SCT Group Research Articles

LGG-38. UNRESECTABLE PEDIATRIC LOW-GRADE GLIOMAS OF THE BRAIN: TARGETED THERAPY COMPARED WITH STANDARD CHEMOTHERAPY AS FIRST-LINE TREATMENT

Abstract BACKGROUND Pediatric low-grade gliomas (pLGG) frequently harbor MAPK-pathway mutations that determine poor response to standard chemotherapy (sCt). Targeted agents against BRAF-V600E mutation (MAPK-i) are emerging as molecularly driven treatments. Few studies have compared sCt with MAPK-i. We aimed to compare response and progression-free survival (PFS) of unresectable brain pLGG treated with sCt or MAPK-i. MAPK-i were used in first line or at relapse. METHODS We conducted a single-center observational retrospective study of all brain pLGG consecutively diagnosed and treated at Gaslini Children’s Hospital between January 2008 and December 2021. Treatment was assessed using RAPNO criteria at 6, 12-18 months, and at last follow-up. MRI studies were reviewed by two experienced neuroradiologists. RESULTS Seventy-one patients were enrolled: 66 received sCt and 10 MAPK-i (5 in first line, 5 after sCt failure). All patients who received MAPK-i were BRAF-V600E mutated. Groups were homogeneous for tumor location and dissemination. sCt group was enriched for pilocytic astrocytoma, MAPK-I group for ganglioglioma. sCt patients were younger. SCt lasted 12-18 months, MAPK-i were continuously given. Tumor size reduction was 19.5% at 6 months and 40.5% at 12-18 months for sCt group; 48% at 6 months and 43.5% at 12-18 months for MAPK-i group. SCt determined at least stable disease in 74.2% of patients; 60% of responders reached the best response at 6 months, 40% at 12-18 months. 5y-PFS was 40.3% (median time for progression: 2.5 years). MAPK-i determined at least stable disease in all patients at first evaluation with long-lasting response (median time of follow-up: 5.1 years). CONCLUSIONS In our study sCt was effective in inducing response but prolonged disease control is not always achieved. BRAF-V600E mutated patients upon MAPK-i start gained a rapid disease control with long-lasting response, also if they have been pretreated. Acknowledgement: this study was supported by ARTUCEBA ONLUS.

Patient Characteristics and Outcomes of Sinusoidal Obstruction Syndrome with and without Hematopoietic Stem Cell Transplant

Introduction Sinusoidal obstruction syndrome (SOS), also called hepatic veno-occlusive disease (VOD) is a condition causing damage of hepatic vascular endothelial cells, it can progress to multi-organ failure and is associated with high mortality ( >80%). It is known to occur mainly after high dose chemotherapy use in hematopoietic stem cell transplant (HSCT) but with recent advances in chemotherapy, there is an increase in its incidence in non-hematopoietic stem cell transplant patients (non-HSCT). Currently, there is limited literature comparing the patient characteristics and survival of SOS in HSCT vs non-HSCT patients. Therefore we conducted this retrospective analysis. Methods We performed a retrospective analysis using the 2016-2020 National inpatient sample (NIS) database, generated by the Health care cost and utilization project (HCUP). We gathered data on all patients who had SOS/VOD during this time period. They were divided into two cohorts, those who received hematopoietic stem cell transplant (HSCT group) vs those who did not receive hematopoietic stem cell transplant (non-HSCT group). Among the two cohorts we compared the patients characteristics, underlying malignancies, comorbidities and mortality. Results From the NIS database during the study period 1740 cases had documented SOS/VOD. Of those, 520(30%) had a history of HSCT and 1220(70%) did not have HSCT. Of the 520 cases with HSCT, 135 (26%) had Acute lymphoblastic leukemia (ALL), 105 (20.2%) had Acute myeloid leukemia (AML), 55 (10.6%) had Non-Hodgkin lymphoma (NHL), 20 (3.8%) had Chronic myeloid leukemia (CML), 15 (2.9%) had Hodgkin lymphoma (HL), the rest were other malignancies which were not included in the search. Of the 1220 cases without HSCT, 320 (26.2%) had ALL, 150 (12.3%) had AML, 90 (7.4%) had Solid tumors, 55 (4.5%) had NHL, 15 (1.2%) had CML, 15 (1.2%) had HL, the rest were likely malignancies not included in the search. ALL was the predominant cancer in both HSCT and non-HSCT groups (26% and 26.2% respectively), followed by AML, with more AMLs noted in the HSCT group (20%) versus the non-HSCT group (12.3%). The study population predominantly consisted of Whites followed by Hispanics and then African-Americans in both groups. The population also consisted predominantly of males across both cohorts. (Table 1). The solid tumors which were associated with SOS in the non-HSCT group included colorectal cancer, liver cancer, pancreatic cancer and Breast cancer in that order (Table 2). Preexisting liver disease was present in 215 (17.6%) of patients in non-HSCT cohort vs 60 (11.5%) patients in SCT cohort. Pre-existing lung disease was insignificant in both groups. Mortality was compared between the two groups after adjusting for primary cancer, age, sex, race and we found that SCT group had higher odds of mortality compared to non-SCT (14.4% vs 7.4%, aOR 1.866, 95% CI 1.29-2.68, p<0.01). Further multivariate analysis could not be carried out due to low sample size. Discussion Although traditionally, SOS/VOD has been thought to be a complication related to SCT, our study goes on to show that there is actually a higher incidence of SOS in the non-SCT patient population. ALL was the most common hematological malignancy encountered and had similar prevalence in both groups indicating that treatment regimens used in this cancer carry a high risk of SOS. Drugs like inotuzumab ozogamicin are the possible culprits although this information could not be obtained from our database. AML patients also exhibited high rates of SOS, more so in the SCT setting. Patients with preexisting liver disease and hematological malignancies could also benefit from close monitoring for symptoms of SOS with a high index of suspicion based on our results. Despite rising incidence in non-SCT patients, SCT patients with SOS continue to have a higher mortality possibly indicating the higher toxicity of chemotherapy regimens used in this setting. Thus, our study brings forth some important differences between HSCT and non-HSCT SOS and enables clinicians to identify the associated risk factors.

