TSC-LAM). TSC is an autosomal dominant genetic multisystems neoplastic disease. A high prevalence of LAM can be detected in adult female TSC patients. Tremendous progress has been made in our understanding and management of this rare disease. Both LAM and TSC are TSC2 or TSC1 mutated diseases that result in overactivation of the mechanistic target of rapamycin (mTOR) pathway. Sirolimus, an mTOR inhibitor, has been approved for LAM treatment in the United States and many other countries. Therapies targeting female sex hormones have shown preclinical efficacy in animal and cell culture-based experiments, but have not been properly investigated clinically. In this review, we summarize current recommendations in the diagnosis and treatment of LAM.

Efficient extraction and sensitive LC-MS quantification of hydroxytyrosol in wine, oil and plasma.

Hydroxytyrosol (HT) possesses significant biological activity. However, the methodologies for its quantification always suffered from low sensitivity, intricate treatment and high sample consumption. Here, we presented the very first attempt for specific extraction of HT through cis-diol recognition mechanism. By using easily prepared zirconia as dispersive solid phase extraction medium, HT from small amount of wine (10 µL), oil (20 mg) and plasma (100 µL) was efficiently purified within ten minutes. Coupled with LC-MS/MS analysis, the method limit of detection (LOD) could reach 1 ng/mL in wine, 0.5 µg/kg in oil and 0.1 ng/mL in plasma. Profited by this superior method, HT analysis was successfully performed in diverse wine and oil products as well as human plasma samples after intake of extra virgin olive oil. In addition, we further confirmed the endogenous HT was undetectable from routine human plasma even after upgrading the detection sensitivity through post isonicotinoyl chloride derivatization.

LC-MS/MS determination of plasma catecholamines after selective extraction by borated zirconia.

For the first time, boronate affinity chromatography and metal oxide affinity chromatography mechanisms for cis-diol-compounds extraction are simultaneously realized on a single material, termed borated zirconia. This material was prepared by hydrolyzing zirconium butoxide with boric acid under non-aqueous environment. The diameter of formed particles is around 200 nm. By extracting catechol under different pH conditions or with phosphate ion competition, the dual affinity mechanisms of borated zirconia are confirmed. Benefiting from such unique feature, borated zirconia can function well under neutral condition. By using borated zirconia for dispersive solid phase extraction, specific capture of cis-diol-containing catecholamines, including epinephrine (E), norepinephrine (NE) and dopamine (DA), was achieved. A reliable LC-MS/MS method was established and validated for quantification of these target analytes in plasma samples after derivatisation with benzoyl chloride. The linear ranges are 0.010-0.200 ng·mL-1 for E and DA, and 0.050-1.000 ng·mL-1 for NE. The limits of quantification are 0.008, 0.020 and 0.004 ng·mL-1 for E, NE and DA respectively. By analyzing samples from healthy volunteers and schizophrenia patients, the plasma concentrations of E, NE and DA were found to be higher for the latter. Graphical AbstractSchematic representation of boronate combined metal oxide affinity chromatography (BMOAC) extraction of cis-diol catecholamines from human plasma by borated zirconia following with benzoyl chloride derivatization and LC-MS determination.

Lung function and systemic inflammation associated with short-term air pollution exposure in chronic obstructive pulmonary disease patients in Beijing, China.

BACKGROUND: Exposure to air pollution is associated with chronic obstructive pulmonary disease (COPD). However, findings on the effects of air pollution on lung function and systemic inflammation in Chinese COPD patients are inconsistent and scarce. This study aims to evaluate the effects of ambient air pollution on lung function parameters and serum cytokine levels in a COPD cohort in Beijing, China. METHODS: We enrolled COPD participants on a rolling basis from December 2015 to September 2017 in Beijing, China. Follow-ups were performed every 3 months for each participant. Serum levels of 20 cytokines were detected every 6 months. Hourly ambient pollutant levels over the same periods were obtained from 35 monitoring stations across Beijing. Geocoded residential addresses of the participants were used to estimate daily mean pollution exposures. A linear mixed-effect model was applied to explore the effects of air pollutants on health in the first-year of follow-up. RESULTS: A total of 84 COPD patients were enrolled at baseline. Of those, 75 COPD patients completed the first-year of follow-up. We found adverse cumulative effects of particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO) on the forced vital capacity % predicted (FVC % pred) in patients with COPD. Further analyses illustrated that among COPD patients, air pollution exposure was associated with reduced levels of serum eotaxin, interleukin 4 (IL-4) and IL-13 and was correlated with increased serum IL-2, IL-12, IL-17A, interferon γ (IFNγ), monocyte displacing protein 1 (MCP-1) and soluble CD40 ligand (sCD40L). CONCLUSION: Acute exposures to PM2.5, NO2, SO2 and CO were associated with a reduction in FVC % pred in COPD patients. Furthermore, short-term exposure to air pollutants increased systemic inflammation in COPD patients; this may be attributed to increased Th1 and Th17 cytokines and decreased Th2 cytokines.

An LC/MS/MS method for analyzing the steroid metabolome with high accuracy and from small serum samples.

Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and lack the evaluation of accuracy. Here, we developed an LC/MS/MS method for the simultaneous quantification of 12 steroid hormones: testosterone, pregnenolone, progesterone, androstenedione, corticosterone, 11-deoxycortisol, cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, estriol, and estradiol. Steroids and spiked internal standards in 100 µl serum were extracted by protein precipitation and liquid-liquid extraction. The organic phase was dried by evaporation, and isonicotinoyl chloride was added for steroid derivatization, followed by evaporation under nitrogen and redissolution in 50% methanol. Chromatographic separation was performed on a reverse-phase PFP column, and analytes were detected on a triple quadrupole mass spectrometer with ESI. The lower limits of quantification ranged from 0.005 ng/ml for estradiol to 1 ng/ml for cortisol. Apparent recoveries of steroids at high, medium, and low concentrations in quality control samples were between 86.4% and 115.0%. There were limited biases (-10.7% to 10.5%) between the measured values and the authentic values, indicating that the method has excellent reliability. An analysis of the steroid metabolome in pregnant women highlighted the applicability of the method in clinical serum samples. We conclude that the LC/MS/MS method reported here enables steroid metabolome analysis with high accuracy and reduced serum consumption, indicating that it may be a useful tool in both clinical and scientific laboratory research.

Long-term efficacy and safety of sirolimus therapy in patients with lymphangioleiomyomatosis.

BACKGROUND: Sirolimus has been confirmed to be effective for lymphangioleiomyomatosis (LAM), a rare multisystem neoplastic disease in women. The long-term effects of sirolimus treatment for LAM, however, are largely unknown. We aimed to analyze the long-term efficacy and safety of sirolimus therapy for LAM with 4-year follow-up. METHODS: In total, 142 sporadic LAM patients who took sirolimus for 1-4 years were retrospectively enrolled for this analysis. The variables used for analysis included pulmonary function tests, arterial blood gas analysis, 6-min walking distance (6MWD), St. George's Respiratory Questionnaires (SGRQ) and serum vascular endothelial growth factor-D (VEGF-D) levels before and after the initiation of sirolimus therapy. The rates of change (slope) in those variables were calculated, and adverse events were also analyzed. RESULTS: In total, 122, 83, 60 and 32 patients out of 142 were followed for 1, 2, 3 and 4 years respectively. Sirolimus treatment improved the change rate in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) compared with the data before treatment (FEV1, - 10 ± 15 vs. - 178 ± 36 ml/y, P <  0.001 and FVC, 54 ± 22 vs.-72 ± 68 ml/y, P < 0.05). In comparison to the baseline measurements, significant improvements were observed in FEV1 at the first year; FVC at 1-2 years; arterial oxygen levels, 6MWD, and SGRQ at 1-3 years; and VEGF-D at 1-4 years. Overall, all variables stabilized or improved during the 4 years of observation. Adverse events related to sirolimus were mild. CONCLUSION: Sirolimus therapy is effective at improving or stabilizing pulmonary function, oxygen levels, exercise capacity, and quality of life in patients with LAM for up to 4 years. VEGF-D is maintained at a lower level for 4 years after treatment. Adverse events related to sirolimus were mild.

Amyloidosis secondary to intrapulmonary Castleman disease mimicking pulmonary hyalinizing granuloma-like clinical features: A rare case report.

RATIONALE: Amyloidosis secondary to intrapulmonary Castleman disease (CD) is a rare benign disease diagnosed by histopathology. It seems to be associated with chronic inflammation, and large amounts of IL-6 produced in the germinal center of CD may enhance the production of precursor of amyloid. PATIENT CONCERNS: We reported a case of an 18-year-old woman presenting with dry cough and dyspnea on exertion for 6 months and detailed exams revealed multiple pulmonary nodules, positive antinuclear antibodies, hypocomplementemia, and thrombocytopenia. DIAGNOSES: A computed tomography-guided percutaneous lung biopsy revealed the histopathological features of pulmonary hyalinizing granuloma (PHG), but video-assisted pulmonary wedge resection for biopsy with immunohistochemical stains finally demonstrated a corrected diagnosis of intrapulmonary CD with secondary amyloidosis. INTERVENTIONS: The patient had received prednisone and Tacrolimus for 6 months. OUTCOMES: There was no significant improvement in pulmonary lesions or platelet level. Chemotherapy to CD was needed. LESSONS: Intrapulmonary CD should be considered in patients with multiple pulmonary nodules irresponsive to corticosteroid and diagnosis of PHG should be carefully considered based on small lung biopsy sample. The treatment of amyloidosis secondary to CD remains to be uncertain.

Chronic eosinophilic pneumonia after trastuzumab and radiation therapy for breast cancer: A case report.

RATIONALE: Chronic eosinophilic pneumonia (CEP) is rare and an idiopathic disorder. The disease has been associated with drugs, infection, or irradiation, and its relationship with asthma remains unclear. PATIENT CONCERNS: We reported a case of a 49-year-old female patient after trastuzumab and radiation therapy for breast cancer. Two months after radiation treatment, the patient complained of productive cough, progressive breathlessness, occasional wheezing, and left pectoralgia. DIAGNOSES: Computed tomography (CT) scan revealed infiltrates in lungs. Without evidence of infection, marked increased eosinophils in a transbronchial biopsy performed from the left upper lobe confirmed the diagnosis of CEP after trastuzumab and radiation therapy. INTERVENTIONS: The patient was started with oral prednisone at 0.5 mg/kg/day. OUTCOMES: A CT scan of the chest obtained 2 weeks after steroid treatment showed diminishment of the lesions, and at the 6-month follow-up, the patient had no complaints of discomfort with no relapse of pulmonary lesions. LESSONS: Physicians should consider CEP as a diagnosis in patients who have had previous exposure to trastuzumab and radiation therapy, especially with a history of asthma. Timely diagnosis and treatment may benefit these patients.