Reactive oxygen species modulator 1, a novel protein, combined with carcinoembryonic antigen in differentiating malignant from benign pleural effusion.

The differential diagnosis of malignant pleural effusion and benign pleural effusion remains a clinical problem. Reactive oxygen species modulator 1 is a novel protein overexpressed in various human tumors. The objective of this study was to evaluate the diagnostic value of joint detection of reactive oxygen species modulator 1 and carcinoembryonic antigen in the differential diagnosis of malignant pleural effusion and benign pleural effusion. One hundred two consecutive patients with pleural effusion (including 52 malignant pleural effusion and 50 benign pleural effusion) were registered in this study. Levels of reactive oxygen species modulator 1 and carcinoembryonic antigen were measured by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. Results showed that the concentrations of reactive oxygen species modulator 1 both in pleural fluid and serum of patients with malignant pleural effusion were significantly higher than those of benign pleural effusion (both p < 0.05). The diagnostic sensitivity and specificity of pleural fluid reactive oxygen species modulator 1 were 61.54% and 82.00%, respectively, with the optimized cutoff value of 589.70 pg/mL. However, the diagnostic sensitivity and specificity of serum reactive oxygen species modulator 1 were only 41.38% and 86.21%, respectively, with the cutoff value of 27.22 ng/mL, indicating that serum reactive oxygen species modulator 1 may not be a good option in the differential diagnosis of malignant pleural effusion and benign pleural effusion. The sensitivity and specificity of pleural fluid carcinoembryonic antigen were 69.23% and 88.00%, respectively, at the cutoff value of 3.05 ng/mL, while serum carcinoembryonic antigen were 80.77% and 72.00% at the cutoff value of 2.60 ng/mL. The sensitivity could be raised to 88.17% in parallel detection of plural fluid reactive oxygen species modulator 1 and carcinoembryonic antigen concentration, and the specificity could be improved to 97.84% in serial detection.

Clinical and genetic characteristics of 100 consecutive patients with Birt-Hogg-Dubé syndrome in Eastern Chinese region.

BACKGROUND: Although an increasing number of patients with Birt-Hogg-Dubé syndrome (BHD) are being recognized in China, clinical and genetic characteristics are not well-defined. In addition, revised diagnostic criteria for the Chinese population was proposed in 2023, we aimed to explore their utility in clinical practice at a rare lung disease center. METHODS: We retrospectively analyzed the data of 100 consecutive patients with BHD diagnosed according to the revised Chinese BHD criteria, encountered at the First Affiliated Hospital of University of Science and Technology of China from Jan 2017 to June 2023. RESULTS: There were 100 patients (including 63 females) from 65 unrelated families in Eastern China, mostly Anhui Province. The common manifestations were pulmonary cysts (99%), pneumothorax (60%), and skin lesions (77%). Renal cancer and renal angiomyolipoma were detected in 5 patients each. 37% of patients had no family history of BHD. In total, 25 FLCN germline mutations were detected, including 6 novel mutations. In addition to hotspot mutation c.1285delC/dupC (17%), the most common mutations were c.1015 C > T (16%), c.1579_1580insA (14%), and exons 1-3 deletion (11%) in FLCN. Higher risk of pneumothorax was associated with exons 1-3 deletion mutation and c.1177-5_1177-3de1CTC compared to the hotspot mutation c.1285dupC (91% [95% CI: 0.31, 46.82, p = 0.015] and 67% [95% CI: 0.35, 71.9, p = 0.302] vs. 30%, respectively). The average delay in diagnosis was 7.6 years after initial symptoms. Chinese diagnostic criteria were mostly consistent with typical pulmonary presentations with supportive genetic evidence. CONCLUSION: In the Eastern Chinese region, patients with BHD present most commonly with pulmonary cysts associated with pneumothorax and skin lesions. However, low incidence of renal cancer along with unexpected renal angiomyolipoma was observed. Genotypic spectrum differed from that reported from other global regions, and genotype association of pneumothorax warrants further research. The revised Chinese criteria for BHD seem more appropriate in diagnosing BHD in Chinese patients.

Preoperative Serum Lipids as Novel Predictors of Survival in 3575 Papillary Thyroid Cancer Patients.

PURPOSE: The objective of this study is to investigate the association between preoperative serum lipids levels and papillary thyroid cancer (PTC) patients' outcomes. METHODS: A retrospective cohort study including 3575 PTC patients from year 2012-2016 with follow-ups in our institute were enrolled. Preoperative serum lipids were divided into categorical variables by Receiver-operating curves. Univariable and multivariable cox regression models were developed and independent risk factors were used to construct a nomogram to predict disease-free survival (DFS) rate. RESULTS: Among the 3575 patients, the mean follow-up time was 56.7 months. Comparing with the patients with high level of triglycerides (TAG≥0.605 mmol/L) and high-density lipoprotein (HDL≥0.935 mmol/L), those with low level of TAG (hazard ratio [HR] 2.28 [95% CI, 1.35-3.83]) and HDL (HR 1.64, [1.02-2.62]) had a significantly higher risk of recurrence in PTCs. The 5-year DFS rate of patients with low level of TAG was 94.4%, which was much lower than that in the high level group (97.2%, P＜0.001). While TC (P = 0.13), LDL (P = 0.07) and VLDL (P = 0.15) were not statistically correlated with PTCs' recurrence. The nomogram model showed clinical predictive value with the c-index of 0.80 (95% CI 0.73-0.87) and 0.82 (95% CI 0.73-0.90) for 3- and 4-year DFS in the training cohorts. CONCLUSION: In the present study, we provide initial evidence that low levels of TAG and HDL were independently associated with the recurrence of PTC, indicating that preoperative serum concentrations of lipids are helpful in predicting PTC patients' prognosis in clinical practice.