Prognostic impacts of participation in prospective surgical clinical trials on surgical outcomes in gastric cancer patients

Various prospective surgical trials have been conducted on treating patients with gastric cancer. In clinical practice, patients and surgeons may hesitate to participate in prospective surgical trials due to trial-related complications. In this study, we evaluated the effects of participation in prospective surgical trials on surgical outcomes after radical gastrectomy for gastric cancer. This study included 1689 patients who underwent curative gastrectomy for gastric cancer between 2016 and 2020. The propensity score weighting (PSW) method was used to adjust for differences in baseline clinicopathological characteristics between patients who participated and those who did not participate in prospective surgical clinical trials. Perioperative outcomes and overall survival were compared between groups. Of the 1689 patients, 309 (18.3%) participated in surgical clinical trials (SCT group). Before PSW, the SCT group had a similar operation time, intraoperative blood loss, complications, major complications, and hospital stay as the non-SCT group but had superior overall survival. After PSW, overall survival and perioperative outcomes were not significantly different between the groups. The present study suggests that participation in prospective surgical trials was not associated with surgical outcomes. Patients and surgeons may participate in prospective surgical trials without fearing adverse effects on surgical outcomes.

Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation for Patients with Decompensated Liver Cirrhosis

Background or PurposeAlthough human umbilical cord blood-derived mesenchymal stem cell transplantation (HUCB-MSCT) resulted in a good short-term therapeutic effect on patients with decompensated liver cirrhosis (DLC), the long-term survival remained unclear. This study aimed to evaluate the impact of HUCB-MSCT on long-term outcomes in patients with DLC. MethodsThis retrospective cohort study included hospitalized patients with decompensated cirrhosis in Liuzhou Hospital of Traditional Chinese Medicine between November 2010 and February 2013. The primary outcome was overall survival (OS). The secondary outcomes were 3-year and 5-year survival rates and the occurrence rate of hepatocellular carcinoma (HCC). ResultsA total of 201 subjects were enrolled, including 36 patients who underwent HUCB-MSCT (SCT group) and 165 patients who did not (non-SCT group). After PSM (1:2), there were 36 patients in the SCT group and 72 patients in non-SCT group. The 3-year and 5-year survival rates of the two groups were 83.3% vs. 61.8% and 63.9% vs. 43.6%, and median OS time was 92.50 and 50.80 months, respectively. HUCB-MSCT treatment was found to be an independent beneficial factor for patient OS (hazard ratio = 0.47; 95% CI: 0.29–0.76; P = 0.002). There was no significant difference in the occurrence rate of HCC between the two groups (P = 0.410). Discussion or ConclusionsHUCB-MSCT may improve long-term OS without increasing the occurrence of HCC in patients with DLC. Trial RegistrationThe Chinese Clinical Trial Registry (ChiCTR2100047550).

Study of Implication of Wbc and Platelet Count among Sickle Cell Disease Patients in Waghodia Region, Vadodara, Gujarat

Introduction: Hematological parameters are very useful profiles in the effective management of the disease However, there is scarcity of studies on the hematological parameters of SCD in Gujarat.
 Objective: The objective of the study was to changes in hematological finding in patients of sickle cell disease.
 Materials and Methods: This Prospective studyincludes total 150 participants who suffering from sickle cell anemia and attending at our Institute Complete blood count (CBC) and sickling test was done from all participants Comparison of results was done between Sickle cell trait and Sickle cell disease Group.
 Results: The mean age of the SCA patients was 25 54±10 years. Maximum participants are found to be from age group 25-30 yr(n=35) followed by 20-25 yr(n=30) of the 150 SCA patients, 89 (59 33%), and 61 (40 6%) were males and females, respectively. The Mean value of WBC count(/cumm) in SCT group is10611±3015 and SCD is 14427±3693 while the Mean value of Platelet count (lacs/cumm) is 3.75±1 i10 and 4 04±0 94 SCT and SCD Group.
 Conclusions: The present study found elevated levels of WBC and PLT among the SCD patients, possibly reflecting spleen effect in these patientsi These hematological parameters present a more descriptive data on SCD patients in Gujarat and may as well provide a useful tool and assist clinicians in the management of SCD patients in india.

Intermittent aerobic-resistance interval training versus continues aerobic training: Improvement in cardiac electrophysiologic and anthropometric measures in male patients post myocadiac infarction, a randomized control trial.

Exercise is a valuable intervention modality for patients post-myocardial infarction (MI). Aerobic and resistance training are both commonly used separately in cardiac rehabilitation. However, the effect of aerobic interval exercise combined with alternating sets of resistance training (super-circuit training, SCT) on cardiac electrophysiologic and anthropometric measures had not been thoroughly investigated. The primary objective of this study was to compare the effectiveness of moderate-intensity continuous-aerobic training (CAT) vs. SCT on cardiac electrical measures (resting electrocardiographic, ECG; a nd heart rate variability, HRV) in patients' post-MI presenting reduced left ventricular function. Second, to examine its effect on anthropometric measures. Twenty-nine men post-MI with reduced left ventricular function were assigned randomly to either 12 weeks of CAT (n = 15) or SCT (n = 14). CAT group performed moderate-intensity activity. SCT group performed high-intensity exercise, alternating between resistance and aerobic training. Differences between CAT and SCT groups were done using independent t-tests, paired t-tests and effect size (ES). Participants in both groups improved their HRV measures (increase in HFnu; p < 0.05; ES > 0.51) and ECG (reduction in QT-dispersion; p < 0.05; ES > 0.51). Only the SCT group had significant improvements in waist circumference (p < 0.05). Exercise improves cardiac electrical measures post-MI. However, in comparison to CAT, SCT may yield greater anthropometric changes. In order to have improvements in cardiac electrical stability, clinicians working with post-MI patients may use both CAT and SCT. However, SCT might result in greater improvements.

