Early Administration Group Research Articles

Early inhibition of the ATM/p53 pathway reduces the susceptibility to atrial fibrillation and atrial remodeling following acute myocardial infarction

Atrial fibrillation (AF) emerges as a critical complication following acute myocardial infarction (AMI) and is associated with a significant increased risk of heart failure, stroke and mortality. Ataxia telangiectasia mutated (ATM), a key player in DNA damage repair (DDR), has been implicated in multiple cardiovascular conditions, however, its involvement in the development of AF following AMI remains unexplored. This study seeks to clarify the contribution of the ATM/p53 pathway in the onset of AF post-AMI and to investigate the underlying mechanisms. The rat model of AMI was established by ligating left anterior descending coronary artery in the presence or absence of Ku55933 (an ATM kinase inhibitor, 5 mg/kg/d) treatment. Rats receiving Ku55933 were further divided into the early administration group (administered on days 1, 2, 4, and 7 post-AMI) and the late administration group (administered on days 8, 9, 11 and 14 post-AMI). RNA-sequencing was performed 14 days post-operation. In vitro, H2O2-challenged HL-1 atrial muscle cells were utilized to evaluate the potential effects of different ATM inhibition schemes, including earlier, middle, and late periods of intervention. Fourteen days post-AMI injury, the animals exhibited significantly increased AF inducibility, exacerbated atrial electrical/structural remodeling, reduced ventricular function and exacerbated atrial DNA damage, as evidenced by enhanced ATM/p53 signaling as well as γH2AX level. These effects were partially consistent with the enrichment results of bioinformatics analysis. Notably, the deleterious effects were ameliorated by early, but not late, administration of Ku55933. Mechanistically, inhibition of ATM signaling successfully suppressed atrial NLRP3 inflammasome-mediated pyroptotic pathway. Additionally, the results were validated in the in vitro experiments demonstrating that early inhibition of Ku55933 not only attenuated cellular ATM/p53 signaling, but also mitigated inflammatory response by reducing NLRP3 activation. Collectively, hyperactivation of ATM/p53 contributed to the pathogenesis of AF following AMI. Early intervention with ATM inhibitors substantially mitigated AF susceptibility and atrial electrical/structural remodeling, highlighting a novel therapeutic avenue against cardiac arrhythmia following AMI.

Factors affecting early antibiotic delivery in open tibial shaft fractures

IntroductionThe incidence of infection in open tibial shaft injuries varies with the severity of the injury with rates ranging from roughly 2% for Gustilo-Anderson type I to nearly 43% for type IIIB fractures. As with all fractures, timely antibiotics administration in the emergency department (ED) is an essential component of fracture management and infection prevention. This study identifies factors associated with the expedient administration of antibiotics for open tibial shaft fractures. MethodsThis retrospective study identified patients treated for open tibial shaft fractures at an academic level 1 trauma center between 2015 and 2021. Open fractures were identified by reviewing patient charts. We used chart reviews to gather demographics, fracture characteristics, postoperative outcomes, trauma activation, and time to antibiotic order, delivery, and operating room. Univariate analysis was used to compare patients who received antibiotics within 1 h of ED presentation to those who did not. Multivariate analysis was performed to investigate factors associated with faster delivery of antibiotics. ResultsAmong 70 ED patients with open tibial shaft fractures, 39 (56%) received early administration of antibiotics. Arrival at the ED via emergency medical service (EMS) as opposed to walking in (98% vs. 74%, p = 0.01) and trauma activation (90% vs. 52%, p < 0.001) were significantly more common in the early administration group than the late group. The early group had shorter intervals between antibiotic order and delivery (0.02 h vs. 0.35 h, p = 0.007). Multivariate analysis suggested that trauma activation, EMS arrival, and arrival during non-overnight shifts were independent predictors of a shorter time to antibiotic administration (odds ratios 11.9, 30.7, and 5.4, p = 0.001, 0.016, and 0.013, respectively). DiscussionEarlier antibiotic delivery is associated with non-overnight arrival at the ED, arrival via EMS, and a coordinated trauma activation. Our findings indicate that in cases where administering antibiotics is critical to achieving positive outcomes, it is advisable to initiate a coordinated trauma response. Furthermore, hospital personnel should be attentive to the need for rapid administration of antibiotics to patients with open fractures who arrive via walk-in or during late-night hours.

Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients.

To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival. Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72h) or delayed administration (after 72h) of HiDAC. The difference in neutrophil recovery time was similar between the early and delayed groups (18days versus 19days, p < 0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p = 0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p = 0.28) as well as a trend towards longer median survival (16months versus 19months, p = 0.69) and overall survival (21months versus 31months, p = 0.47). A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed administration of pegfilgrastim in these patients.

Safety of Early Bevacizumab Administration after Central Venous Port Placement for Patients with Colorectal Cancer.

