tbuckley/cabot-search huggingface dataset:
SAT0443 RECONCILIATION OF URATE LOWERING THERAPIES DURING HOSPITALIZATION AND THE IMPACT OF RHEUMATOLOGIC CONSULTATION ON MANAGEMENT OF INPATIENT GOUT FLARES
Authors: Mitali Sen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Hospitalizations complicated by gout flares have an impact on patient care. Delayed diagnosis and suboptimal management can lead to prolonged discomfort, impair chronic outcomes of the disease and lengthen the hospitalization <sup>(1)</sup>. Patients on urate lowering therapy (ULT) are frequently admitted to the hospital for unrelated causes but there is variability in inpatient medication management of the urate lowering agent and acute management of the flare. <h3>Objectives</h3> In this descriptive study, we analyse the variability of reconciliation of ULT on admission and discharge and the impact of rheumatology consultation on acute and chronic management of gout. <h3>Methods</h3> Patients- above the age of 18- admitted to our tertiary care hospital from 01/01/2010 to 01/01/2016 with an ICD-9 or an ICD-10 diagnosis of gout were reviewed. The first 200 patients underwent a retrospective chart review as a pilot study for an ongoing project. We reviewed patient demographics, laboratory testing, and co-morbid conditions; medications on admission and discharge, incidence of gout flare- diagnosis and management during hospitalization, rheumatology consultation and discharge plan for these patients. <h3>Results</h3> Of the 200 patients reviewed, 2.69 admissions per person. We further described the patients who had a gout flare during hospitalization (n =54, 27%). 66% of these patients were males, mean age 69.8 years and BMI 31.78kg/m<sup>2</sup>. A majority of patients had hypertension, renal disease, and dyslipidemia (Table 1). 70% of the patients were on chronic medications for gout (Table 2). 29.6% of these patients were continued on these agents upon admission and only 64.8% of these patient was eventually discharged on these drugs. Rheumatology consulted for 68.5% of the patients. Arthrocentesis was more frequently performed when rheumatology was consulted (70% vs.17.6%; p&lt;0.001). Rheumatology consultation did not decrease length of stay in the hospital. 78.5% of the patients managed by primary team were discharged on a ULT or colchicine compared to 100% in the group managed by rheumatology consult team (100% vs 78.5%; p&lt;0.0431). Outpatient rheumatology follow up was documented in discharge papers for 62% of the patients managed with rheumatology consult compared to 11.7% in the comparison group. (62% vs 11.7%; p&lt;0.002). <h3>Conclusion</h3> Rheumatology consultation improved adherence to guidelines in diagnosis and management of gout flare and improved the discharge planning and follow up. <h3>References</h3> [1] Robinson PC, Kempe S, et al. Epidemiology of inpatient gout in Australia and New Zealand: temporal trends, comorbidities and gout flare site. Int J Rheum Dis. 2016Jul26. doi: 10.1111/1756-185X.12941. <h3>Disclosure of Interests</h3> None declared
Upstaging of head and neck cancers due to extranodal extension: An Indian study.
Authors: Deepa M. Joseph, Sagar Raut, Rajesh Pasricha, Sweety Gupta
Journal: Journal of Clinical Oncology (2019)

e17553 Background: Latest AJCC staging has included extranodal extension (ENE) in nodal staging of head and neck cancers (HNC) in view of its prognostic significance. Presence of clinical ENE makes the disease N3b and the stage grouping will be stage IVB. This retrospective analysis was done with an objective to find out the percentage of patients with HNC getting upstaged because of ENE and their treatment outcome. Methods: A retrospective analysis of all HNC patients registered in our department from January 2018 to January 2019 were done to identify the presence of ENE and their staging. AJCC criteria was used for defining clinical and radiological ENE. The site, subsite, stage and presence of ENE were documented. Results: A total of 562 patients were registered with HNC. Among them 40 patients were identified to have ENE (7.1%). There were 35 males and 5 females. There were 17 cases with ca oropharynx, 13 oral cavity, four hypopharynx, three supraglottis, two glottis, and one maxillary carcinoma. Tumour size varied from 1.5 cm to 8 cm with an average of 4.9cm. Majority of the patient had a T4a disease, with 18 patients in the category. T stage varied from T1 – 1, T2 – 7, T3 – 7, T4b – 6, missing data – 1. 33 patients had clinically documented ENE and six were radiological and one patient had pathological ENE. Nine had skin involvement and the rest (24) had either muscle invasion or soft tissue involvement. Various treatment approaches were tried. Two patients received neoadjuvant chemotherapy (NACT) followed by chemoradiation (CTRT). On treatment at present. One NACT followed by surgery and later CTRT. Developed recurrence. Four patients received palliative chemotherapy, but developed progressive disease (PD), on best supportive care (BSC). Nine patients received palliative radiotherapy, six patients are on treatment and one had PD. Five patients received radical CTRT, 5 on treatment and one had PD. One received palliative RT followed by palliative chemo, but developed PD. 13 patients are on treatment and rest of the patients are either dead, lost to follow up or on BSC. Conclusions: Majority of the patients with ENE had a T4a disease. No special site predilection was identified. Various treatment modalities tried but none of them produced any significant difference in outcome. In conclusion, patients with ENE had a poor prognosis irrespective of the treatment modality selected.
