DCS Group Research Articles

364-OR: Unsupervised Approach Systematically Analyzes the Multiomics Profiles Associated with T2D Insulin Insensitivity—An IMI-RHAPSODY Study

Considerable heterogeneity exists in Type 2 diabetes disease onset and subsequent outcomes. Multi-omics analysis may provide a means to better assess inter-patient variations and design personalised approaches. Previous T2D biomarker discovery mainly focused on associating biomarkers with clinical pre-assigned patients. Here, we attempt to group T2D patients with similar multi-omics profiles using a multi-omics integrating clustering approach, Similarity Network Fusion (SNF). Each T2D subgroup’s unique omics profiles were then associated with T2D progression. In both cohorts, 180 and 1195 circulating lipids and proteins from a total of 1,134 subjects in DCS and GoDARTS cohorts group patients into two subgroups. Two subgroups are likely to represent the different stages of T2D insulin insensitivity with differences at HOMA2 (p=0.0008;4.2e-11;1.1e-09, -B, -IR and -S, DCS), C-peptide (p=3.7e-11;2.5e-06) and overall disease progression (HR=0.6;0.7). This is the first study solely relying on integrated lipidomics and proteomics to capture the stages of T2D insulin insensitivity, allowing potential novel biomarker discovery which may be masked by traditional approaches. In both cohorts, a number of discriminative omics features can be observed. Immune proteins, such as IL-18R, CLP, IL-1R and COD antigen showed strong but differing associations with insulin insensitivity, which may be related to the inflammation associated with T2D. Moreover, growth factors such as GHR and IGFs also exhibit strong associations with the present study. For lipids, patients with less severe insulin insensitivity exhibit elevated levels of sphingomyelins. In conclusion, we systematically analysed the multi-omics profiles associated with T2D insulin insensitivity. The molecular signatures may be used to investigate molecular mechanisms underpinning progression and provide insights for precision medicine. Disclosure S.Li: None. I.J.Dragan: None. K.Simons: Other Relationship; Lipotype, I have no there compoanz. L.A.Donnelly: None. V.T.Tran: None. F.Mehl: None. L.M.'t hart: Research Support; European Union. M.Ibberson: Consultant; Novo Nordisk Foundation. G.A.Rutter: Consultant; Sun Pharmaceutical Industries Ltd. E.Pearson: Speaker's Bureau; Novo Nordisk, Lilly, Illumina. R.Slieker: None. J.Beulens: None. M.K.Hansen: None. D.Kuznetsov: None. M.J.Gerl: Employee; Lipotype GmbH.

Comparison of Outcome of DHS (Dynamic Hip Screw) Vs Cannulated Screws in Managing Fracture of Neck of Femur

Objectives: To compare the outcome of DHS (dynamic hip screw) vs cannulated screws in managing fracture of neck of femur. Study Design: Randomized controlled trial. Study Duration: 22-06-2021 to 21-12-2021 (6 months) Settings: Department of Orthopedic, D.G Khan Hospital, D.G Khan. Materials & Methods: A total of 60 patients with fresh fracture neck of femur, 18 to 60 years of age of both genders were included. The DCS group was managed by internal fixation with Dynamic hip screw and CS group was treated by internal fixation with cannulated screws. All patients were followed for 3 months for outcome. Results: Total 60 patients of fracture of femur neck was recruited. Mean age and mean duration of fracture was 44.42 ± 12.45 years and 10.67 ± 5.66 days. In DCS group, mean age and duration of fracture was 44.57 ±11.60 years and 10.23 ± 5.86 days respectively. In CS group, mean age and mean duration of fracture was 44.27 ± 13.46 years and 11.10 ± 5.51 days respectively. In DCS group, satisfactory outcome was found in 25 (83.33%) patients while in CS group, it was found in 13 (43.33%) patients. After applying chi-square test, it was noted that DCS group had significantly (P=0.003) higher proportion of satisfactory outcome as compared to CS group. Conclusion: Results of this study showed that DCS group had significantly higher proportion of satisfactory outcome as compared to CS group in cases of femur neck fractures. Most of the patients were between 41-60 years of age but difference of satisfactory outcome between DHS group and CS group was not significant. Regarding male patients, significantly higher rate of satisfactory outcome was noted in DHS group as compared to CS group. Keywords: femur neck fracture, dynamic hip screw, cancellous screw.