Bevacizumab (BEV) requires an adequate withdrawal period to avoid BEV-related complications during major surgery. However, the safety of BEV administration immediately after surgical placement of the central venous (CV) port, a minor surgery, is still unclear. This study aimed to investigate whether BEV is safe when administered early after CV port placement. We retrospectively evaluated 184 patients with advanced colorectal cancer (CRC) treated with a BEV-containing regimen and divided them into two groups according to the interval between CV port implantation and chemotherapy initiation, with the early administration group being ≤7 days and late administration group being >7 days. Complications were then compared between the two groups. The early-administration group was significantly older and had a higher rate of colon cancer than the late-administration group. Overall, 24 (13%) patients developed CV port-related complications. Male sex was a risk factor for complications (odds ratio [OR], 3.154; 95% CI, 1.19-8.36). The two groups showed no significant difference in the frequency of complications (p = 0.84) or patient characteristics (after the inverse probability of treatment weighting, p = 0.537). In conclusion, the frequency of complications is not affected by the timing of BEV initiation after CV port implantation. Thus, early BEV administration after CV port placement is safe.

Early Thrombomodulin Improved Disseminated Intravascular Coagulation After Cardiac Surgery

BackgroundDisseminated intravascular coagulation (DIC) is a fatal complication in postoperative patients. Recombinant human thrombomodulin (rhTM) has been used to treat DIC in some settings; however, the use of rhTM as a therapy for DIC has not been established in the field of cardiovascular surgery. This study aimed to investigate the efficacy and optimal timing of rhTM treatment in patients with DIC after cardiovascular operation. MethodsData were retrospectively collected from patients in whom DIC developed after open cardiac operation and who were treated with rhTM. DIC scores, laboratory data, and major complications were assessed. The end point was the 30-day all-cause mortality. Risk factors influencing mortality were extracted for the survival and nonsurvival groups. ResultsA total of 27 patients with postoperative DIC were treated with rhTM. The 30-day mortality rate was 51.9%. Multivariate analysis revealed that rhTM administration ≥5 days after DIC diagnosis was associated with increased mortality. The early administration group (≤4 days after DIC diagnosis) showed significantly improved DIC scores, reduced C-reactive protein levels, and increased number of platelets after rhTM treatment compared with before treatment. ConclusionsEarly administration of rhTM after DIC diagnosis was associated with a decreased 30-day mortality rate in patients after cardiovascular operation.

Early adjuvant chemotherapy administration for patients with advanced stage (III-IV) malignant ovarian germ cell tumors is associated with a survival benefit (153)

Objectives: Malignant ovarian germ cell tumors (MOGCTs) are usually chemo-sensitive but characterized by rapid tumor growth. While for patients with epithelial ovarian carcinoma, delay in adjuvant chemotherapy administration is associated with worse oncologic outcomes, data for patients with MOGCT are scarce. The present study aimed to evaluate the impact of adjuvant chemotherapy administration timing on the survival of patients with advanced-stage MOGCTs who underwent surgical resection. Methods: The National Cancer Database (NCDB) was accessed. Patients with no history of another tumor diagnosed between 2004 and 2015 with stage III-IV MOGCT, who underwent surgical resection and received multi-agent chemotherapy, had known surgery-chemotherapy intervals, and at least one month of follow-up were identified. Overall survival (OS) was compared between patients who received chemotherapy 1-4 weeks (early administration group) and 4-12 weeks (late administration group) from surgery with the log-rank test following generation of Kaplan-Meier curves. A Cox model was constructed to control for a priori selected confounders. Results: A total of 622 patients with advanced-stage MOGCT who met the inclusion criteria were identified. The median surgery-chemotherapy interval was 25 days (IQR: 18). The early and late chemotherapy administration groups included 393 (63.2%) and 229 (36.8%) patients, respectively. Patients in the early administration group were younger (median age: 22 vs 24 years, p<0.001) compared to those in the late administration group. However, the two groups were comparable in terms of patient race, insurance status, presence of medical comorbid conditions, tumor histology, and disease stage (p>0.05). By univariate analysis, patients in the early administration group had better OS than those in the late administration group (p=0.004); 5-year OS rates were 87.5% and 77.6%, respectively. After controlling for patient age, race, presence of medical comorbid conditions, tumor histology, and disease stage, late chemotherapy administration was associated with worse survival (HR: 1.99, 95% CI: 1.34, 3.01). Conclusions: For patients with advanced-stage MOGTCs, administration of chemotherapy within four weeks from surgery should be strongly considered since delay may be associated with worse overall survival. Objectives: Malignant ovarian germ cell tumors (MOGCTs) are usually chemo-sensitive but characterized by rapid tumor growth. While for patients with epithelial ovarian carcinoma, delay in adjuvant chemotherapy administration is associated with worse oncologic outcomes, data for patients with MOGCT are scarce. The present study aimed to evaluate the impact of adjuvant chemotherapy administration timing on the survival of patients with advanced-stage MOGCTs who underwent surgical resection. Methods: The National Cancer Database (NCDB) was accessed. Patients with no history of another tumor diagnosed between 2004 and 2015 with stage III-IV MOGCT, who underwent surgical resection and received multi-agent chemotherapy, had known surgery-chemotherapy intervals, and at least one month of follow-up were identified. Overall survival (OS) was compared between patients who received chemotherapy 1-4 weeks (early administration group) and 4-12 weeks (late administration group) from surgery with the log-rank test following generation of Kaplan-Meier curves. A Cox model was constructed to control for a priori selected confounders. Results: A total of 622 patients with advanced-stage MOGCT who met the inclusion criteria were identified. The median surgery-chemotherapy interval was 25 days (IQR: 18). The early and late chemotherapy administration groups included 393 (63.2%) and 229 (36.8%) patients, respectively. Patients in the early administration group were younger (median age: 22 vs 24 years, p<0.001) compared to those in the late administration group. However, the two groups were comparable in terms of patient race, insurance status, presence of medical comorbid conditions, tumor histology, and disease stage (p>0.05). By univariate analysis, patients in the early administration group had better OS than those in the late administration group (p=0.004); 5-year OS rates were 87.5% and 77.6%, respectively. After controlling for patient age, race, presence of medical comorbid conditions, tumor histology, and disease stage, late chemotherapy administration was associated with worse survival (HR: 1.99, 95% CI: 1.34, 3.01). Conclusions: For patients with advanced-stage MOGTCs, administration of chemotherapy within four weeks from surgery should be strongly considered since delay may be associated with worse overall survival.

