Association between the modified lung immune predictive index and clinical outcomes of advanced non-small cell lung cancer treated with first-line immune checkpoint inhibitors combined with chemotherapy.

Background: As revealed by previous studies, the modified lung immune predictive index (mLIPI) can predict outcomes in patients with lung cancer receiving single-agent immunotherapy. However, the application value of the mLIPI for patients treated with combination immunotherapy requires further investigation. In this study, we aimed to explore the relationship between the mLIPI and the efficacy of treatment together with the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving first-line immune checkpoint inhibitors (ICIs) combined with platinum-based chemotherapy. Methods: In this retrospective study, we enrolled patients with advanced NSCLC treated with ICIs plus chemotherapy from March 2019 to June 2022. The patients were classified into good, intermediate, and poor/very poor groups according to their mLIPI before treatment. We further calculated the disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the three groups. The predictive ability of the mLIPI was evaluated by plotting a time-dependent receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results: A total of 209 patients were included in this study. There were 75 patients in the good group, 114 patients in the intermediate group, and 20 patients in the poor/very poor group. The median PFS was 11.2 months [95% confidence interval (CI): 8.763-13.704] in the good group; 8.1 months (95% CI: 7.354-8.846) in the intermediate group; and 5.4 months (95% CI: 2.142-8.658) in the poor/very poor group. The median OS was not reached in the good group, 29.5 months (95% CI: 23.555-35.512) in the intermediate group, and 14.5 months (95% CI: 8.567-20.366) in the poor/very poor group (P<0.05). Multivariate analysis showed that the mLIPI was independently associated with PFS and OS (P<0.05); the AUC values of the mLIPI for predicting PFS at 3, 6, and 9 months were 0.673, 0.637, and 0.614, respectively, and for predicting OS at 6, 12, and 24 months were 0.715, 0.655, and 0.625, respectively. Conclusions: The pretreatment mLIPI could be used to predict outcomes in patients with NSCLC receiving first-line ICIs plus chemotherapy.

Preliminary study of low-dose photodynamic therapy on the oxidative stress response of Cutibacterium acnes.

PURPOSE: The objective of this study was to investigate the influence of photodynamic therapy (PDT) employing different, lower 5-aminolevulinic acid (ALA) dosages on the proliferative activity of Cutibacterium acnes (C. acnes). METHODS: In this in vitro bacterial experiment, we examined the effects of PDT using different doses of ALA (0.05 mmol/L; 0.1 mmol/L; 0.5 mmol/L; 1.0 mmol/L; 2.5 mmol/L). To elucidate the underlying mechanisms, we assessed colony-forming units (CFUs), bacterial staining for live/dead, antioxidant enzyme activity, and gene expression of oxidative stress markers following treatment with different doses of ALA-PDT. RESULTS: Our findings demonstrate that CFU, bacterial staining for live/dead, as well as the activity and gene expression of superoxide dismutase (SOD) and catalase (CAT), all exhibited significant increases when the ALA concentration was 0.1/0.5 mmol/L. However, both CFU and cell growth of C. acnes decreased when the ALA concentration reached 1.0 mmol/L. CONCLUSION: Lower concentration of ALA-PDT (0.1/0.5 mmol/L) appears to promote the growth of C.acnes while higher doses (1.0 /2.5 mmol/L) are associated with eradication. The procedure is possibly mediated by the activation of antioxidant-related genes and enzyme expression in cells.

Sleep quality, circadian preferences, and mood among patients with acne vulgaris: a case-control study.