Study of damage control strategy for non-traumatic diseases: a single-center observational study

BackgroundDamage control strategy (DCS) has been introduced not only for trauma but also for acute abdomen, but its indications and usefulness have not been clarified. We examined clinical characteristics of patients who underwent DCS and compared clinical characteristics and results with and without DCS in patients with septic shock.MethodsWe targeted a series of endogenous abdominal diseases in Kansai Medical University Hospital from April 2013 to March 2019. Clinical characteristics of 26 patients who underwent DCS were examined. Then, clinical characteristics and results were compared between the DCS group (n = 26) and non-DCS group (n = 31) in 57 patients with septic shock during the same period.ResultsAll 26 patients who underwent DCS had septic shock, low mean arterial pressure (MAP) before the start of surgery, and required high-dose norepinephrine administration intraoperatively. Their discharge mortality rate was 12%. Among the patients with septic shock, the DCS group had a higher SOFA score (P = 0.008) and MAP was lower preoperatively, but it did not increase even with intraoperative administration of large amounts of fluid replacement and vasoconstrictor. There was no significant difference in 28-day mortality and discharge mortality between the two groups.ConclusionsDCS may be useful in patients with severe septic shock.

Polymer-Based Versus Polymer-Free Stents in High Bleeding Risk Patients: Final 2-Year Results From Onyx ONE.

Resolute Onyx polymer-based zotarolimus-eluting stents (ZES) were noninferior in safety and effectiveness to BioFreedom polymer-free biolimus A9-coated stents (DCS) in high-bleeding-risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) at 1 year. This study reports the final 2-year results of the randomized Onyx ONE trial. The Onyx ONE (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients) trial randomly assigned HBR patients to treatment with ZES or DCS. Following 1-month DAPT, event-free patients received SAPT (either aspirin or a P2Y12 inhibitor at physician discretion). The primary safety endpoint, a composite of cardiac death, myocardial infarction, or stent thrombosis at 1 year, was determined at 1 year. Rates of primary and secondary endpoints were calculated after final follow-up at 2 years. A total of 1,003 patients were randomly allocated to ZES and 993 patients to DCS. Follow-up was complete in 980 (97.7%) ZES patients and 962 (96.9%) DCS patients at 2 years. The primary safety endpoint occurred in 208 (21.2%) patients in the ZES group and 199 (20.7%) patients in the DCS group (risk difference: 0.5%; 95%CI: -3.1% to 4.2%; P=0.78) at 2 years without significant differences in individual components of the composite endpoint. The secondary effectiveness endpoint occurred in 217 (22.1%) patients in the ZES group and 202 (21.0%) patients in the DCS group (risk difference: 1.1%; 95%CI: -2.5% to 4.8%; P=0.54). Among patients at HBR treated with 1-month DAPT followed by SAPT, the Resolute Onyx polymer-based ZES had similar 2-year outcomes for the primary safety and secondary effectiveness endpoint compared with the BioFreedom polymer-free DCS. (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy [DAPT] for High-Bleeding Risk Patients [Onyx ONE]; NCT03344653).

Physiology dictated treatment after severe trauma: timing is everything

IntroductionDamage control strategies in resuscitation and (fracture) surgery have become standard of care in the treatment of severely injured patients. It is suggested that damage control improves survival and decreases the incidence of organ failure. However, these strategies can possibly increase the risk of complications such as infections. Indication for damage control procedures is guided by physiological parameters, type of injury, and the surgeon’s experience. We analyzed outcomes of severely injured patients who underwent emergency surgery.MethodsSeverely injured patients, admitted to a level-1 trauma center ICU from 2016 to 2020 who were in need of ventilator support and required immediate surgical intervention ( ≤24 h) were included. Demographics, treatment, and outcome parameters were analyzed.ResultsHundred ninety-five patients were identified with a median ISS of 33 (IQR 25–38). Ninety-seven patients underwent immediate definitive surgery (ETC group), while 98 patients were first treated according to damage control principles with abbreviated surgery (DCS group). Although ISS was similar in both groups, DCS patients were younger, suffered from more severe truncal injuries, were more frequently in shock with more severe acidosis and coagulopathy, and received more blood products. ETC patients with traumatic brain injury needed more often a craniotomy. Seventy-four percent of DCS patients received definitive surgery in the second surgical procedure. There was no difference in mortality, nor any other outcome including organ failure and infections.ConclusionsWhen in severely injured patients treatment is dictated by physiology into either early definitive surgery or damage control with multiple shorter procedures stretched over several days combined with aggressive resuscitation with blood products, outcome is comparable in terms of complications.

Clinical efficacy of digital chest drainage system in cardiac valve surgery.

