Monkeypox virus infection of human astrocytes causes gasdermin B cleavage and pyroptosis.

Monkeypox virus (MPXV) infections in humans cause neurological disorders while studies of MPXV-infected animals indicate that the virus penetrates the brain. Pyroptosis is an inflammatory type of regulated cell death, resulting from plasma membrane rupture (PMR) due to oligomerization of cleaved gasdermins to cause membrane pore formation. Herein, we investigated the human neural cell tropism of MPXV compared to another orthopoxvirus, vaccinia virus (VACV), as well as its effects on immune responses and cell death. Astrocytes were most permissive to MPXV (and VACV) infections, followed by microglia and oligodendrocytes, with minimal infection of neurons based on plaque assays. Aberrant morphological changes were evident in MPXV-infected astrocytes that were accompanied with viral protein (I3) immunolabelling and detection of over 125 MPXV-encoded proteins in cell lysates by mass spectrometry. MPXV- and VACV-infected astrocytes showed increased expression of immune gene transcripts (IL12, IRF3, IL1B, TNFA, CASP1, and GSDMB). However, MPXV infection of astrocytes specifically induced proteolytic cleavage of gasdermin B (GSDMB) (50 kDa), evident by the appearance of cleaved N-terminal-GSDMB (30 kDa) and C-terminal- GSDMB (18 kDa) fragments. GSDMB cleavage was associated with release of lactate dehydrogenase and increased cellular nucleic acid staining, indicative of PMR. Pre-treatment with dimethyl fumarate reduced cleavage of GSDMB and associated PMR in MPXV-infected astrocytes. Human astrocytes support productive MPXV infection, resulting in inflammatory gene induction with accompanying GSDMB-mediated pyroptosis. These findings clarify the recently recognized neuropathogenic effects of MPXV in humans while also offering potential therapeutic options.

Comparison of contrast-enhanced ultrasonography and MRI results obtained by expert and novice radiologists indicating short-term response after transarterial chemoembolisation for hepatocellular carcinoma.

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.

Blood lipid profile, HbA1c, fasting glucose, and diabetes: a cohort study and a two-sample Mendelian randomization analysis.

PURPOSE: The prevalence of diabetes is increasing worldwide. The associations between the lipid profile and glycated hemoglobin (HbA1c), fasting glucose, and diabetes remain unclear, so we aimed to perform a cohort study and a two-sample Mendelian randomization (MR) study to investigate the causality between blood lipid profile and HbA1c, fasting glucose, and diabetes. METHODS: A total of 25,171 participants from the Taiwan Biobank were enrolled. We applied a cohort study and an MR study to assess the association between blood lipid profile and HbA1c, fasting glucose, and diabetes. The summary statistics were obtained from the Asian Genetic Epidemiology Network (AGEN), and the estimates between the instrumental variables (IVs) and outcomes were calculated using the inverse-variance weighted (IVW) method. A series of sensitivity analyses were performed. RESULTS: In the cohort study, high-density lipoprotein cholesterol (HDL-C) was negatively associated with HbA1c, fasting glucose, and diabetes, while the causal associations between HDL-C and HbA1c (ßIVW = - 0.098, p = 0.003) and diabetes (ßIVW = - 0.594, p < 0.001) were also observed. Furthermore, there was no pleiotropy effect in this study using the MR-Egger intercept test and MR-PRESSO global test. CONCLUSIONS: Our results support the hypothesis that a genetically determined increase in HDL-C is causally related to a reduction in HbA1c and a lower risk of diabetes.

[The optimal examination duration for the detection of epileptiform discharge in outpatient video-electroencephalography].