Structural and pragmatic language in young children with sex chromosome trisomy (XXX, XXY, XYY): Predictive value for neurobehavioral problems one year later

Objective: To investigate pragmatic language abilities in young children with an increased risk for adverse neurobehavioral and neurocognitive outcomes due to an extra X or Y chromosome (sex chromosome trisomy; SCT) and to investigate to what degree early structural and pragmatic language abilities are predictive of neurobehavioral problems one year later. Method: In total, 72 children with SCT and 71 controls aged 3-7 years were included. Language assessments included parent-reported pragmatic language skills and direct assessment of structural language abilities. Parent-reported behavioral outcomes were measured one year after the initial language assessment. Results: Children with SCT demonstrated weaker pragmatic language skills compared to controls. These differences were not driven by karyotype, time of diagnosis, or ascertainment bias and irrespective of the presence of structural language impairment. Odds of having pragmatic difficulties was 23 times higher in the SCT group, with 25% of the children not meeting age-expectations. In addition, language, in particular pragmatic language, was an important predictor for later affective, oppositional defiant, pervasive developmental, attention deficit, and social-emotional problems in young children with SCT. Conclusions: This study is one of the first studies that directly illustrates the relationship between language and behavioral outcomes in children with SCT. Our results stress the importance to closely monitor pragmatic language in addition to structural language in clinical care of children with SCT, as pragmatic language abilities could serve as an early marker for children at risk for developing behavioral problems.

Testing the effectiveness of an SCT-based training program in enhancing health self-efficacy and outcome expectations among college peer educators.

Peer health education (PHE) is a widely implemented prevention approach among college populations. While social cognitive theory (SCT; Bandura, 2004) has been assumed to account for the underlying mechanisms of PHE, no studies have tested the utility of an SCT-based training program in improving health-related outcomes among peer educators. The present study developed, implemented, and tested the effectiveness of a 15-week, SCT-based wellness coaching training program in enhancing health self-efficacy (HSE) and outcome expectations (HOE) among undergraduate peer educators. The quasi-experimental design included an SCT training group (n = 39), alternative training group (n = 46), and no-treatment control group (n = 46) and gathered data from participants at pretest, posttest, and 6-week follow-up. Results of a split-plot multivariate analysis of variance revealed a significant interaction effect for group and time when considering HSE and HOE together. Follow-up analyses indicated that the interaction was significant for HOE, but not for HSE. The SCT group reported significantly lower HOE than the control group at pretest but showed no differences in HOE scores compared to the other two groups at posttest or follow-up. Findings also revealed significant improvements in the SCT group's HSE scores over time. The findings provide initial empirical support for the effectiveness of SCT-based training programs in promoting positive health-related beliefs and attitudes among peer educators. Further, this study demonstrates that the process of training peer educators may be utilized as a health promotion strategy in and of itself. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effectiveness of Short-Course Antibacterial Therapy on Acute Cholecystitis after Successful Percutaneous Transhepatic Gallbladder Drainage: A Retrospective Study.

Background: The aim of this study was to evaluate the outcome of short- and long-course antibacterial therapy after successful percutaneous transhepatic gallbladder drainage in patients with mild to moderate acute cholecystitis. Patients and Methods: We compared the effect of short-course antibacterial therapy retrospectively (SCT; ≤3 days) and long-course antibacterial therapy (LCT; ≥4 days) after successful drainage of acute cholecystitis. The study outcomes involved three-month recurrence and 30-day mortality rates, as well as hospital stay length. Results: We included 132 patients with acute cholecystitis who underwent successful percutaneous transhepatic gallbladder drainage (PTGBD) and excluded 174 patients. We then grouped these patients (78 males and 54 females), according to the duration of antibacterial therapy. Short- and long-course antibacterial therapy groups comprised 54 (40.9%) and 78 (59.1%) patients, respectively. We did not observe significant differences in the three-month recurrence (p = 0.761) and 30-day mortality (p = 0.151) rates between these groups and observed only two deaths in the LCT group. The median hospital stay for the SCT group was six days (interquartile range [IQR], 5-7 days), compared with nine days (IQR, 8-10 days) for the LCT group (p < 0.001). Conclusions: A duration of three days or less of antibacterial therapy may be adequate for patients with mild to moderate acute cholecystitis after successful PTGBD.

Impact of Single versus Double Clamp Technique on Blood Lactate Levels and Postoperative Complications in Coronary Artery Bypass Surgery.