PURPOSE: Poor sleep and mood may be predisposing factors for acne. We aimed to investigate the associations between acne and sleep quality, circadian preferences, and mood. METHODS: This case-control study recruited patients with acne and age- and sex-matched healthy controls. We used the Investigator's Global Assessment to evaluate acne severity and various validated questionnaires to measure sleep quality, daytime sleepiness, sleep apnea, circadian preference, and mood symptoms. RESULTS: A total of 81 patients with acne (age: 21.6 ± 5.0 years, 52% female) and 76 controls were recruited. Compared to controls, patients had a higher score on the Pittsburgh Sleep Quality Index (5.2 ± 2.6 vs. 4.1 ± 2.3, p = 0.008) and State-Trait Anxiety Inventory (State: 44.6 ± 9.7 vs. 40.6 ± 6.6, p = 0.003; Trait: 47.9 ± 8.2 vs. 45.3 ± 6.2, p = 0.03), and a lower score on a reduced version of the Morningness and Eveningness Questionnaire (13.9 ± 2.6 vs. 14.7 ± 2.3, p = 0.05) and Epworth Sleepiness Scale (7.4 ± 3.4 vs. 8.6 ± 3.6, p = 0.04). Acne severity was associated with sleep quality (ß = 0.33), eveningness (ß = 0.34), depression (ß = 0.66), and anxiety (State: ß = 1.73; Trait: ß = 1.21), even when adjusted for education level and family history of acne. CONCLUSION: Acne is highly associated with poor sleep and mood. Dermatologists are advised to attend closely to the psychological impact of acne. Improvements in sleep and mood may benefit the treatment of acne.

Whole exome sequencing identified a novel POT1 variant as a candidate pathogenic allele underlying a Li-Fraumeni-like family.

Background: Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like (LFL) syndrome are rare hereditary diseases characterized by predisposition to a diverse spectrum of cancer types, primarily sarcoma. The pathogenic variants underlying the majority of LFL cases remain to be explored. Methods: We performed whole-exome sequencing (WES) on 13 core members of a large LFL family with highly aggregated incidences of cancers, including cases with sarcoma, non-small cell lung cancer and cardiac angiosarcoma, and conducted a comprehensive literature review of candidate gene associations in LFS/LFL syndromes or sarcoma to identify potential pathogenic germline variants. Results: No germline variants in the best-known LFL/LFS-associated gene TP53 were detected. Of all the genes associated with LFS/LFL or sarcoma that we have surveyed, we identified a novel p.P35L germline variant in POT1 (protection of telomeres 1). Germline and somatic alterations in POT1 have been implicated in a series of familial cancers, including angiosarcoma, glioma, melanoma and colorectal cancer. This particular variant is located in the telomere-binding OB1 domain, which is important in maintaining the proper telomere length, and showed high conservation across different POT1 orthologues. No record of the variant was found in any of the 1000 genomes, ExAC, gnomAD, dpSNP and COSMIC databases. Prediction algorithms and in silico structural analysis suggested completely disrupted protein structure and function of POT1 in the presence of this mutation. Conclusions: Leveraging WES, we identified a novel germline risk allele, p.P35L in POT1, that likely predisposes to LFL syndrome. Our results support the routine testing of POT1 and other LFL/LFS-associated genes in the risk populations to enable early cancer diagnosis, prevention and intervention.

Long-Term Clinical Benefit in EGFR-Mutant Lung Adenocarcinoma With Local Squamous Cell Carcinoma Transformation After EGFR TKI Resistance: A Case Report.

The histological transformation from adenocarcinoma (ADC) to squamous cell carcinoma (SCC) is rare but recurrently occurs post TKI treatment in EGFR-mutated non-small cell lung cancer patients with a very limited number of clinical cases published. The outcome of patients after SCC onset is poor as no established treatment guidelines were available. Here we report a case who was initially diagnosed with lung ADC with EGFR L858R driver mutation and demonstrated a partial response (PR) to gefitinib for 27 months before disease progression. The rapidly progressive lung metastatic lesions were determined as an SCC histology with positive PD-L1 expression. Besides EGFR L858R, the metastatic SCC harbored the amplification of CD274 and PDCD1LG2 detected by targeted next-generation sequencing (NGS), which encode PD-L1 and PD-L2, respectively. The disease remained stable on the combination therapy of pembrolizumab plus chemotherapy for eight months until the primary ADC lesion progressed. After the failure of progressed primary ADC lesion with radiotherapy and immunotherapy, systemic ADC metastases were developed in multiple locations including kidney, liver, and chest wall with EGFR L858R mutation but negative PD-L1 expression. The patient then received the combination therapy of bevacizumab plus chemotherapy and the disease remained stable for five months. Since August 2021, afatinib has been administrated which led to a PR and the disease has remained stable up till present. This study demonstrated a primary lung ADC who developed systemic ADC metastases and local SCC transformation with distinct molecular features. The patient has achieved long-term clinical benefit upon multiple lines of chemotherapy and immunotherapy, which provided valuable insight into the treatment of advanced SCC-transformed lung ADC patients.