Early administration of dobutamine in the treatment of septic shock patients with tumor-a retrospective comparative cohort study.

BackgroundStudies have found that dobutamine may be beneficial to protect organs function in patients with septic shock, but there is still a lack of relevant research in septic shock patients with tumor. The study sought to explore the role of the early administration of dobutamine in the treatment of septic shock patients with tumors.MethodsWe retrospectively collected the data of tumor patients who developed septic shock at Sun Yat-sen University Cancer Center between June 2008 and November 2021. All the patients were divided into the following 3 groups: (I) the early administration group (<3 days, n=15); (II) the late administration group (≥3 days, n=22); and (III) the non-administration group (n=85). The primary observation indicator was 28-day mortality, and the secondary observation indicators included the shock reversal rate, the length of stay in the intensive care unit (ICU) and the duration of mechanical ventilation. There was no statistical difference in the basic data of the three groups.ResultsThe early administration group had a significant decrease in 28-day mortality compared to the late and non-administration groups (log-rank P=0.018). The comparison between the groups showed that the 28-day mortality of the early administration group was significantly lower than that of the non-administration group [20.0% vs. 58.8%, P=0.013, hazard ratios (HRs) =0.248, 95% confidence intervals (CIs): 0.077–0.796]. There was no statistically significant difference in 28-day mortality between the late administration group and the non-administration group (63.6% vs. 58.8%, P=0.682, HR =0.983, 95% CI: 0.543–1.778). Additionally, the early administration group had a significantly increased shock reversal rate (P=0.014), shortened length of stay in the ICU (P<0.001), and reduced duration of mechanical ventilation (P=0.049).ConclusionsEarly use of dobutamine may be beneficial to reduce the in-hospital mortality of septic shock patients with tumor, but the sample size of this study was small, which still needs to be confirmed by a multi-center randomized controlled clinical study.

Dapagliflozin Improves Diabetic Cardiomyopathy by Modulating the Akt/mTOR Signaling Pathway.

Background Dapagliflozin can significantly improve heart failure, and Cx43 is one of the molecular mechanisms of heart failure. This study investigated the effect of dapagliflozin on Cx43 and Akt/mTOR signaling pathway in ventricular myocytes. Methods A rat model of type 2 diabetes mellitus was established by high-fat diet combined with streptozotocin, and the animals were treated randomly with dapagliflozin. The morphological changes of the myocardium were observed by hematoxylin eosin staining, and the expression and distribution of Cx43 in ventricular myocytes were detected by immunohistochemistry. And Western blot determined the expressions of Cx43, Akt, mTOR, p62, and LC3 proteins in rat myocardium. Results Compared with the normal control group, the heart rate of diabetic rats decreased significantly (p < 0.05), QRS wave of ECG widened, and QT interval prolonged (p < 0.05). Dapagliflozin treatment in diabetic rats resulted in improvements in these ECG indexes (p < 0.05) with early administration group obtaining greater efficacy than the late administration group (p < 0.05). In the normal control group, the cardiomyocytes were arranged orderly, and the expression of Cx43 was dense, uniform, and regular, which was higher than that in the intercalated disc. In the diabetic control model group, the cardiomyocytes were enlarged and presented disorderly with detection of Cx43 in the cytoplasm. Early use of dapagliflozin better improved these myocardial tissue lesions. Of note, as diabetic rats exhibited decreased expression of Cx43, Akt, and mTOR (p < 0.05), increased p62 expression (p < 0.05), and decreased LC3-II/I ratio (p < 0.05), administration of dapagliflozin partially reversed the expression of the above proteins (p < 0.05) with greater improvement in the early administration group compared with the late administration group (p < 0.05). Conclusions Dapagliflozin increases the expression of Cx43 in cardiomyocytes of diabetic rats and thereby alleviates heart failure partly through regulating the Akt/mTOR signaling pathway.