The portable digitalized suction was used widely in thoracic surgery. The aim of the study was to access the early outcomes of using the portable digitalized suction system after cardiac surgery. We invested 80 patients including 30 women (mean age 72.7 ± 9.2years) who underwent cardiac surgery at our hospital, excluded coronary artery bypass grafting only, with or only aortic surgery, emergency operation, and patients with hemodialysis. Patients were categorized as those treated with digital chest drainage system (DCS group, n = 38) or analog chest drainage system (ACS group, n = 42), and the following data were analyzed in two groups. The primary endpoint was the duration of chest drainage, and the secondary endpoints were the rate of drainage-related complications and the length of hospitalization. The duration of drainage was significantly shorter in the DCS group (ACS vs. DCS = 94.8 ± 31.5 vs. 81.1 ± 20.6h, p = 0.036). The duration needed for rehabilitation completion was significantly shorter in the DCS group (ACS vs. DCS = 10.7 ± 1.2 vs. 9.6 ± 1.5days, p = 0.047), and the length of hospitalization was significantly shorter in the DCS group (ACS vs. DCS = 21.9 ± 5.3 vs. 18.8 ± 7.2days, p = 0.031). This study provided evidence that DCS might be effective for patients who underwent cardiac valve surgery.

The importance of natural disasters’ governance for macroeconomic performance and countries resilience

Purpose Natural disasters can undermine decades of development and threaten hundreds of lives. Previous research studies highlighted that natural disasters can cripple economic growth of one or many countries. The purpose of this paper is to ask the usefulness of natural disasters governance for macroeconomic performance and countries’ resilience. For that, this research emphasizes on the effects of natural disasters economic damages on the macroeconomic performance. Design/methodology/approach The used technique is the unbalanced panel data model which allows testing a big cross-section of population despite when one temporal observation for an individual is unavailable. The methodology focuses on testing the effect of natural disasters’ economic damages upon the main macroeconomic aggregates. For the study relevance, various tests were carried out by taking into account the different levels of development. So, two groups have been studied: developing countries (LDCs group) and developed countries (DCs group). Findings Findings point up that the effects of natural disasters’ economic damages differ from aggregate to another. In spite of the differences according to the development levels, effects are more serious for developing countries. Originality/value The originality of paper is justified by the lack of empirical studies that have questioned the links between natural disasters, macroeconomic performance and countries’ resilience. Furthermore, this study can be distinguished by the analysis of the effects for various aggregates at once and, in the same time, by allowing the comparison of these impacts by level of development.

Abstract 119: Immunotherapy with dendritic cells inhibited tumor growth on an ID8 orthotropic mouse model of ovarian cancer

Abstract Background and Purpose: Ovarian cancer is the most frequent cause of death from gynecologic malignancy. Recently, immunotherapies have been suggested as ways to treat this malignancy. However, the ideal of immunotherapy has not been realized yet in ovarian cancer patients. Therefore, we investigated effects of monocyte-derived dendritic cells (mono DCs) and new-generation DCs subset (new DCs) on an ID8 orthotropic mouse model of ovarian cancer. Methods: Mono DCs were prepared from bone marrow of C57BL/6 mice. We isolated monocyte from bone marrow by monocyte isolation kit. Isolated monocyte was incubated for 7 days with IL-4 and GM-CSF. In addition, monocytes were pulsed with LPS and ID8 tumor lysate while incubating. Likewise new DCs were isolated from bone marrow of C57BL/6 mice. We isolated lineage negative cells from bone marrow using lineage cell depletion kit. Isolated cells were incubated with IL-4 and GM-CSF; also the cells were pulsed by ID8 tumor lysate and Rg3, which is a ginsenoside. Orthotropic model of ID8 was made on C57BL/6 mice. We injected 5x106 cells into peritoneal cavity. 4 weeks after cell injection, mice were grouped into three groups, which were vehicle, mono DCs and new DCs. Mice were injected with mono DCs and new DCs. 5x106 cells of DCs were injected 1 time/week for three weeks. One week later, mice were sacrificed and organs were harvested such as peritoneum, phren, ovary and tumor mass for histologic analysis. Results: DCs treated groups showed lower ascites formation than vehicle group. Ascites were fewest in new DCs group. Survival rate was lowest in vehicle group. Each survival rate is 0% in vehicle, 63% in new DCs and 80% in mono DCs. Also tumor growth at ovary was more decreased in mono DCs and new DCs group. In addition, mono DCs-treated mice showed low level of metastasis to other organs. Conclusion: Immunotherapy with dendritic cells showed inhibition of tumor growth and metastasis on mouse ovarian cancer. These results indicated that DCs treatments are able to be a potential therapy for ovarian cancer. It also could have synergy with the combined treatment of existing anticancer drugs. However, there are several limitations such as a relatively high dose of DCs and the procedure of isolating DCs needed large amount of bone marrow. We will continue to study and improve these issues. Citation Format: Min-Je Kim, Joo-won Kim, Ju-hyun Kim, Young-Jae Lee, Shin-Wha Lee, Yong-Man Kim. Immunotherapy with dendritic cells inhibited tumor growth on an ID8 orthotropic mouse model of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 119.

