Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Effectiveness of a double-carbapenem combinations against carbapenem-resistant Gram-negative bacteria

The emergence of carbapenem-resistant organisms posed considerable threat to global health while only limited treatment options are available and led to efforts to discover a novel way to treat them. To evaluate in vitro synergistic activity of meropenem plus ertapenem, a total of 203 carbapenem-resistant strains, collected from 12 provinces and municipalities in China, were examined with a dual carbapenem combination therapy. The statistical software R was used for analysis. Two hundred and one (201) of carbapenem-resistant strains mainly produced four types of carbapenemase: KPC-2 (n = 142, 69.95%), OXA-232 (n = 7, 3.45%), NDM (n = 38, 18.72%; 36 NDM-1, 1 NDM-4, 1 NDM-5), and IMP (n = 15, 7.39%; 1 IMP-26, 10 IMP-30, 4 IMP-4). Fifty-one out of two hundred and three (51/203 or 25.12%) of the examined strains showed a synergistic effect for the meropenem plus ertapenem combination throughout the checkerboard method, while only three isolates showed potential clinically relevant synergy (3/203, 1.48%). An additive effect was observed in 55/203 (27.09%) of the examined strains. Ninety-seven of the examined isolates (47.78%) showed fractional inhibitory concentration (FIC) greater or equal to 2 (indicating antagonism). The synergistic activity of meropenem plus ertapenem combination suggests this combination can be a possible way to treat the infection caused by the carbapenem-resistant organisms, especially for IMP or NDM producer with a lesser minimum inhibitory concentration (MIC) and the infected individual who was not recommended to use colistin or tigecycline.     

Hypofractionated radiation therapy for invasive breast cancer: From moderate to extreme protocols

Adjuvant irradiation is the standard treatment after breast conservative surgery. Normofractionated regimen with an overall treatment time of 5 to 6 weeks is often considered as a limiting factor for irradiation compliance. In order to answer this issue, moderate and more recently extreme hypofractionated protocols appeared. We report here oncological outcomes and toxicity of hypofractionated breast irradiation. After defining the frame of moderate and extreme hypofractionated breast irradiations based on overall treatment time, patient selection criteria were listed. According to their levels of proof, the results of moderate and extreme hypofractionated breast irradiation were analysed. Overall treatment time for moderate hypofractionated breast irradiation ranged from 3 to 4 weeks, while for extreme hypofractionated breast irradiation, it was less than 1 week. For moderate hypofractionated breast irradiation, whole breast irradiation was currently performed with or without lymph node irradiation. Moderate hypofractionated breast irradiation has proven to be as safe and as efficient as normofractionated breast irradiation with level IA evidence. For extreme hypofractionated breast irradiation, phase III randomized trials confirmed that accelerated partial breast irradiation was non-inferior in terms of local control compared to normofractionated whole breast irradiation (with external beam radiation therapy and multicatheter brachytherapy), with similar acute and late toxicity. While the use of intraoperative breast irradiation remains under debate, new very accelerated partial breast irradiation (overall treatment time not exceeding 2 days) protocols emerged with encouraging results. Accelerated partial breast irradiation is warranted for extreme hypofractionated breast irradiation and is indicated for low-risk breast cancers. Moderate and extreme hypofractionated breast irradiation regimens are validated and can be routinely proposed according to patient selection criteria.     

Short-Duration Prednisolone in Children with Nephrotic Syndrome Relapse: A Noninferiority Randomized Controlled Trial

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不同药物方案治疗儿童双相情感障碍疗效比较及代谢指标观察

目的 探讨儿童双相情感障碍经不同药物方案治疗后代谢指标的变化及治疗疗效。方法 回顾性分析2017年1月至2020年1月于该院就诊的220例儿童双相情感障碍患儿的临床资料。根据治疗方法分组，单纯采用非典型抗精神病药物治疗的112例患儿纳入对照组，采用非典型抗精神病药物联合心境稳定剂治疗的108例患儿纳入研究组。比较两组基线资料水平，治疗前后代谢指标空腹胰岛素（FIN）、糖化血红蛋白（HbAlc）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平变化，以及代谢综合征发生情况及临床疗效。结果 两组患儿年龄、性别、病程等基线资料比较差异均无统计学意义（P > 0.05）。研究组总有效率为92.6%，高于对照组（82.1%，P < 0.05）。治疗前，两组FIN、HbAlc水平比较差异无统计学意义（P > 0.05）；治疗后，对照组FIN水平高于治疗前，且高于研究组（P < 0.05）；但研究组治疗前后FIN水平比较差异无统计学意义（P > 0.05）；两组治疗前后HbAlc水平比较差异无统计学意义（P > 0.05）。治疗前，两组TC、TG、HDL-C、LDL-C水平比较，差异无统计学意义（P > 0.05）；治疗后，对照组TC、TG水平均高于治疗前，且高于研究组（P < 0.05）；但研究组治疗前后TC、TG水平比较差异无统计学意义（P > 0.05）；两组治疗前后HDL-C、LDL-C水平比较差异无统计学意义（P > 0.05）。研究组代谢综合征发生率（2.8%）低于对照组（9.8%）（P < 0.05）。结论 儿童双相情感障碍采用非经典抗精神病药物联合心境稳定剂治疗对代谢指标水平影响较小，且疗效显著。     