Performance of different methods for detecting T790M mutation in the plasma of patients with advanced NSCLC after developing resistance to first-generation EGFR-TKIs in a real-world clinical setting.

Several approaches to the detection of T790M mutations in patient plasma or tissue samples have been implemented to date. The present study was designed to assess the ability of different technologies to detect the T790M mutation in plasma samples and to evaluate the relative rates of re-biopsy and subsequent patient management in a clinical setting. Data from patients with advanced NSCLC who visited the Department of Respiratory Medicine of the First Hospital Affiliated to Wenzhou Medical University between December 2014 and July 2018 were retrospectively collected. Following re-biopsy, these patients were evaluated for the presence of the T790M mutation via next-generation sequencing (NGS), amplification refractory mutation system or Roche Cobas z480 (Cobas) analyses of tissue samples. T790M mutation status in tumor tissue samples was calculated as a standard reference used to establish the sensitivity, specificity and concordance of three circulating tumor DNA detection approaches, including NGS, droplet digital PCR (ddPCR) and super amplification refractory mutation system (SuperARMS). Subsequent patient management was also recorded. In total, 287 patients with advanced non-small cell lung cancer were evaluated, of whom 55.4% (159/287) underwent tissue re-biopsy, 76.7% (122/159) underwent sequencing analysis of plasma and/or tissue samples, and 59.0% (72/122) were found to harbor the T790M mutation. The rates of plasma sample T790M detection via NGS, ddPCR and SuperARMS were 60.0, 59.3 and 60.0%, respectively. Only 32 patients with T790M mutations (44.4%, 32/72) were treated with third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), while 19 continued treatment with first-generation TKIs, 13 underwent chemotherapy, 1 switched to treatment with anlotinib, 4 succumbed to pericardial or brain metastases, and 3 were lost to follow-up. Additionally, 2 patients exhibited histological transformation from adenocarcinoma to small cell lung cancer, while 17/97 patients who were evaluated for brain metastases during treatment exhibited intracranial progression. Of these, 8 patients had been treated with osimertinib. In this study of a real-world clinical setting, fewer patients than expected underwent re-biopsy and gene sequencing. Of the tools available for the analysis of plasma samples, NGS exhibited the highest sensitivity and concordance with the results of tissue-based T790M detection strategies. It was additionally found that only a subset of patients harboring the T790M mutation were ultimately treated using third-generation EGFR-TKIs.

Diagnostic performance of the metagenomic next-generation sequencing in lung biopsy tissues in patients suspected of having a local pulmonary infection.

PURPOSE: This study aims to evaluate the diagnostic application and performance of the metagenomic next-generation sequencing (mNGS) in patients suspected of local pulmonary infection by comparing it to the traditional pathogen detection methods in lung tissue specimens obtained by a computerized tomography-guided biopsy (CT-guided biopsy). METHODS: We retrospectively reviewed patients, admitted to the First Affiliated Hospital of Wenzhou Medical University, China from May 2018 to December 2020, who were suspected of local pulmonary infection. All cases received a CT-guided lung biopsy, tissue samples were sent both for conventional examinations (CE) and mNGS tests. The sensitivity and specificity of the two diagnostic approaches were compared. RESULTS: 106 patients enrolled, 76 patients were diagnosed with a pulmonary infection. Among 49 patients with identified pathogens, CE confirmed pathogenic infections in 32 cases. Mycobacterium spp. and fungi accounted for 37.5% (12/32) and 28.1% (9/32), respectively, with bacteria 34.4% (11/32). The mNGS examination detected extra pathogenic microorganisms in 22 patients that were consistent with the patients' clinical and radiographic pictures. The sensitivity of mNGS was 53.9% vs. 42.1% for the CE, while the specificity was 56.7% versus 96.7%. For detection rate, mNGS was significantly superior to CE in bacterial (96.3% vs. 40.7%, p < 0.05), and mixed infections (100% vs. 50%, p < 0.05), but inferior to CE in fungal (60% vs. 90%, p > 0.05) and Mycobacterium spp. infections (66.7% vs. 100%, p > 0.05) with no significant difference. Among 31 cases diagnosed with lung abscess, the diagnostic performance of the detection rate was 67.7% (21/31) in favour of mNGS compared to 29.0% (9/31) for CE (p < 0.05). Most polymicrobial infections were induced by anaerobic species that coexisted with Streptococcus constellatus. And Klebsiella pneumoniae was the most common isolated monomicrobial infection. CONCLUSIONS: The most commonly detected causative pathogens for local pulmonary infections were bacteria, Mycobacterium spp. and fungi. Compared with the CE, the advantages of mNGS in the pathogens detection lie in the discovery of bacterial and mixed infections, as well as in the detection of lung abscess. Conversely, mNGS is not good enough to be recommendable for the detection of Mycobacterium spp. and fungi.

