Comparing the efficacy of endovascular treatment for iliac vein compression syndrome with or without acute deep venous thrombosis: A single-center retrospective study.

BACKGROUND: To compare the efficacy of endovascular treatment for iliac vein compression syndrome (IVCS) with or without acute deep venous thrombosis of lower extremity. METHODS: This study retrospectively analyzed the clinical data of 300 IVCS patients, who received endovascular treatment between January 2013 and December 2017. According to whether IVCS was complicated by deep venous thrombosis or not, these patients were divided into non-thrombotic iliac vein lesion group (NIVL group, n = 127) and post-thrombotic iliac vein lesion group (PIVL group, n = 173). After endovascular treatment, all patients were followed up to assess the symptoms improvement and to evaluate the patency of iliac vein. RESULTS: The technical success rate was 98% (294/300), and percutaneous transluminal angioplasty with stenting was adopted in 294 cases. The incidence of perioperative complications was 36.33% (109/300), but no severe complications occurred. During a mean follow-up of 22.3 months (range 6-30 months), 9(6.82%, 9/132) patients in PIVL group had recurrence of deep venous thrombosis, but nobody had deep venous thrombosis and varicose veins recurrence in NIVL group. The effective rate of endovascular treatment in NIVL group and PIVL group was 96.88% and 90.15% (P = 0.050), while the cumulative primary patency of iliac vein in NIVL group was significantly higher than that in PIVL group (P = 0.008). CONCLUSIONS: The endovascular treatment is an effective, feasible, safe method for treating IVCS. There is no difference in the efficacy of IVCS patients with or without deep venous thrombosis, but the medium and long-term patency of patients with deep venous thrombosis is lower than that in patients without deep venous thrombosis.

First Report of Fruit rot Caused by Phytophthora nicotianae on Passion Fruit in Guangxi Province, China.

Passion fruit (Passiflora edulis) is an economically important fruit crop in many tropical and subtropical regions worldwide. In recent years, passion fruit was widely cultivated in Guangxi Province. In 2020, a rot disease occurred on immature fruit of passion fruit in several commercial orchards of Nanning, Guangxi, caused about 50% incidence. The first appeared as small, irregular, water-soaked, brown lesions on immature fruit. As the disease progressed, the lesions rapidly enlarged, causing fruit rot. A layer of sparse white mycelia appeared on the lesions at high humidity. The disease first developed in June, its peak periods from August to September. Five diseased fruits were collected from five different orchards. The edges of symptomatic fleshy mesocarp tissue were cut into pieces (5 mm × 5 mm), surface-sterilized in 75% ethanol solution for 60 s, rinsed three times with sterilized distilled water, and plated on potato dextrose agar (PDA). Plates were incubated at 25°C in the dark. After 5 days, similar white colonies with abundant aerial mycelia developed from all plated tissue samples. Five isolates were obtained, and they were identified as Phytophthora nicotianae based on morphological characteristics and DNA analysis. Spherical hyphal swellings were commonly produced. Numerous sporangia were formed in sterile soil extract. Sporangia were ovoid or obpyriform, papillate, and measured 25 to 58 µm (average 41 µm) × 21 to 45 µm (average 29 µm). Chlamydospores were spherical and 19 to 43 µm in diameter (average 30 µm) (Erwin and Ribeiro 1996). The genomic DNA of a representative isolate Seg2-5 was extracted from mycelia through modified CTAB method (Murray and Thompson 1980). The rDNA internal transcribed spacer (ITS) region, ypt1, and coxII were amplified and sequenced with primers ITS1/ITS4 (White et al., 1990), Yph1F/Yph2R (Schena et al. 2008), and FM75F/FM78R (Villa et al. 2006), respectively. BLAST searches of the ITS, ypt1, and coxII sequences (Accession No. MW470847, MW770870, and MW770871) showed 99 to 100% identity with sequences of P. nicotianae (Accession No. JF792540, MK058408, and MH551183). Based on morphological characteristics and phylogenetic analysis, isolate Seg2-5 was identified as P. nicotianae. To confirm pathogenicity, asymptomatic and immature fruits 'Mantianxing' of passion fruit were previously disinfested in 0.5% sodium hypochlorite. Mycelial plugs of isolate Seg2-5 were placed onto the surface of fruits by nonwounded and pin-prick inoculation. Blank plugs were used as negative controls. Each treatment had five replicates and the test was repeated twice. Fruits were maintained in plastic boxes at 28°C and the initial disease spots appeared at 3 dpi or 5 dpi with wounded or non-wounded inoculation. After 7 to 10 days, all inoculated fruits showed similar symptoms as observed initially in the field, whereas control fruits remained healthy. P. nicotianae was successfully reisolated and identified from the inoculated fruits based on morphological characters and ITS sequence, thus confirming Koch's postulates. P. nicotianae had been previously isolated from passion fruit in South Africa (Van and Huller 1970), Vietnam (Nguyen et al. 2015), and Fujian Province of China (Luo et al. 1993). To our knowledge, this is the first report of P. nicotianae infecting passion fruit in Guangxi Province, China.

