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Corticosteroids are considered the standard first-line treatment for moderate/severe acute graft versus host disease (aGVHD), yet there is no consensus on the optimal management of patients that are steroid-refractory (SR). Infliximab is a chimeric monoclonal antibody with anti-TNF-α activity that has previously demonstrated efficacy in SR-aGVHD. We performed a retrospective review of 59 patients at Indiana University who underwent allogeneic stem cell transplantation and developed SR grade III-IV aGVHD from January 2007 to August 2018. Infliximab was administered 10 mg/kg weekly intravenously. Response criteria was in accordance with Martin et al (BBMT 2009; 12:777-784). Median age of treated patients was 49.5 years (range, 34.5-60) and median time from transplant to diagnosis of aGVHD was 106 days (range, 42-185) Patients received a median of 12 days (range, 8-20) of systemic steroids prior to infliximab. At the start of infliximab, 52 (88%) patients were on non-steroidal immunosupressants and 39 (66%) on non-absorbable steroids concurrently with systemic steroids. Patients received a median of 3 doses of infliximab with 37 (62.7%) patients receiving There was no significant difference between responders (n=16) and non-responders (n=43) in baseline demographic, transplant-related characteristics, initial GVHD prophylaxis regimen, number of non-steroidal systemic immunosuppressants at time of aGVHD diagnosis, or use of non-absorbable steroids. There was no difference in time from diagnosis of aGVHD to start of infliximab (median 16 vs. 11 days, P=0.06). Responders were less likely to have liver aGVHD involvement vs. non-responders (18% vs. 53%, P=0.016) and had slower tapering of systemic steroids, both at median time to 50% steroid dose (18 vs. 12 days, P=0.02) and 25% steroid dose (36 vs. 24 days, P=0.01). Responders had lower incidence of bacterial infection (44% vs. 74%, P=0.04), but not viral infections (56% vs. 47%, P=0.57). Responders had a longer overall survival (median 20.3 vs. 2.8 months, P=0.01). Our single center report of 59 patients with SR-aGVHD treated with infliximab is among the largest reported. The outcomes of response to SR-aGVHD are poor and there is an unmet need for better agents. Additional studies with greater patient numbers are needed to identify factors associated with improved response to infliximab.

In the original version of this article, author ‘Aisha Al-Khinji’ was incorrectly listed as ‘Aisha Ahmed’. This has now been corrected in both the PDF and HTML versions of the article to ‘Aisha Al-Khinji’.

The motion of microstructural interfaces is important in modeling twinning and structural phase transformations. Continuum models fall into two classes: sharp-interface models, where interfaces are singular surfaces; and regularized-interface models, such as phase-field models, where interfaces are smeared out. The former are challenging for numerical solutions because the interfaces need to be explicitly tracked, but have the advantage that the kinetics of existing interfaces and the nucleation of new interfaces can be transparently and precisely prescribed. In contrast, phase-field models do not require explicit tracking of interfaces, thereby enabling relatively simple numerical calculations, but the specification of kinetics and nucleation is both restrictive and extremely opaque. This prevents straightforward calibration of phase-field models to experiment and/or molecular simulations, and breaks the multiscale hierarchy of passing information from atomic to continuum. Consequently, phase-field models cannot be confidently used in dynamic settings. This shortcoming of existing phase-field models motivates our work. We present the formulation of a phase-field model – i.e., a model with regularized interfaces that do not require explicit numerical tracking – that allows for easy and transparent prescription of complex interface kinetics and nucleation. The key ingredients are a re-parametrization of the energy density to clearly separate nucleation from kinetics; and an evolution law that comes from a conservation statement for interfaces. This enables clear prescription of nucleation – through the source term of the conservation law – and kinetics – through a distinct interfacial velocity field. A formal limit of the kinetic driving force recovers the classical continuum sharp-interface driving force, providing confidence in both the re-parametrized energy and the evolution statement. We present some 1D calculations characterizing the formulation; in a companion paper, we present more extensive 2D calculations.