Low platelet counts in patients with glioblastoma.
Authors: Assad Ali, Addisson Barnett, Anas Saeed Bamashmos, Hong Li, Wei (Auston) Wei, Soumya Sagar, Gene H. Barnett, Lilyana Angelov, Alireza Mohammad Mohammadi, David M. Peereboom, Glen Stevens, John H. Suh, Jennifer S. Yu, Erin Sennett Murphy, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2019)

e13565 Background: Radiotherapy and concurrent chemotherapy with Temozolomide (TMZ) have myelosuppressive effect, and thrombocytopenia is commonly seen in this patient population seen in 5-10% of glioblastoma (GBM) patients. There is a lack of data analyzing the thrombocytopenia and it’s on the progression free survival (PFS) or overall survival (OS) of these patients. The primary objective of this study was to identify the degree of thrombocytopenia in newly diagnosed GBM patients receiving concurrent TMZ based chemoradiation (CRT). Secondary objectives included associations between thrombocytopenia PFS, and OS. Methods: We retrospectively reviewed 484 newly diagnosed GBM patients who underwent surgery followed by standard of care CRT. We also analyzed the association between platelet counts and age, sex, MGMT methylation status, and extent of surgical resection. Platelet count was collected at the time of surgery, CRT start date, and two, four, six, and ten weeks post-CRT start date. Patients were grouped into quartiles according to their platelets count. Results: Of the 484 patients collected, 308 were males, 139 had gross total resection of the tumor, 229 patients were older than 65 years, and 171 (42.1%) were MGMT methylated. In a univariate analysis, a platelet count less than 180,000 (lowest quartile) was associated with higher mortality (HR 1.63, P &lt; 0.001) but had no significant association with PFS (HR 1.16, P = 0.48). Among the 118 patients who had platelet count lower than 180,000, 4 had platelets count less than 100,000 necessitating their TMZ to be stopped during CRT. In a multivariate analysis model adjusting for age, gender, MGMT status, and type of surgery, platelet counts less than 180,000 was also associated with significantly higher mortality (HR 1.60, P &lt; 0.001). Conclusions: Our study concluded that patients who had platelet counts less than 180,000 at the time of surgery or CRT with TMZ had significantly higher mortality (HR 1.60, P &lt; 0.001) but had no association with PFS (HR 1.16, P = 0.48).[Table: see text]
Endocrinopathies associated with immune checkpoint inhibitors: Standard of care at veterans administration medical centers.