Clinical evaluation of a laboratory-developed test using clone E1L3N for the detection of PD-L1 expression status in non-small cell lung cancer.

BACKGROUND: Programmed death ligand 1 (PD-L1) has been used as a diagnostic marker to identify patients that will benefit from immune checkpoint inhibitors in non-small cell lung cancer (NSCLC). Immunohistochemistry with E1L3N clone is one of the most widely used and inexpensive laboratory-developed tests for PD-L1, but still need to be compared and validated with standard methods for clinical application. METHODS: We investigated the performance of E1L3N clone for PD-L1 testing in 299 tumor tissues of NSCLC patients and its comparability with FDA-approved 22C3 clone. RESULTS: The results show that the negative coincidence rate, weak positive coincidence rate, and positive coincidence rate were 97.4%, 92.2%, and 97.6% using the E1L3N assay relative to the 22C3 assay, respectively. An overall agreement of 96.3% was achieved between these two assays. We also found that the overall concordances were 97.8% and 93.9% for PD-L1 detection in large and small specimens, respectively, and no significant difference was obtained between these two assays (p = 0.076). In addition, the expression of PD-L1 was not detected in tumor tissues of benign lung disease using both the E1L3N and 22C3 assays. CONCLUSION: E1L3N can be used as a reliable alternative antibody clone to evaluate PD-L1 expression status for NSCLC patients.

Isotretinoin plus 420 nm intense pulsed light versus isotretinoin alone for the treatment of acne vulgaris: a randomized, controlled study of efficacy, safety, and patient satisfaction in Chinese subjects.

Either isotretinoin or intense pulsed light (IPL) proved to be effective to alleviate acne lesions, but the combined treatment has rarely been reported. The study aimed to evaluate the efficacy, safety, and patient satisfaction of isotretinoin and 420 nm IPL combined treatment. Forty-seven patients with facial acne with Global Evaluation Acne (GEA) graded 2-4 were randomized into study group and control group. The patients in the control group received oral isotretinoin for 8 weeks. The patients in the study group were treated with oral isotretinoin for 8 weeks, together with a biweekly 420 nm IPL treatment for 4 weeks. Topical agents included adapalene and fusidic acid. Efficacy was evaluated using digital photographies taken at baseline and week 12 by an independent dermatologist, including GEA grade, lesion count, lesion reduction percentage, and effective rate. All patients completed a questionnaire about dermatology life quality index (DLQI) and satisfaction visual analog scale (VAS) on week 12, and were followed up for another 2 months. Adverse events were recorded. The patients in the study group experienced significant reduction in GEA grade, total lesions, and inflammatory lesions on week 12, compared with the control group (p < 0.05). The patients in the study group reported lower DLQI and higher VAS satisfaction (p < 0.05) and experienced lower incidence of relapse (p < 0.05). No severe adverse event was identified in both groups. Compared with isotretinoin alone, isotretinoin and 420 nm IPL combined treatment proved to be more effective within limited treatment duration. It was well-tolerated and the patients' satisfaction was high.