A companion paper presented the formulation of a phase-field model – i.e., a model with regularized interfaces that do not require explicit numerical tracking – that allows for easy and transparent prescription of complex interface kinetics and nucleation. The key ingredients were a re-parametrization of the energy density to clearly separate nucleation from kinetics; and an evolution law that comes from a conservation statement for interfaces. This enables clear prescription of nucleation through the source term of the conservation law and of kinetics through an interfacial velocity field. This model overcomes an important shortcoming of existing phase-field models, namely that the specification of kinetics and nucleation is both restrictive and extremely opaque. In this paper, we present a number of numerical calculations – in one and two dimensions – that characterize our formulation. These calculations illustrate (i) highly-sensitive rate-dependent nucleation; (ii) independent prescription of the forward and backward nucleation stresses without changing the energy landscape; (iii) stick–slip interface kinetics; (iii) the competition between nucleation and kinetics in determining the final microstructural state; (iv) the effect of anisotropic kinetics; and (v) the effect of non-monotone kinetics. These calculations demonstrate the ability of this formulation to precisely prescribe complex nucleation and kinetics in a simple and transparent manner. We also extend our conservation statement to describe the kinetics of the junction lines between microstructural interfaces and boundaries. This enables us to prescribe an additional kinetic relation for the boundary, and we examine the interplay between the bulk kinetics and the junction kinetics.

Aims and objectives: The aim of this research is to see the effectiveness of neural mobilization on posterior myofascial chain flexibility. Methodology: Samples of 70 subjects were recruited for the study. Pre mobilization readings for finger floor distance, tibiotarsal angle and finger floor grades were taken for each individual, after whom slump mobilization was given and post mobilization readings were again taken in the same sequence after mobilization. Results: Both finger floor distance and grades were significantly changed, while tibiotarsal angle showed no significant difference. Discussion: Neural mobilization tries to restore the nervous system’s movement and elasticity, rehabilitating its normal functions by relieving the tensions in the muscular chains thereby increasing its flexibility.

Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated.This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM).Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P .0001).Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. © 2018 American Cancer Society.

Background: HIV infection is the strongest of all known risk factors for the development of tuberculosis. Tuberculosis is the most common opportunistic infection and the number one cause of death in HIV/AIDS patients in developing countries. Materials and Methods: The aim of this study is to assess and compare the outcome of pulmonary tuberculosis in HIV-seropositive and HIV-seronegative patients. This was cross-sectional, observational and prospective study conducted at tertiary care center in western Maharashtra from May 2010 to April 2012. A total 50, HIV-seronegative patients and 50 HIV-seropositive patients of both genders, with pulmonary tuberculosis fulfilling inclusion criterion (age > 18 years, newly detected pulmonary tuberculosis) were included in present cross-sectional, observational, prospective and comparative study. Results: Of the total 50 HIV-seropositive patients, 36 (72%) males were newly detected pulmonary tuberculosis (PTB) with mean age of 40.61 ± 8.74 years and 14 (28%) were females with mean age 37.72 ± 9.54 years. Of total 50 patients amongst HIV seronegative-group patients with PTB, 29 (58%) were males with mean age of 42.44 ± 5.79 years and 21 (42%) were females with mean age of 38.9 ± 7.91 years. A total 10/50 (20%) patients in HIV-seropositive group and 3/50 (6%) HIV-seronegative group had evidence of jaundice. There was a statistical difference between development of jaundices in HIV and HIV-seronegative group ['P' = 0.037]. Total 9/36 (25%) male patients and 2/14 (14.28%) females patients died in HIV-seropositive group with no death recorded amongst in HIV-seronegative groups with high mortality in HIV-seropositive group ['P' < 0.0001]. Total 4 male and 4 female patients had inflammatory response syndrome (IRIS). Total 40/50 (80%) patients were sputum negative at the end of 6 th month (2 nd follow-up) among HIV-seropositive group. Total 49/50 (98%) become a sputum negative at the end of 2 nd follow-up, 6 month among HIV-seronegative group there was a statistically significant difference between two group ['P' = 0.021]. Total 10/50 (20%) and 1/50 (2%) patients were diagnosed with multidrug resistant tuberculosis (MDR-TB) among HIV-seropositive group and HIV-seronegative group, respectively ['P' = 0.002]. There was high prevalence of middle and lower lobe lesions and bilateral extensive pulmonary tuberculosis (BEPT) in patients with HIV-seropositive group patients and upper lobe, miliary shadow and cavitary lesions in HIV-seronegative group patients ['P' < 0.02]. The cavitary lesions were significantly low in HIV-seropositive group with low CD+4 counts. Duration of stay was significantly more in HIV-seropositive group compared with HIV seronegative- seropositive group ['P' < 0.01]. Conclusions: We found high prevalence of MDR-TB pulmonary tuberculosis in HIV-seropositive patients. Mortality was significantly high in HIV-seropositive patients than HIV-seronegative patients. Jaundice was more prevalent in HIV-seropositive patients than HIV-seronegative patients. There was high prevalence of middle and lower lobe lesions and BEPT in patients with HIV-seropositive group patients and upper lobe, miliary shadow and cavitary lesions in HIV-seronegative group patients. The cavitary lesions were significantly low in HIV-seropositive group with low CD+4 counts. Duration of stay was significantly more in HIV-seropositive group compared with HIV-seronegative group. Success rate of directly observed treatment short-course was less (80%) in HIV-seropositive group.