IntroductionCardiopulmonary bypass (CPB) is associated with hyperlactatemia, which leads to adverse clinical outcomes. No study has examined the effect of different clamping techniques on postoperative hyperlactatemia (PHL). Thus, we aimed to evaluate the impact of two different techniques on PHL and the clinical outcomes in patients undergoing isolated coronary artery bypass surgery.MethodsThis retrospective study included 100 patients who underwent isolated CPB either with single clamp technique (SCT, n=47) or double clamp technique (DCT, n=53). Demographic and preoperative laboratory data, as well as operative features and arterial blood lactate levels at the onset and at the end of CPB, were collected from patient charts.ResultsBlood lactate levels collected at the end of CPB did not differ significantly between groups whereas intraoperative lactate increased significantly in both groups (P<0.005). PHL developed in 16 patients (32%). There was no meaningful difference in SCT and DCT in this regard. Left internal mammary artery was used more frequently in the DCT group than in the SCT group. While the cross-clamp time was significantly longer in the SCT group, there was no difference regarding CPB time. Among postoperative complications, only the incidence of stroke was significantly higher in the DCT group than in the SCT group (10.6% vs. 0%, P=0.020). CPB time, cross-clamp time and numbers of proximal saphenous graft and distal anastomosis showed a significant positive correlation with the postoperative lactate level. In the regression analysis, CPB time emerged as the only independent predictor of PHL (OR 1.04, CI 95% 1.01-1.07, P=0.011).ConclusionThere was no difference in postoperative blood lactate levels between SCT and DCT groups.

Study of Prevalance of Nephropathy among Sickle Cell Disease Patients in Waghodia Region, Vadodara, Gujarat

Introduction: Sickle-cell disease (or drepanocytosis) is a life-long blood disorder Characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickle cell disease (SCD) has several complications, including chronic renal failure, manifesting with hypertension (high blood pressure) proteinuria (protein loss in the urine), hematuria (redblood cells in urine) and worsening anaemia. Progression to end-stage renal failure confers a poor prognosis.&#x0D; Objective: The objective of the study was to determine the Prevalence of Nephropathy among sickle cell disease patients.&#x0D; Materials and Methods: This cross sectional study includes a total 150 participants who suffering from sickle cell anemia and attending our Institute. Renal function test and Urine examination of all participants was done. Estimated Glomerular Filtration Rate (eGFR) calculated using the Cockroft Gault formula. Comparison of results was done between Sickle cell trait and Sickle cell disease Group.&#x0D; Results: The mean age of the SCA patients were 25.54±10 years. Maximum participants are found to be from age group 25-30 yr(n=35) followed by 20-25 yr(n=30). Of the 150 SCA patients, 89 (59.33%), and 61 (40.66%) were males and females, respectively. The Mean value of S.Creatinine of SCT group is 0.73±0.46 mg/dl and SCD is 1.0±0.35 mg/dl, while the Mean value of eGFR is 134.19±87.21 ml/min and 124.20 ±58.25 ml/min in SCT and SCD Group respectively.&#x0D; Conclusions: From our study we conclude that the Derangement of Kidney function in sickle cell disease is frequent in our setting especially among young adult. It concerns SCD as well as SCT patients. Albuminuria is more frequent in homozygote patients and its prevalence increase with age. Age ≥ 25 years is associated with high risk of CKD in SCA group and albuminuria in SCD.

Pregnancy Outcomes in Women with Sickle Cell Trait

IntroductionSickle cell trait (SCT) is a heterozygous condition in which individuals inherit one copy of the hemoglobin S allele (Hb S) which harbors a point mutation in codon 6 of the beta globin gene and one copy of the hemoglobin A allele (Hb A). SCT is a highly prevalent state affecting 300 million people worldwide with 5.5 million births annually. Individuals with SCT are generally asymptomatic with a normal life expectancy unlike their counterparts with sickle cell disease (Hb SS). Historically, they had been considered to have a benign condition with no adverse outcomes on quality or length of life. More recently extensive literature has been published regarding the potential morbidity associated with SCT, especially under extremes of stress or high oxygen demand states. There is a paucity of high-quality data addressing the implications of SCT on pregnancy but pregnant women with SCT appear to have an increased risk of maternal and fetal complications. We looked at the association between SCT and maternal and fetal complications via retrospective analysis.MethodsWe extracted data from the electronic medical records at our tertiary medical center on all deliveries that occurred between January 2015 and December 2020. A total of 21,198 deliveries occurred in this time frame. One hundred and sixty-two women with sickle cell trait (7.6%) were identified and matched in a 2:1 fashion to women without SCT controlling for age, gravidity, and race. Subgroup analysis by age, hemoglobin (Hb), body mass index (BMI), history of hypertension, and type-2 diabetes were carried out however subgroup analyses by a history of deep vein thrombosis or pulmonary embolism (DVT/PE) and chronic kidney disease (CKD) were not conducted due to the small frequencies in the “Yes” groups.ResultsThe median age was 27.5 years and 92.5% were African American. Of the cohort, 31.7% carried private insurance, 65.4% carried federal insurance (Medicaid) and 2.9% were self-pay (defined as other). Despite the lack of statistical significance between the two cohorts, some variables were noted to have numerically noticeable differences. Vaso-occlusive crisis (VOC) was seen in 1.9% of the SCT group (n=3) and in none of the control group and pyelonephritis/UTI was seen in 11.7% of the SCT group vs 7.1% in the control group (p-value 0.123) [Table 1].On subgroup analysis by age (≤ 35 years vs >35 years) a statistically significant difference was seen in pregnancy-related hypertensive disorders (PRHD which includes gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome) (60% of women with SCT vs 30% in women without SCT, p-value 0.05). VOC was only noted in women with SCT ≤ 35 years [Table 2]. When the cohorts were analyzed by Hb value ( ≤ 10 g/dL vs >10 g/dL), a statistically significant difference in PRHD was noted in women with Hb <10 g/dL (61% of in women with SCT vs 38.4% in women without SCT, p-value 0.033) [Table 3]. No differences were noted in subgroup analysis by essential hypertension, BMI, or type-2 diabetes.DiscussionDespite the relatively small cohort, it is evident that SCT is not a benign condition in pregnancy. The racial and socioeconomic disparities are evident by the higher percentage of African Americans (92.5%) and women lacking private insurance coverage (68.3% of the cohort were covered by Medicaid or uninsured) who suffered adverse outcomes.VOC was noted exclusively in women with SCT (0.6% of the entire cohort) consistent with the notion that stress and/or hypoxia induce sickling. The interesting findings in this cohort were related to PRHD which occurred more frequently in women with SCT older than 35 years and in women with SCT and a Hb ≤10 g/dL. Although advanced maternal age and severe anemia are known risk factors for preeclampsia, the higher incidence of PRHD in women with SCT and advanced age (>35 years) or anemia (Hb ≤10 g/dL) warrants specific examination in future studies. Additionally, studies are needed to interrogate the pathophysiology of the hypertensive disease that occurs in SCT pregnancies. One limitation of the current retrospective study is that we were unable to define the precise subtype of the PRHD. In future studies, we would specifically examine the incidence of pre-eclampsia causing PRHD in individuals with SCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Single Center Retrospective Analysis of Letermovir for Cytomegalovirus Prophylaxis after Allogeneic Stem Cell Transplant in Cytomegalovirus Seropositive Recipients or Donors