Multisystem involvement Langerhans cell histiocytosis in an adult: A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare condition wherein Langerhans cells proliferate abnormally, adversely impacting organs including lymph nodes, bones, skin, lungs, and pituitary gland. The LCH disease course varies widely among patients from a self-limiting condition to one that progresses rapidly and culminates in death. It is uncommon for multisystem LCH to be observed in adults. Herein we describe a woman suffering from multi-system LCH involvement. CASE SUMMARY: A 37-year old Chinese woman was admitted to the hospital in June 2019 suffering from dyspnea that had progressed over the course of 5 years. Her medical history included: central diabetes insipidus (DI) that had been treated via radiotherapy, desmopressin acetate, and bromocriptine; bilateral pneumothorax with two surgeries having been performed to remove bullae; and autoimmune hepatitis that had been unsuccessfully treated using a combination of methylprednisolone and mycophenolate mofetil. A chest computed tomography (CT) scan revealed the presence of multiple pulmonary cysts of varying sizes. We re-analyzed right pulmonary bullae samples that had been removed in 2014, performed a systematic 18F-FDG PET/CT analysis, and convened a multidisciplinary medical team to diagnose and treat this patient. As a result, we were able to eventually diagnose this patient with LCH that was not associated with BRAF-V600E mutations. CONCLUSION: We hope to emphasize the importance of systemic evaluation and of cooperation between multidisciplinary physicians with the goal of improving awareness and detection of this orphan disease.

Primary pulmonary lymphoma manifesting as diffuse ground glass opacities: a case report and literature review.

Primary pulmonary lymphoma is a rare clinical neoplasm, and its atypical manifestation frequently leads to misdiagnosis. Here, we have reported a rare case of a 55-year-old man who presented with cough, dizziness, and fatigue. His chest computed tomography (CT) revealed diffuse ground glass pulmonary opacities. Bronchoscope lavage demonstrated lymphocyte predominance, while transbronchial biopsy indicated chronic inflammation. The administration of a broad-spectrum antibiotic regime supplemented with a high dosage of methylprednisolone was ineffective in improving the general condition of the patient, and the diffuse ground glass pulmonary opacities continued to worsen. CT-guided percutaneous lung biopsy confirmed the diagnosis of primary pulmonary lymphoma-diffuse large B-cell (PPL-DLBCL) without extrapulmonary involvement. The patient's general condition improved with the systemic chemotherapy of CHOP. In the context of a systemic review of relevant literature, pulmonary lymphoma should be considered in the differential diagnosis of diffuse ground glass pulmonary opacities, and bronchoscopy is recommended for pathological diagnosis. Moreover, CT-guided percutaneous lung biopsy should also be adopted whenever necessary.

Disseminated Talaromyces marneffei And Mycobacterium avium Infection Accompanied Sweet's Syndrome In A Patient With Anti-Interferon-γ Autoantibodies: A Case Report.

BACKGROUND: Patients with high-titer anti-IFN-γ autoantibodies present disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections. Due to its rare occurrence and non-specific symptoms, this syndrome is difficult to diagnose during early disease stages. Here, we report a case with high-concentrations of serum anti-IFN-γ autoantibodies who presented with disseminated Talaromyces marneffei and NTM disease accompanied Sweet's syndrome. CASE PRESENTATION: A 62-year-old Chinese woman with no previous history was admitted to our hospital in August 2016 due to intermittent fever for 2 years, left chest wall redness, and swelling for 3 months. During hospitalization, the patient was confirmed with disseminated T. marneffei and successfully treated with antifungal therapy. In July 2017, upon second admission, Mycobacterium avium intracellular (MAC) pulmonary infection was established after positive cultures from the right lung tissue. The patient failed treatment after 1 month of anti-NTM therapy due to side effects. In May 2018, she was confirmed as having disseminated MAC disease accompanied by hand rashes, which was considered as Sweet's syndrome. High-level anti-IFN-γ antibodies in the patient serum were detected upon comparison with normal controls (2.85-fold increase). Following anti-NTM therapy, both symptoms and pulmonary infiltration gradually improved, and joint destruction and lymphadenitis remained. CONCLUSIONS: Patients with anti-interferon-γ autoantibodies should be considered for severe, recurrent infections in adults in the absence of other known risk factors. Sweet's syndrome is a common skin manifestation of the syndrome.

A comparison of EGFR mutation status in tissue and plasma cell-free DNA detected by ADx-ARMS in advanced lung adenocarcinoma patients.