Polymer-free drug-coated coronary stents in diabetic patients at high bleeding risk: a pre-specified sub-study of the LEADERS FREE trial.

Diabetics are at increased risk after stent implantation and potentially sensitive to the type of stent and dual anti-platelet therapy (DAPT). The randomized, double-blind LEADERS FREE trial compared 2432 patients at high bleeding risk (HBR) receiving either a polymer-free BA9-coated stent (DCS) or a bare metal stent (BMS) with 1 month of DAPT, and showed superior safety and efficacy of the DCS at 2 years. We report outcomes at 2 years of the pre-specified diabetic subgroup. The diabetic sub-group comprised 805 (33.1%) patients; 262 (10.8%) were insulin-dependent (IDDM). Compared to non-diabetics, diabetics were younger and had more risk factors and multi-vessel disease. They suffered higher rates of death (15.6 vs. 12.2%, p = 0.01), cardiac death (8.3 vs. 5.9%, p = 0.02), myocardial infarction (MI) (11.1 vs. 7.8%, p = 0.009) and definite/probable stent thrombosis (3.1 vs. 1.7%, p = 0.01), but rates of clinically-indicated TLR (9.1 vs. 9.5%, p = 0.93) and BARC 3-5 bleeding (10.2 vs. 8.4%, p = 0.20) were comparable. Compared to diabetic patients treated with a BMS, diabetic DCS recipients required less clinically driven TLR (6.3 vs. 12.2%, p = 0.006). The primary safety endpoint (cardiac death, MI, definite/probable stent thrombosis) occurred numerically less frequently in the DCS group (14.9 vs. 19.7%, p = 0.10), and was significantly lower in IDDM patients (13.8 vs. 25.4%, p = 0.03). BARC 3-5 was similar for patients treated with DCS (9.9%) and BMS (10.5%, p = 0.84). In diabetic HBR patients, DCS significantly reduced re-intervention rates over BMS, and showed a strong trend towards a safety benefit at 2years. ClinicalTrials.gov number: NCT01623180.

Sternal semi-closure using a bioresorbable osteosynthesis device: a new method for delayed sternal closure.

To evaluate the safety and efficacy of our new delayed sternal closure (DSC) method, involving sternal semi-closure using a bioresorbable osteosynthesis device and complete skin closure. Between 2013 and 2017, 36 patients underwent DCS at our hospital. The patients were divided into two groups based on the method used for DSC. The later conventional DSC group consisted of 18 patients undergoing late complete sternal closure following fixation of pulmonary and hemodynamic instability, and the new DSC group consisted of 18 patients undergoing early sternal semi-closure a few days after surgery. In the new DSC group, the sternum was fixed with Super Fixsorb MX40, followed by complete skin closure. Respiratory and hemodynamic conditions, such as systolic blood pressure, cardiac index, tidal volume, and regional oxygen saturation, were significantly more stable in the new DCS group than in the conventional DSC group. The hospital stay was also significantly shorter in the new DSC group. Although there were no serious complications, one patient from the new DCS group suffered deformity of the sternum, which was managed successfully. The sternal semi-closure method decreases pulmonary and cardiac instability during DSC, making early DSC possible.

Uncomplicated common bile duct stone removal guided by cholangioscopy versus conventional endoscopic retrograde cholangiopancreatography.

Although previous studies have reported the possibility of therapeutic ERCP without fluoroscopy, more robust documentation of fluoroscopy-free common bile duct stone (CBDS) clearance is needed. Technically, "digital cholangioscopy" (DCS) may be used to confirm CBDS clearance. We aimed to compare the feasibility, safety, and radiation exposure between patients with CBDS undergoing stone removal by DCS and conventional ERCP (cERCP). Fifty (50) consecutive patients with a CBDS size < 15mm underwent DCS (SpyGlass DS Direct Visualization System, Boston Scientific, Marlboro, MA, USA) between December 2015 and October 2016. Of 202 consecutive patients undergoing cERCP during the same time frame, 50 matched pairs were created using propensity score matching analysis. In the DCS group, patients underwent biliary cannulation and CBDS removal without fluoroscopy followed by DCS to confirm complete CBDS clearance. A final occlusion cholangiogram was performed as the current standard of care to confirm CBDS clearance. Cannulation success rates were similar between the DCS and cERCP groups (98 vs. 98%). By intention-to-treat analysis, CBDS clearance in the DCS and cERCP groups was not different (90 vs. 98%; p = 0.20, respectively). DCS had successful CBDS removal in 45 cases, whereas 5 (10%) failed for clearance by DCS due to technical limitations. Adverse events were not different between both groups. In the management of uncomplicated CBDS, our data confirmed the feasibility of DCS for CBDS clearance as it showed efficacy and safety comparable to those of cERCP. Although certain conditions may limit its effectiveness, DCS offers the ability to perform CBDS clearance without the need for fluoroscopy unit and can avoid radiation exposure while ERCP under fluoroscopy remains the current standard of care in patients with CBDS.