Association between Administration of Systemic Corticosteroids and the Recovery of Olfactory and/or Gustatory Functions in Patients with COVID-19: A Prospective Cohort Study

AIM: This study is a prospective cohort study aimed to assess the effect of systemic corticosteroids administration time in the recovery of gustatory and olfactory sensations dysfunction (ageusia and anosmia) in COVID-19 patients. MATERIALS AND METHODS: Sixty-seven COVID-19 patients with symptoms of ageusia and anosmia were recruited (that their COVID infection was confirmed using polymerase chain reaction). Daily 10 mg of systemic corticosteroids were prescribed in the 1st week and then reduced to 5 mg in the 2nd week to all the patients to observe taste and smell sensation recovery. All data were recorded and then analyzed. Patients were then grouped into two groups (early and late groups) according to the duration of their taste and smell dysfunction. RESULTS: Regression analysis showed that early corticosteroid administration resulted in a significant decrease in recovery time of ageusia and anosmia (0.27 [0.2–0.35], p &lt; 0.001). Patients in the early administration group (&lt;1 week) showed faster improvement in regaining taste and smell functions than in the late administration group (&gt;1 week) with significant difference (p &lt; 0.001). CONCLUSIONS: The use of systemic corticosteroids in early phases of covid-19 infection help in faster recovery of ageusia and anosmia.

Comparison of 1.0 g/kg of 20% mannitol initiated at different time points and effects on brain relaxation in patients with midline shift undergoing supratentorial tumor resection: a randomized controlled trial.

Previous studies have suggested the use of 1.0 g/kg of 20% mannitol at the time of skin incision during neurosurgery in order to improve brain relaxation. However, the incidence of brain swelling upon dural opening is still high with this dose. In the present study, the authors sought to determine a better timing for mannitol infusion. One hundred patients with midline shift who were undergoing elective supratentorial tumor resection were randomly assigned to receive early (immediately after anesthesia induction) or routine (at the time of skin incision) administration of 1.0 g/kg body weight of 20% mannitol. The primary outcome was the 4-point brain relaxation score (BRS) immediately after dural opening (1, perfectly relaxed; 2, satisfactorily relaxed; 3, firm brain; and 4, bulging brain). The secondary outcomes included subdural intracranial pressure (ICP) measured immediately before dural opening; serum osmolality and osmole gap (OG) measured immediately before mannitol infusion (T0) and at the time of dural opening (TD); changes in serum electrolytes, lactate, and hemodynamic parameters at T0 and 30, 60, 90, and 120 minutes thereafter; and fluid balance at TD. The time from the start of mannitol administration to dural opening was significantly longer in the early administration group than in the routine administration group (median 66 [IQR 55-75] vs 40 [IQR 38-45] minutes, p < 0.001). The BRS (score 1/2/3/4, n = 14/26/9/1 vs 3/25/18/4, p = 0.001) was better and the subdural ICP (median 5 [IQR 3-6] vs 7 [IQR 5-10] mm Hg, p < 0.001) was significantly lower in the early administration group than in the routine administration group. Serum osmolality and OG increased significantly at TD compared to levels at T0 in both groups (all p < 0.001). Intergroup comparison showed that serum osmolality and OG at TD were significantly higher in the routine administration group (p < 0.001 and = 0.002, respectively). Patients who had received early administration of mannitol had more urine output (p = 0.001) and less positive fluid balance (p < 0.001) at TD. Hemodynamic parameters, serum lactate concentrations, and incidences of electrolyte disturbances were comparable between the two groups. Prolonging the time interval between the start of mannitol infusion and dural incision from approximately 40 to 66 minutes can improve brain relaxation and decrease subdural ICP in elective supratentorial tumor resection.

The Association Between Early Administration of Noninvasive Ventilation and Short-Term Outcome for Acute Heart Failure.

BackgroundAcute decompensated heart failure (ADHF) is a life-threatening disease that requires emergent intervention. Although noninvasive positive pressure ventilation (NPPV) is crucial for treating ADHF, the earliest time point for administering NPPV remains unknown. In this study, we hypothesized that early NPPV administration for patients with acute heart failure in the emergency department (ED) would lead to a better outcome.MethodologyThis is a single-center retrospective cohort study at an ED of a community hospital in Japan. The data were collected from consecutive patients who were administered NPPV for ADHF in the ED from April 2016 to September 2018. The primary exposure was the timing of NPPV administration (within 30 minutes versus over 30 minutes after arrival). The primary outcome was 30-day mortality.ResultsA total of 115 patients were included in this study. Overall, the median age was 78 (interquartile range [IQR] = 70-84 years), and 63 (54.9%) patients were male. The median time from the arrival at the ED to NPPV administration for the patients was 14 minutes (IQR = 8-30 minutes). Overall, 72% (83/115) of the patients were categorized as early administration group (<30 minutes). The total 30-day mortality was 7.0% (8/115), and the total tracheal intubation rate was 11% (13/115). Early NPPV administration for patients with ADHF was associated with lower 30-day mortality (3.6% vs. 16%; p = 0.04) and shorter length of oxygenation (four days vs. seven days; p < 0.01). Multivariate logistic regression test showed that 30-day mortality was significantly lower in the early treatment group (adjusted odds ratio = 0.19; 95% confidential interval = 0.04-0.90).ConclusionsAlthough further investigation is needed, early NPPV administration for patients with ADHF in the ED was associated with lower 30-day mortality.