Authors: Brett Johnson, David P. Tuck, Spyridon Ganas, Nicholas Bayless, Nikesh Kotecha, Nhan Do
Journal: Journal of Clinical Oncology (2019)

e14148 Background: Multiple different immune checkpoint inhibitors (ICI) have now received FDA approval for nearly 70 separate indications covering 14 different tumor types. Patients treated with these agents in clinical trials have an observed incidence of immune related adverse events (irAEs), including endocrinopathies, which may increase morbidity and mortality. Limited information describes the incidence and impact of these events outside of clinical trials. Methods: Retrospective data from the Veterans Health Administration (VA) of patients treated with ICI has been aggregated to understand the impact of these events in a standard of care setting, with a goal of improving patient care through predictive models and contributing to the understanding of the mechanisms and response to treatment. Results: Between October 2015 and December 2018, 10,280 patients were prescribed ICI at VA medical centers, with an average age of 70 years (range 20-99). A total of 11098 ICI orders, allowing for combinations or sequential treatments. Overall, nivolumab was prescribed 6024 times (54.3%), pembrolizumab 3976 (35.8%), ipilimumab 565 (5.1%) and atezolizumab 519 (4.6%). Avelumab (13) and durvalumab (1) had limited use. A candidate set of potential endocrine adverse events was estimated based on selected ICD10 codes recorded for the first time after treatment with ICI (Table). Conclusions: The frequency of endocrine immune related adverse events has been reported to be 5-10%. Here we have identified a cohort of ICI treated patients who may have developed endocrine adverse events. This cohort will be used to evaluate phenotyping, potential biomarkers and models of predictive risk.[Table: see text]
Case 39-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Raymond M. Hakim, Paul B. Googe
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 90-year-old woman was admitted to the hospital because of diarrhea, nausea, and vomiting.She was in a static state of health until several weeks earlier, when intermittent diarrhea developed. Ten days before admission the diarrhea became nearly constant, and the patient vomited small amounts of bile-stained fluid. Her physician found that peristaltic sounds were diminished; there was no distention, tenderness, or mass. Rectal examination disclosed a soft fecal impaction. A glycerin suppository was administered with satisfactory results, and the patient attended her 90th birthday party five days before entry. Three days later she again vomited and . . .
Effect of temozolomide on neurogenesis and anxiety in the adult mouse brain.
Authors: Syed Hussaini, Mihyeon Jang
Journal: Journal of Clinical Oncology (2019)

e23082 Background: The hippocampus is one of two regions in the adult brain where new neurons are generated well into adulthood. Newborn neurons develop from neural stem cells, and are consequently integrated into the hippocampal circuitry to function in learning and memory. Temozolomide (TMZ) is a commonly used alkylating agent for treatment of malignant gliomas. In this study, we examine the effects of TMZ on adult neurogenesis and cognitive function in the murine model. Methods: Adult male mice (8-week-old) were injected daily with TMZ (25 mg/kg, i.p.) for 2, 2.5 and 3.5 weeks to estimate progenitor proliferation, neuronal maturation and animal behavior respectively. For progenitor proliferation, a single dose of BrdU (50mg/kg, i.p.) was injected at 2 weeks and the mice sacrificed 2 hours later. For maturation analysis, five separate doses of EdU (41.1 mg/kg, i.p.) were injected over five days starting at 2 weeks. Three weeks after first EdU injection mice were sacrificed. Both BrdU and EdU are novel thymidine analogues that label dividing cells. Immunostaining was performed on hippocampal brain slices to label progenitors at different stages of development. For behavioral analysis, daily tests measuring anxiety, memory and motor activity were started at 2 weeks into TMZ administration. Results: TMZ significantly reduced the resident radial glia-like and non-radial glia-like population (MCM2+Nestin+), as well as the overall proliferating progenitor pool (n = 2, p &lt; 0.05). In addition, it significantly reduced the population of Type-3 neuroblasts (EdU+DCX+NeuN-) (n = 4, p &lt; 0.05). During neuronal maturation, immature new neurons (EdU+DCX+NeuN+) and mature new neurons (EdU+DCX-NeuN+) were also reduced by TMZ (n = 4, p &lt; 0.05). These effects of TMZ coincided with specific behavioral deficits. While TMZ had no effect on working memory and locomotor activity, mice that underwent TMZ administration showed significantly increased anxiety on the open field test (n = 7, p &lt; 0.05). Conclusions: Our findings demonstrate TMZ significantly impairs cellular proliferation of neural stem cells and fate-committed neuroblasts, and increases anxiety with sparing of non-hippocampal-dependent memory. TMZ may thus be associated with specific deficits in hippocampal function in the adult brain, providing mechanistic insight into adverse effects that may be observed with TMZ treatment.