HLA-corrected tumor mutation burden and homologous recombination deficiency for the prediction of response to PD-(L)1 blockade in advanced non-small-cell lung cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been shown to be beneficial for some patients with advanced non-small-cell lung cancer (NSCLC). However, the underlying mechanisms mediating the limited response to ICIs remain unclear. PATIENTS AND METHODS: We carried out whole-exome sequencing on 198 advanced NSCLC tumors that had been sampled before anti-programmed cell death 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy. Detailed clinical characteristics were collected on these patients. We designed a new method to estimate human leukocyte antigen (HLA)-corrected tumor mutation burden (TMB), a modification which considers the loss of heterozygosity of HLA from conventional TMB. We carried out external validation of our findings utilizing 89 NSCLC samples and 110 melanoma samples from two independent cohorts of immunotherapy-treated patients. RESULTS: Homology-dependent recombination deficiency was identified in 37 patients (18.7%) and was associated with longer progression-free survival (PFS; P = 0.049). Using the HLA-corrected TMB, non-responders to ICIs were identified, despite having a high TMB (top 25%). Ten patients (21.3% of the high TMB group) were reclassified from the high TMB group into the low TMB group. The objective response rate (ORR), PFS, and overall survival (OS) were all lower in these patients compared with those of the high TMB group (ORR: 20% versus 59%, P = 0.0363; PFS: hazard ratio = 2.91, P = 0.007; OS: hazard ratio = 3.43, P = 0.004). Multivariate analyses showed that high HLA-corrected TMB was associated with a significant survival advantage (hazard ratio = 0.44, P = 0.015), whereas high conventional TMB was not associated with a survival advantage (hazard ratio = 0.63, P = 0.118). Applying this approach to the independent cohorts of 89 NSCLC patients and 110 melanoma patients, TMB-based survival prediction was significantly improved. CONCLUSION: HLA-corrected TMB can reconcile the observed disparity in relationships between TMB and ICI responses, and is of predictive and prognostic value for ICI therapies.

A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy.