Background: Non-communicable diseases like DM2, cardiac diseases, chronic respiratory disorders, brain disorders like stroke have created a havoc in developing countries, especially India which harbors 2nd largest population in the world. The present study was planned in this area to capture the data regarding epidemiology, risk factors of DM2, and use this information to plan health program to formulate effective preventive measures, including raising general awareness about the disease in that geographical area.Methods: The present cross sectional study was carried out in population of Karad area of Satara district in Maharashtra state. The study duration was of 1 year, from 1st February 2018 to 1st February 2019.Results: Out of total 1100 study population in the present study, 99 (9%) were diagnosed as diabetics (DM2) while 1001 were normal/non-diabetics. Majority of the diabetic patients were of the age group 41 to 50 years. Females (47%) showed slightly more prevalence of diabetes as compared to males (53%). Majority of the diabetic patients were having sedentary lifestyle, which consisted of 69 patients (70%), which was statistically significant, as compared to non-diabetic group.Conclusion: Thus, findings of the present study amply clarifies that DM2 is on longer a disease of urban population. Its prevalence is increasing in rural population, as well. Lack of awareness, sedentary lifestyle, faulty dietary habits, etc. are some of the reasons for such high prevalence.

Background: Derangements in stress hormone levels i.e. steroids, thyroid hormones is routinely encountered in almost all the seriously ill patients, which have been found to be associated with morbidity and mortality. The present study was planned to assess the thyroid hormone derangements in seriously ill patients, with respect to mortality.Methods: The present study was a retrospective, observational, record-based study done at Krishna Institute of Medical Sciences, Karad, Maharashtra, India.Results: Out of total 170 patients, 108 were females (63.5%) and 62 (36.4%) were males. On age wise analysis, it was found that majority of the patients were in the age group >50 years comprising of 78 (45.8%) patients. Thyroid hormonal status was deranged in 94 patients (55%), out of which 53 (31%) died and 41 patients (24%) were alive. Most common derangement was seen in free T3 (triiodothyronine), with 60% of the patients showing lowered values, 35% showing raised values and 5% showing normal values. T4 (thyroxine) levels were normal in major bulk of the patients.Conclusions: Serum T3 levels should be routinely done in critically ill patients, to detect any thyroid disorders, which might go undetected until it is too late.

Background: Subclinical hypothyroidism (SCH) is defined by increase in serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) and free triiodothyronine (FT3) levels within normal range, coupled with absence of typical clinical symptoms. The present study was undertaken to analyse the SCH associated comorbidities, especially lipid disturbances, thyroid autoantibodies, etc.Methods: The present study was retrospective observational study, which was carried out at a tertiary health care center.Results: Out of the 100 patients, majority were in the age group 21 to 30 years (31 patients), followed by 26 patients in age group >51 years and least in age group 41 to 50 years. Prevalence showed female predilection, with female: male ratio of 1.9:1. Most common symptom reported was general fatigue, which was encountered in 40 patients, followed by weight gain, menstrual abnormalities, and constipation. 10 patients were asymptomatic. Serum TSH range in the patients was 5 to 21.1 µIU/l, while mean TSH was 10.9 µIU/l. 20 patients were found to have serum TSH>10.Conclusions: Despite high prevalence, detection rate of subclinical hypothyroidism is very low. Carrying out epidemiological study on national scale is need of the hour, as lack of typical clinical features makes the detection less likely and it has numerous complications, if untreated.