Objective: To determine the optimal examination duration by evaluating the detection rate of epileptiform discharges (EDs) with different examination duration of video-electroencephalography (EEG) in outpatients. Methods: Patients with EDs who underwent 4-hour EEG examination from Xuanwu Hospital, Capital Medical University from October 2020 to November 2021 were retrospectively enrolled, and the detection rates of EDs were calculated with examination duration of 0-0.5 h, 0-1 h, 0-2 h, 0-3 h, and 0-4 h (group A, B, C, D and E), respectively. For each patient, EDs in each hour (group H1, group H2, group H3, group H4) were counted, and the standardized amount of EDs was calculated. For each patient, EDs in wakefulness, drowsiness, non-rapid eye movement-Ⅰ (NREM-Ⅰ), NREM-Ⅱ and NREM-Ⅲ were counted, and the standardized amount of EDs in each state was calculated. Meanwhile, the sleep duration per hour of each patient was also counted (group H1', group H2', group H3', group H4'). The Wilcoxon paired test was used for intergroup comparison to determine the optimal examination duration. Results: A total of 80 patients were enrolled, and aged [M(Q1, Q3)]31 (21, 39) years (range: 5-68 years). There were 38 males and 42 females. The detection rate of EDs was 42.5% (34/80) in group A, 81.3% (65/80) in group B, and 100.0% (80/80) in group C, group D and group E, respectively. The standardized amount of EDs of H1, H2, H3 and H4 was 24.8% (7.8%, 44.2%), 41.5% (25.9%, 63.3%), 15.1% (1.3%, 27.8%) and 1.3% (0, 14.5%), respectively. The standardized amount of EDs of H2 was significantly higher than that of H1, H3 and H4 (all P<0.05). The standardized amount of EDs in wakefulness, drowsiness, NREM-Ⅰ, NREM-Ⅱ and NREM-Ⅲ were 9.6% (0, 28.2%), 3.6% (0, 16.9%), 3.3% (0, 11.8%), 47.3% (21.9%, 72.5%) and 0 (0, 11.5%), respectively. The standardized amount of EDs in NREM-Ⅱ was significantly higher than that in wakefulness, drowsiness, NREM-Ⅰ and NREM-Ⅲ (all P<0.05). The sleep duration in the group of the H1', H2', H3' and H4' was 13.6 (2.5, 23.6), 35.8 (16.5, 54.2), 14.5(0, 34.7) and 0 (0, 14.6) minutes, respectively. The sleep duration in the group of the H2' group was significantly longer than that in the group of H1', H3' and H4' (all P<0.05). Conclusion: The study recommends 2 hours video-EEG in outpatients, which not only ensures the detection rate of EDs, but also facilitates patient cooperation and optimizes the allocation of medical resources.

Addition of dexamethasone to manage acute phase responses following initial zoledronic acid infusion.

Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is the most common adverse reaction to initial zoledronic acid infusion. Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR. INTRODUCTION: Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is due to immunomodulatory actions and is the most common adverse reaction to zoledronic acid (ZOL). The aims of our study were to compare the differences between acetaminophen and dexamethasone plus acetaminophen on the incidence and severity of APRs and to clarify the clinical factors related to APR with initial ZOL infusion. METHODS: Patients with osteoporosis receiving their first ZOL infusion (N = 96) were assigned into two groups and given either acetaminophen (58 patients, control group) or acetaminophen plus dexamethasone (38 patients, study group). APRs were assessed through telephone interviews 2 weeks later post-infusion. Clinical, demographic, and serologic data were recorded. RESULTS: There was a significant increase in the incidence and severity of any APR in the control group than the study group (67% vs. 34%, p = 0.003; 0.69 ± 0.50 vs. 0.34 ± 0.48, p = 0.001). Among the APRs, only myalgia incidence and score were significantly higher in the control group than in the study group. Multivariate analysis demonstrated that previous use of osteoporosis medication and participation in the study group was negatively related to the occurrence of any APR or myalgia. Advanced age was shown to significantly increase myalgia. Study group participants had significantly reduced severity of myalgia. The adherence for redosing ZOL was significantly higher in the study group. CONCLUSION: Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR, especially myalgia, and increasing adherence following initial ZOL infusion.

The combination of soluble tumor necrosis factor receptor type 1 and fibroblast growth factor 21 exhibits better prediction of renal outcomes in patients with type 2 diabetes mellitus.

PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

Highly Efficient Ag3PO4/g-C3N4 Z-Scheme Photocatalyst for Its Enhanced Photocatalytic Performance in Degradation of Rhodamine B and Phenol.

