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1.
PURPOSE: To determine how often positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose (FDG-PET) detects extensive-stage small-cell lung cancer (SCLC) in patients considered to have limited-stage disease based on conventional staging procedures, and to determine the impact of PET on treatment planning for presumed limited-stage SCLC. PATIENTS AND METHODS: We prospectively performed pretreatment FDG-PET on 24 patients determined by conventional staging methods to have limited-stage SCLC (defined as disease that could be encompassed within a reasonable radiotherapy portal, excluding bilateral supraclavicular disease). PET images were evaluated for evidence of extensive-stage disease. Tumor-node-metastasis system staging was also assigned for each patient, with and without PET information. RESULTS: FDG-PET demonstrated findings consistent with extensive-stage SCLC in three of 24 patients. FDG-PET correctly upstaged two (8.3%) of 24 patients to extensive-stage disease (95% CI, 1.03% to 27.0%). PET correctly identified tumor in each SCLC mass (primary or nodal) that was suspected on computed tomography (CT) imaging, thus giving a lesion-based sensitivity relative to CT of 100%. PET identified unsuspected regional nodal metastasis in six (25%) of 24 patients, and the radiation therapy plan was significantly altered to include the PET-positive/CT-negative nodes within the high-dose region in each of these patients. Brain PET images in 23 patients disclosed no evidence of brain metastasis. CONCLUSION: FDG-PET has high sensitivity for SCLC and appears to be of value for initial staging and treatment planning of patients with presumed limited-stage disease.  相似文献   
2.

Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Methods

A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.

Results

The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.

Conclusions

Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells.  相似文献   
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This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity. Interestingly, they also have a significant role in immunotherapy and vaccination. Signals generated by TLRs are transduced through NFκB signaling and MAP kinases pathway to recruit pro-inflammatory cytokines and co-stimulatory molecules, which promote inflammatory responses. The excess production of these cytokines leads to grave systemic disorders like tumor growth and autoimmune disorders. Hence, regulation of the TLR signaling pathway is necessary to keep the host system safe. Many molecules like LPS, SOCS1, IRAK1, NFκB, and TRAF3 are involved in modulating the TLR pathways to induce appropriate response. Though quantification of these TLRs helps in correlating the magnitude of immune response exhibited by the animal, there are several internal, external, genetic and animal factors that affect their expression patterns. So it can be concluded that any identification based on those expression profiles may lead to improper diagnosis during certain conditions.  相似文献   
6.
BACKGROUND: Earlier we showed cardiac isoform of alpha-2 macroglobulin (CA2M) to be an early marker of cardiac hypertrophy. DESIGN: In this study, we tried to explore the possibility of using this protein as a marker for diagnosis of cardiac diseases. METHODS: A total of 593 samples were analyzed for the presence of CA2M using sandwich enzyme-linked immunosorbent assay. RESULTS: Samples include various cardiac diseases (230), non-cardiac ailments (263) and controls (100). CONCLUSION: Levels of CA2M in cardiac diseases were significantly higher than other sample groups but moderately elevated in leprosy. This protein could be considered for diagnosis of cardiac diseases as a serum marker.  相似文献   
7.
Pituicytoma is a rare low-grade tumor (WHO Grade I) of pituicytes involving the sellar–suprasellar region, and originating from the specialized glial cells of the neurohypophysis. Clinically and radiologically, they closely mimic pituitary adenoma or meningioma. Diagnosis requires histopathological examination of the resected tissue. This uncommon glial neoplasm is a rarity, with only 57 cases reported in the literature so far. We report three cases of pituicytoma (aged between 7 and 24 years) presenting with reduced vision, headache and features of hypercortisolism in one case. Radiologically, these lesions mimicked meningioma, hypothalamic chiasmatic glioma and pituitary microadenoma, respectively. The second case is a 7-year-old girl, the youngest case on record. Since this tumor is uncommon, it is frequently misdiagnosed. Awareness of this entity is essential for planning management and treatment. We present a brief review of all cases reported in the medical literature, and describe the clinical symptomatology, associated endocrinological abnormalities, imaging characteristics, behavior and outcome.  相似文献   
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Hammock valve, also known as anomalous mitral arcade is a rare mechanism for congenital mitral insufficiency. We report a case of a two-week-old neonate who presented with features of heart failure and an apical systolic murmur. Echocardiogram showed severe mitral regurgitation and abnormal mitral valve with direct attachment of mitral leaflets to papillary muscle without intervening chordae tendinae, typical of hammock valve. Heart failure was controlled with ionotrpes and diuretics. The literature on the hammock mitral valve is reviewed.  相似文献   
10.
Lung ultrasound (LUS) plays a critical role in the SARS‐CoV‐2 pandemic. Evidence is mounting on its utility to diagnose, assess the severity and as a triage tool in the ED. Sonographic features correlate well to computed tomography (CT) chest findings and a bedside LUS performed by a trained clinician along with clinical examination, could be an alternative to chest X‐ray and CT chest in these highly infectious patients. In this article, we have described a step‐by‐step approach to LUS in COVID patients and the CLUE (COVID‐19 LUS in the ED) protocol, which involves an anatomical parameter, the severity of lung changes, objectively scored using the validated LUS scoring system and a physiological parameter, oxygen requirement. We believe this CLUE protocol can help risk‐stratify patients presenting to ED with suspected COVID‐19 and aid clinicians in making appropriate disposition decisions.  相似文献   
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