tbuckley/cabot-search huggingface dataset:
PB1783 PROGRAMMED CELL DEATH‐1 AND PROGRAMMED CELL DEATH LIGANDS EXPRESSION IN NODAL PERIPHERAL T‐CELL LYMPHOMA
Authors: T. Asawapanumas, N. Tungnantachai, T. Assanasen, C. Polprasert, U. Bunworasate, T. Intragumtornchai, K. Wudhikarn
Journal: HemaSphere (2019)

Background: Program cell death‐1/Program cell death ligands (PD‐1/PD‐Ls) is an important element of immune response regulation in human. Activation of PD‐1/PD‐Ls results in an inhibition of cellular mediated immune response. Several cancers including lymphoma exhibit abnormal PD‐1/PD‐Ls expression which may contribute to treatment failure and worse outcome. However, data of PD‐1/PD‐Ls expression in peripheral T cell lymphomas (PTCLs) has been sparsely described. Herein, we described expression patterns of PD‐1/PD‐Ls in PTCLs and explored their correlation with clinical parameters. Aims: To describe expression features of PD‐1/PD‐Ls in PTCLs and explore their correlation with clinical characteristics and outcomes Methods: We included 51 adult PTCLs diagnosed and followed up at King Chulalongkorn Memorial Hospital between 2550 and 2561. Medical records were abstracted for detailed clinical data. Paraffin embedded tissue archives were further stained for PD‐1, PD‐L1 and PD‐L2 which were independently interpreted for expression level and intensity by two hematopathologists. Membranous staining more than 5% was used as a positive cut off criteria. Correlation with clinical parameters was then analyzed. Results: Of 51 PTCLs, PD‐1, PD‐L1 and PD‐L2 were seen in 27.5%, 49.0% and 68.6% of PTCLs respectively. The expression patterns and frequency of PD‐1/PD‐Ls have varied among different histologic subtypes. There was no significant difference in baseline clinical characteristics between PD‐Ls expression status. With median follow up duration of 15 months, the 1‐year event free survival (EFS) and overall survival (OS) were 43.9 % and 61.6% respectively. Neither EFS nor OS was different among PD‐L1 or PD‐L2 expression cohort (1‐year EFS 39.3% in negative PD‐L1 lymphoma vs 46.9% in positive PD‐L1 lymphoma, 1‐year EFS 40.5% in negative PD‐L2 lymphoma vs 49.5% in positive PD‐L2 lymphoma) (1‐year OS 55.2% in PD‐L1 negative lymphoma vs 59.5% in PD‐L1 positive lymphoma, 1‐year OS 57.7% in PD‐L2 negative lymphoma vs 56.8% in PD‐L2 positive lymphoma). Univariate cox regression analysis showed that performance status was the only prognostic factor for survivals. PD‐1 and PD‐Ls expression status, either on lymphoma cells or non‐tumor stroma, were not predictive factors for treatment outcomes. Summary/Conclusion: Aberration expression of PD‐1/PD‐Ls could be seen in PTCLs and was varied among histologic subtypes. Clinical characteristics, treatment response and survivals were not statistically different among PD‐1 and PD‐Ls expression patterns. image
The Cardiovascular Legacy of Good Glycemic Control: Clues About Mediators From the DCCT/EDIC Study
Authors: Matthew C. Riddle, Hertzel C. Gerstein
Journal: Diabetes Care (2019)