Association of early administration of furosemide with improved oxygenation in patients with acute heart failure.

AimsOptimal pharmacological treatment for chronic heart failure has been established. However, treatments that can improve the prognosis of acute heart failure (AHF) are controversial. Although intravenous diuretics may be one optimal treatment option, little evidence has shown the effect of early administration of diuretics on clinical outcomes in patients with AHF. The aim of this study was to evaluate the association between door‐to‐furosemide (D2F) time, improved oxygenation, and in‐hospital mortality in patients hospitalized for AHF.Methods and resultsWe screened 494 patients hospitalized for AHF in Miyazaki Prefectural Nobeoka Hospital. AHF patients who were treated with intravenous furosemide within 24 h of arrival at the hospital were included in this study. D2F time was defined as the time from patient arrival at the hospital to the first intravenous dose of furosemide. The early administration group was defined as those with D2F time ≤60 min, whereas the non‐early group was defined as those with D2F time >60 min. The primary outcome was the rate of improved oxygenation at Day 1. The secondary outcomes were in‐hospital mortality and cardiac death.There were 219 patients treated with the first intravenous dose of furosemide within 24 h analysed after the exclusion of 275 patients. The median D2F time was 55 min (interquartile range: 30–120 min) in the final cohort. The early administration group included 121 patients (55.3%). The rate of improved oxygenation was higher in the early group than the non‐early group [median 16.7% (interquartile range: 0.0–40.0) vs. 0.0% (0.0–20.6), respectively, P < 0.001]. During the study period, there were six patients (5.0%) with in‐hospital mortality in the early group and nine patients (9.2%) in the non‐early group (P = 0.218). Cardiac death was observed less frequently in the early group than in the non‐early group, but without statistical significance (3.3% and 9.2%, respectively) (P = 0.067). The univariable logistic regression analyses showed that early administration of furosemide was associated with improved oxygenation [odds ratio (OR): 2.26; 95% confidence interval (CI): 1.31–3.91; P = 0.004], but not with in‐hospital mortality (OR: 0.52; 95% CI: 0.18–1.50; P = 0.225) or cardiac death (OR: 0.34; 95% CI: 0.10–1.13; P = 0.079). In multivariable analyses adjusted for risk score or relevant variables, early administration of furosemide was consistently associated with improvement of oxygenation.ConclusionsThe present study showed that in AHF patients, the early administration of furosemide was associated with improved oxygenation.

Never Too Early: Parenteral Nutrition Administration in Elderly Emergency General Surgery Patients

Objectives: Elderly patients requiring emergency general surgery (EGS) are at high risk for complications due to preexisting malnutrition. Thus, correcting nutritional deficits perioperatively is essential to improve outcomes. However, even in patients unable to tolerate enteral nutrition, initiation of parenteral nutrition (PN) is often delayed due to concerns of associated complications. In this study, we hypothesized that in elderly EGS patients with relative short-term contraindications to enteral nutrition, early administration of PN is as safe as delayed administration. Furthermore, early PN may improve outcomes by enhancing caloric intake and combatting malnutrition in the immediate perioperative period. Design and Setting: A single-institution, retrospective review was performed at a quaternary academic medical center. Participants: Participants consisted of 58 elderly patients &gt;65 years of age admitted to the EGS service who required PN between July 2017 and July 2020. Measurements: Postoperative outcomes of patients started on PN on hospital day 0-3 (early initiation) were compared to patients started on PN on hospital day 4 or later (late initiation). Bivariate analysis was conducted using the Chi-square or Fisher’s exact test for categorical variables and the Wilcoxon-Mann-Whitney test and F-test for continuous variables. Results: Fifty-eight patients met inclusion criteria, with 27 (46.6%) patients receiving early PN and 31 (53.4%) receiving late PN. Both groups shared similar baseline characteristics, including degree of frailty, body mass index, and nutritional status at time of admission. Complications associated with PN administration were negligible, with no instances of central venous catheter insertion-related complications, catheter-associated bloodstream infection, or factors leading to early termination of PN therapy. A significantly higher proportion of patients in the early administration group met 60% of their caloric goal within 72 hours of admission (62.9% versus 19.5%, p=0.0007). Patients receiving late PN demonstrated a significantly higher rate of unplanned admission to the intensive care unit (38.7% versus 14.8%, p=0.04). Moreover, there was a 21.5% reduction in mortality among patients in the early initiation group compared to patients in the late initiation group (33.3% versus 54.8%, p=0.10). Conclusions: Early initiation of PN in hospitalized elderly EGS patients was not associated with increased adverse events compared to patients undergoing delayed PN administration. Furthermore, patients receiving early PN demonstrated a 2.6-fold decrease in the rate of unplanned admission to the intensive care unit and trended toward improved mortality. Based on these results, further prospective studies are warranted to further explore the safety and potential benefits of early PN administration in elderly surgical patients unable to receive enteral nutrition.