Hepatic SOS is a potentially life-threatening complication occurring in up to 14% following HCT. Sirolimus (Siro) plus tacrolimus (FK) is an accepted regimen for graft-versus-host disease (GvHD) prophylaxis, with target Siro trough levels 10-20 ng/mL suggested to prevent acute GvHD (Blood 2016 128:3429). We previously reported that higher trough Siro levels might increase the risk of SOS, although a small sample size precluded detailed analysis. (Pharmacotherapy 2012; 32:441-5). In this study, we investigated if Siro and FK levels at specified times post-transplant are associated with an increased risk of SOS following non-busulfan, myeloablative conditioning. We analyzed 260 consecutive patients with hematological malignancies treated at Indiana University from 2007 to 2016 who underwent allogeneic HCT following myeloablative conditioning using TBI-based (n=151) or non-busulfan chemotherapy only (n=109) regimens. Patients received Siro plus FK for GvHD prophylaxis. No prophylaxis for SOS was used. Trough levels of Siro (target 5-15 ng/mL) and FK (target 5-10 ng/mL) were obtained at least twice weekly through day 30. SOS occurred in 28 patients at a median of 22 (range, 12-58) days for a cumulative incidence of 10.8%. Nine patients died of other causes before day 40 and were excluded from further analysis. Siro and FK troughs were compared in patients who developed SOS (n=28) with those who did not (n=223). Baseline characteristics were similar between the two groups. Mean Siro trough levels were higher between days 11-20 following transplant in patients who developed SOS (10.3 vs 8.5 ng/mL, P=0.008), while there was no significant difference in mean trough levels between days 0-10 (P=0.67) and days 21-30 (P=0.37) (Fig. 1). Patients with mean Siro trough level >9 ng/mL had higher incidence of SOS compared with those with Siro ≤ 9 ng/ml (71.4% vs. 41.7%; P=0.003). No differences in mean FK levels during the same time intervals were observed between those developing SOS and others. On multivariable analysis, mean Siro trough level >9 ng/ml between days 11-20 post-transplant was associated with an increased risk of SOS (odds ratio [OR] 3.9, 95% CI: 1.6-9.8, P=0.003), together with a longer time from diagnosis to transplant (P=0.004) and use of a TBI-based regimen (P=0.006). Among patients who did not develop SOS, mean Siro trough levels ≤9 ng/ml between days 11-20 were not associated with an increased risk of grade II-IV acute GvHD at day 100 compared with levels >9 ng/mL (13.8% vs. 17.3%, P=0.99). We conclude that mean trough Siro levels >9 ng/mL between days 11-20 post-transplant significantly increase the risk of SOS. Targeting lower Siro trough levels (e.g., 5-10 ng/mL) may reduce the risk of SOS without increasing acute GvHD. By interfering with endothelial cell function and potential healing following damage caused by TBI and/or high-dose chemotherapy, higher Siro levels could lead to SOS.

Background: Venomous snake bite is a common and frequently devastating environmental and occupational disease, especially in rural areas of Maharashtra India. Aims & Objectives: To determine the clinical profi le and outcome of snakebite cases in rural western Maharashtra. Material & Methods: This was a retrospective study conducted over one year period (January 2009 to December 2009) at a tertiary health care centre in Maharashtra. Results: Out of 167 admitted snakebite 103 (61.67%) were complicated snake bites. Total 88 (85.43%) patients were with vasculo-toxic snake bite. Total 15 (14.56%) patients were with neuroparalytic snakebite. Total 35 (39.77%) patients out of 88 with vasculotoxic snakebite developed local cellulitis requiring fasciotomy and or debridement, 17 (19.31%) patients had clinical and laboratory parameters favoring DIC. Total 12 (13.63%) patients had ARF, one developed AMI and one developed cortical venous sinus thrombosis (CVT). Out of 88 patients with vasculotoxic snakebite 2 died with case fatality rate of 2.27% (2/88). Out of 15 patients with neuroparalytic snake bite 13 (86.66%) required artifi cial ventilatory support and one patient developed delayed peripheral neuropathy. Overall mortality was 1.94% (2/103). The needle to ASV time was positively correlated with duration of hospital admission, complications and mortality ('p' < 0.02). Conclusions: Snakebite is a common life-threatening emergency in the study area. Delay in hospitalization is associated with poor prognosis and increased mortality rate due to consumptive coagulopathy, renal failure and respiratory failure. Unusual complications like AMI, CVT and delayed peripheral neuropathy were observed in present study.