BACKGROUND: Previous studies have shown that there are different methods used to detect the epidermal growth factor receptor (EGFR) mutation status in plasma cell-free DNA (cfDNA) for advanced lung adenocarcinoma patients including the ADx-Amplification Refractory Mutation System (ADx-ARMS). We explored the performance of the ADx-ARMS in detecting the EGFR mutations in cfDNA. METHODS: This prospective cohort study enrolled patients who presented with advanced (stage IIIb/IV) lung adenocarcinoma. EGFR mutations in plasma cfDNA and tumor tissues by ADx-ARMS were detected. Next-generation sequencing (NGS) in plasma was performed in patients with inconsistent gene region mutations in the plasma and matched tissue samples. We calculated the clinical parameters of the ADx-ARMS for EGFR mutation status in the plasma of cfDNA, using the tumor tissues as the standard for measurement. The objective response rate (ORR) and progression-free survival (PFS) were also calculated for patients receiving first-generation EGFR-tyrosine kinase inhibitors (TKIs) therapy. RESULTS: In total, 203 patients were included in the final analysis. Mutations were discovered in 58.6% (119/203) of the tumor tissues and 31.0% (63/203) were detected EGFR mutations in both tumor tissues and matched plasma. The sensitivity and the specificity setting for detecting the EGFR mutations in the plasma using the ADx-ARMS were configured to 52.9% and 98.8%. An ORR of 64.8% was observed among the 71 patients who were identified as being EGFR-positive in their tumor tissues, who had received treatments using Gefitinib or Icotinib. Next, the ORR was observed to be 69.0% among the 42 patients with an EGFR mutation in their plasma. The median PFS of the patients with an EGFR mutation in tumor tissues and plasma were 10.0 vs. 11.0 months (P=0.175). The median PFS of the patients with an EGFR wild-type in the plasma was 8.7 months, which was significantly shorter than the EGFR mutant-type in plasma (P=0.001). CONCLUSIONS: Using ADx-ARMS as an approach with high specificity but moderate sensitivity to detect the EGFR mutations in plasma cfDNA and EGFR mutation status in plasma cfDNA using the ADx-ARMS can predict the tumor response for EGFR-TKIs.

The performance of serum cryptococcal capsular polysaccharide antigen test, histopathology and culture of the lung tissue for diagnosis of pulmonary cryptococcosis in patients without HIV infection.

BACKGROUND: Clinicians may fail to make an early diagnosis of pulmonary cryptococcosis (PC) without HIV infection. Serum cryptococcal capsular polysaccharide antigen (CrAg) test, histopathology and culture of lung tissue play different roles in diagnosis of PC. OBJECTIVE: To investigate the performance of serum CrAg test, histopathology and culture of the lung tissue in diagnosis of PC without HIV infection. PATIENTS/METHODS: From January 2011 to September 2017, patients with proven PC were recruited from a teaching hospital in southern China. Those patients with HIV infection, PC confirmed by surgery or PC with probable or possible diagnosis were excluded from the study. Latex agglutination test and CrAg lateral flow assay were used for detection of serum CrAg. Lung biopsy and needle aspiration were performed under computed tomography guidance. RESULTS: Eighty-nine patients with proven PC including 41 male (46.1%) and 48 female (53.9%) were enrolled. Fifty-one (57.3%) patients had underlying disease. Positive CrAg test was found in 83 (93.3%) cases. Among six cases with negative CrAg test, PC was confirmed by histology in two cases and positive culture in four cases. The histopathological results of 77 (86.5%) cases revealed cryptococcal granuloma and 12 cases showed chronic inflammation, which was confirmed by positive culture. Among 65 cases, the diseased tissue of 46 (70.8%) cases presented Cryptococcus neoformans in the culture and one case was diagnosed with lung cancer coexisting with PC. CONCLUSION: Our findings showed that serum CrAg test is rapid and sensitive in diagnosing PC, histology is important for confirming PC and culture plays a complementary role. Biopsied lung tissue should be submitted for cultures whenever feasible.

Responses to crizotinib and chemotherapy in patients with lung adenocarcinoma harboring a concomitant EGFR mutation and ALK gene rearrangement: A case report and review of the literature.