Early results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for locally advanced gastric cancer

Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival. Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed. Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.

Effects of a dynamic core stability program on the biomechanics of cutting maneuvers: A randomized controlled trial.

Deficits in trunk control predict ACL injuries which frequently occur during high-risk activities such as cutting. However, no existing trunk control/core stability program has been found to positively affect trunk kinematics during cutting activities. This study investigated the effectiveness of a 6-week dynamic core stability program (DCS) on the biomechanics of anticipated and unanticipated side and crossover cutting maneuvers. Thirty-one male, varsity footballers participated in this randomized controlled trial. Three-dimensional trunk and lower limb biomechanics were captured in a motion analysis laboratory during the weight acceptance phase of anticipated and unanticipated side and crossover cutting maneuvers at baseline and 6-week follow-up. The DCS group performed a DCS program three times weekly for 6weeks in a university rehabilitation room. Both the DCS and control groups concurrently completed their regular practice and match play. Statistical parametric mapping and repeated measures analysis of variance were used to determine any group (DCS vs control) by time (pre vs post) interactions. The DCS resulted in greater internal hip extensor (P=.017, η2 =0.079), smaller internal knee valgus (P=.026, η2 =0.076), and smaller internal knee external rotator moments (P=.041, η2 =0.066) during anticipated side cutting compared with the control group. It also led to reduced posterior ground reaction forces for all cutting activities (P=.015-.030, η2 =0.074-0.105). A 6-week DCS program did not affect trunk kinematics, but it did reduce a small number of biomechanical risk factors for ACL injury, predominantly during anticipated side cutting. A DCS program could play a role in multimodal ACL injury prevention programs.

Effectiveness of induction chemotherapy consisting of docetaxel, cisplatin, and S-1 (DCS) followed by esophagectomy for cT4 esophageal cancer

Introduction: The prognosis of cT4 esophageal cancer is dismal unless the tumor is completely removed by esophagectomy after induction treatment successfully reducing the tumor volume. However, esophagectomy for cT4 esophageal cancer after induction treatment is associated with high morbidity and mortality rates and recommended induction treatment remains unclear. The aim of the study is to evaluate the feasibility and efficacy of 3-course chemotherapy consisting of docetaxel, cisplatin, and S-1 (DCS) followed by esophagectomy in comparison with 2-course chemotherapy consisting of 5-FU, doxorubicin, and nedaplatin (FAN) for cT4 esophageal cancer in a prospective cohort study. Methods: Since 2002, we have performed a prospective cohort study of induction treatment in patients with cT4 esophageal cancer. FAN chemotherapy, 40-66 Gy chemoradiotherapy, and DCS chemotherapy was performed in patients with cT4 esophageal cancer during the period of 2002-2006, 2006-2013, and 2013-2016, respectively. The short- and long-term results of DCS group (n = 18) were compared with FAN group (n = 17). In DCS group’s patients, cStage III and IV diseases were found in 1 and 17 respectively, whereas the respective number was 3 and 14 in the FAN group’s patients. Results: The completion rate of the planned therapy was 89% and 65% in the DCS and FAN group, respectively (p = 0.121). The response rate for primary tumor (83%) of DCS group was significantly higher than that (35%) of FAN group (p = 0.006). However, the occurrence rate of the toxicity grade 3 or higher was not significantly different between two groups: 61% and 47% in the DCS and FAN group, respectively (p = 0.505). There were no treatment-related deaths during the chemotherapy in two groups. The esophagectomy rate was 67% of DCS group and 59% of FAN group, respectively (p = 0.733). R0 resection rate was 61% of DCS group and 47% of FAN group, respectively (p = 0.505). There were not significantly different between two groups but DCS group showed high Esophagectomy and R0 resection rates in comparison with FAN group. The surgery-related morbidity rate was 75% and 50% in DCS and FAN groups, respectively (p = 0.378). There were not significantly different between the 2 groups. The surgery-related mortality was occurred in two patients of FAN group, but there were not in DCS group. The 5-years overall survival rates for all patients, the 45% of DCS group was significantly better than 12% of FAN group (p = 0.029). Conclusion: The induction DCS therapy is safe and feasible, and has strong power to reduce tumor volume (response rate: 83%) even in cases of T4 esophageal tumor. Esophagectomy and R0 resection rates after the DCS therapy were better than those after the FAN therapy. Furthermore, the 5-years overall survival rates for all patients in DCS group significantly better than that in FAN group. Therefore, the DCS therapy may be promising as the induction treatment for cT4 esophageal cancer.