Background: Up to 70% of allogeneic stem cell transplant (alloSCT) recipients who are cytomegalovirus (CMV) seropositive experience CMV reactivation and up to a third are complicated by end-organ disease. Letermovir, an antiviral agent targeting CMV, is FDA-approved for prophylaxis of CMV reactivation in CMV seropositive recipients of alloSCT. 1-4 In CMV seropositive recipients, letermovir use up to week 14 after alloSCT has demonstrated a significantly lower incidence of clinically significant CMV infection (csCMVi) and an overall mortality benefit as far as 24 weeks after transplant. 5-8 However, data on csCMVi beyond 24 weeks is lacking. Additionally, more information is needed on letermovir use in patients who had prior alloSCT, are CMV seronegative, have a detectable CMV viral load but without csCMVi, and/or are high risk*.Methods: This is a single-center, retrospective, comparative cohort analysis of 524 patients who received alloSCT at Barnes-Jewish Hospital from January 2016 to June 2019. Of those, 191 patients were excluded because both the recipient and donor were seronegative for CMV. Patient information was obtained from the electronic medical record systems after IRB approval of the protocol. Gray's sub-distribution methods (while account for death as competing risk) were used to calculate the incidence of csCMVi and to assess the effect of letermovir on csCMVi. Univariate and multivariate Cox proportional hazards models were fitted for the effect of letermovir on overall survival (OS), and time-dependent Cox model was used to determine the effect of csCMVi on OS.Results: Out of 333 patients, 149 received letermovir. The median follow-up period was 13.38 months (0.033 to 63.8 months). A univariate analysis demonstrated that csCMVi was associated with worse OS (HR 2.173, 95% CI 1.602-2.948). Among those who received letermovir, there were reductions in csCMVi for the overall cohort and for high-risk patients at 100 days, 180 days, and 365 days after alloSCT. In seropositive recipients receiving seropositive alloSCT (CMV +/+), there were reductions in csCMVi at days 100, 180, and 365 after transplant. In seropositive recipients receiving seronegative alloSCT (CMV +/-), there was a reduction in csCMVi at 100 days after transplant. There was a reduction in CMV-related mortality at day 180 post-transplant (p=0.03) but not at day 365 (p=0.46). Additionally, for the overall cohort, the letermovir group showed worse OS from days 180-365 (HR 1.938, 95% CI 1.143-3.285). In CMV seronegative patients receiving seropositive SCT (CMV -/+), no difference in csCMVi was detected at days 100, 180, and 365. A landmark analysis of Day 100 IgG level effect on csCMVi incidence demonstrated that lower IgG level (<485) is associated with higher csCMVi rates after Day 100 (p=0.004). Day 100 CD4 level was not found to be predictive of csCMVi (p=0.744).Conclusion: Letermovir prophylaxis reduces csCMVi overall and in high risk and CMV seropositive patients. We observed a reduction in CMV-related mortality at 180 days after transplant with letermovir prophylaxis. A worsening of OS after day 180 and a trend towards worse non-relapse mortality was surprising and may be related to a higher degree of immunosuppression associated with post-transplant cyclophosphamide (PTCy) use, haploidentical SCT, thymoglobulin use, prior SCTs, and CMV high-risk* patients. Additionally, letermovir was stopped at day 100 at which point survival worsens and the incidence of csCMVi precipitously increases. Our results suggest that there may be additional benefit to extending letermovir therapy past day 100 in the high-risk groups, haploidentical SCT group, patients with low IgG levels at day 100, and subclinical CMV viremia.*High risk patients were defined as those receiving haploidentical, mismatched related, mismatched unrelated, umbilical cord blood, T-cell depleted graft stem cell transplants or immunosuppression with methylprednisolone > 1 mg/kg or 2 or more immunosuppressants. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The effect of salmon calcitonin against glutamate-induced cytotoxicity in the C6 cell line and the roles the inflammatory and nitric oxide pathways play.

