Current Diagnosis and Management of Small-Cell Lung Cancer

Small-cell lung cancer (SCLC) is an aggressive disease with distinct pathological, clinical, and molecular characteristics from non–small-cell lung cancer. SCLC has high metastatic potential, resulting in a clinically poor prognosis. Early concurrent chemo-radiation is the standard of care for limited-stage SCLC (LS-SCLC). Prophylactic cranial irradiation (PCI) is recommended for patients with LS-SCLC without progression of disease after initial therapy. A combination of etoposide and cisplatin or carboplatin remains the mainstay of first-line treatment for ES-SCLC, with the addition of atezolizumab, now becoming standard. Most SCLCs initially respond to therapy but almost invariably recur. Topotecan and amrubicin (in Japan) remain the primary chemotherapy options for relapsed SCLC. Immunotherapy, including nivolumab with or without ipilimumab, is now available for refractory disease. In general, the poor prognosis of SCLC has not improved significantly for more than 3 decades. Recently, next-generation molecular profiling studies have identified new therapeutic targets for SCLC. A variety of proapoptotic agents, compounds capitalizing on DNA-repair defects, immunotherapy agents, and antibody–drug conjugates are being evaluated in SCLC, with a number of them showing early promise.     

分析蓝光照射、白蛋白治疗新生儿黄疸效果

目的探讨蓝光照射联合白蛋白治疗新生儿黄疸的临床效果。方法选取2018年1月—2018年12月医院收治的136例新生儿黄疸患儿,按随机数字表法分为A组(68例)和B组(68例),A组采取蓝光照射进行治疗,B组在此基础上联合白蛋白进行治疗,并比较不同组患儿治疗疗效。结果B组患儿治疗有效率较A组明显增加(P<0.05);B组患儿治疗前间接胆红素(IBIL)、总胆红素(TBIL)、γ-谷氨酰基转移酶(γ-GT)、游离脂肪酸(FFA)和超敏C反应蛋白(hsCRP)水平比较差异无统计学意义(P>0.05),治疗后B组患儿IBIL、TBIL、γ-GT、FFA和hs-CRP水平明显小于A组(P<0.05)。结论蓝光照射联合白蛋白静滴治疗新生儿黄疸临床疗效较好,有助于减轻胆红素水平以及改善临床症状。     

Decreased efficacy of UV inactivation of Staphylococcus aureus after multiple exposure and growth cycles

UV disinfection is a relatively simple and cost-efficient disinfection method, especially for in-home greywater treatment. In this study, a bench scale experiment was performed using a LED collimated UV-C beam with a peak wavelength of 256?nm to determine if potentially pathogenic bacteria such as Staphylococcus aureus may become enriched in a semi-recirculating greywater system with UV as the sole disinfection step. A statistically significant (P?<?0.001) decreasing trend in UV-C efficacy was observed between the 1st and 6th UV exposure-growth cycles of S. aureus (ATCC 25923), resulting in a 1.5 decrease in log₁₀ removal (P?<?0.00000) by the 5th iteration. An eleven-point dose-response curve of the 7th iteration of S. aureus was estimated and compared to the dose-response curve of the original strain; due to a longer apparent shoulder period and a decay constant of lesser degree, the dose required for a 4-log reduction of the enriched S. aureus was estimated to be ～1.9 times greater (22.0?mJ?cm^?2 versus 11.8?mJ?cm^?2). However, experimental results with S. epidermidis (ATCC 12228) and two wild strains, S. aureus and S. warneri, exhibited no trend of increased resistance. UV doses exceeding 20?mJ?cm^?2 are generally sufficient in achieving a 4-log reduction of bacteria in drinking water systems; however, the results exhibited in this study suggest that when recirculation is involved, there may be a need for UV doses exceeding what is necessary for a 4-log reduction to suppress the enrichment of strains which could pose a public health risk.     

Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis

The aim of this study was to investigate the association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury (RILI) after intensity-modulated radiotherapy (IMRT) for lung cancer. The normal lung relative volumes receiving greater than 5, 10, 20 and 30 Gy (V5–30) mean lung dose (MLD), and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5–30) for the bilateral and ipsilateral lungs of 83 patients were recorded. Any association of clinical factors and dose–volume parameters with Grade ≥2 RILI was analyzed. The median follow-up was 12.3 months; 18 (21.7%) cases of Grade 2 RILI, seven (8.4%) of Grade 3 and two (2.4%) of Grade 4 were observed. Univariate analysis revealed the located lobe of the primary tumor. V5, V10, V20, MLD of the ipsilateral lung, V5, V10, V20, V30 and MLD of the bilateral lung, and AVS5 and AVS10 of the ipsilateral lung were associated with Grade ≥2 RILI (P < 0.05). Multivariate analysis indicated AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI (P = 0.010, OR = 0.272, 95% CI: 0.102–0.729). Receiver operating characteristic curves indicated Grade ≥2 RILI could be predicted using AVS5 of the ipsilateral lung (area under curve, 0.668; cutoff value, 564.9 cm³; sensitivity, 60.7%; specificity, 70.4%). The incidence of Grade ≥2 RILI was significantly lower with AVS5 of the ipsilateral lung ≥564.9 cm³ than with AVS5 < 564.9 cm³ (P = 0.008). Low-dose irradiation relative volumes and MLD of the bilateral or ipsilateral lung were associated with Grade ≥2 RILI, and AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI for lung cancer after IMRT.     

基于不同体位定位CT探讨不同勾画者勾画保乳术后部分乳腺外照射靶区差异

目的 比较基于不同体位定位CT下不同勾画者勾画保乳术后部分乳腺外照射(EB-PBI)靶区差异。方法 2016-2017年间27例保乳术后拟行EB-PBI的患者在自由呼吸状态下序贯完成俯卧位及仰卧位模拟定位3DCT扫描。5位勾画者分别在两种不同体位CT图像上基于术腔金属夹完成瘤床(TB) 靶区勾画和临床靶区(CTV) 的构建。比较两种体位不同勾画者间的靶体积、变异系数(COV)、匹配指数(MD)差异。结果 无论仰卧位还是俯卧位时,不同勾画者所勾画TB、CTV均不同(P<0.001、P=0.001、P<0.001、P=0.001)。俯卧位时不同勾画者CTV交集比仰卧位大5.79cm³(P=0.011)。仰卧位时5位勾画者的COVCTV显著大于俯卧位(P=0.014)。仰卧位时5位勾画者的MDTBTB及MDTBCTV均显著劣于俯卧位(P<0.001、P=0.001)。结论 与仰卧位相比,基于俯卧位构建EB-PBI靶区可显著减少不同勾画者间差异,提高勾画者间的一致性。因此,在自由呼吸状态下基于俯卧位施行EB-PBI更为合理。     

Temporal interference stimulation targets deep brain regions by modulating neural oscillations

BackgroundTemporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range with the goal of non-invasive targeted deep brain stimulation. Yet, the current intensities required in human (sensitivity) to modulate deep brain activity and if superficial brain region are spared (selectivity) at these intensities remains unclear.ObjectiveWe developed an experimentally constrained theory for TI sensitivity to kHz electric field given the attenuation by membrane low-pass filtering property, and for TI selectivity to deep structures given the distribution of modulated and unmodulated electric fields in brain.MethodsThe electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05–2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1–2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms, and then coupled to a validated current-flow model of the human head.ResultsAmplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. Both experiment and model confirmed the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. Adaptation mechanism (e.g. GABA_b) enhanced sensitivity to amplitude modulated waveform in contrast to unmodulated kHz and produced selectivity in modulating gamma oscillation (i.e. Higher gamma modulation in amplitude modulated vs unmodulated kHz stimulation). Selection of carrier frequency strongly affected sensitivity to amplitude modulation stimulation. Amplitude modulated stimulation with 100 Hz carrier frequency required ∼5 V/m (corresponding to ∼13 mA at the scalp surface), whereas, 1 kHz carrier frequency ∼60 V/m (∼160 mA) and 2 kHz carrier frequency ∼80 V/m (∼220 mA) to significantly modulate gamma oscillation. Sensitivity is increased (scalp current required decreased) for theoretical neuronal membranes with faster time constants.ConclusionThe TI sensitivity (current required at the scalp) depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency. TI selectivity is governed by network adaption (e.g. GABA_b) that is faster than the amplitude-modulation frequency. Thus, we show neuronal and network oscillations time-constants determine the scalp current required and the selectivity achievable with TI in humans.