Ag3PO4/g-C3N4 heterojunctions, with different g-C3N4 dosages, were synthesized using an in situ deposition method, and the photocatalytic performance of g-C3N4/Ag3PO4 heterojunctions was studied under simulated sunlight conditions. The results revealed that Ag3PO4/g-C3N4 exhibited excellent photocatalytic degradation activity for rhodamine B (Rh B) and phenol under the same light conditions. When the dosage of g-C3N4 was 30%, the degradation rate of Rh B at 9 min and phenol at 30 min was found to be 99.4% and 97.3%, respectively. After five cycles of the degradation experiment for Rh B, g-C3N4/Ag3PO4 still demonstrated stable photodegradation characteristics. The significant improvement in the photocatalytic activity and stability of g-C3N4/Ag3PO4 was attributed to the rapid charge separation between g-C3N4 and Ag3PO4 during the Z-scheme charge transfer and recombination process.

Tunable light absorption of graphene using topological interface states.

A tunable light absorption of graphene using topological interface states (TISs) is presented. The monolayer graphene is embedded in the interface of asymmetric topological photonic crystals (ATPCs). A strong absorption phenomenon occurs by the excitation of TISs. It is found that the absorption spectra are intensively dependent on the chemical potential of graphene and the periodic number of the ATPCs. Furthermore, the absorption can be rapidly switched in a slight variation of chemical potential, which is modulated by the applied gate voltage on graphene. This study not only opens up a new approach for enhancing light-monolayer graphene interactions, but also provides for practical applications in high absorption optoelectronic devices. This strong absorption phenomenon is different from those in Fabry-Perot resonators, nano-cavities photonic crystal, and traditional topological photonic crystals (TPCs).

Synchronous renal cell carcinoma and pheochromocytoma presenting as acute decompensated heart failure.

We report a 49-year-old woman who presented with a hypertensive crisis and acute heart failure and reduced left ventricular systolic function. An abdominal ultrasonography revealed a huge lobulated heterogeneous mass at the lower pole of the right kidney and a mass over the left suprarenal area, which were further delineated by magnetic resonance imaging. The patient underwent laparoscopic right radical nephrectomy and left adrenalectomy. Histopathological analysis confirmed the diagnoses of clear cell renal cell carcinoma of the right kidney with metastasis to the lung; and atypical pheochromocytoma of the left adrenal gland. Target therapy was initiated, which resulted in stabilization of the patient's tumors and the recovery of her heart function. To avoid a delayed diagnosis and catastrophic outcome, clinicians should consider such rare causes of acute decompensated heart failure.

[Comparison of efficacy and safety between two different methods of nephroureterectomy in two centers].

OBJECTIVE: To compare the efficacy and safety of complete transperitoneal laparoscopic nephroureterectomy (CTNU) and traditional retroperitoneoscopic nehroureterectomy (TRNU) for the management of upper urinary tract urothelial carcinoma(UTUC). METHODS: We retrospectively collected the clinical data of UTUC patients who underwent CTNU or TRNU surgery from January 2011 to December 2018 in Peking University First Hospital and Fujian Provincial Hospital, and compared the clinical characteristics, perioperative parameters, and follow-up results between the CTNU and TRNU surgeries. RESULTS: Finally, a total of 266 cases were included, with 94 cases in the CTNU group and 172 cases in the TRNU group. The proportion of left side lesions was bigger in TRNU group when compared with CTNU group (P<0.05). No significant differences were observed in clinical characteristics, such as age, gender, body mass index (BMI), American society of anesthesiologists score (ASA score) and tumor laterality. All surgery procedures were completed. The vascular resparing was performed by reason that left arteria renalis was injured accidently during surgical operation in one case of TRNU group. No serious complications were observed in both CTNU and TRNU groups. In CTNU group, operating time was (202.9±76.7) min, estimated blood loss was (68.4±73.3) mL, drainage duration was (3.9±1.5) d, drainage volume was (181.7±251.5) mL, and postoperative hospital stay was (7.8±4.1) d. In TRNU group, operating time was (203.5±68.7) min, estimated blood loss was (130.2±252.1) mL, drainage duration was (4.3 ±1.6) d, drainage volume was (179.1±167.5) mL, and postoperative hospital stay was (8.2±3.7) d. The estimated blood loss in CTNU group was significantly less than that in TRNU group (P=0.005).The median follow-up time was 39 months (range: 1-88 months). The 5-year overall survival rate (OS), cancer specific survival rate (CSS), intra-vesical recurrence free survival rate (IvRFS), disease free survival rate (DFS) of CTNU group was 75.6%, 86.9%, 73.8%, 57.5%, respectively. The OS, CSS, IvRFS and DFS of TRNU group was 66.3%, 83.5%, 75.9%, 58.6%, respectively.No significant differences were observed in the OS, CSS, IvRFS and DFS between the CTNU and TRNU groups. CONCLUSION: CTNU technique is a safe and effective surgical option, and further prospective randomized controlled trial is needed for further evaluation.

