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.
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.
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.
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.
•Osimertinib 160 mg exhibited promising ORR and survival benefit in EGFR T790M-positive NSCLC patients with CNS metastasis.•As it caused only grade 1–2 adverse events, osimertinib 160 mg also showed a tolerable safety profile.•It is suitable for BM or LM patients after EGFR TKI treatment and those treated with EGFR T790M-targeting agents or radiotherapy.
Background Mobilized CD34+ cells in peripheral blood have angiogenic potential, which is an important factor in active hair growth. In addition, activated autologous platelet‐rich plasma (PRP) has ...been reported to induce the proliferation of dermal papilla cells.
Objectives To investigate the clinical efficacy of interfollicular injection of CD34+ cell‐containing PRP preparation for pattern hair loss.
Patients and methods CD34+ cell‐containing PRP preparation was injected on the scalps of 13 patients with pattern hair loss, and 13 patients were treated with interfollicular placental extract injection as a control. The numbers of platelets in PRP were microscopically counted and CD34+ cells were evaluated with flow cytometry.
Results Three months after the first treatment, the patients presented clinical improvement in the mean number of hairs, 20.5 ± 17.0% (P < 0.0001), mean hair thickness, 31.3 ± 30.1% (P < 0.0001), and mean two‐point score, 84.4 ± 51.7% (P < 0.0001) compared with baseline values. At 6 months, the patients presented clinical improvement in mean hair count, 29.2 ± 17.8% (P < 0.0001), mean hair thickness, 46.4 ± 37.5% (P < 0.0001), and mean two‐point score, 121.3 ± 66.8% (P < 0.0001) compared with baseline. The MIXED procedure revealed that CD34+ cell‐containing PRP treatment presented a higher degree of improvement than placental extract treatment in hair thickness (P = 0.027) and overall clinical improvement (P = 0.023).
Conclusion Our data suggest that the interfollicular injection of autologous CD34+ cell‐containing PRP preparation has a positive therapeutic effect on male and female pattern hair loss without remarkable major side‐effects.
Background
In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been ...suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection.
Methods
Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted.
Results
Data from 937 patients were available for evaluation. The overall 5‐year disease‐free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5‐year disease‐free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5‐year disease‐free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five‐year disease‐free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic.
Conclusion
Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.
Antecedentes
En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica.
Métodos
Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo.
Resultados
Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas.
Conclusión
La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.
This multinational multicentre cohort study was undertaken to investigate the prognostic value of tumour location in T2 gallbladder cancer and to clarify the adequate extent of surgical resection. Although tumour location influenced prognosis, it was not an independent prognostic factor in T2 gallbladder cancer. T2 gallbladder cancer requires extended cholecystectomy including hepatic resection and lymph node dissection, regardless of the location.
challenges current TNM system
Interfaces, such as grain boundaries, phase boundaries, and surfaces, are important in materials of any microstructural size scale, whether the microstructure is coarse-grained, ultrafine-grained, or ...nano-grained. In nanostructured materials, however, they dominate material response and as we have seen many times over, can lead to extraordinary and unusual properties that far exceed those of their coarse-grained counterparts. In this article, we focus on bimetal interfaces. To best elucidate interface structure–property–functionality relationships, we focus our studies on simple layered composites composed of an alternating stack of two metals with bimetal interfaces spaced less than 100 nm. We fabricate these nanocomposites by either a bottom–up method (physical vapor deposition) or a top–down method (accumulative roll bonding) to produce two distinct interface types. Atomic-scale differences in interface structure are shown to result in profound effects on bulk-scale properties.
An organic field‐effect transistor (OFET) memory device based on pentacene is fabricated using an additional poly(α‐methyl styrene) gate dielectric layer (PαMS, see figure) that has charge‐trapping ...ability (an electret). The device has excellent non‐volatile OFET memory characteristics, believed to originate from the stored charges in PαMS layer and transferred from the semiconductor to the polymeric gate electret.
Background
There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence ...trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF.
Methods
Patients undergoing elective PD or pylorus‐preserving PD with duct‐to‐mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long‐term complications and quality of life 2 years after PD.
Results
A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (−2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (−10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent‐related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non‐pancreatic disease and high body mass index (23·3 kg/m2 or above) predicted clinically relevant POPF.
Conclusion
External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov).
Internal stenting is better
Jung WH, Kang D‐H, Han JY, Jang JH, Gu B‐M, Choi J‐S, Jung MH, Choi C‐H, Kwon JS. Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive ...disorder.
Objective: Obsessive–compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD.
Method: Twenty unmedicated patients with OCD and 20 age‐, sex‐, and IQ‐matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task.
Results: Compared with controls, patients with OCD showed increased ventral striatal activation in the no‐loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no‐gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation.
Conclusion: These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.
AIMS: Cyanobacteria have been used as sustainable bioresource producers for foods, feeds and other valuable natural products. However, selection of a new species (other than Arthrospira), with ...advantageous properties for alimentary purposes, continues to be a challenge due to potential toxicity and low biomass productivity. In this study, we report a valuable filamentous cyanobacterium isolated from Korea. METHODS AND RESULTS: Morphological and phylogenetic analyses demonstrated that the isolate belongs to the genus Leptolyngbya, and consequently designated Leptolyngbya sp. KIOST‐1. Interestingly, Leptolyngbya sp. KIOST‐1 possessed numerous advantageous characteristics for biomass production, similar to Arthrospira. The isolate readily propagated in SOT medium with efficient biomass productivity, and its optimum growth was observed at 30°C under alkaline and saline conditions. Moreover, more than half of the cellular components in Leptolyngbya sp. KIOST‐1 were composed of protein, with approx. 40% of essential amino acids. Most importantly, no significant cytotoxicity was detected in the isolate. CONCLUSIONS: Leptolyngbya sp. KIOST‐1 has a number of advantageous characteristics for alimentary purposes due to its efficient productivity, high protein content and lack of potential cytotoxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: Leptolyngbya sp. KIOST‐1 may be considered a potential candidate for industrial biomass production, similar to Arthrospira.
A memory cell consisting of a Pt/VO2/Pt switch element and a Pt/NiO/Pt memory element connected in series. By applying a voltage higher than Vth of 0.6 V, the switch element reaches the on state and ...the cell can be accessed. Since reset and set voltages are higher than Vth, information can be written by simply applying an appropriate voltage to a selected cell. By applying a voltage lower than Vth to the other cells, we can keep the other cells in the off state and prevent interference between the selected cell and the others.
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