Case report: Indolent drug-related pneumonitis with alectinib therapy in the treatment of non-small cell lung cancer.

Molecular targeting therapy is becoming the standard of care for some patients with anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma. Drug-related pneumonitis (DRP) has been identified as an infrequent but potentially severe adverse effect. Herein, we report a 50-year-old woman with ALK-rearranged advanced lung adenocarcinoma who developed interstitial lung disease associated with alectinib therapy. At 102-day of treatment, chest CT revealed scattered ground glass opacities (GGOs) involving both lungs. Since she was asymptomatic and alectinib provided a beneficial tumor treatment response, alectinib therapy was continued. However, 2 months later, she presented with progressive dyspnea and diffuse GGOs on chest computed tomography. There was no evidence for infection or other etiologies for her lung complication. Alectinib was discontinued and steroid therapy was initiated which was followed by improvement in respiratory symptoms and chest CT findings; DRP was diagnosed. Although rare, alectinib therapy can cause DRP of indolent onset.

Birt-Hogg-Dubé syndrome in Chinese patients: a literature review of 120 families.

OBJECTIVE: To clarify the epidemiological and clinical features of Birt-Hogg-Dubé syndrome (BHDS) in Chinese patients. METHODS: We identified reports on Chinese patients with BHDS by searching the China Academic Journals Database, Wanfang Chinese Database, and PubMed databases, either in Chinese or English languages published from January 1, 2008 to December 31, 2020. Studies without sufficient clinical data were excluded and cases under 18 years old were excluded. RESULTS: Twenty papers were included and comprised 120 families with 221 cases. Most families with BHDS were reported from institutions in Beijing (66.7%) and Jiangsu Province (15.8%); 80.8% of cases were reported within the past five years. The average duration from clinical presentation to diagnosis was 9.6 years. The average age was 47.0 ± 13.9 years (range, 18-84 years) and the ratio of male to female was 1:1.6. The most common manifestations of BHDS were multiple pulmonary cysts (92.4%), spontaneous pneumothorax (71.0%), skin lesions (18.1%) and renal tumors (3.6%). Pulmonary cysts were predominantly distributed in the lower lobe on chest CT imaging. Family history of spontaneous pneumothorax was identified in 84.7% of the families and average number of pneumothoraxes was 1.8 (range, 1-6). The FLCN gene mutation c.1285dupC/delC in exon 11 was the most frequent mutation observed (17.4% of patients). The recurrence rate of pneumothorax after conservative treatment (including tube thoracostomy) was 29/41 (71%) while the pneumothorax recurred after surgical treatment (pulmonary bullectomy or pleurodesis) in only 4/37 (11%). CONCLUSIONS: Although BHDS has been increasingly reported in the recent years, only minority of families were reported from institutions outside of Beijing and Jiangsu Province. The dominant clinical manifestations were pulmonary cysts associated with recurrent pneumothorax, while skin lesions and renal tumors were less commonly reported. Delayed diagnosis along with suboptimal management appear to represent critical challenges for Chinese patients with BHDS.

Three-month outcomes of recovered COVID-19 patients: prospective observational study.

AIMS: A novel coronavirus SARS-CoV-2 has resulted in an ongoing global pandemic of Coronavirus disease 2019 (COVID-19). However, the outcomes of recovered patients have not been well defined. METHODS: This is a prospective observational follow-up study of survivors with COVID-19 from a designated tertiary center in Hefei, China. We examined chest computed tomography (CT) scanning, pulmonary function, 6-min walk distance (6MWD), and 36 item Short Form General Health Survey (SF-36). RESULTS: Among 81 enrolled patients, 62 (77%) patients and 61 (75%) patients, respectively, completed 1-month and 3-month follow-ups. Abnormal CT findings were still present in 73% of patients at 1 month and 54% at 3 months, whereas chest CT scan scores improved progressively at 1-month (5.0 ± 5.1) and 3-month follow up (3.0 ± 4.5) compared with that during hospitalization (11 ± 6.8). Mild restrictive pulmonary impairment was detected in 11% and 10% of patients at 1-month and 3-month follow up, respectively. The 6MWD was 523 ± 77 m in male patients and 484 ± 58 m in female patients, which was significantly lower than in healthy controls (606 ± 68 m, 568 ± 78 m, p < 0.001). SF-36 scores were significantly impaired in the domains of role physical (RP), role emotional (RE), and social functioning (SF) compared with the normal age-matched population. RP was improved at 3-month compared with 1-month follow up in the 41-64 years group (p < 0.01). Multivariable analysis showed that older age (over 40 years) and steroid administration during hospitalization were independently associated with worse chest CT scores at 3-month follow up. CONCLUSIONS: At 3 months, chest CT abnormalities were present in one half of COVID-19 survivors and worse chest CT scores were independently associated with older age and steroid administration during hospitalization. Residual pulmonary function impairments were modest, whereas exercise capacity and SF-36 scores were significantly lower than the general population. Support program and further follow-up evaluations may be needed.The reviews of this paper are available via the supplemental material section.