[Morphometric analysis program combined with magnetoencephalogram in the localization of epileptogenic foci in MRI-negative pharmacoresistant focal epilepsy patients].

Objective: To investigate the value of morphometric analysis program (MAP) combined with magnetoencephalogram (MEG) in the localization of epileptogenic foci in MRI-negative pharmacoresistant focal epilepsy (MNPFE) patients. Methods: A total of 42 consecutive MNPFE patients from Epilepsy center, Xuanwu Hospital, Capital Medical University from January 2015 to December 2016 were enrolled. The analysis process of MAP and magnetoencephalography (MEG) were performed independently. When the MAP+ region and the MEG+ region was in the same lobe, the MAP+ region was defined as the MAP+MEG+ region. The analysis results of MAP and MEG were used to do correlation analysis with surgical outcomes separately or simultaneously. Results: The positive rate of MAP was 69% (29/42), and the complete resection of MAP+ region was significantly associated with seizure-free outcome (P=0.027). The positive detection rate of MEG was 100% (42/42), and there was no significant association between the complete resection of MEG+ region and seizure-free outcome (P=0.517). The positive rate of MAP+MEG+ was 43% (18/42), and the complete resection of MAP+MEG+ region was significantly associated with seizure-free outcome (P=0.009). Conclusion: The combination of MAP which indicates subtle structural abnormalities and MEG which pictures electrophysiological features could probably achieve better epileptogenic foci localization in MNPFE patients.

[Clinical analysis of five cases of autism spectrum disorder complicated with epilepsy with chromosome copy number variation].

Objective: To explore the clinical features and genetic causes of autism spectrum disorder (ASD) patients with epilepsy. Methods: The clinical data of five patients with ASD and epilepsy admitted to Xuanwu Hospital between September 2017 and September 2018 were collected, including medical history, intelligence level, developmental level, physical examination, neuroimaging and electroencephalogram. High-throughput whole-genome sequencing was applied to five patients and their parents. Results: Of five patients, four were male and one was female. All five patients had mild mental retardation, and one patient had significant growth retardation and craniofacial deformity. The average epilepsy onset age was 6.3 years old (7 months to 16 years). The main epileptic type was tonic-clonic seizure with abnormal EEG results. All patients have a favorable response to anti-epileptic drugs. Whole-exome sequencing (WES) revealed copy number variation in all 5 patients. Among them, 3 cases were reported to be pathogenic, and 2 cases were not reported (chromosome 16p13.3 duplication and chromosome 21q22.3 deletion). Conclusions: The results of current study support that autism spectrum disorders with seizures is often associated with copy number variations, such as Williams-Beuren region duplication syndrome, chromosome 15q11.2 duplication syndrome and chromosome 15q11.2 deletion syndrome. We reported two novel copy number variations (chromosome 16p13.3 duplication and chromosome 21q22.3 deletion) in two autism spectrum disorder patients with epileptic seizures.

Ultra-slow light in one-dimensional Cantor photonic crystals.

Ultra-slow light and complete transmission properties in one-dimensional Cantor photonic crystals are presented. In contrast to traditional dielectric photonic crystals, the proposed structure has large group delay, slower group velocity, and a high quality factor within the same layers and materials. This study shows that larger than 1 µs group delay and slower than 1 m/s group velocity are achieved in the fifth-order Cantor photonic crystal with 52.75 µm length. This ultra-slow-light structure is very promising for application in advanced slow-light devices. A high quality factor of 109 and multiband filters with complete transmission can also be obtained by using this approach.

Time-resolved inline digital holography for the study of noncollinear degenerate phase modulation.