Background: Relapsed or refractory acute myeloid leukemia (R/R AML) portends a poor prognosis, thus salvage chemotherapy is commonly used as a bridge to HSCT, however the optimal salvage regimen remains unknown. For decades cytarabine (Ara-C) has served as the backbone of regimens frequently used in the R/R setting. MEC is among the most studied regimens for R/R AML; up to 66% of patients achieve complete remission (CR), with a median survival of 36 weeks (Arcese et al., J Clin Oncol. 1991). The Ara-C couplets regimen was shown to have a similar overall response rate (ORR) of 55%, in a single study (Larson et al., Leukemia & Lymphoma. 2012). Currently, there are no studies directly comparing these regimens. Here, in a multi-institution retrospective analysis we assessed the efficacy and toxicity of MEC and Ara-C couplets therapy. Methods: We analyzed the records of 136 patients treated between 1998 and 2017. There were 87 patients (15 from University of Illinois and 72 from Indiana University) treated with MEC (mitoxantrone 8 mg/m2 IV, etoposide 80 mg/m2 IV and Ara-C 1 g/m2 x 5 days) and 49 patients (36 from University of Illinois and 13 from University of Chicago) treated with Ara-C couplets (mitoxantrone 30 mg/m2 daily and Ara-C dosed at 2 g/m2 twice daily or 3 g/m2 daily; both drugs given on days 1 and 5). The primary endpoint was comparison of response rates. Secondary endpoints included progression free survival (PFS), overall survival (OS), duration of hospitalization, hematologic and non-hematologic toxicities, and success in proceeding to HCT. Results: The median age of the MEC group was 52 years (yr) (range: 20-75 yr) vs 55 yr (22-75 yr) in the Ara-C couplets group. There were significantly more white patients in the MEC group (72% vs 41%; p = 0.004). The incidence of unfavorable cytogenetics was similar between groups; 32 in the MEC group (36.8%) and 19 in the Ara-C couplets group (38.7%). High-risk patients, as defined by Charlson Comorbidity Index (CCI) ≥4, comprised 29 of 87 (33.3%) of MEC, and 26 of 49 (53.1%) of Ara-C couplets patients (p = 0.03). Time from initial diagnosis to diagnosis of R/R AML was similar between groups, 303 days (MEC) and 306 days, respectively (p = 0.10). CR or CRi (ORR) was achieved in 44% of MEC, and 55% of the Ara-C couplets patients. OS was 159 days and 186 days, respectively (p = 0.055). PFS was 66 days in the MEC group and 113 days in the Ara-C couplets group (p = 0.56). In total, 27 (31%) of the MEC patients and 24 (49%) Ara-C couplets patients underwent HCT (p = 0.04). Within the MEC group, the median number of days to ANC and platelet recovery was 34 days and 35 days, respectively. ANC and platelet recovery was slightly longer within the Ara-C couplets group, at 41 days and 55 days, respectively (p = 0.02 for platelet recovery). The median duration of hospitalization was similar, 29 days for MEC and 30 days for Ara-C couplets. The most common adverse event was febrile neutropenia (FN), occurring in 93% of the MEC and 78% of the Ara-C couplets patients (p = 0.01). Notably, grade 3/4 GI toxicity occurred in 15 MEC (17.2%) and one (2.0%) of the Ara-C couplets patients (p = 0.01). There were no significant differences between groups in terms of pulmonary, liver, renal, cardiac or neurologic toxicities. Conclusions: This is the first large multi-institutional retrospective study directly comparing salvage regimens in a racially diverse population of R/R AML patients. While matched for a number of variables (including the incidence of unfavorable cytogenetics), patients receiving Ara-C couplets did have a significantly higher CCI. Despite this, use of the Ara-C couplets regimen resulted in improved ORR, significantly improved efficacy as a bridge to HCT, and led to a significant comparative decrease in the incidence of FN and grade 3/4 GI toxicities. Our retrospective analysis suggests that this regimen should be considered as an effective, safe salvage regimen in this population. Disclosures Patel: Janssen: Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Khan:Teva: Speakers Bureau. Stock:Jazz Pharmaceuticals: Consultancy. Odenike:ABBVIE: Honoraria, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI/Baxalta: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Dava Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncotherapy Science: Research Funding; Agios: Research Funding; Celgene: Research Funding; NS Pharma: Research Funding; Janssen: Research Funding; Astex: Research Funding; Gilead Sciences: Research Funding.