Photoacoustic treatment mitigates cognitive dysfunction in a model of sleep-wake rhythm disturbance

Sleep-wake rhythm disturbances,which are characterized by abnormal sleep timing or duration,are associated with cognitive dysfunction.Photoacoustic treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improving cognitive behavior in abnormal sleep-wake pattern experiments.In this study,we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance model.We established a model of sleep rhythm disturbance in C57 BL/6 J mice via a sleep deprivation method involving manual cage tapping,cage jostling,and nest disturbance.We used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive function.Our results indicated that an intervention in which the mice were exposed to blue light(40-Hz flickering frequency)for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep deprivation.However,interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points,as well as 2 Hz-blue light at 3 intervention time points(subjective day time,subjective night time,and offset time points),had no positive effects on circadian rhythm shift or memory deficits.Additionally,a 2000-Hz sound intervention during subjective day time attenuated the24-hour-acrophase shift and memory decline,while 440-Hz and 4000-Hz sounds had no effect on circadian rhythms.Overall,these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake rhythm.All animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University,China(approval No.20171102)on November20,2017.     

Spontaneous recovery of fear differs among early – late adolescent and adult male mice

Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.     

新氨基糖苷类抗生素89－07给药方案研究

用小鼠败血症系统感染模型，以感染小鼠肾匀浆活菌计数为标准，以庆大霉素为对照药，探讨日剂量单次与分两次给药两种方案对新氨基糖苷类抗生素８９—０７体内抗留作用的影响。结果表明大肠杆菌９０－０２０、绿脓假单胞菌３—３７４、金葡球菌９０—５０６对抗生素８９—０７和庆大霉素均敏感（ＭＩＣ范围０．０６２５～２ｍｇ／Ｌ）；抗生素８９—０７和庆大霉素日剂量单次给药组（ＯＤ）３株实验菌的肾匀浆活菌计数值由给药前的４．９４±０．０９、４．６０±０．２７、４．８６±０．１０１ｇｃｆｕ／ｍｌ分别降至１．９４±０．１９、１．８４±０．２５、１．８８±０．２５１ｇｃｆｕ／ｍｌ（给药后７～８ｈ）．日剂量分两次给药组（ＢＩＤ）则分别降至２．９５±０．４８、２．８７±０．３７、３．４４±０．２７１ｇｃｆｕ／ｍｌ。ＯＤ组对３株实验菌的最大杀菌作用Ｅｍａｘ分别为３．０２、２．９７和２．８５１ｇｃｆｕ／ｍｌ，ＯＤ给药方案的体内杀菌作用明显优于ＢＩＤ方案。     

Isolation impairs place preference conditioning to morphine but not aversive learning in mice

Morphine (8–100 mg/kg IP) induces place preference conditioning in mice. The effect of two different periods of isolation (15 and 30 days) was examined. Mice isolated for 15 days but not 30 days exhibited place preference conditioning to morphine (8 mg/kg). After 30 days of isolation morphine could not induce place preference conditioning with the following doses (8, 16, 64, 100 mg/kg). Social regrouping of male mice previously isolated for 30 days with naive female mice for 15 or 30 days resulted in a reappearance of the conditioned place preference to morphine (16 mg/kg). The specificity of this associative deficit was examined by testing learning in isolated compared to non-isolated mice in two distinct settings: escape learning in the Morris water maze and passive avoidance acquisition and retention. On the Morris water maze isolated mice did not differ from non-isolated mice regarding place learning, the probe trial or extinction. Isolated mice were unimpaired in passive avoidance acquisition and retention. It was concluded that the deficits in place preference conditioning were not the result of a global learning impairment in isolated mice. Received: 10 April 1996 /Final version: 20 September 1996