D-Cycloserine enhances durability of social skills training in autism spectrum disorder

Backgroundd-Cycloserine (DCS) enhances extinction learning across species, but it has proven challenging to identify consistent benefit of DCS when added to therapeutic interventions. We conducted a placebo-controlled trial of DCS to potentiate social skills training in autism spectrum disorder (ASD) but found substantial improvement in both the DCS and placebo groups at the conclusion of active treatment. Here, we assess the impact of DCS 11 weeks following active treatment to evaluate the impact of DCS on treatment response durability.MethodsStudy participants included 60 outpatient youth with ASD, ages 5–11 years, all with IQ above 70, and significantly impaired social functioning who completed a 10-week active treatment phase during which they received weekly single doses of 50 mg of DCS or placebo administered 30 min prior to group social skills training. Following the 10-week active treatment phase, blinded follow-up assessments occurred at week 11 and week 22. The primary outcome measure for our durability of treatment evaluation was the parent-rated social responsiveness scale (SRS) total raw score at week 22.ResultsAnalysis of the SRS total raw score demonstrated significant decrease for the DCS group compared to the placebo group (p = 0.042) indicating greater maintenance of treatment effect in the DCS group. DCS was well tolerated, with irritability being the most frequently reported adverse effect in both groups.ConclusionsThe findings of this study suggest that DCS may help youth with ASD to maintain skills gained during sort-term social skills training. Larger-scale studies with longer follow-up will be necessary to further understand the long-term impact of DCS paired with structured social skills training.Trial registrationClinicalTrials.gov, NCT01086475

Day care PNL using 'Santosh-PGI hemostatic seal' versus standard PNL: A randomized controlled study.

IntroductionTo compare the outcomes of tubeless day care PNL using hemostatic seal in the access tract versus standard PNL.Material and methodsIt was a prospective randomized controlled study. Cases were randomized to either the day care group with hemostatic seal (DCS) or the control group where patients were admitted and a nephrostomy tube was placed at the conclusion of surgery.ResultsA total of 180 cases were screened and out of these, 113 were included in the final analysis. The stone clearance rates were comparable in both the groups. The mean drop in hemoglobin was significantly lower in DCS group than the control group (1.05 ±0.68 vs. 1.30 ±0.58 gm/dl, p = 0.038).Mean postoperative pain score, analgesic requirement (paracetamol) and duration of hospital stay were also significantly lower in the DCS group (3.79 ±1.23 vs. 6.12 ±0.96, 1.48 ±0.50 vs. 4.09 ±1.11 grams and 0.48 ±0.26 vs. 4.74 ±1.53 days respectively; p <0.05). The incidence of urine leakage through the access tract site was significantly lower in the DCS subgroup when compared to the controls (3.6% vs. 21.1%, p <0.05). Cases in the DCS group resumed their normal activities in a significantly shorter time (8.05 ±3.05 vs.18.42 ±4.42 days; p <0.05). Higher proportion of cases in the DCS group got re-admitted, although it was not a statistically significant number (7.1% vs. 1.8%; p = 0.21).ConclusionsTubeless day care PNL with composite hemostatic tract seal is considered safe. It resulted in a significant reduction of blood loss and analgesic requirement with significantly reduced hospital stay, nephrostomy tube site morbidity and time required to resume normal activity when compared to the standard PNL. However, patients must be compliant with the given instructions and should have access to a health care facility, as few of them may need re-admission.