Recent works demonstrated that digital time-resolved holography is the prospective approach to study nonlinear light-matter interaction processes. In this Letter, we present a straightforward inline holographic approach for studying degenerate phase modulation induced by an inclined collimated pump beam in the isotropic sample. The method is based on a minimization of the difference between experimentally acquired data and simulated inline holograms obtained from a numerical model of pump-probe interaction in optical nonlinear media. A sophisticated experimental data processing algorithm is implemented to provide high sensitivity and a signal-to-noise ratio eligible for soft interaction with a collimated pump beam. The integral phase shift determined by our method can be used to estimate the nonlinear refractive index and the relaxation time for material with a low damage threshold. We validated our approach for the case of soda-lime and BK7 glasses.

Prognostic impact of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in nasopharyngeal carcinoma: A retrospective study of 180 Taiwanese patients.

OBJECTIVES: Nasopharyngeal cancer (NPC) is an endemic disease in Taiwan. Prognostic factors the anatomical TNM stage are important for its prognostic stratification. An elevated neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor prognosis in various solid tumours. In this study, we analysed the prognostic impact of the NLR in NPC in Taiwan. DESIGN: Single-institution retrospective study. SETTING: Medical centre. PARTICIPANTS: One hundred and eighty patients with NPC treated at the Far Eastern Memorial Hospital, Taiwan, from January 2007 to December 2013. MAIN OUTCOME MEASURES: The association between the clinical or haematological presentations and the prognosis. RESULTS: The majority of the 180 patients included in this study were men (80%) and were <65 years old (91.7%). A neck mass (55.6%) was the most common clinical presentation, followed by nasal (39.4%) and aural (30.6%) symptoms. In addition, the majority (75.4%) of patients had advanced stage (III and IV) disease. Patients with a high NLR (≧3.6) had significantly lower progression-free survival, overall survival and disease-specific survival rates. The association between high NLR and poor prognosis was more pronounced in patients with advanced disease than in those with early-stage NPC. The results of a multivariate analysis revealed that advanced age, clinical symptoms including headache, diplopia and facial numbness, advanced disease stage, and high NLR were independent prognostic factors. CONCLUSION: A high NLR is an independent poor prognostic factor of NPC in Taiwan.

[Clinical features and gene analysis of TBC1D24 gene mutation related early-onset focal myoclonic epilepsy].

Objective: To investigate the clinical features and genetic characteristics of patients with TBC1D24 gene mutation related early-onset focal myoclonic epilepsy. Methods: Clinical data of 3 patients with TBC1D24 gene mutation related early-onset focal myoclonic epilepsy of Xuanwu Hospital from November 2016 to June 2017 was collected and analyzed.Candidate gene mutations were screened by second generation sequencing. Results: Among the 3 patients, 1 was male and 2 were females.Seizure onset age was 4 months, 3 years and 5 years after birth respectively. Two patients had family history of epilepsy.They all had prolonged episodes of focal myoclonus. Two patients had mental retardation.Scalp electroencephalograms (EEG) was recorded in all 3 cases and myoclonic seizures were captured.The ictal EEGs were normal in all cases. In one patient, the ictal EEG of generalized seizure showed alpha rhythm originating from left fronto-central region. Brain magnetic resonance imaging (MRI) was normal in 2 patients. Abnormal signal was found bilaterally in cerebellum in 1 patient. The gene screening showed that two patients carried compound heterozygous mutation of TBC1D24 gene and one carried homozygous mutation, all of which were de novo mutations.All the patients were treated with multiple antiepileptic drugs (AEDs) and seizures were uncontrolled in 2 patients. One patient was followed up for 10 months without recurrence. Conclusions: TBC1D24 gene related early-onset focal myoclonic epilepsy is clinically characterized by early onset, prolonged focal myoclonus which relieved with sleep, mental retardation and poor response to AEDs.The interictal and ictal EEG usually show normal. Genetic analysis can assist in diagnosis and genetic counseling.

Simultaneously Targeting Myofibroblast Contractility and Extracellular Matrix Cross-Linking as a Therapeutic Concept in Airway Fibrosis.

