Critical Care 2017, 21(Suppl 1):P349 Introduction Imbalance in cellular energetics has been suggested to be an important mechanism for organ failure in sepsis and septic shock. We hypothesized that such energy imbalance would either be caused by metabolic changes leading to decreased energy production or by increased energy consumption. Thus, we set out to investigate if mitochondrial dysfunction or decreased energy consumption alters cellular metabolism in muscle tissue in experimental sepsis. Methods We submitted anesthetized piglets to sepsis (n = 12) or placebo (n = 4) and monitored them for 3 hours. Plasma lactate and markers of organ failure were measured hourly, as was muscle metabolism by microdialysis. Energy consumption was intervened locally by infusing ouabain through one microdialysis catheter to block major energy expenditure of the cells, by inhibiting the major energy consuming enzyme, N+/K + -ATPase. Similarly, energy production was blocked infusing sodium cyanide (NaCN), in a different region, to block the cytochrome oxidase in muscle tissue mitochondria. Results All animals submitted to sepsis fulfilled sepsis criteria as defined in Sepsis-3, whereas no animals in the placebo group did. Muscle glucose decreased during sepsis independently of N+/K + -ATPase or cytochrome oxidase blockade. Muscle lactate did not increase during sepsis in naïve metabolism. However, during cytochrome oxidase blockade, there was an increase in muscle lactate that was further accentuated during sepsis. Muscle pyruvate did not decrease during sepsis in naïve metabolism. During cytochrome oxidase blockade, there was a decrease in muscle pyruvate, independently of sepsis. Lactate to pyruvate ratio increased during sepsis and was further accentuated during cytochrome oxidase blockade. Muscle glycerol increased during sepsis and decreased slightly without sepsis regardless of N+/K + -ATPase or cytochrome oxidase blocking. There were no significant changes in muscle glutamate or urea during sepsis in absence/presence of N+/K + -ATPase or cytochrome oxidase blockade. ConclusionsThese results indicate increased metabolism of energy substrates in muscle tissue in experimental sepsis. Our results do not indicate presence of energy depletion or mitochondrial dysfunction in muscle and should similar physiologic situation be present in other tissues, other mechanisms of organ failure must be considered. , and long-term follow up has shown increased fracture risk [2]. It is unclear if these changes are a consequence of acute critical illness, or reduced activity afterwards. Bone health assessment during critical illness is challenging, and direct bone strength measurement is not possible. We used a rodent sepsis model to test the hypothesis that critical illness causes early reduction in bone strength and changes in bone architecture. Methods 20 Sprague-Dawley rats (350 ± 15.8g) were anesthetised and randomised to receive cecal ligation and puncture (CLP) (50% cecum length, 18G needle single pass through anterior and posterior wa...

BackgroundThis phase II study assessed the response rate and toxicity profile of weekly paclitaxel and capecitabine in patients with metastatic or recurrent squamous cell carcinoma of the esophagus (SCCE)MethodsPatients with histologically confirmed SCCE were treated with paclitaxel 80 mg/m2 intravenously on days 1 and 8 plus capecitabine 900 mg/m2 orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until disease progression or unacceptable toxicity.ResultsBetween 2006 and 2009, 32 patients were enrolled. Twelve patients were chemotherapy-naïve. Twenty patients had received prior chemotherapy including platinum-based regimens. Patients received a median of 5 cycles of treatment (range, 1-12). The response rate was 75% (95%CI; 50.5~99.5%) in the first-line and 45% (95%CI; 26.9~73.1%) in the second-line. With a median follow-up of 20.7 months, median progression-free survival was 5.2 months (95% CI, 4.0 to 6.4) for all patients and median overall survival (OS) was 11.7 months (95% CI, 5.5 to 18.0) for all patients. The median OS was 14.3 months (95% CI, 10.6 to 18.0) for patients receiving therapy as 1st line and 8.4 months (95% CI, 6.6 to 10.1) for those receiving as 2nd-line therapy. Grade 3/4 neutropenia was observed in 53.3% of the patients, which was the most common cause of dose reduction. G3 non-hematologic toxicity included stomatitis (9.4%), asthenia (6.3%), and hand-foot skin reaction (3.1%).ConclusionsWeekly paclitaxel and capecitabine is a highly active and well-tolerated regimen in patients with metastatic or recurrent SCCE in the first-line as well as second-line setting.