BACKGROUND: Up to 40% of patients with non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) present with disease progression in the central nervous system (CNS), either as brain metastases (BM) or leptomeningeal metastases (LM). Osimertinib (80 mg), a third-generation, irreversible, oral EGFR TKI, has shown efficacy in active CNS metastases. However, efficacy of osimertinib 160 mg in BM or LM is unclear. PATIENTS AND METHODS: This prospective, single-arm, two cohort study evaluated the efficacy of osimertinib 160 mg in T790M-positive BM or LM NSCLC patients who progressed on prior EGFR TKI (NCT03257124) treatment. The primary end points were objective response rate (ORR) (H1 = 30%) for the BM cohort and overall survival (OS) (H1 = 5 months) for the LM cohort. RESULTS: The median follow-up duration was 10.1 months and 9.6 months for the BM and LM cohorts, respectively. In the BM cohort, intracranial ORR and disease control rate were 55.0% and 77.5%, respectively. The median progression-free survival (PFS) was 7.6 months [95% confidence interval (CI) 5.0-16.6]; the median OS was 16.9 months [95% CI 7.9-not reached (NR)]. In the LM cohort, intracranial disease control rate was 92.5% and complete response rate was 12.5%. The median OS was 13.3 months (95% CI 9.1-NR); the median PFS was 8.0 months (95% CI 7.2-NR). Subgroup analyses based on previous exposure to T790M-targeting agents, including osimertinib 80 mg or other third-generation EGFR TKIs, showed no difference in PFS in both the BM (n = 18, P = 0.39) and LM (n = 17, P = 0.85) cohorts. Previous radiotherapy favored PFS in the BM cohort (hazard ratio 0.42, P = 0.04). The most common adverse events were decreased appetite, diarrhea, and skin rash; however, most were grade 1-2. CONCLUSION: Thus, osimertinib 160 mg demonstrated promising ORR and survival benefit with a tolerable safety profile in EGFR T790M-positive NSCLC patients with CNS metastasis who progressed on prior EGFR TKIs.

Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial.

Background: Chromosomal rearrangements involving RET, which are found in about 1% of non-small cell lung cancer (NSCLC), define a unique molecular subset. We performed this study to examine the efficacy and safety of vandetanib 300 mg daily in this patient population. Patients and methods: This study was a multi-center, open-label, phase II clinical trial. Patients were enrolled if they had metastatic or recurrent NSCLC with a RET rearrangement, which was confirmed by fluorescence in situ hybridization, had progressive disease against platinum-based doublet chemotherapy, and had a performance status of 0-2. The primary endpoint was the objective response rate. Results: A total of 18 patients were enrolled in this study between July 2013 and October 2015. Patients were aged 35-71 years; three had a performance status of 2, and the majority were a heavily pretreated population (≥ two different previous chemotherapy regimens in 72% of the patients). Among the 17 evaluable patients, three had a partial response (objective response rate = 18%) and eight had a stable disease (disease control rate = 65%). Among these patients, the partial response or disease stabilization was durable for more than 6 months in eight patients. Vandetanib also showed a progression-free survival of 4.5 months, and an overall survival of 11.6 months during a median follow-up duration of 14 months. The safety profile was comparable with previous studies of vandetanib. Most vandetanib-related adverse events were mild with prevalent hypertension and rash (in >70% of patients). Grade 3 toxicity included hypertension (n = 3), QT prolongation (2), and elevation of aminotransferases (1), and as a consequence the dose was reduced in four patients. There were no adverse events associated with grade 4 or 5 toxicity. Conclusion: Vandetanib is moderately active in pretreated patients with advanced NSCLC-harboring RET rearrangements.

Suberoylanilide hydroxamic acid, a novel histone deacetylase inhibitor, improves the development and acetylation level of miniature porcine handmade cloning embryos.

Histone deacetylase inhibitors (HDACis) can change the histone acetylation and significantly enhance the developmental competence of the pre-implantation SCNT embryo. To select a proper histone deacetylase inhibitor to improve the success rate and potentially developmental ability of handmade cloning (HMC) embryos of miniature porcine, we compared the effect of two histone deacetylase inhibitors (SAHA vs. VPA) on HMC embryo development, their histone acetylation level and the expression level of relevant genes. The blastocyst rate and number of blastocyst cells of HMC embryos treated with SAHA (SAHA-HMC) or VPA (VPA-HMC) were significantly higher than those of control (Control-HMC), respectively, but there were no significant difference between SAHA-HMC and VPA-HMC groups. In addition, the acetylation level (AcH4K8) of Control-HMC and VPA-HMC embryos at the blastocyst stage, respectively, was significantly lower than that of in vitro fertilized (IVF) and SAHA-HMC embryos. However, the acetylation H4K8 of the blastocysts had no significant difference between SAHA-HMC and the IVF groups. The SAHA-HMC blastocysts indicated comparative expression levels of Oct4 and HDAC1 (histone deacetyltransferase gene) with those of IVF blastocysts. In contrast, the expression levels of Oct4 were lower and those of HDAC1 were higher in the VPA-HMC and Control-HMC blastocysts, respectively, compared to those of the IVF blastocysts. Our results demonstrated that the HMC embryos treated by SAHA could promote the pre-implantation development and increase the levels of histone H4K8 acetylation and the expression of the OCT4 gene, yet decrease the expression of the HDAC1 gene to the comparable level of the IVF embryos. Our results proved that SAHA may be a better histone deacetylase inhibitor for porcine HMC compared to VPA, and furthermore, it may indicate that SAHA can effectively correct the abnormal histone acetylation during the HMC embryo development and subsequently improve the full-term developmental potential of the HMC embryos after embryo transplantation.