S3210 Assessment of Factors Which May Predict Crohn’s Disease Relapse in Patients Initiating Ustekinumab Therapy

INTRODUCTION: Ustekinumab is a biologic agent, acting against the p40 subunit of IL 12 and IL 23, approved for use in Crohn’s disease (CD). Currently, ustekinumab is approved for every 8 week dosing following initiation. However, we have clinically observed the need for every 4 week dosing, in a cohort of patients not achieving control with every 8 week administration. Of note, such a subset of CD patients was not assessed in the UNITI trial. The aim of our study was to identify patient or clinical factors that could indicate the need for a shorter ustekinumab dosing interval to obtain and maintain remission of CD. METHODS: The pharmacy database was searched for all patients initiating ustekinumab for histologically confirmed CD. Patients were then divided into 2 groups following initiation based on occurrence of next dose, either standard schedule (8 weeks after initial dose) or early administration (4 weeks following). Data collected for all included demographic information, smoking status, extent of disease and disease duration. Stepwise logistic regression was used to identify predictors for early dosing. Potential predictors not identified by the logistic model were forced in. Beta coefficients/odds ratios and 95% confidence intervals were calculated to estimate the magnitude of the effect. RESULTS: A total of 57 CD patients were eligible for study. The majority of patients overall were female (68%) and non-Hispanic white (52%). A total of 44 patients were in the standard group and 13 patients were in the early administration group. No difference in age, gender, race, smoking status or disease duration was present between groups. Colonic CD disease extent was significantly different between standard and early groups (one colonic segment involved in 36.4% of standard vs 84.6% of early patients, P < 0.003). We further forced in age, sex, race, smoking status, and duration of disease as likely to impact occurrence of early ustekinumab dosing. Again, only extent of disease on colonoscopy showed a statistically significant result (OR 9.56, CI 1.41–64.88, P < 0.01). CONCLUSION: Extent of colonic disease may identify those CD patients at risk for earlier than 8 week dosing following initiation of ustekinumab. We identified that patients with one colonic segment involvement have higher odds to be on early administration than those that have multiple colonic segment involvement. Further evaluation of this clinical phenomenon is warranted to completely understand ustekinumab use in CD.

Effects of repeated epinephrine administration and administer timing on witnessed out-of-hospital cardiac arrest patients

BackgroundRepeated administration of epinephrine is associated with unfavorable cerebral outcome after out-of-hospital cardiac arrests (OHCA), but the timing of epinephrine administration has not been considered. AimThe aim of the study was to analyze the effects of repeated epinephrine administration after OHCA on favorable cerebral function coded by cerebral performance categories (CPC 1–2). MethodsA nationwide, retrospective, population-based observational study was conducted by using Utstein-style data between 2010 and 2012 in Japan. The total of 11,876 cardiogenic and witnessed OHCA were stratified into 3 categories by the number of times epinephrine was administered (single, double, and three or more). In addition, the time elapsed between the emergency call and the initial epinephrine administration was divided into 3 time intervals (5 to 20min for the early administration group [EAG], 21 to 26min for the intermediate administration group [IAG], and 27 to 60min for the late administration group [LAG]). The primary endpoint was CPC 1–2 at 1month after cardiac arrest. A multivariable logistic regression was used for analysis. ResultsAchievement of CPC 1–2 at 1month was 4.8% for single, 2.4% for double, and 1.7% for three or more administered doses. For single and three or more administrations, CPC 1–2 was significantly higher in the IAG than in the LAG (adjusted odds ratio [AOR], 3.54, 3.02; 95% confidence interval [CI], 2.04–6.39, 1.16–9.43, for single and three or more administrations, respectively). The EAG showed significantly higher achievement of CPC 1–2 in all the epinephrine administration groups (AOR, 9.26, 7.57, 4.07; 95% CI, 5.44–16.59, 3.39–19.60, 1.59–12.69, for single, double, and three or more administrations, respectively). ConclusionRepeated epinephrine administration improved CPC 1–2 outcome when epinephrine was administrated within 20min after an emergency call for witnessed cardiogenic OHCA.