Previous studies have indicated that, in lung cancers, the gene rearrangement of ALK is mutually exclusive with mutations in the epidermal growth factor receptor (EGFR) gene. However, the coexistence of EML4-ALK fusions and EGFR mutations (double positive) has been occasionally reported, with frequencies ranging from 0-8%. Currently, no consensus standard therapy exists for tumors with double positive mutations. In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy. A review of the literature revealed a total of 65 cases, including our case, harboring double positive mutations, and of these cases, 39 (60.0%) patients had received an EGFR tyrosine kinase inhibitor (EHGR-TKI), and 15 (23%) patients had received crizotinib treatment, the majority of whom had crizotinib selected for them as a second-line or third-line therapy. The disease control rate (DCR) of EGFR-TKI was 72.2%, with the progression-free survival (PFS) being 11.9 months, whereas the DCR of crizotinib was 93.3%, with the PFS being 10 months.

Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive epidermal growth factor receptor (EGFR) mutations detection in lung cancer patients, but the existing methods have limitations in sensitivity or in availability. In this study, we evaluated the performance of a novel assay called ADx-SuperARMS in detecting EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma. METHODS: A total of 109 patients with metastatic advanced adenocarcinoma were recruited who provided both blood samples and matched tumor tissue samples. EGFR mutation status in plasma samples were tested with ADx-SuperARMS EGFR assay and tumor tissue samples were tested with ADx-ARMS EGFR assay. The clinical sensitivity, specificity, positive prediction value (PPV), and negative prediction value (NPV) of ADx-SuperARMS EGFR assay were calculated by using EGFR mutation status in tumor tissue as standard reference. A receiver operating characteristic (ROC) analysis was implemented and an area under the curve (AUC) was calculated to evaluate sensitivity and specificity of exon 19 deletion (E19Del) and L858R mutation detection. The objective response rate (ORR) were calculated according to the EGFR mutation status determined by ADx-superARMS as well. RESULTS: 0.2% analytical sensitivity and 100% specificity of the ADx-SuperARMS EGFR assays for EGFR E19Del, L858R, and T790M mutants were confirmed by using a series of diluted cell line DNA. In the clinical study, EGFR mutations were detected in 45.9% (50/109) of the plasma samples and in 56.9% (62/109) of the matched tumor tissue samples. The sensitivity, specificity, PPV and NPV of the ADx-SuperARMS EGFR assay for plasma EGFR mutation detection were 82.0% (50/61), 100% (48/48), 100% (50/50), and 81.4% (48/59), respectively. In ROC analysis, ADx-SuperARMS achieved sensitivity and specificity of 88% and 99% in E19Dels as well as sensitivity and specificity of 89% and 100% in L858R, respectively. Among the 35 patients who were plasma EGFR mutation positive and treated with first generation of EGFR-tyrosine kinase inhibitors (TKIs), 23 (65.7%) achieved partial response, 11 (31.4%) sustained disease, and 1 (2.9%) progressive disease. The ORR and disease control rate (DCR) were 65.7% and 97.1%, respectively. CONCLUSIONS: ADx-SuperARMS EGFR assay is likely to be a highly sensitive and specific method to noninvasively detect plasma EGFR mutations of patients with advanced lung adenocarcinoma. The EGFR mutations detected by ADx-SuperARMS EGFR assay could predict the efficacy of the treatment with first generation of EGFR-TKIs. Hence, EGFR blood testing with ADx-SuperARMS could address the unmet clinical needs.

Diagnosis of tuberculous pleurisy with combination of adenosine deaminase and interferon-γ immunospot assay in a tuberculosis-endemic population: A prospective cohort study.

The aim of this study was to identify the optimal cut-off value of T cell enzyme-linked immunospot assay for tuberculosis (T-SPOT.TB) and evaluate its diagnostic performance alone (in the peripheral blood) or in combination with the adenosine deaminase (ADA) activity test (in peripheral blood and the pleural fluid) in patients with tuberculous pleurisy.Adult patients presenting with pleural effusion were included in this prospective cohort study. Tuberculous pleurisy was diagnosed by T-SPOT.TB in peripheral blood and a combination of T-SPOT.TB and ADA activity test in pleural fluid and peripheral blood. Receiver operating characteristic (ROC) curve in combination with multivariate logistic regression was used to evaluate the diagnostic performance of the assays.Among a total of 189 patients with suspected tuberculous pleurisy who were prospectively enrolled in this study, 177 patients were validated for inclusion in the final analysis. ROC analysis revealed that the area under the ROC curve (AUC) for T-SPOT.TB in pleural fluid and peripheral blood was 0.918 and 0.881, respectively, and for the ADA activity test in pleural fluid was 0.944. In addition, 95.5 spot-forming cells (SFCs)/2.5 × 10 cells were determined as the optimal cut-off value for T-SPOT.TB in pleural fluid. Parallel combination of T-SPOT.TB and ADA activity test in pleural fluid showed increased sensitivity (96.9%) and specificity (87.5%), whereas serial combination showed increased specificity (97.5%). The combination of 3 assays had the highest sensitivity at 97.9%, with an AUC value of 0.964.T-SPOT.TB in pleural fluid performed better than that in peripheral blood and the ADA activity test in pleural fluid for tuberculous pleurisy diagnosis. The optimal cut-off value of T-SPOT.TB in pleural fluid was 95.5 SFCs/2.5 × 10 cells. Combination of 3 assays might be a promising approach for tuberculous pleurisy diagnosis.

