Intestinal bacterial indicator phylotypes associate with impaired DNA double-stranded break sensors but augmented skeletal bone micro-structure.
肠道细菌指示系统类型与受损的 DNA 双链断裂传感器相关，但增强了骨骼微结构。
- 作者列表："Maier I","Liu J","Ruegger PM","Deutschmann J","Patsch JM","Helbich TH","Borneman J","Schiestl RH
:Intestinal microbiota are considered a sensor for molecular pathways, which orchestrate energy balance, immune responses, and cell regeneration. We previously reported that microbiota restriction promoted higher levels of systemic radiation-induced genotoxicity, proliferative lymphocyte activation, and apoptotic polarization of metabolic pathways. Restricted intestinal microbiota (RM) that harbors increased abundance of Lactobacillus johnsonii (LBJ) has been investigated for bacterial communities that correlated radiation-induced genotoxicity. Indicator phylotypes were more abundant in RM mice and increased in prevalence after whole body irradiation in conventional microbiota (CM) mice, while none of the same ten most abundant phylotypes were different in abundance between CM mice before and after heavy ion irradiation. Muribaculum intestinale was detected highest in female small intestines in RM mice, which were lacking Ureaplasma felinum compared with males, and thus these bacteria could be contributing to the differential amounts of radiation-induced systemic genotoxicity between the CM and RM groups. Helicobacter rodentium and M.intestinale were found in colons in the radiation-resistant CM phenotype. While the expression of interferon-γ was elevated in the small intestine, and lower in blood in CM mice, high-linear energy transfer radiation reduced transforming growth factor-β with peripheral interleukin (IL)-17 in RM mice, particularly in females. We found that female RM mice showed improved micro-architectural bone structure and anti-inflammatory radiation response compared with CM mice at a delayed phase 6 weeks postexposure to particle radiation. However, microbiota restriction reduced inflammatory markers of tumor necrosis factor in marrow, when IL-17 was reduced by intraperitoneal injection of IL-17 neutralizing antibody.
: 肠道菌群被认为是分子途径的传感器，协调能量平衡、免疫反应和细胞再生。我们以前报道过，微生物群限制促进了更高水平的全身辐射诱导的遗传毒性、增殖淋巴细胞活化和代谢途径的凋亡极化。针对辐射诱导的遗传毒性相关的细菌群落，研究了携带约氏乳杆菌 (LBJ) 丰度增加的限制性肠道菌群 (RM)。指标系统类型在 RM 小鼠中更丰富，在常规微生物群 (CM) 小鼠中全身照射后患病率增加,而相同的十种最丰富的系统类型在重离子照射前后 CM 小鼠之间的丰度没有差异。在 RM 小鼠中，肠杆菌在雌性小肠中检测到最高，与雄性相比，它们缺乏脲原体,因此，这些细菌可能有助于 CM 和 RM 组之间辐射诱导的全身遗传毒性的差异量。在耐辐射 CM 表型的结肠中发现幽门螺杆菌和 M.int estinale。虽然干扰素-γ 在 CM 小鼠小肠中的表达升高，在血液中的表达降低，但高线性能量转移辐射降低转化生长因子-β 与外周白细胞介素 (IL)-17 在 RM 小鼠中，特别是在雌性小鼠中。我们发现，在暴露于粒子辐射后 6 周的延迟阶段，与 CM 小鼠相比，雌性 RM 小鼠表现出改善的微结构骨结构和抗炎辐射反应。然而，当通过腹腔注射 IL-17 中和抗体降低 IL-17 时，微生物群限制降低了骨髓中肿瘤坏死因子的炎症标志物。
METHODS:OBJECTIVES:To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN:A multicenter randomized sham-controlled clinical trial. SETTING:Twelve ICUs in Canada. PATIENTS:We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS:Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS:The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS:Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.
METHODS:RATIONALE:The long-term effects of delivering approximately 100% of recommended calorie intake via the enteral route during critical illness compared to a lesser amount of calories are unknown. OBJECTIVES:Our hypotheses were that achieving approximately 100% of recommended calorie intake during critical illness would increase quality of life scores, return to work and key life activities and reduce death and disability six months later. METHODS:We conducted a multicenter, blinded, parallel group, randomized clinical trial, with 3957 mechanically ventilated critically ill adults allocated to energy-dense (1.5 kcal/ml) or routine (1.0 kcal/ml) enteral nutrition. MEASUREMENTS AND MAIN RESULTS:Participants assigned energy-dense nutrition received more calories (% recommended energy intake, mean (SD) (energy-dense: 103% (28) vs. usual: 69% (18)). Mortality at day-180 was similar (560/1895 (29.6%) vs. 539/1920 (28.1%); relative risk 1.05 (95%CI, 0.95 to 1.16)). At a median [IQR] of 185 [182, 193] days after randomization, 2492 survivors were surveyed and reported similar quality of life (EuroQol five dimensions five-level quality of life questionnaire visual analogue scale, median [IQR]: 75 [60-85]; group difference: 0 (95%CI, 0 to 0)). Similar numbers of participants returned to work with no difference in hours worked or effectiveness at work (n=818). There was no observed difference in disability (n=1208) or participation in key life activities (n=705). CONCLUSIONS:The delivery of approximately 100% compared to 70% of recommended calorie intake during critical illness does not improve quality of life, or functional outcomes, or increase the number of survivors six months later. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT02306746.
METHODS:BACKGROUND:Provision of enteral nutrition with jejunal feeding in upper gastrointestinal obstruction is highly recommended. Access to jejunum can be obtained surgically, percutaneously, or endoscopically. Our institution routinely and preferentially utilizes a silicone nasojejunal tube that is inserted past the obstruction endoscopically. We use a custom dual channel tube that allows feeding at the distal tip and another channel 40 cm from the tip that enables decompression proximally. This is a report of our experience with this custom nasojejunal tube. METHODS:This is a prospective observational study of 201 patients who underwent endoscopic nasojejunal wire-guided feeding tube insertions for obstruction of either the esophagus or the stomach including both benign and malignant pathologies between January 2015 to June 2018 in Hospital Sungai Buloh and Hospital Sultanah Aminah, Malaysia. The indications for tube insertion, insertion technique, and tube-related problems were described. RESULTS:The nasojejunal tube was used to establish enteral feeding in patients with obstructing tumors of the distal esophagus in 65 patients (32.3%) and gastric outlet obstruction in 72 patients (35.8%). There were 54 patients (26.9%) who required reinsertion. The most common reason for reinsertion was unintentional dislodgement, where 32 patients (15.9%) followed by tube blockage 20 patients (10.0%). Using our method of advancement under direct vision, we had only 2 cases of malposition due to severely deformed anatomy. We had no incidence of aspiration in this group of patients and overall, the patients tolerated the tube well. CONCLUSIONS:The novel nasojejunal feeding tube with gastric decompression function is a safe and effective method of delivery of enteral nutrition in patients with upper gastrointestinal obstruction. These tubes if inserted properly are well tolerated with almost no risk of malposition and are tolerated well even for prolonged periods of time until definitive surgery could be performed.