The prevalence of migraine in university students: a systematic review and meta-analysis.

Our aim was to determine the prevalence of migraine amongst university students. Migraine is highly prevalent amongst university students, but the exact frequency remains inconsistent between studies. PubMed, Embase and Google Scholar databases were used to identify studies dealing with the prevalence of migraine amongst university students published between 1 January 1988 and 31 August 2014. The pooled migraine prevalence was calculated using DerSimonian and Laird's random-effects model. Heterogeneity of the results was investigated using subgroup analysis and the trend of migraine prevalence according to the publication year and sample size was determined by cumulative analysis. Data were combined from 56 independent studies, analysing a total of 34,904 students. The pooled migraine prevalence was 16.1% [95% confidence interval (CI) 13.6%-18.9%]: 11.3% (95% CI 8.8%-14.4%) amongst male students and 21.7% (95% CI 18.0%-25.8%) amongst female students. Subgroup analysis revealed that diagnostic criteria (P < 0.0001) and gender distribution (P = 0.004) significantly affected migraine prevalence. Cumulative analysis found that the 95% CI became narrower with ascending publication year and sample size. Many studies agree that migraine is highly prevalent amongst university students, but diverse methodologies lead to substantial heterogeneity in the results. It is shown that gender and diagnostic criteria significantly influence the migraine prevalence and may partially explain the heterogeneity between studies.

Epidemiological investigation of a tap water-mediated hepatitis E virus genotype 4 outbreak in Zhejiang Province, China.

An outbreak of acute hepatitis recently occurred in a nursing home in Zhejiang Province, China. The objectives of this study were to confirm the outbreak and identify the aetiology, source and transmission patterns. All residents and staff in or near the nursing home during the period from 1 October 2014 to 21 May 2015 were investigated regarding hygiene and for epidemiological information including water and food (eating meat especially pork products). Serum and stool specimens were collected for detection of hepatitis E virus (HEV) antibodies using ELISA and RNA using RT-PCR. Samples that were RNA positive were genotyped. Of 185 senior residents and 24 staff in the nursing home, there were 37 laboratory-confirmed cases during the outbreak. Of these cases, 12 patients (three deaths) were symptomatic with jaundice, a common clinical symptom for hepatitis E infection. HEV strains were isolated from three cases and they formed a single cluster within genotype 4d. A case-control study was conducted to investigate potential risk factors for the outbreak and the results revealed that cases more often washed their dishes and rinsed their mouths using tap water than the controls (P < 0·05). Based on hygiene investigation and meteorological information, it is likely that HEV-infected sewage and faeces contaminated the water network on rainy days. Collectively, these results suggest that the outbreak of HEV genotype 4 infection was most likely caused by contaminated tap water rather than food.

[Value of three-dimensional liver acceleration volume acquisition multiphase dynamic contrast-enhanced magnetic resonance imaging in detection of accessory hepatic veins in Budd-Chiari syndrome].