Clinical features and short-term outcomes of patients with COVID-19 due to different exposure history.

An ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has spread around the world. However, the clinical characteristics and outcomes of patients with COVID-19 related to different modes of exposure have not been well defined. We aimed to explore the clinical features and outcomes of COVID-19 related to one-time community exposure versus continuous household exposure.Retrospective case-control study involving COVID-19 patients admitted to a tertiary designated center in China was performed. Patients were enrolled if they had known exposure history of one-time community exposure or continuous household exposure. Twenty patients were compared in terms of demographic characteristics, clinical presentation, chest CT images, laboratory results, treatments, and clinical outcomes at 1-month follow-up.There were 10 patients in one-time community and continuous household exposure groups respectively. Males compromised 80% and 40% while the median ages were 37.5 and 51 years old in the 2 groups, respectively. Fever and cough were most common symptoms. Ground-glass opacities were presented on chest CT scan in 90% and 70% of the patients, and the median CT scores were 7 and 16 on admission, respectively. Three patients ranked severe in the community exposure group while 7 patients were severe or critical in household exposure group. On 1-month follow-up, all patients were improved clinically but COVID-19 IgG antibody detected positive. Median follow-up CT scores were 0 and 13 while pulmonary function test abnormalities were 0/9 and 2/7 in the 2 groups, respectively.COVID-19 patients with one-time community exposure tended to be mild in severity and had better outcomes, comparing to those with continuous household exposure.

[Emission spectrum of liquid CO-N2 mixture at shock compression].

Driving a copper projectile to impact a cryo-target made of aluminous alloy at the speed of 2.21 km x s(-1) with a two stage light gas gun, a proper one dimensional shockwave with a speed of 18.76 km x s(-1) was generated and directly acted on a uniform liquid in target, which was condensed by proportional gaseous carbon monoxide and nitrogen. At the measurement of Hugoniots, the full linear spectrum entirely dissociated with the plasma under the shock pressure of 33.5 GPa was caught by the use of intensified charge coupled device and accurate spectrographic technology. From the analysis of the spectrum, the authors know that the transient spectrograph with six channels can be used to measure and record the course of shock compression-irradiancy reliably, and the emitted spectral lines of shock compressed products indicated that the thermal dissociation and phase transition had occurred in homogeneous liquid of CO-N2. Furthermore, comparing the spectral intensity of lower central wavelength with that of higher, the fact of stronger intensity of 488 nm also validates that changes from "optic thin" to "optic thick" exist indeed in dense hydrocarbon liquid acted on by shock pressure.

Clinic-pathologic features and gene fusion pattern of ALK and ROS1 in non-small cell lung cancer show association with household coal combustion.

BACKGROUND: Lung cancer induced by burning coal can be etiologically and clinically different from lung cancer caused by smoking. Despite previous work, the gene fusion patterns in lung cancer patients affected by household coal combustion still deserve further study. METHODS: Non-small cell lung cancer (NSCLC) patients exposed to household coal use (HCU) were recruited from rural areas in China's Yunnan Province, certain areas in this region had notably high lung cancer rate nationwide. Reverse transcription-polymerase chain reaction (RT-PCR) was used for detection of ALK, ROS1, RET and NTRK1 rearrangements. Eighteen studies on ALK fusions were summarized and compared with present work. RESULTS: Among the 205 patients, there were 112 (54.6%) coal users and 96 (46.8%) smokers, union set had 145 (70.7%) subjects, in which 63 (30.7%) were double-positive for HCU and smoking. HCU patients featured with younger age and advanced stage. Union set patients covered larger age span (range, 40-82 years old), showed clear early-onset, and made the majority of stage IIIA-IV cases. Double-positive individuals were mainly in later stage, but with wider age span (range, 38-75 years old). In addition, 18 patients (8.8%) had EML4-ALK rearrangement, with apparently higher-than-average variant 3 ratio (77.8% vs. 44%). Five ROS1 fusion cases (2.5%) were identified, all were CD74-ROS1 (E6/E34), and had HCU experience. ALK and ROS1 fusions were mutually exclusive. Both ALK fusions and total gene rearrangement events (ALK and ROS1) showed association with HCU and overall exposure (tobacco and coal). Suggesting there could be unique gene fusion patterns in lung cancer patients affected by coal use. CONCLUSIONS: Present study found clinic-pathologic features and gene fusion patterns in NSCLC showed association with household coal combustion. Our findings may help evaluate the impact of coal use on the pathogenesis of lung cancer, and also highlight the significance of integrating different exposure histories into clinical and theoretical research.