Background: The optimal setting to treat AYA patients remains a complex decision involving access to different treatment regimens, clinical trial availability, and appropriate psychosocial support. There are data to support that AYA patients with acute lymphoblastic leukemia (ALL) have better outcomes and improved overall survival when treated on pediatric inspired treatment protocols. However, limited data exist for similar patients with AML. We, therefore, sought to assess the variation in outcomes between AML patients within the AYA population treated in our pediatric setting versus adult setting. Methods: A retrospective review of patients with newly diagnosed AML aged 17-25 years old (n=33) treated at either the Indiana University Simon Cancer Center (n=20) or Riley Hospital for Children at Indiana University Health (n=13) between 2006 and 2018 was completed. All patients in the adult setting received standard induction therapy with the 7+3 (standard-dose cytarabine, anthracycline) regimen, while patients in the pediatric setting received an ADE (daunorubicin, cytarabine, etoposide) backbone +/- investigational agents per clinical trial protocols. Data were analyzed with t-tests using IBM SPSS v25 software. This study was approved by the Indiana University Institutional Review Board. Results: Median age was 23 years in patients treated in the adult setting (range 19-25) compared with 17 years (range 17-20) in the pediatric setting. As per the most recent NCCN risk classification for AML, patients in the adult setting were classified as 55% poor risk, 35% intermediate risk, and 10% favorable risk; in the pediatric setting, risk classification was 15% poor risk, 62% intermediate risk, and 23% favorable risk. The incidence of FLT3 mutations was n=4 (20%) in the adult setting and none in the pediatric setting. Clinical trial enrollment was markedly lower in the adult setting with no patients enrolled compared with 54% (7/13) enrolled in the pediatric setting. Complete response (CR) was achieved in 85% of patients treated in the adult setting, but only 62% of patients treated in the pediatric setting. Relapse post induction was higher in the pediatric setting (n=6, 46%) compared to the adult setting (n=5, 40%), and median time to relapse was shorter in the pediatric setting (275 days vs. 344 days). During induction, no statistically significant differences in toxicities were found as measured by ICU interventions (dialysis, mechanical ventilation/NIPPV, and/or use of vasopressors) and identified infections (bacteremia, pneumonia, and/or clostridium difficile). Clostridium difficile infections were increased in the adult setting (15% vs. 0%), but identified bacteremia was higher in the pediatric setting (38% vs. 20%). The median time to allogeneic stem cell transplantation in the adult setting was 117.5 days compared to a median of 223 days seen in the pediatric setting. Incidence of relapse post stem cell transplantation was higher in the adult setting (36% vs. 17%). Proportion of overall survival was 50% (n=10) in the adult setting and 28% (n=8) in the pediatric setting. The highest mortality was seen in poor-risk patients (90%) in the adult setting and intermediate risk patients (62.5%) in the pediatric setting. A trend was seen towards improved overall survival in the adult setting with median overall survival of 739.5 days in the adult setting compared to 415 days in the pediatric setting (p=0.11). In both settings, patients that proceeded to stem cell transplantation had conferred survival benefit: median 1128 vs. 414.5 days in the adult setting and median 530.5 vs. 486.5 days in the pediatric setting. Conclusion: Despite having a higher risk population and lower clinical trial enrollment, we found a trend towards higher complete response rate after induction, reduced relapse rate after induction, shorter time to transplant, longer time to relapse post-transplant, improved survival in the transplant population, and improved median overall survival without a clear increase in toxicity in patients treated in our adult setting. This is in contrast to data in ALL, which suggests improved patient outcomes in AYA patients treated with pediatric based regimens. Our data is limited by a small sample size and a single institution experience. Larger, multicenter studies are needed to understand the optimal AML treatment strategy in the AYA population. Table. Table. Disclosures No relevant conflicts of interest to declare.

e19005Background: R/R AML has a poor prognosis, thus salvage chemotherapy is used as a bridge to HSCT, however the optimal regimen remains unknown. MEC is commonly used as salvage; ~ 66% of patient...

73 Background: Childhood cancer patients have distinct health-related needs as they transition from patient to survivor and from pediatric to adult-based care. This study used the Transition Readiness Assessment Questionnaire (TRAQ) to assess transition readiness and compare variation in readiness perceptions between patients, parents, and physicians. Methods: The TRAQ was completed by patients between ages 12 to 26 and their parent and oncologist at Geisinger Medical Center from Sept. 2015 to Dec. 2016. Surveys were scored according to validated methods (min. 1, max. 5). Statistical analysis was completed using SAS 9.4. Results: The study enrolled 49 patients, including 6 patients (12.2%) and 43 survivors (87.8%). There were 29 males (59.2%). The patient’s mean age at the time of survey was 18.4 years. Cancer types included: acute lymphoblastic leukemia (n = 17), lymphoma (n = 12), and sarcoma (n = 7). There were no significant differences in overall TRAQ scores between parents, patients, and physicians (mean 3.2, 3.5, and 3.7, respectively). The highest interobserver agreement was seen between patients and parents; the lowest was seen between physicians and patients. The greatest competency was assessed in the activity of talking with providers, and the lowest was measured in appointment keeping. In the domain of tracking health issues, providers assigned higher scores than patients (p = 0.003) and parents (p = 0.001). In the skill of talking with providers, patients ranked themselves higher than providers (p = 0.003). There was no significant variation in scores based on disease type, length of therapy, or insurance type. Patient age at diagnosis, patient age at therapy completion, and patient age at survey were correlated with higher patient (p = 0.004, p = 0.002, p = 0.0001, respectively), parent (p = 0.017, p = 0.019, p = 0.0001, respectively), and physician (p = 0.027, p = 0.03, p = 0.0001, respectively) scores. Conclusions: This study demonstrated that the overall assessment of transition readiness in the adolescent and young adult oncology population was similar between patients, parents, and physicians. The TRAQ is a tool that can be effectively used to guide healthcare transition in this population.