Objective: To investigate the application value of three-dimensional liver acceleration volume acquisition (LAVA) multiphase dynamic contrast-enhanced magnetic resonance imaging (MRI) in the detection of accessory hepatic veins (AHVs) in Budd-Chiari syndrome. Methods: A retrospective analysis was performed for the clinical data of 202 patients with Budd-Chiari syndrome who underwent LAVA multiphase dynamic contrast-enhanced MRI and digital subtraction angiography (DSA). MRI or DSA was used to determine the number of AHVs with a diameter of ≥5 mm. With DSA as the gold standard, the Kappa test was used to evaluate the consistency between these two methods in the detection of AHVs. The receiver operating characteristic (ROC) curve was plotted to evaluate the detection rate of AHVs by MRI. The paired chi-square test was used to compare the difference between MRI and DSA in the detection of occluded openings of AHVs. Results: Among the 202 patients, 139 had AHVs detected by MRI, and 63 did not have AHVs detected by MRI; 123 had AHVs detected by DSA, and 79 did not have AHVs detected by DSA. These two methods showed good consistency in the detection of AHVs (κ= 0.631). The area under the ROC curve was 0.868, and MRI had high sensitivity and specificity in the detection of AVHs. MRI detected the occluded openings of 24 AHVs, and DSA detected the occluded openings of 27 AHVs; there was no significant difference in the number of AHVs with occluded openings detected between MRI and DSA (χ2 = 2.2568, P = 0.1330). Conclusion: LAVA multiphase dynamic contrast-enhanced MRI can accurately detect AHVs in Budd-Chiari syndrome and helps to evaluate the patient's condition and select therapeutic methods.

Small-cell lung cancer detection in never-smokers: clinical characteristics and multigene mutation profiling using targeted next-generation sequencing.

BACKGROUND: Once regarded as a smoker's disease, small-cell lung cancer (SCLC) has been occasionally detected in never-smokers as smoking rates decrease worldwide. We investigated the clinical and genetic characteristics of SCLC in never-smokers. PATIENTS AND METHODS: Patients diagnosed with SCLC were grouped into smokers and never-smokers. The clinical outcomes of the two groups were compared. For SCLC in never-smokers, somatic mutation profiling was carried out using the AmpliSeq™ Cancer Hotspot Panel v2 and semiconductor sequencing technology. Epidermal growth factor receptor (EGFR) mutation was confirmed by PNAClamp™. RESULTS: In total, 391 SCLC patients treated over a 5-year period were analyzed. Fifty patients (13%) were never-smokers. The median overall survival was 18.2 months in never-smokers and 13.1 months in smokers (P = 0.054). Never-smoking history was independently a good prognostic factor [hazard ratio = 0.645, 95% confidence interval (CI) 0.456-0.914], as were limited disease (HR = 0.372, 95% CI 0.294-0.471), and lower age (HR = 0.709, 95% CI 0.566-0.888). The objective response rates to first-line etoposide/cisplatin therapy were similar between never-smokers and smokers (75% versus 81%). Of 28 genetically evaluable never-smokers, EGFR mutations were detected in four cases (two L858R, one deletion in exon 19, and one G719A). Other mutations were in TP53 (n = 26), RB1 (n = 7), PTEN (n = 5), MET (n = 4), and SMAD4 (n = 3). CONCLUSIONS: Never-smokers with SCLC are increasingly prevalent and have a better prognosis than smokers with SCLC in Korea. Our study warrants further investigation in this group.

A randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small-cell lung cancer.

BACKGROUND: It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases. PATIENTS AND METHODS: We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome. RESULTS: The median age was 58 years (range, 29-85) with ECOG 0-1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months [95% confidence interval (CI), 9.2-20.0] in the SRS group and 15.3 months (95% CI, 7.2-23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression [median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy), P = 0.248]. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance. CONCLUSIONS: Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients. CLINICAL TRIALS NUMBER: NCT01301560.

Seroprevalence of severe fever with thrombocytopenia syndrome virus in southeastern China and analysis of risk factors.