Recent evidence has shown that salmon calcitonin (sCT) has positive effects on the nervous system. However, its effect and mechanisms on glutamate-induced cytotoxicity are still unclear. The current experiment was designed to examine the effect of sCT on glutamate-induced cytotoxicity in C6 cells, involving the inflammatory and nitric oxide stress pathways. The study used the C6 glioma cell line. Four cell groups were prepared to evaluate the effect of sCT on glutamate-induced cytotoxicity. The control group was without any treatment. Cells in the glutamate group were treated with 10mM glutamate for 24h. Cells in the sCT group were treated with various concentrations (3, 6, 12, 25, and 50µg/mL) of sCT for 24h. Cells in the sCT + glutamate group were pre-treated with various concentrations of sCT for 1h and then exposed to glutamate for 24h. The cell viability was evaluated with an XTT assay. Nuclear factor kappa b (NF-kB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), caspase-3, and caspase-9 levels in the cells were measured by ELISA kits. Apoptosis was detected by flow cytometry method. sCT at all concentrations significantly improved the cell viability in C6 cells after glutamate-induced cytotoxicity (p < 0.001). Moreover, sCT significantly reduced the levels of NF-kB (p < 0.001), TNF-α, and IL-6 levels (p < 0.001). sCT also decreased nNOS, NO, and cGMP levels (P < 0.001). Furthermore, it decreased the apoptosis rate and increased the live-cell rate in the flow cytometry (P < 0.001). In conclusion, sCT has protective effects on glutamate-induced cytotoxicity in C6 glial cells by inhibiting inflammatory and nitric oxide pathways. sCT could be a useful supportive agent for people with neurodegenerative symptoms.

Early developmental impact of sex chromosome trisomies on attention deficit-hyperactivity disorder symptomology in young children.

Individuals with sex chromosome trisomies ([SCT], XXX, XXY, and XYY)) are at increased risk for neurodevelopmental problems, given that a significant portion of the sex chromosome genes impact brain functioning. An elevated risk for psychopathology has also been described, including attention deficit‐hyperactivity disorder (ADHD). The present study aimed at identifying early markers of ADHD, providing the first investigation of ADHD symptomology in very young children with SCT. The variety, type, and severity of ADHD symptomology in 1–6‐year‐old children with SCT (n = 104) were compared with population‐based controls (n = 101) using the strengths and weaknesses of ADHD symptoms and normal‐behavior (SWAN) parent‐report questionnaire. ADHD symptomology was significantly more prevalent in SCT and already present from toddlerhood on, compared to controls. ADHD inattention symptoms were significantly increased in all karyotypes (XXX, XXY, and XYY), boys with XYY also showed significantly more hyperactivity/impulsivity symptoms than controls. Inattentiveness was more pronounced with increasing age for SCT, in contrast to controls. Within the SCT group, 24% of the children had significantly elevated ADHD symptoms at a clinical level. Already from an early age on, SCT is associated with a risk for ADHD, suggesting that its neurodevelopmental risk lies anchored in early brain maturation. Studying this genetically vulnerable population allows for the prospective study of risk markers to facilitate early and preventive interventions.

First-Line Choice for Severe Aplastic Anemia in Children: Transplantation from a Haplo-Identical Donor Versus Immunosuppressive Therapy

Background: Severe aplastic anemia (SAA) is a fatal disorder in children if treated inappropriately. According to the current algorithm, transplantation from a matched related donor (MRD) is recommended as the first-line option in children with SAA, if a MRD is unavailable, IST with a combination of anti-thymocyte globulin (ATG) and cyclosporine (CsA) represents the first-line choice. However, numerous limitations of immunosuppressive therapy (IST) exists. IST children may have incomplete recovery, and appear to be associated with an increased risk of clonal evolution and subsequent relapse. Additionally, the unavailability of horse-ATG in China also make the response of IST at a discount greatly. At the same time, great progresses in recent years in haploidentical transplantation might also promote changes in the algorithm of SAA treatment.Methods: We retrospectively compared the outcomes of children with SAA who received IST or who underwent hematopoietic stem cell transplantation (HSCT) from a haplo-identical donor (HID) as first-line choice between 2007 and 2016. The conditioning regimen for SCT from a haploidentical donor consisted of intravenous busulfan, cyclophosphamide and rabbit ATG. All of children were administered with granulocyte colonystimulating factor (G-CSF)-primed bone marrow (BM) combined with G-CSF-primed peripheral blood (PB) hematopoietic stem cells.Results: A total of 52 SAA children under the age of 17 years were initially treated with IST (n=24) or haplo-identical HSCT (n=28) as first-line choice. The last follow-up for all surviving patients was June 1, 2017. In IST group, by 6 months, 15 of the 21 subjects (71.4%) improved with first-line IST and achieved a partial response (n=10) or complete response (n=5). In SCT group, 27 patients (96.4%) achieved primary engraftment at a median of 12 (range, 10-21) days except one suffered from primary graft failure. The cumulative incidences (CI) of grade II-IV and of grade III-IV acute graft versus host disease (GVHD) were 48.1±1.0% and 11.1±0.4%, respectively. The 3-year CI of extensive chronic GVHD was 3.7±0.1%. The estimated 10-year overall survival were 73.4±12.6% and 89.3±5.8% in patients treated with IST or HID-HSCT (P=0.806). However, the failure-free survival was significantly inferior in patients receiving IST than in those undergoing transplantation from a HID [52.6±10.5% versus 89.3±5.8, P=0.008]. In univariate analysis, the choice of first-line immunosuppressive therapy was the only adverse predictor for failure-free survival. At the last follow-up, completely normal blood count was observed in 11 of 20 (55.0%) and 24 of 25 (96.0%) alive cases in IST and HID-HSCT cohort (P=0.003).Conclusions: Based on the superior FFS, high rate of engraftment and acceptable incidence of GVHD, the choice of HID HSCT for SAA children without a matched related donor as a first choice option seems reasonable. These suggest that SCT from a haplo-identical donor could be considered as first-line choice in children who lack a matched related donor, especially in experienced transplantation centers. DisclosuresNo relevant conflicts of interest to declare.