Comparative study between Dynamic Condylar Screw and Locking Plate Fixation in fractures of distal femur in adults-A study of 30 cases

Background: The aim of treatment of the distal femoral fractures has been a balance between the goal of anatomical alignment and need for early function of limb. Objective: 1. To compare the rigidity of fixation achieved. 2. To compare the restoration of anatomical joint surface. Methodology: 30 patients of distal femoral fractures admitted to Department of Orthopaedics, at Government Medical College, Rajindra Hospital, Patiala. Only those cases were selected where ORIF is indicated like in patients with displaced intra-articular fractures, multiple injuries, severe ipsilateral limb injuries, displaced extra-articular supracondylar fractures, pathological fractures and most open fractures. Results: Among 30 patients, 16 cases (54%) sustained A type and 14 cases (46%) suffered type C supracondylar fracture as per AO classification. In DCS group, most (80%) of the patients had A type of fracture. In LCP group, most (75%) of the patients had C type of fractures. Bone grafting was done in 8 (24%) cases at the time of primary fixation of fractures. In DCS group bone grafting was done in two cases and in LCP group in 6 cases. In the DCS group, we had 2 cases (6%) in which only one inter fragmentary screw and 1 case in which 2 inter fragmentary screws were fixed in the distal fragment along with DCS lag screw and plate to give additional support. Conclusion: LCP is the implant of choice in comminuted fractures of distal end of femur and in elderly patients DCS can be used in distal femur fractures only when there is an uncomminuted bone stock of atleast 4 cm above the intercondylar notch. Key Words: Supracondylar, Intercondylar, Inter fragmentary screws, Bone grafting

Mutated Regions of Nucleophosmin 1 Elicit CD8+ T-Cell Responses in Patients with Acute Myeloid Leukemia

ObjectiveStimulating lymphocytes from healthy donors by DCs loaded with NPM1mut peptides in vitro in order to induce specific cellular immune responses against the peptides. And detecting the NPM1mut peptide specific T-cell in peripheral blood of patients with NPM1mut positive acute myeloid leukemia (AML), to provide a theoretical basis for immune therapy of AML.Methods1. NPM1 mutation detection: newly diagnosed patients of AML underwent gene mutations screening routinely.2. Samples collection: peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood collected from healthy donors with HLA-A* 0201 or A*1101 and NPM1mut positive AML patients in complete remission.3. Inducing differentiation of PBMCs into DCs: non-adherent cells were removed from PBMCs suspension, and then adherent cells were subsequently cultured for 5 days with GM-CSF and IL-4 to induce differentiation. Then cells were cultured in medium containing GM-CSF, IL-4, IL-6, IL-1β, TNF-α, and PGE2 for another 2 days to induce maturation.4. Generation of NPM1-specific cytotoxic T cells: DCs were pulsed with different NPM1 peptides followed by irradiation with 40 GY. The non-peptide pulsed DCs group was set as negative control. The above mentioned DCs were then co-incubated with their own PBMCs, maintained by IL-2 and IL-7. On day 7 of co-incubation, the same treated DCs as mentioned above were added again to restimulate lymphocytes.5. ELISPOT analysis and intracellular staining: peptide-stimulated T cells were tested by ELISPOT and intracellular staining method on day 7 and 14 . These two methods both detected the secretion of IFN-γ of cytotoxic T cells. T2 cells were used as target cells, and in terms of HLA-A*1101 positive donors, their own DCs were used as targets.Results1. In the Han Chinese population, the most common alleles of HLA-A loci were A* 1101, A*2402, and A*0201 allele.2. Through prediction of the aforementioned software, HLA-A*0201 restricted wild type NPM1 amino acid sequences (DLWQWRKSL), mutated NPM1-A/D amino acid sequences (AIQDLCLAV), and HLA-A*1101 restricted mutated NPM1-A/D amino acid sequences (AVEEVSLRK) were synthesized. There were no proper epitopes for either HLA-A*1101 restricted wild type NPM1 protein or HLA-A*2402 restricted wild type and mutated NPM1 protein.3. Expression of surface antigens of DCs on day 7 were as follows: CD14(2.6%), CD80(43.4%), CD83(7.8%), CD86(99.9%), HLA-DR(67.1%), which was consistent with DCs phenotype.4. About 10 days after DCs were co-incubated with their own PBMCs, the number of lymphocytes increased significantly, especially in the NPM1mut peptide pulsed group. On day 7 of co-incubation, ELISPOT analysis results of all samples were negative. However, 3 cases’ ELISPOT results were positive for the mutated peptide holes on day 14, in contrast, the results of the wild type peptide holes were negative. The NPM1mut peptide-specific T lymphocytes positive rate [=(average number of spots in mutated peptide holes-the average number of spots in negative control holes)/total lymphocytes per hole] was about 1/2500. Intracellular staining showed that in the aforementioned 3 cases, the proportion of CD8+IFN-γ+cells of the mutant peptide group was higher than either the wild type peptide group or negative control group, but there was no difference between the later two groups.5. 6 peripheral blood samples of patients with NPM1mut +AML were performed ELISPOT analysis, with only 1 case (16.7%) showing a approaching positive result.ConclusionsNPM1mut peptide pulsed DCs can stimulate their own PBMCs from healthy donors in vitro to produce mutated NPM1 specific T lymphocytes, and it is expected to be used as immune therapy of AML. The mutated NPM1 specific CTL in NPM1mut+AML patients are almost undetectable that indicates immune system have been comprised because of chemotherapy and disease, and can not responses to antigens efficiently. Perhaps AML patients can accept CTL transfusion from their relatives. Our study provide an experimental basis for cellular immunotherapy of AML. DisclosuresNo relevant conflicts of interest to declare.