Evaluation of Hematopoietic Stem Cell Mobilization Rates with Early Plerixafor Administration for Adult Stem Cell Transplantation

The addition of plerixafor to high-dose colony-stimulating growth factor has been shown to improve stem cell mobilization rates in autologous transplant patients with multiple myeloma and non-Hodgkin lymphoma. This study evaluates the change in administration time of plerixafor to determine if cell mobilization rates are similar between the US Food and Drug Administration–approved administration time of 11 hours before apheresis and an earlier administration time of 16 hours before apheresis. Medical records of patients age ≥ 18 years undergoing autologous stem cell transplantation requiring the use of plerixafor after at least 4 days of granulocyte colony-stimulating factor therapy to complete stem cell mobilization from January 1, 2010 through September 30, 2014 were retrospectively reviewed. The primary outcome was CD34+ cell mobilization success rates when plerixafor was administered 11 ± 2 hours (standard administration group) compared with 16 ± 2 hours before cell apheresis (early administration group), as defined as collection of ≥2 × 106 CD34+ cells/kg. Secondary outcomes included the number of plerixafor therapy days required to collect a total of ≥2 × 106 CD34+ cells/kg, the number of apheresis cycles required to achieve ≥2 × 106 CD34+ cells/kg, the median CD34+ cells/kg collected in each apheresis session, and the rates of reported adverse events that occurred in the standard administration time group compared with the early administration time group. Of the 197 patients included, 114 patients received plerixafor 11 ± 2 hours before apheresis and 83 patients received plerixafor 16 hours ± 2 hours before apheresis. Ninety-four percent of patients in the early administration group achieved successful stem cell mobilization compared with 81.6% in the standard administration group (P = .0111). The median number of plerixafor days to reach the collection goal of ≥2 × 106 CD34+ cells/kg was 1 day for each group (P = .323), and the median number of apheresis days to reach the collection goal was 2 days for the standard administration group compared with 1 day for the early administration group (P = .0156). Most adverse events were similar between the 2 groups except for fever, which occurred in 4.8% of the patients in the early administration group and none of the patients in the standard administration group. This study demonstrates plerixafor effectively mobilizes peripheral blood stem cells when given at an early administration time of 16 hours before apheresis compared with standard administration of 11 hours before apheresis. However, further prospective studies could strengthen these results.

Promoting effective child development practices in the first year of life: does timing make a difference?

BackgroundThere is an increasing need for parenting programs aimed at promoting parent–child interaction. A variety of interventions have been proposed. The use of audiovisual materials for parents has been shown to be effective but limited information is available on the optimal timing for its use, particularly for new parents during the first year of life of their children. The aim of this study is to compare the effectiveness of a video administered at two different times to first-time parents in modifying parental knowledge, attitudes and intentions with regards to effective care practices.MethodsOpen randomized controlled trial carried out in a referral mother and child hospital. Eligible parents were randomly assigned to receive a video at one month (early intervention) or at seven months (late intervention) of age of their child. The video addressed four specific activities related to early child development: reading aloud to the baby, early exposure to music, promotion of early socialization for parents and for children. The primary outcome was the proportion of parents who declared that their knowledge, attitudes and intentions changed after having seen the video at one or seven months of age of the child.ResultsOne hundred and five families were randomly allocated either to the early (53) or to the late (52) intervention group. For 99 families (52 in the early and 47 in the late group) a complete outcome evaluation was available. Parents included in the early administration group more frequently reported modifications in their knowledge of the suggested practices while parents in the late group more frequently reported a change in their attitudes. This finding was consistent across all four practices. The video was found to influence parental intentions in the great majority of interviewed parents with no significant difference between groups (82.7% and 87.2% in the early and late intervention group, respectively).ConclusionsAudiovisual materials can be an effective complementary tool in programs aimed at supporting parents, particularly those dealing with their first baby. The results provide some useful insights into the differential benefits of using audiovisual aids at different times during the first year of life of the baby.Trial registrationClinicalTrials.gov NCT02120430Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2431-14-222) contains supplementary material, which is available to authorized users.

A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment

sBackgroundClomiphene citrate (CC) is most commonly used as a first-line treatment of infertility. However, a disturbance of endometrial growth by the adverse effects of the CC has been recognized. Since a thin endometrium is recognized as a critical factor of implantation failure, preventing CC-induced thinning of the endometrium is important. This study was undertaken to investigate whether the modified CC treatments are useful to prevent a thin endometrium in patients undergoing CC treatments.MethodsThis study is a prospective, randomized controlled study. The study was performed at the Saiseikai Shimonoseki General Hospital during a 4-month period (May 2012 to September 2012). Sixty-six infertile women who had a thin endometrium (< 8 mm) during the standard CC treatment (50 mg/day on days 5–9 of the menstrual cycle) were enrolled. The patients were randomly divided into three groups: 22 patients were given 25 mg/day CC on days 5–9 (half-dose group), 22 patients were given 50 mg/day CC on days 1–5 (early administration group) and 22 patients received a standard CC treatment again (control group). Endometrial thickness at the induction of ovulation was assessed by ultrasonography. The primary endpoint of this study was an endometrial thickness.ResultsHalf dose administration and early administration improved the endometrial thickness (≥ 8 mm) in 14 patients (70%) and in 19 patients (90%) respectively, while only 3 patients (15%) improved in endometrial thickness in the control group. The mean endometrial thickness was also significantly higher in the half dose group (8.6 ± 1.5 mm) and early administration group (9.4 ± 1.5 mm) compared to the control group (6.7 ± 1.8 mm). No side effect was observed in this study.ConclusionsThe modified treatment with a half-dose or early administration of CC significantly increased endometrial thickness in patients with a history of thin endometrium caused by the standard CC regimen. The modified CC treatments in this study can be beneficial for patients with a thin endometrium as a result of standard CC treatment.Trial registrationClinical Trial Registration Number: UMIN000007959.