Solitary pleural myeloma diagnosed by semi-rigid thoracoscopy: A case report and literature review.

Multiple myeloma (MM) is characterized by abnormal proliferation of neoplastic plasma cells. Pleural effusion as an initial presentation of this disease is rare, as is true pleural myeloma. We herein present a case of solitary pleural myelomatous lesion in a 70-year-old male patient diagnosed by pleural biopsy via semi-rigid thoracoscopy followed by histopathological examination. Furthermore, a review of the related English literature identified 22 cases of pleural myeloma, only 3 of which were diagnosed by video-assisted thoracoscopy. To the best of our knowledge, this is the first reported case of a solitary pleural myelomatous lesion diagnosed by pleural biopsy via semi-rigid thoracoscopy. Patients with MM with pleural involvement, including the present case, appear to have a short survival despite aggressive treatment. Our patient received chemotherapy with bortezomib, epiadriamycin and dexamethasone; however, he deteriorated rapidly after one cycle of chemotherapy and succumbed to the disease 8 weeks after the initial presentation. According to our experience, semi-rigid thoracoscopy is an effective and safe method for obtaining a pleural specimen for histopathological evaluation.

Pseudomembranous Aspergillus tracheobronchitis: a potential for high mortality in low-risk patients.

Pseudomembranous Aspergillus tracheobronchitis (PMATB) is a relatively uncommon form of invasive pulmonary aspergillosis. PMATB is characterized by necrosis and sloughing of the respiratory epithelium resulting from the invasion of the tracheobronchial mucosa by Aspergillus species. The prognosis for patients with PMATB and underlying immune compromise is poor, but existing data suggest that the outcome of PMATB occurring in patients without overt immune compromise is favorable. To investigate the clinical features and prognosis for immunocompetent patients with PMATB in the study center, 10 patients with histologically and microbiologically confirmed PMATB lacking overt immune compromise over a 9-year period were retrospectively identified. Although all patients ultimately received systemic antifungal therapy, 4 patients required mechanical ventilation and 3 patients died. This report indicates that PMATB occurring in immunocompetent patients may exhibit an aggressive course, with rapid progression of lung parenchymal involvement and a fatal outcome.

[Bronchoscopic and CT findings of invasive tracheobronchial and pulmonary aspergillosis in patients without immunodeficiency].

OBJECTIVE: To explore the bronchoscopic and CT findings of invasive tracheobronchial and pulmonary aspergillosis in patients without immunodeficiency. METHODS: Clinical data and bronchoscopic and CT findings of 6 patients with tracheobronchial and pulmonary aspergillosis were reviewed from January 2004 to August 2008. RESULTS: All the patients had no immunodeficiency diseases. The bronchoscopic findings mostly presented in 2 forms: single endobronchial nodule and ulcerative or pseudomembranous tracheobronchitis. The lesions were diffusely distributed or localized. Chest CT showed tracheal or bronchial wall thickening in the early stage, and with disease progression, local consolidation or multiple nodules and cavitation became the most common findings. The nodules and cavities were predominantly peribronchial. A solitary nodule was found in 2 patients. All the cases had been misdiagnosed as other diseases, and repeated courses of antibiotics or corticosteroids had been tried. CONCLUSIONS: Ulcerative or pseudomembranous tracheobronchitis and single nodule are the most common bronchoscopic findings of invasive tracheobronchial aspergillosis. Local consolidation, multiple nodules and cavitation with predominantly peribronchial distribution are the most common CT findings.