Pericardial effusion is frequently found in patients with hypothyroidism, but it is rarely associated with cardiac tamponade. Hypothyroidism complicated by cardiac tamponade is rarely referenced in the medical literature. Here we report an unusual case of a 45-year-old female, who presented with breathlessness and was found to have hypothyroidism with large pericardial effusion with cardiac tamponade. Treatment included an emergency pericardiocentesis followed by thyroxine hormone replacement.

Introduction: Chemotherapy induced peripheral neuropathy (CIPN) is a recognized clinical outcome of vinca alkaloid based therapy that frequently results in dose reduction or therapy discontinuation, but the determinants of interpatient variability remain unpredictable. Previous pharmacogenetics studies have demonstrated that vincristine is metabolized through the CYP3A system with the CYP3A5*3 variant (GG allele at rs776746) having the least efficacy in metabolizing vincristine to its inactive metabolite M1 and conferring higher risk of neurotoxicity. Similarly, a single nucleotide polymorphism (SNP) in the promoter of the CEP72 gene (TT allele at rs924607) has been described as being significantly associated with increased risk and severity of vincristine-associated peripheral neuropathy in the pediatric population. Our recent studies have further studied the incidence of this risk allele and its correspondence with CIPN in the adult population treated with vincristine. This study aimed to investigate if an additive SNP analysis, both for CYP3A5*3 and CEP72, would determine increased predictability of CIPN in patients treated with vinca alkaloids. Methods: A retrospective case-control study of patients was completed in patients that were exposed to vinca alkaloids (vincristine, vinorelbine, and vinblastine) at Geisinger Medical Center from 2007-2015. Available samples of these patients were identified in the Geisinger MyCode bio banking project and the SNP of interest was genotyped using the TaqMan® SNP Genotyping Assay, with genotypic discrimination performed using SDS software (Applied Biosystems). Cases of CIPN were confirmed with retrospective chart review. Statistical analysis was conducted using SAS (SAS Institute Inc.) software, version 9.4. All genotyping and chart review was conducted by personnel blinded to sample identity. Results: A total of 121 patients had genotype mapping completed, of which 60 patients received vincristine, 33 received vinblastine, and 28 received vinorelbine. CIPN was detected in 35.5% of the study population. The CEP72 risk allele (TT) was detected in 14.9% (n=18) of the cohort and the CYP3A5*3 risk allele (GG) was detected in 89.2% (n=108) of the cohort, with similar incidence in each drug class. The median age of this population was 61 years of age with 52.9% (n=64) being males. Multivariate logistic regression analysis, controlling for age and sex, did not demonstrate a significant model for the recessive genetic model of both SNPs with all vinca alkaloids (p=0.33), vincristine alone (p=0.26), vinorelbine alone (p=0.98), or vinblastine alone (p=0.97). The incidence of the inactive G/G allele for CYP3A5*3 was seen in 87.5% (n=21) of the vincristine cohort with neuropathy, The incidence of neuropathy was higher in patients with the TT genotype (75%) in patients receiving vincristine therapy than with the CT or CC genotype (35.7%). As consistent with prior findings, a similar dominant effect was not detected in vinorelbine or vinblastine groups. In the vincristine population (n=60), diseases that were treated included diffuse large B-cell lymphoma (n=29), acute lymphoblastic leukemia (n=6), oligoastrocytoma (n=5), and Ewing's sarcoma (n=2). No disease specific variation in neuropathy incidence and association with TT genotype was detected. Patients received a median three doses of vincristine at 2 mg each (total 6 mg) before detection of CIPN. Four patients (6.67%) of the patients required dose adjustment of chemotherapy, including dose reduction (n=2) or early discontinuation (n=2). Conclusions: This study demonstrates that the CEP72 genotype confers predictive modeling for patients receiving vincristine-based therapy and that including CYP3A5*3 analysis in an additive model is not associated with an increased predictive model for CIPN in patients receiving vinca alkaloid based therapy. In our population, the high incidence of the inactive G/G allele of CYP3A5*3 made it difficult to discern a significant effect in patients that experienced neuropathy. Larger studies are needed to include a more diverse population to confirm this predictive association and to understand if this can help guide precision-based chemotherapy administration and favorably impact disease prognosis. Disclosures No relevant conflicts of interest to declare.

e14107Background: Chemotherapy-induced neuropathy (CIN) frequently results in dose reduction or therapy discontinuation. An associated risk of vincristine-related neuropathy has been previously rep...

e19035Background: 90Y-Ibritumomab tiuxetan (90Y-IT) as radioimmunotherapy in the treatment of B-cell non-Hodgkin lymphoma (NHL) has been approved for consolidation and salvage treatment of follicul...