FRI0578 LACC1 MUTATION IN THREE SIBLINGS WITH POLYARTHRITIS WITHOUT SYSTEMIC MANIFESTATIONS
Authors: Ankita Singh, Deepti Suri, Prince Jacob, Katta Mohan Girisha, Ankur Jindal, Surjit Singh
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is a complex group of disorders characterized by wide phenotypic diversity and genetic heterogeneity. It has multifactorial etiology varying among different subtypes. There are emerging reports on new gene loci being identified especially in families with many affected members (1,2) <h3>Objectives</h3> To report 3 siblings with polyarthritis who were detected to have mutation in Laccase domain containing 1 (<i>LACC 1</i>) gene. <h3>Methods</h3> We reviewed case records of 3 siblings with infantile onset polyarthritis and performed whole exome sequencing on their DNA samples for <i>LACC1</i>, <i>MMP2</i> and <i>WISP</i> genes. <h3>Results</h3> A non-consanguineous family from north-western part of India reported with 3 daughters having polyarticular joint disease. The chronology of symptoms was similar in all 3 children. Joint symptoms started in later half of infancy with swelling of knee and ankle. This disease was progressive and over the following 2 years there was involvement of small joints and cervical spine too (Figure 1) along with deformities and contractures. The investigations at the time of first evaluation are given in Table 1. Radiographs in all 3 sisters showed osteoporosis and erosion of vertebrae (Figure 2). The children were initially started on naproxen. Later, in view of rheumatoid factor positivity in eldest sister we decided to give them a trial of oral prednisolone (initially 1 mg/kg and subsequently tapered) and subcutaneous methotrexate (10 mg/m<sup>2</sup>/week). Methotrexate was continued on long term basis. Over the next 24 months of follow-up the clinical improvement has been sustained. Whole-exome-sequencing in all three girls has revealed mutation in <i>LACC1</i> gene [Exon 4; c.832G&gt;C; p.(Ala278Pro), Homozygous, Autosomal recessive]. <h3>Conclusion</h3> This case report further provides evidence to the emerging association of <i>LACC1</i> mutation with familial aggregation of JIA (1,2). Long term follow-up of these patients is necessary to determine the natural course of this intriguing clinical entity. <h3>References</h3> [1] Wakil SM, Monies DM, Abouelhoda M, Al-Tassan N, Al-Dusery H, Naim EA, et al. Association of a Mutation in LACC1With a Monogenic Form of Systemic Juvenile Idiopathic Arthritis: Monogenic Systemic Juvenile Idiopathic Arthritis. Arthritis &amp; Rheumatology. 2015Jan;67(1):288–95. [2] Karacan I, Uğurlu S, Şahin S, Everest E, Kasapçopur Ö, Tolun A, et al. LACC1 Gene Defects in Familial Form of Juvenile Arthritis. J Rheumatol. 2018May;45(5):726–8. <h3>Disclosure of Interests</h3> None declared
Case 45-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1984)

Presentation of Case First admission. A 61-year-old man was admitted to the hospital because of oliguric renal failure The patient was well until three weeks earlier, when he began to notice urinary frequency in small amounts. Five days before admission he experienced frank chills and felt warm but did not take his temperature. He observed that his urinary volume was decreasing progressively. One day before entry he consulted a urologist, who removed 10 ml of urine via a catheter after the patient voided. Examination showed proteinuria and a few red cells and white cells per high-power field. An intravenous . . .
The effect of antibiotic use on survival of patients with resected pancreatic ductal adenocarcinoma.