Exchange Transfusion in Neonatal Sepsis- An Old Wine in New Bottle

Neonatal Sepsis, second major cause of mortality, is killing more than one million neonates annually worldwide [1]. Globally, of three million annual neonatal sepsis cases India has the highest incidence of clinical sepsis (17,000/ 1, 00,000 live births) [2]. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the treatment of neonatal sepsis and septic shock [3]. The main aim of this study was to assess the efficacy of exchange transfusion in neonatal sepsis as compared to standard therapy. Neonates with septic shock (Sclerema) admitted to our NICU from dec 2017 to dec 2018 were included in the study. 43 neonates who received ETs were compared with 43 neonates who received of standard care therapy. The mortality rate was 27.9% in the ET group and 30.1% in the ScT group statistically insignificant. The duration of hospital stay in exchange transfusion babies was less(14.9 days) as compared to control group(22.7days) which was statistically significant(p&lt;0.05). In the era of increasing antibiotic resistance, the need of hour is to find alternative measures in sepsis. Exchange transfusion can be one of the prime modality in treatment of severe neonatal sepsis, which is one of the major cause of deaths worldwide. Exchange transfusion being cheaper as compared to other modalities of treatment (eg; IVIG) needs further research on use and long term complications in neonatal sepsis.

Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis.

Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. We predicted that the impact of an additional sex chromosome on neurodevelopment would depend on common autosomal variants involved in synaptic functions. Methods: We analysed data from 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Two comparison groups were formed from 370 children from a twin study. Three indicators of phenotype were: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Preselected regions of two genes, CNTNAP2 and NRXN1, were tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis. Results: There was wide phenotypic variation in the SCT group, as well as overall impairment on all three phenotypic measures. There was no association of phenotype with CNTNAP2 or NRXN1 variants in either the SCT group or the comparison groups. Supplementary analyses found no indication of any impact of trisomy type on the results, and exploratory analyses of individual SNPs confirmed the lack of association. Conclusions: We cannot rule out that a double hit may be implicated in the phenotypic variability in children with SCTs, but our analysis does not find any support for the idea that common variants in CNTNAP2 or NRXN1 are associated with the severity of language and neurodevelopmental impairments that often accompany an extra X or Y chromosome. Stage 1 report: http://dx.doi.org/10.12688/wellcomeopenres.13828.2.

Efficacy and tolerability of short contact therapy with tretinoin, clindamycin, and glycolic acid gel in acne: A randomized, controlled, assessor-blinded two-center trial: The MASCOTTE study.

Retinoids and antibiotics topical treatments are commonly used as first line therapy in mild to moderate acne. However, irritant contact dermatitis is a common side effect of topical retinoids. A strategy to increase local tolerability is the "short contact therapy" (SCT) approach, consisting in the application of the product with the complete removal after 30 to 60 minutes using a non-aggressive cleanser. A gel containing tretinoin 0.02%, clindamycin 0.8%, and glycolic acid 4% in polyvinyl alcohol (MP-gel) has shown to be effective as monotherapy in mild to moderate acne with a tolerability profile similar to other topical retinoids. So far, no trials have been performed with this gel comparing the tolerability profile of SCT with standard application therapy (SAT). We conducted a 2-center randomized parallel groups, controlled, assessor-blinded study, comparing MP-gel applied as SCT in comparison with MP-gel used as SAT (The "MASCOTTE" trial). Forty-six subjects (nine men and 37 women, mean age 23 ± 4 years, range 18-31 years) with mild-to-moderate acne were enrolled, after their written informed consent in a randomized, parallel groups controlled, assessor-blinded 8-week trial. Twenty-three were assigned to MP-gel once daily (evening application) using the SCT approach (ie, complete removal of product after 1 hour using a gentle cleanser), and 23 were randomized to the SAT approach with the same gel. The primary endpoint was the evolution of the tolerability score (TS) assessed evaluating four items: erythema, dryness, stinging, and burning, using a 4-point score scale (from 0: no symptom to 3: severe symptom). Secondary endpoints were the evolution of global acne grading system (GAGS) score (range: from 0 to >39) and the investigator global assessment (IGA of acne severity) score (range from 0 to 4). TS was evaluated at 2, 4, and 8 weeks. GAGS and IGA scores were evaluated at baseline and at week eight. At week eight, an efficacy global score (EGS) (from 1: no efficacy to 4: very good efficacy) and a tolerability global score (TGS) (from 1: very low tolerability to 3: very good tolerability) evaluation were also done. All the evaluations were performed by an investigator unaware of treatment groups allocation (SCT or SAT). Thirty-eight subjects (83%) completed the 8-week treatment period. Eight subjects (two in the SCT group and six in the SAT group) dropped out prematurely due to low skin tolerability. In the SCT the TS at week two was 1.3 ± 1.7, in the SAT group TS was significantly higher (3.1 ± 1.7) (P = .028). TS was significantly lower in SCT group vs SAT also at weeks four and eight (P = .01; ANOVA test). The GAGS score at baseline was 19 ± 7 in the SCT group and 23 ± 4 in the SAT group (NS). At week 8 the GAGS score in SCT was significantly reduced to 8.5 ± 2.8 (-55%) (P = .001 vs baseline) and was also significantly lower in comparison with SAT group (8.5 vs 15; P = .0054). The IGA scores at baseline were 1.9 ± 0.6 in SCT and 2.4 ± 0.7 in SAT group. At week eight, in comparison with baseline values IGA score was reduced significantly by 48% in SCT and by 30% in SAT. EGS and TGS were significantly higher (better clinical efficacy and better tolerability) in SCT in comparison with SAT (3.6 ± 0.5 and 2.9 ± 0.3 vs 2.7 ± 0.6 and 1.5 ± 0.7; respectively). This tretinoin, clindamycin, glycolic acid gel, applied as SCT, has shown a better skin tolerability and at least a comparable clinical efficacy in comparison with the standard application modality in the treatment of mild-to-moderate acne. The SCT therefore could be an effective treatment strategy which could improve subjects' compliance and adherence.