Arterial walls have a regular and lamellar organization of elastin present as concentric fenestrated networks in the media. In contrast, elastin networks are longitudinally oriented in layers adjacent to the media. In a previous model exploring the biomechanics of arterial elastin, we had proposed a microstructurally motivated strain energy function modeled using orthotropic material symmetry. Using mechanical experiments, we showed that the neo-Hookean term had a dominant contribution to the overall form of the strain energy function. In contrast, invariants corresponding to the two fiber families had smaller contributions. To extend these investigations, we use biaxial force-controlled experiments to quantify regional variations in the anisotropy and nonlinearity of elastin isolated from bovine aortic tissues proximal and distal to the heart. Results from this study show that tissue nonlinearity significantly increases distal to the heart as compared to proximally located regions ([Formula: see text]). Distally located samples also have a trend for increased anisotropy ([Formula: see text]), with the circumferential direction stiffer than the longitudinal, as compared to an isotropic and relatively linear response for proximally located elastin samples. These results are consistent with the underlying tissue histology from proximally located samples that had higher optical density ([Formula: see text]), fiber thickness ([Formula: see text]), and trend for lower tortuosity ([Formula: see text]) in elastin fibers as compared to the thinner and highly undulating elastin fibers isolated from distally located samples. Our studies suggest that it is important to consider elastin fiber orientations in investigations that use microstructure-based models to describe the contributions of elastin and collagen to arterial mechanics.

H1N1 influenza is an emerging threat that is life threatening to pregnant women in the third trimester. Pregnant women are a high-risk group for morbidity and mortality from influenza (H1N1). During the current pandemic of H1N1 influenza, few cases of H1N1 have been reported in pregnancy. We report a case of H1N1 influenza in a 23-year old female with 28 weeks of gestation, who developed acute respiratory distress syndrome, required mechanical ventilation and eventually recovered. KEYWORDS: H1N1; Acute Respiratory Distress Syndrome; Pregnancy; InfluenzaInternet Journal of Medical Update 2012 January;7(1):73-76

Background: Leptospirosis is an emerging spirochetal zoonosis world wide. Leptospirosis is common zoonosis that is under reported and under diagnosed in India. The aim of this study was to study the clinical profile outcome and prognostic factors in human leptospirosis at tertiary care centre. Settings and Design: This was a retrospective study of leptospira positive patients who were admitted in tertiary care centre. The study was conducted in 2010, over a period of 6 month from July to December. Materials and Methods: All patients who presented with clinical features and tested IgM positive for leptospirosis were taken into the study and analyzed based on modified Faine's criteria. Results: Out of total 23 patients there were 21 males and 2 females, with mean age was 32 years. Maximum incidence of cases was found in month of July and August. Out of total 23 patients, 18 (78.26%) were farmers and 5 (21.73%) were laborers. Predominant complaints were fever, jaundice, myalgia, and headache. All 23 had positive results for IgM against leptospira. Liver function tests were deranged in 16 (69.56%) and renal functions were deranged in 12 (52.17%). Total 7 (30.43%) patients had Weil's syndrome and 7 (30.43%) had acute respiratory distress syndrome (ARDS). Total 7 (30.43%) patients had neuroleptospirosis, out of which 5 (21.73%) had aseptic meningitis, one had paraparesis secondary to lumbar radiculopathy and one had meningoencephalitis. Hyperkalemia was present in 6 (26.08%) patients, 7 (30.43%) patients had hypokalemia. Total 11 (47.82%) patients had metabolic acidosis (pH Conclusions: Leptospirosis was unexpectedly found to be positive in many of our patients who were having pyrexia with multiorgan dysfunction during the monsoons. Hepatic dysfunction, acute renal failure, ARDS, and neuroleptospirosis in decreasing frequency were the commonest complication. Daily dialysis, ventilatory support and intensive care management has definitely reduced morbidity and mortality associated with leptospirosis with multi-organ failure.

In the present paper a double funnel port grain configuration is studied in detail. The neutrality of the grain configuration is compared with the neutrality of a single funnel port grain configuration. After optimization of double funnel port grain dimensions to achieve maximum neutrality, the predicted pressure–time profile of realized grain is compared with the achieved pressure-time profile from rocket motor static testing. A close match was obtained between the two profiles. Thus, double funnel port grain configuration is established which can be utilized for estimating burning rate of propellant compositions at any desired pressure with good neutrality.