Authors: Merve Hasanov, Chirayu Mohindroo, Jane Rogers, Laura Prakash, Michael J. Overman, Gauri Rajani Varadhachary, Robert A. Wolff, Milind M. Javle, David R. Fogelman, Shubham Pant, Matthew H. G. Katz, Michael Paul Kim, Ching-Wei David Tzeng, Florencia McAllister
Journal: Journal of Clinical Oncology (2019)

e15773 Background: Recent studies showed that gut microbial dysbiosis can affect carcinogenesis and tumor responses to therapies. Antibiotics, key pharmacologic agents that modulate microbiota diversity and bacterial strains, can lead to dysbiosis. Recent studies have postulated a tumor promoting effect for some pancreatic ductal adenocarcinoma (PDAC)-associated gut bacteria. However, the effects of antibiotic use on PDAC patients outcome is yet to be discovered. Methods: We examined a total of 342 patients who were diagnosed with PDAC between 2003-2015 and underwent primary tumor resection. Antibiotic exposure was defined as the use of antibiotics for ≥7 days between diagnosis and surgery. We collected data on patient demographics, presurgical antibiotic use, duration, type and reason, disease and therapy characteristics, and prognostic parameters. We analyzed and compared the objective responses, progression free survival (PFS) and overall survival (OS). Results: From a total 342 patients with resected PDAC, 147 patients (43%) used antibiotics for ≥7 days duration during the presurgical period. The most frequently used antibiotics were quinolones (80.4%), beta-lactams (38.2%), nitroimidazoles (23%), glycopeptides (15.3%), tetracyclines (8.6%), and macrolides (6.7%). The median OS for patients with antibiotic use was 1007 vs. 940 days for those without antibiotic use (p = 0.57). The median PFS was 374 for patients with antibiotic use and 313 days for those without antibiotic use (p = 0.51). The effect of individual antibiotics was examined and statistical analysis was done for possible confounding factors including disease stage, treatment type, and the reason for antibiotic use. Tetracyclines use was found to be significantly associated with worse survival on resected PDAC patients and was not affected by confounding factors such as skin infections. The median OS of patients who had tetracycline for ≥7 days was 687 vs. 1004 days for those not exposed to this antibiotic (HR 1.836; p = 0.015). Although not statistically significant, PFS was shorter with tetracycline use. Conclusions: We conducted the first retrospective, single-center cohort study on resected PDAC patients examining the potential influence of antibiotic use on survival. Tetracycline use in resectable PDAC patients is associated with clinically significant decreased PFS and statistically significant worse OS. Further multicenter studies with larger population would be necessary to confirm these findings that could help clinical practice for infectious treatment in PDAC patients.
Ipilimumab versus placebo after complete resection of stage III melanoma: Long-term follow-up results the EORTC 18071 double-blind phase 3 randomized trial.
Authors: Alexander M. M. Eggermont, Vanna Chiarion-Sileni, Jean Jacques Grob, Reinhard Dummer, Jedd D. Wolchok, Henrik Schmidt, Omid Hamid, Caroline Robert, Paolo Antonio Ascierto, Jon M. Richards, Celeste Lebbe, Virginia Ferraresi, Michael Smylie, Jeffrey S. Weber, Michele Maio, Fareeda Hosein, Veerle de Pril, Michal Kicinski, Stefan Suciu, Alessandro Testori
Journal: Journal of Clinical Oncology (2019)

2512 Background: Since 2015, ipilimumab (Ipi) is an approved treatment for stage III melanoma based on a significantly (P=0.0013) prolonged recurrence-free survival (RFS) (Eggermont et al, Lancet Oncology, 2015). At a median follow-up of 5.3 years, RFS (HR=0.76) and distant metastasis-free survival (DMFS) (HR=0.76), assessed by an IRC, and overall survival (OS) (HR=0.72) were prolonged in the Ipi group as compared to the placebo (Pbo) group (Eggermont et al, NEJM, 2016), despite a 53.3% (Ipi) vs 4.6% (Pbo) treatment discontinuation rate due to adverse events. Methods: In this randomized double-blind trial, eligible patients (pts) included those ≥18 yrs of age who underwent complete resection of stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis). 951 pts were randomized (stratified by stage and region) 1:1 to Ipi 10 mg/kg (n=475) or placebo (Pbo, n=476) q3w for 4 doses, then every 3 mos for up to 3 yrs until completion, disease recurrence, or unacceptable toxicity. Here, we report the comparison between the Ipi and Pbo groups regarding the long-term efficacy outcomes using the local investigator assessments. Results: Overall, 20%/44%/36% of pts had AJCC-7 stage IIIA/IIIB/IIIC, 42% ulcerated primary, and 58% macroscopic lymph node involvement. Median follow-up was 6.9 yrs. The RFS, DMFS and OS benefit observed in the Ipi group was long-lasting (almost 10% difference at 7 years) and consistent across subgroups: no significant predictive factors could be detected. Conclusions: In this phase III trial, Ipi, administered at 10 mg/kg, as adjuvant therapy provided, at a 6.9 yr median follow-up, a sustained improvement in the RFS, DMFS, and OS long-term results in patients with high-risk stage III melanoma. Clinical trial information: NCT00636168. [Table: see text]