Severe fever with thrombocytopenia syndrome virus (SFTSV) has been prevalent for some time in China and it was first identified in 2010. However, the seroprevalence of SFTSV in the general population in southeastern China and risk factors associated with the infection are currently unclear. Blood samples were collected from seven counties across Zhejiang province and tested for the presence of SFTSV-specific IgG antibodies by ELISA. A total of 1380 blood samples were collected of which 5·51% were seropositive for SFTSV with seroprevalence varying significantly between sites. Seroprevalence of SFTSV in people who were family members of the patient, lived in the same village as the patient, or lived in a different village than the patient varied significantly. There was significant difference in seroprevalence between participants who bred domestic animals and participants who did not. Domestic animals are probably potential reservoir hosts and contact with domestic animals may be a transmission route of SFTSV.

A phase-1b study of everolimus plus paclitaxel in patients with small-cell lung cancer.

BACKGROUND: The mammalian target of rapamycin (mTOR) pathway is dysregulated in small-cell lung cancer (SCLC) and everolimus is an oral mTOR inhibitor. METHODS: This phase-1b study assessed everolimus safety at the levels of 2.5, 5, or 10 mg once daily in combination with paclitaxel (175 mg m(-2)) once every 3 weeks in previously treated SCLC patients. The primary end point was to determine the maximum tolerated dose of everolimus. RESULTS: Among 21 enrolled patients, common drug-related adverse events were anaemia, neutropenia, thrombocytopenia, pain, hyperglycemia, and stomatitis. Out of 11 evaluable patients treated with everolimus at the level of 5 mg, 1 patient experienced dose-limiting toxicity (DLT) of grade 4 febrile neutropenia and grade 3 thrombocytopenia. The other two DLTs (grade 4 thrombocytopenia and grade 3 hyperglycemia) occurred in two out of three patients receiving everolimus 10 mg. The overall objective response rate was 28%. CONCLUSION: Everolimus showed an acceptable safety profile and preliminary antitumour activity at the dose of 5 mg once daily when combined with 3-weekly paclitaxel 175 mg m(-2) in patients with SCLC.

Prospective analysis of quality of life in elderly patients treated with adjuvant chemotherapy for non-small-cell lung cancer.

BACKGROUND: Given the more comorbidities with a decline in physiologic reserve, it can be challenging to make appropriate treatment decisions in the elderly. PATIENTS AND METHODS: Here, we prospectively evaluated and compared the health-related quality of life (HRQOL) of patients aged ≥ 65 with aged <65 who were treated with a postoperative chemotherapy for completely resected stage Ib, II or IIIa non-small-cell lung cancer (NSCLC). Either four cycles of paclitaxel (Taxol)-carboplatin (PC) or vinorelbine-cisplatin (NP) was used. The HRQOL was assessed with EORTC QLQ-C30 and EORTC QLQ-LC13. RESULTS: Between October 2008 and October 2011, a total of 139 patients (aged <65, n = 73; ≥ 65, n = 66) were enrolled, and 127 (91.4%) completed the questionnaire. Overall, the quality of life (QOL) in elderly patients did not significantly deteriorate with adjuvant chemotherapy and the time trend of QOL in elderly patients was similar to that of younger patients. Although the elderly suffered from increased treatment-related adverse events involving sore mouth, peripheral neuropathy and alopecia compared with the baseline, the same time trends were also observed in younger group. The mean dose intensities (MDIs) for PC and NP regimen were not significantly different between the two age groups. CONCLUSIONS: Postoperative chemotherapy did not substantially reduce HRQOL in elderly NSCLC patients, and HRQOL during and after adjuvant chemotherapy did not significantly differ by age.

Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer.