Impact of Posttransplant Imatinib Administration on Philadelphia-Chromosome Positive Acute Lymphocytic Leukemia

Philadelphia-chromosome positive acute lymphocytic leukemia (Ph+ALL) is an intractable disease. After the development of imatinib, a tyrosine kinase inhibitor, the outcome of chemotherapy, especially remission induction rate, has been improved. Its long-term prognosis is, however, still poor, mainly because of high relapse rate, and therefore allogeneic stem cell transplantation (allo-SCT) is considered to be the only curative option. Recently, adopting the idea of minimal residual disease (MRD) in a treatment strategy of Ph+ALL as well as chronic myeloid leukemia (CML), it was reported that even in hematologically complete remission (CR), positive MRD at allo-SCT was a strong predictor for relapse after allo-SCT. Although it is ideal to perform allo-SCT in MRD-negative condition, it is sometimes difficult to achieve such treatment effect, despite the administration of imatinib. There are some reports dealing with posttransplant imatinib administration, but its efficacy and administration methods are still controversial. To evaluate the effect of posttransplant imatinib administration, we retrospectively analyzed 34 Ph+ALL patients who received allo-SCT at 7 transplant centers in Japan between January 1989 and September 2007. Study admission criteria were allo-SCT for the first time, non-manipulation and MRD positive at allo-SCT. Median age at allo-SCT was 40 years old, 18 patients were transplanted in hematological CR, 14 patients were transplanted from unrelated donors and 20 patients from relative donors. Seven out of 34 patients received posttransplant imatinib administration. We proposed two strategies for posttransplant imatinib administration. One was early administration, where imatinib was administered upon detecting MRD after allo-SCT. The other was prophylactic administration, where imatinib was administered as soon after allo-SCT as possible. Overall survival was significantly better in patients with posttransplant administration (29.6% in patients without posttransplant imatinib vs. 66.7% in those with posttransplant imatinib at 3 years, p=0.03). In contrst, there was no significant difference in event-free survival (EFS) between two groups (29.6% in patients without posttransplant imatinib vs. 0% in those with posttransplant imatinib at 3 years, p=0.29).(Figure) As for details of MRD in patients with posttransplant imatinib administration, the duration of negative MRD was 9 months, 6 months, and 2 months or more in the early administration group, while in the prophylactic administration group it was 29 months, 12 months, and 9 months or more. It seemed that the duration of negative MRD was longer in the prophylactic group, but in all patients whose observation periods were longer than 1 year, MRD became positive in both groups and this lead to hematological relapse. The fact that posttransplant imatinib administration, even prophylactic administration, was no significant effect on event-free survival revealed the limitation of imatinib administration after allo-SCT. Although it is a great thing to achieve longer duration of negative MRD, posttransplant imatinib administration could not be a fundamental solution for Ph+ALL patients whose MRD was positive at allo-SCT. Considering the cure for Ph+ALL, MRD at allo-SCT has a profound impact on long-term EFS and posttransplant intervention seems to have limitation. To achieve a fundamental solution, the key would be to achieve negative MRD at allo-SCT, for example, by using new drugs, like nilotinib, dasatinib and other secondgeneration tyrosine inhibitors in case imatinib was inadequate to achieve negative MRD. MRD-based strategy is essential for a cure of Ph+ALL.

Long-term effectiveness of early administration of glycoprotein IIb/IIIa agents to real-world patients undergoing primary percutaneous interventions: results of a registry study in an ST-elevation myocardial infarction network

To evaluate the clinical impact of early administration of glycoprotein IIb/IIIa agents (IIb/IIIa agents) in the context of a dedicated hub and spoke network allowing very prompt pharmacological/mechanical interventions. Using a prospective database, we conducted a cohort study of ST-elevation myocardial infarction (STEMI) patients (n = 1124) undergoing primary percutaneous coronary interventions (PPCIs) and IIb/IIIa agents administration (period, 2003-2006). Comparisons were planned between patients receiving early IIb/IIIa agents administration (in hub/spoke centre emergency departments or during ambulance transfer; early group, n = 380) or delayed administration (in the catheterization laboratory; late group, n = 744). The primary outcome measure was long-term overall mortality/re-infarction. Baseline characteristics of the two groups were largely comparable. Angiographically, early group patients more often achieved pre-PPCI TIMI Grade 2-3 and TIMI Grade 3 flow. Clinically, the early administration group experienced lower 2-year risk of unadjusted mortality/re-infarction (17 vs. 23%; P = 0.01). After adjustment for potential confounders, early administration was associated with favourable outcome in the overall population (HR = 0.71, P = 0.03) and in high-risk subgroups (TIMI risk index >25, HR = 0.64, P = 0.02; Killip class >1, HR = 0.54, P = 0.01). In patients treated by PPCI within a STEMI network setting, early administration of IIb/IIIa agents may provide long-term clinical benefits. Notably, these results appeared magnified in high-risk patients.