Fibrosis after solid organ transplantation is considered an irreversible process and remains the major cause of graft dysfunction and death with limited therapies. This remodeling is characterized by aberrant accumulation of contractile myofibroblasts that deposit excessive extracellular matrix (ECM) and increase tissue stiffness. Studies demonstrate, however, that a stiff ECM itself promotes fibroblast-to-myofibroblast differentiation, stimulating further ECM production. This creates a positive feedback loop that perpetuates fibrosis. We hypothesized that simultaneously targeting myofibroblast contractility with relaxin and ECM stiffness with lysyl oxidase inhibitors could break the feedback loop, reversing established fibrosis. To test this, we used the orthotopic tracheal transplantation (OTT) mouse model, which develops robust fibrotic airway remodeling. Mice with established fibrosis were treated with saline, mono-, or combination therapies. Although monotherapies had no effect, combining these agents decreased collagen deposition and promoted re-epithelialization of remodeled airways. Relaxin inhibited myofibroblast differentiation and contraction in a matrix-stiffness-dependent manner through prostaglandin E2 (PGE2 ). Furthermore, the effect of combination therapy was lost in PGE2 receptor knockout and PGE2 -inhibited OTT mice. This study revealed the important synergistic roles of cellular contractility and tissue stiffness in the maintenance of fibrotic tissue and suggests a new therapeutic principle for fibrosis.

First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study.

BACKGROUND: Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. PATIENTS AND METHODS: Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. RESULTS: Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group. CONCLUSIONS: First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.

Are bilateral decubitus views necessary in assessing for vertebral compression fractures using DXA vertebral fracture assessment?

The purpose of this study is to assess the differences in VFA diagnostic accuracy when using bilateral decubitus views and whether diagnostic accuracy is affected by scoliosis. Our findings show that the current practice of performing only one side is valid; however, bilateral views can improve specificity in scoliosis. INTRODUCTION: The diagnostic accuracy of vertebral fracture assessment (VFA) can be influenced by poor patient position and scoliosis. This study aims to assess the differences in VFA diagnostic accuracy for right and left lateral decubitus views and the effect of scoliosis. METHODS: One hundred fourteen postmenopausal women received right and left lateral thoracolumbar spine dual-energy VFA and radiography. Cobb angles were measured from the posteroanterior absorptiometry image, and lumbar spine radiography was the standard reference for vertebral fracture and also provides the levels investigated. McNemar's test was used to compare accuracy between the two decubitus position and Fisher's exact test was used for patients with and without scoliosis. RESULTS: Forty-two vertebral fractures (VFs) were identified. There was no significant difference in sensitivity (p = 0.125) or specificity (p = 0.866) between the left lateral decubitus (64.3, 97.2%) and right lateral decubitus (76.2, 91.1%), respectively, views. Scoliotic patients had a significantly worse specificity (92.7 vs 98.1%, p = 0.003) than patients without scoliosis; however, a combination of both decubitus positions significantly improved specificity (p < 0.001). CONCLUSION: Right and left side lateral decubitus views have excellent agreement with radiography and similar diagnostic accuracy in the detection of VFs. Thus, the current practice of performing only one side is valid. With scoliosis, bilateral decubitus views can improve the specificity of detecting VF; however, this would increase radiation dose.

Immunohistochemical studies and fluorodeoxyglucose uptake on positron emission tomography in pharyngeal cancer for predicting radiotherapy-based treatment outcomes.

OBJECTIVES: This study correlated immunohistochemical studies with fluorodeoxyglucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) and identified prognostic factors for radiotherapy (RT)-based treatment outcomes in patients with squamous cell carcinoma of the oropharynx and hypopharynx. METHODS: Genomic data from pre-treatment biopsy specimens (Glut1, CAIX, VEGF, HIF-1α, EGFR, Ki-67, Bcl-2, CLAUDIN-4, YAP-1, c-Met and p16) of 76 patients were analysed using tissue microarrays. FDG uptake was evaluated using the maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG). RESULTS: The overexpression of Glut1 positively associated with increased values of the SUVmax, MTV and TLG, whereas VEGF and HIF-1α expression with the MTV and TLG, respectively. A VEGF immunoreactive score (IRS) >2 (P = 0.001, hazard ratio [HR] = 3.94) and an MTV defined by an SUV of 2.5 (MTV2.5) >14.5 mL (P = 0.004, HR = 3.31) were prognostic factors for low cause-specific survival, whereas a VEGF IRS >2 (P = 0.02, HR = 2.83) for low primary relapse-free survival. CONCLUSION: The overexpression of Glut1, VEGF and HIF-1α associated with increased FDG uptake. For patients with pharyngeal cancer requiring RT, the treatment outcome can be stratified by VEGF and MTV2.5.