BACKGROUND: We compared late thoracic radiotherapy (TRT) with early TRT in the treatment of limited-disease small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS: Patients with LD-SCLC received four cycles of etoposide plus cisplatin every 21 days. Patients were randomly assigned to receive either TRT administered concurrently with the first cycle (early TRT) or the third cycle (late TRT) of chemotherapy. The primary end point was complete response rate. RESULTS: Two hundred twenty-two patients were randomly assigned.Late TRT was not inferior to early TRT in terms of the complete response rate (early v late; 36.0% v 38.0%). Other efficacy measures including overall survival [median, 24.1 v 26.8 months;hazard ratio (HR) 0.93; 95% CI = 0.67­1.29] and progression free survival (median, 12.4 v 11.2 months; HR 1.09; 95%CI = 0.80­1.48) were not different between two arms. No statistical difference was noted in the pattern of treatment failures.However, neutropenic fever occurred more commonly in the early TRT arm than the late TRT arm (21.6% v 10.2%; P = 0.02) [corrected]. CONCLUSION: In LD-SCLC treatment, TRT starting in the third cycle of chemotherapy seemed to be noninferior to early TRT, and had a more favorable profile with regard to neutropenic fever.

Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study.

INTRODUCTION: Dacomitinib showed superior progression-free survival (PFS) and overall survival compared to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations in the ARCHER1050 study. However, because that study did not include patients with brain metastases, the efficacy of dacomitinib in patients with brain metastases has not been clarified. PATIENTS AND METHODS: This single-arm phase II study enrolled 30 patients with treatment-naïve advanced NSCLC harboring activating EGFR mutations from January 2021 to June 2021 and started them on dacomitinib (45 mg/day). All patients had non-irradiated brain metastases with a diameter of ≥5 mm. The primary endpoint was confirmed intracranial objective response rate (iORR). RESULTS: Patients had exon 19 deletions (46.7%) and L858R mutations in exon 21 (55.3%). The confirmed iORR was 96.7% (29/30), with an intracranial complete response of 63.3%. Median intracranial PFS (iPFS) was not reached, with 12- and 18-month iPFS rates of 78.6% [95% confidence interval (CI) 64.8% to 95.4%] and 70.4% (95% CI 54.9% to 90.1%), respectively. In the competing risk analysis, the 12-month cumulative incidence of intracranial progression was 16.7%. Regarding the overall efficacy for intracranial and extracranial lesions, the overall ORR was 96.7%, and the median PFS was 17.5 months (95% CI 15.2 months-not reached). Grade 3 or higher treatment-related adverse events were reported in 16.7% of patients, and 83.3% required a reduced dacomitinib dose to manage adverse events. However, none permanently discontinued dacomitinib treatment due to treatment-related adverse events. CONCLUSIONS: Dacomitinib has outstanding intracranial efficacy in patients with EGFR-mutant NSCLC with brain metastases.

Evaluation of radial and ulnar blood flow after radial artery cannulation with 20- and 22-gauge cannulae using duplex Doppler ultrasound.

This study evaluated ulnar and radial artery blood flow after radial artery cannulation during general anaesthesia using Doppler ultrasound. A total of 80 patients were randomly assigned to receive radial artery cannulation with either a 20-G or 22-G cannula. Arterial diameter, peak systolic velocity, end-diastolic velocity, resistance index and mean volume flow were measured at four time points in both arteries: before anaesthesia; 5 min after intubation; immediately after cannulation; and 5 min after cannulation. After radial artery cannulation, ulnar diameters and blood flow were significantly increased, and persisted until 5 min after cannulation. Radial blood flow was decreased immediately after cannulation and recovered to pre-cannulation values 5 min after cannulation. There were no statistical differences between groups at each time point. Radial artery cannulation causes compensatory increase in ulnar artery blood flow, and the difference in cannula size has minimal effect on this change.

The value of placental vascularization indices for predicting preeclampsia and fetal growth restriction in different stages of gestation: A prospective and longitudinal study.