Autologous Vs. Allogeneic Stem Cell Transplantation in Double-Expressor Lymphoma

Purpose: Dual expression of MYC and BCL2 proteins (Double Expressor Lymphoma-[DEL]) is an important prognostic factor in patients (pts) with diffuse large B-cell lymphoma (DLBCL) who are treated with standard chemo-immunotherapy. Studies have suggested that pts with these biomarkers have inferior survival compared to pts who were non-DEL after autologous stem cell transplantation (autoSCT). For this reason, allogeneic stem cell transplantation (alloSCT) has been advocated for its potential graft-versus-lymphoma effect. Data are limited however regarding the outcomes in pts with relapsed DEL who were treated with autoSCT vs. alloSCT. Methods: Data from pts with relapsed DEL/DLBCL who underwent auto- and alloSCT as their first transplant at our center and in whom archived tumor material was available were analyzed. Cutoff values of 40% for MYC and 70% for BCL2 were established by immunohistochemistry (IHC). The majority of autoSCT pts (84%) underwent chemo-mobilization of stem cells with rituximab (R) for in-vivo purging; rituximab was also given on days+1 and +8 with BEAM conditioning (J Clin Oncol 2005; 23:2240-7; Clin Cancer Res 2018; 24:2304-11). Conditioning for the alloSCT was myeloablative (n=16, 50%), reduced-intensity (n=6, 19%), and nonmyelablative (n=10,31%). The study was IRB-approved at our center. Kaplan-Meier analysis and corresponding log-rank/Gray's tests were used to estimate and compare overall survival (OS), progression-free survival (PFS), and cumulative incidence (CI) of non-relapse mortality and relapse by SCT group. Standard multivariable Cox regression was used to evaluate associations between SCT type and OS/PFS after controlling for differences in baseline characteristics and cause-specific multivariable Cox regression was used for competing-risk outcomes [non-relapse mortality (NRM) and relapse]. Results: The study included 161 autoSCT and 32 alloSCT pts treated between 2000-2018. Median age was 59 (range,18-80) and 55 years (range, 21-66), respectively (P=0.009). Male gender was 62.7 vs 50.0%, respectively (P= 0.234). Fifty-one (32.5%) autoSCT pts and 9 (28.1%) alloSCT pts had an elevated serum LDH (P= 0.683) and 41/148 (27.7%) autoSCT and 11/25 (44.0%) alloSCT pts were PET-positive at study entry (P=0.106). The time from diagnosis to transplant was 20.0 and 25.2 months, respectively, (P=0.068), and the distribution of the years of transplant was similar between both groups (P=0.317). Significant differences between treatment groups were observed for prior number of chemotherapies, disease status, stage, and HCT-CI score at transplant. Pts. receiving alloSCT were more heavily pretreated [median 3 prior therapies, (range 1-8) vs. a median of 2, (range 1-6); P=0.0001], had more advanced stage III-IV disease (P=0.035), and more refractory disease (P=0.010) at transplant. In addition, a higher percentage of alloSCT pts had an HCT-CI of &amp;gt;4 (28.1% vs. 10.2%, P=0.018) at study entry. Allogeneic transplant characteristics included matched siblings (n=18; 56.3%), matched unrelated (n=13, 40.6%) and haplo-identical (n=1, 3.1%) donors. With a median follow-up for autoSCT surviving pts of 65 months (range, 5-217 months) and 93 months (range, 34--124 months) for alloSCT pts, the OS at 5-years were 59% and 34%, respectively (P= 0.0001) (Figure1). The PFS rates at 5-years were 49% and 31%, respectively (P = 0.002). AutoSCT had a similar rate of relapse to alloSCT but a lower rate of NRM. The 5-year CI of relapse was 37% vs 28%, respectively (P = 0.611) and the 5-year NRM rates were 14% vs 41 % (P=0.0001), respectively (Figure 2). The associations between SCT group and outcomes persisted after adjusting for differences between groups (alloSCT vs. autoSCT HR= 3.46/p=0.0004 for OS; HR=2.67/p=0.005 for PFS; HR=4.74/p=0.009 for NRM; HR=2.22/p=0.080 for relapse). The 100-day CI of grade II-IV and III-IV acute GVHD in the alloSCT group was 37.5 and 9.4%, respectively. The 1-year CI of chronic GVHD was 25.0%. C onclusions: This study is the first to show that autoSCT confers a superior survival in pts with relapsed DEL/DLBCL compared to alloSCT. Our conclusions are supported by long-term follow-up. The use of novel nonmyeloablative regimens in a larger number of pts receiving an alloSCT and ongoing studies at our center with targeted investigational agents after autoSCT may improve results. Disclosures Khouri: Pfizer: Research Funding; Bristol Myers Squibb: Research Funding. Iyer:CRISPR: Research Funding; Spectrum: Research Funding; Daiichi Sankyo: Consultancy; Trillium: Research Funding; Curio Biosciences: Honoraria; Target Oncology: Honoraria; Afffimed: Research Funding; Merck: Research Funding; Legend Biotech: Consultancy; Rhizen: Research Funding; Seattle Genetics, Inc.: Research Funding. Popat:Bayer: Research Funding; Novartis: Research Funding. Qazilbash:Angiocrine: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy; Janssen: Research Funding; Bioline: Research Funding. Champlin:DKMS America: Membership on an entity's Board of Directors or advisory committees; Actinium: Consultancy; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy; Takeda: Patents &amp; Royalties; Genzyme: Speakers Bureau.