Th and Treg response induced by Aspergillus fumigatus pulsed dendritic cells in vitro

Background Dendritic cells (DCs) can recognize the pathogen-associated molecular patterns (PAMP) of Aspergillus fumigatus (A. fumigatus), activating the immune response. During A. fumigatus infection, a Th and Treg response induced in the fungi-pulsed DCs is not yet well understood. Methods In this study, bone marrow-derived dendritic cells (BMDCs) were separated and proliferated from C57BL/6 mice. A. fumigatus pulsed DCs were generated and cultured with CD4+ T cells derived from the spleen of C57BL/6 mice in vitro. CD4+ T cells differentiation after co-culture were analyzed by flow cytometry, ELISA, and real-time PCR analysis. Results The A. fumigatus pulsed DCs exhibited increased Th1 and Treg frequency, Th1-related cytokines (IFN-γ and IL-12), Treg-related cytokines (TGF-β) and T-bet, and Foxp3 mRNA levels compared with the control group. There was no significant difference between A. fumigatus pulsed DCs group and the control group about Th17 and Th2 frequency. Conclusions The inactivated conidia of A. fumigatus were able to activate BMDCs and made them capable of triggering T cell responses in vitro. A. fumigatus loaded DCs was a weak inducer of Th17 and Th2, but induced a strong Th1 and Treg response.

656P - Treatment Strategy for Conversion Therapy Using Docetaxel/Cddp/S-1 (Dcs) or Dcs-Trastuzumab (Dcs-T) According to Her2 Status in Metastatic Gastric Cancer Patients

ABSTRACT Aim: The feasibility of chemotherapy,” which is an attempt to convert an initially unresectable cancer to resectable status, has not been fully examined in patients (pts) with unresectable metastatic gastric cancer (UMGC). We have developed a triplet-drug combination regimen consisting of docetaxel, CDDP, and S-1 (DCS), and recently we carried out a feasibility study of DCS-trastuzumab (DCS-T) for pts with HER2-positive UMGC. We reported that both regimens are associated with a high response rate and downstaging in pts with initially UMGC. The aim of this study was to clarify the conversion rate and prognosis in pts with initially UMGC treated with DCS or DCS-T according to their HER2 status. Methods: Pts with UMGC were enrolled in clinical trials of DCS or DCS-T chemotherapy. Pts received oral S-1 (40 mg/m2 BID) on days 1-14, intravenous cisplatin (60 mg/m2), and docetaxel (50-80 mg/m2) on day 8 every 3 weeks. In the DCS-T group, trastuzumab was added on day 8 at a dose of 8 mg/kg in the first cycle and 6 mg/kg in the second cycle and thereafter. Conversion surgery was considered when pts underwent downstaging as determined by conventional examinations or staging laparoscopy and were deemed able to tolerate a curative surgical operation. Results: The study included 100 pts in the DCS group: median age, 63 years; PS, 0/1/2: 47/27/26 pts; and well-differentiated/undifferentiated adenocarcinoma, 39/61 pts. The objective response rate was 81.4%. Conversion was achieved in 35/100 (35%) pts and 28/33 (84.8%) underwent curative surgery. A total of 24 (72.7%) of the 33 resected cases were histological chemotherapeutic responders. The median OS of the resected pts was 47.8 months. The DCS-T study included 16 pts: median age, 60 years; PS 0/1/2, 10/4/2 pts; HER2 3 + , 13 pts; HER2 2 + /FISH + , 3 pts. The objective response rate was 100%. Non-curative factors disappeared in 10 of 16 cases and R0 resection was carried out in 9 (56.3%). A pathological response was seen in 8 (88.9%) of the resected cases. At a median follow-up of 14.1 months (range, 4.7 – 29.3 months), median OS was not yet reached. Conclusions: DCS and DCS-T provided a high conversion rate and better prognosis. Our data warrant further prospective investigations to establish a conversion therapeutic strategy for UMGC pts according to their HER2 expression status. Disclosure: All authors have declared no conflicts of interest.