INTRODUCTION: To assess value of placental vascularization indices (PVIs) for predicting preeclampsia (PE) and fetal growth restriction (FGR) in different stages of pregnancy in high-risk women. METHOD: PVIs derived from 3-dimensional power doppler(3DPD) imaging were measured at seven stages of pregnancy: 11-13+6w, 15-19+6w, 20-23+6w, 24-27+6w, 28-31+6w, 32-36+6w, and ≥37w. PE and FGR were used as outcomes in logistic regression models. Area under the receiver operating characteristic (ROC) curve (AUC) of each PVI was calculated, cut-off points were determined to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Finally, AUCs combined with baseline characteristics, uterine artery pulsatility index (UTPI) and PVIs were used to determine whether PVIs could increase the predictive value. RESULTS: Adverse outcomes occurred in 10.9% of pregnancies. Statistical differences appeared in 32-36+6w only. AUCs of vascularization index (VI) and vascularization flow index (VFI) for 32-36+6w were 0.79 (0.70-0.87, p: 0.000), and 0.78 (0.69-0.88, p: 0.000). Sensitivity, specificity, PPV, NPV, PLR, and NLR for VI were 0.91, 0.63, 20%, 98%, 2.39, and 0.15, and those for VFI were 0.62, 0.84, 29%, 95%, 3.75, and 0.45. AUC increased from 0.79 to 0.85 by adding PVIs to baseline characteristics and UTPI model. No statistical significance was found before 32w. DISCUSSION: VI and VFI were valuable for predicting PE and FGR at the 32-36+6w stage, while their values before 32w were poor.

Adjuvant durvalumab for esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a placebo-controlled, randomized, double-blind, phase II study.

BACKGROUND: We evaluated the efficacy of adjuvant durvalumab after neoadjuvant concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: This randomized, double-blind, phase II study included patients with ESCC who underwent curative surgery after neoadjuvant CCRT. Patients were randomized to receive either durvalumab (20 mg/kg/i.v. every 4 weeks for 12 months) or placebo in a 1:1 ratio and were stratified by age and pathologic tumor stage. The primary endpoint was disease-free survival (DFS). RESULTS: Between March 2016 and June 2018, 86 patients were randomized to the durvalumab (n = 45) or placebo (n = 41) arm. The median follow-up duration was 38.7 months. There was no difference in DFS [hazard ratio (HR) 1.18, 95% confidence interval (CI) 0.62-2.27, P = 0.61] or overall survival (HR 1.08, 95% CI 0.52-2.24, P = 0.85) between the two arms. Subgroup analysis was performed for patients for whom the post-CCRT programmed death-ligand 1 (PD-L1) expression profile could be assessed (n = 54). In the PD-L1-positive group, based on tumor proportion score ≥1%, durvalumab was associated with longer overall survival compared with the placebo (36-month survival rate: 94% versus 64%; HR 0.42, 95% CI 0.10-1.76), while in the PD-L1-negative group, it was associated with shorter overall survival (42% versus 55%; HR 1.53, 95% CI 0.48-4.83), showing the tendency of interaction between post-CCRT PD-L1 status and adjuvant durvalumab therapy for overall survival (interaction P = 0.18). CONCLUSIONS: We failed to demonstrate that adjuvant durvalumab improved survival after neoadjuvant CCRT in patients with ESCC. However, post-CCRT PD-L1 expression could predict the survival of patients who receive adjuvant durvalumab after neoadjuvant CCRT, which needs to be validated.

Nanosecond field-induced quenching of the luminescence from Er-doped silicon nanocrystals.

Er-doped Si-rich SiO2 gate oxide layers containing silicon nanocrystals are prepared by implantation of Si+ and Er+ into SiO2 thin films. The photoluminescence from both Si nanocrystals around 700-850 nm and Er3+ ions at 1.54 microm is strongly quenched by applying electric field in the Si-rich oxide layer. The quenching time and the recovery time of the photoluminescence from Si nanocrystals are less than 50 ns under pulsed field modulation. The quenching rate of the luminescence increases with increasing the density and reducing the size of the silicon nanocrystals. Our results indicate that the fast quenching process originates from the quantum confined Stark effect and enhanced exciton ionization by carrier tunneling between the silicon nanocrystals under the high electric field.