Aims:To explore nurse's, physician's and family member's experiences of withholding or withdrawing life-sustaining treatment in an intensive care unit. Background: In South Korea, withholding or withdrawing life-sustaining treatment is legalised by the enforcement of the Hospice, Palliative Care and Life-sustaining Treatment Decision-making Act (2018). The Act (2018) is the first legal ground for making decisions regarding life-sustaining treatment in South Korea. Design: Focused ethnography. The standards for reporting qualitative research checklist is used. Methods: Interview data are collected between August 2018 and January 2019 using semi-structured interviews with 23 nurses, 10 physicians and four family members in a South Korean intensive care unit. The interview data are analysed following the thematic analysis of Braun and Clarke.Results: An overarching theme of 'constructing death' is identified from the experiences of nurses, physicians and family members regarding withholding or withdrawing life-sustaining treatment in a South Korean intensive care unit. Family members had the strongest power in the withholding or withdrawing life-sustaining treatment process whilst the process had to be based on medical consideration. All the research participants shared the purpose and motivation of withholding or withdrawing lifesustaining treatment as the dying patient's dignity. Due to the South Korean national health insurance system, the relationships between medical staff and family members were driven by customer ideology. Conclusion:The impact and linkage of the context of familism culture and health insurance with the process of withholding or withdrawing life-sustaining treatment in South Korea are shown in this research. The findings of this research inspire future studies to uncover the impact of the cultural context in the decision-making process of a patient's death, to explore the dynamics of family members under cultural values and to explore the influence of the healthcare system and medical costs on the relationships between medical staff and family members.

Aims: To explore younger adults' experiences of stroke rehabilitation to inform practice, education and future health policy.Design: Qualitative analysis of digital and other media sources on public platforms. Methods:Between March and June 2020, the experiences of younger adult stroke survivors aged 18 to 45 at the time of the stroke were collected. Data were gathered from publicly available sources, including social media, and from English-speaking users. In total, 117 accounts from 103 participants were identified from films, autobiographical books, blogs, websites, videos, Twitter and Instagram. Data analysis followed narrative and multimodal analysis with a focus on rehabilitation needs.

e15552 Background: We previously demonstrated the efficacy of irinotecan (CPT) and cisplatin (Cis) combination therapy as neoadjuvant therapy for locally advanced gastric cancer [Newman E et al. J Gastrointest Surg. 2002.]. This trial was designed to add cetuximab (C) to both induction treatment and adjuvant chemoradiation (CRT) with bolus 5-FU/LV. Methods: Pts with untreated locally advanced (T3, T4 or N+) gastric/GE cancers were eligible. Neoadjuvant therapy consisted of Cis 25mg/m2 + CPT 75mg/m2 on d1,8 q21d x 4, C 400mg/m2 on d1, then 250mg/m2 qwk. Curative (R0) resection was performed 4–6 wks later. Adjuvant CRT with 5-FU/LV (425/20/m2 qd x 5 on wks 1,14,19; 400/20/m2 qd x 4 on wk 5, x 3 on wk 9) was given with C 250mg/m2 qwk. Results: Since 11/05, 21 pts [median age 59 (32–82); 9 Caucasian, 11 Asian, 1 Hispanic; 15 male, 20 PS 0–1] received neoadjuvant therapy. The most common toxicities were gr 3 neutropenia (38%), gr 2 rash (33%), gr 2 fatigue (29%); gr 4 included 1 pt each of diarrhea, neutropenia, & hypomagnesemia. 3 did not complete neoadjuvant therapy, due to gr 3 rash, diarrhea and GI bleeding (2 had gastrectomy; 1 lost to f/u). All 18 pts who completed neoadjuvant therapy were surgically explored. 4 had occult metastases, and went off study. 14 underwent R0 gastrectomy (see table); 8 were downstaged, 2 had stable disease, 4 were upstaged compared to the preoperative EUS. There was no postoperative mortality. Of 14 resected pts, 2 did not receive adjuvant therapy (prolonged postoperative recovery), 1 too early to assess, and 11 remaining receiving CRT. The most common toxicities for CRT were gr 3 nausea, gr 3 emesis, gr 2 and 3 fatigue, 3 pts each and 1 each of gr 4 neutropenia and thrombocytopenia. Among the 18 pts who completed neoadjuvant therapy, 5 died of disease, 1 is alive with disease, 12 remain NED with median f/u of 11.6mos (4.1–27.7mos). Conclusions: The addition of C to CPT/Cis as neoadjuvant therapy and to postoperative adjuvant CRT is well tolerated. The regimen induces a favorable pathologic response on the primary tumor. Ongoing evaluation includes K-ras mutation status on outcome and survival benefit. [Supported in part by a grant from BMS.] [Table: see text]