Diabetes is defined by hyperglycemia, but whether optimizing glycemic control can reduce its complications was long in doubt. In 1968 Siperstein et al. proposed the hypothesis that microvascular injury accompanying diabetes could be genetically determined (1), and there was concern that, even if the “glucose hypothesis” (2,3) were valid, seeking good control of hyperglycemia was overly risky. Nevertheless, epidemiologic evidence linking hyperglycemia with both microvascular and cardiovascular complications prompted assessment of the effects of intensive glycemic control in the Diabetes Control and Complications Trial (DCCT) for type 1 diabetes (T1D) and the UK Prospective Diabetes Study (UKPDS) for type 2 diabetes (T2D). When the results of the DCCT were reported in Las Vegas on a hot (>110°F) day in June 1993, many people were surprised by the approximately 50% reduction of microvascular changes that was associated with 6.5 years of maintaining hemoglobin A1c (HbA1c) close to 7% (53 mmol/mol) compared with 9% (75 mmol/mol) in the control arm (4). Because the DCCT participants were young, cardiovascular events were too few to analyze and long-term effects on cardiovascular risk remained unknown. Results in T2D from the UKPDS reinforced the message of the DCCT. More intensive glycemic control attaining about a 1% difference in HbA1c in T2D for 10 years led to 25% lower rates of microvascular outcomes (5) and a nonsignificant 16% lower rate of myocardial infarction (5).

For more than two decades after these reports the dominant view has been that improving glycemic control reduces eye, nerve, and kidney complications but not cardiovascular risk. Four large randomized clinical trials testing whether seeking HbA1c levels at or below 7% could reduce cardiovascular events showed limited benefits during their periods of active treatment (5–8). Although analysis of data pooled from these four trials …
Abstract 9378: Glucose Fluctuations Aggravate the Vulnerability of Diabetic Heart Against Ischemia/reperfusion Mediated via microRNAs Modulation
Authors: Yasushi Teshima, Naohiko Takahashi, Luong Cong Thuc, Satoru Nishio, Shotaro Saito, Akira Fukui, Osamu Kume, Mikiko Nakagawa, Tetsunori Saikawa
Journal: Circulation (2012)

[Objective] Frequent hypoglycemia attack reportedly increased cardiovascular events and mortality in patients with diabetes mellitus (DM). In the present study, we investigated whether glucose fluctuations may increase the susceptibility to ischemia/reperfusion in diabetic rat heart and the involvement of microRNA (miRNA) as well. [Methods and Results] In in vitro experiments, cultured cardiomyocytes were alternately exposed to high (450 mg/dL) and low (30 mg/dL) concentrations of glucose for 5 days. Exposure to glucose fluctuations increased level of reactive oxygen species (ROS) and made cardiomyocytes more vulnerable to oxidative stress compared to sustained high glucose exposure. In in vivo experiments, rats were divided into 3 groups: control, DM, and DM with glucose fluctuations. DM was induced by intravenous injection of streptozotocin (60 mg/kg) and glucose fluctuation was induced by 24h-fasting and insulin injection (0.5 IU/kg). Isolated hearts were subjected to 20min global ischemia followed by 30min reperfusion. The infarct size was larger in diabetic hearts with glucose fluctuations than those with consecutive hyperglycemia. Electron microscopy disclosed that mitochondria were swollen and structure of cristae was destroyed in diabetic heart, and those changes were aggravated by glucose fluctuations. The level of ROS and activities of intracellular antioxidant enzymes were analyzed in search of possible mechanisms. Level of ROS was increased, and activities of catalase and superoxide dismutase were down-regulated in the heart with glucose fluctuations compared to sustained hyperglycemia. Further, microarray analysis was performed to explore the expression profiles of miRNAs in each group. Expressions of mir-200c and -141 were more abundant in the hearts exposed to glucose fluctuations than those with sustained high glucose level. We also confirmed that these miRNAs seem to contribute to the decreased activities of antioxidant enzymes and subsequent ROS increase. [Conclusions] Glucose fluctuations increased ROS level and enhanced ischemia/reperfusion injury in diabetic heart. Up-regulations of mir-200c and -141 may account for ROS increase by suppressing antioxidant enzymes.
Time to Change the Limited-Stage Paradigm for Small Cell Lung Cancer?
Authors: Stephen G. Chun, Steven E. Schild, Jeffrey A. Bogart
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Efficacy of 177Lu Peptide Receptor Radionuclide Therapy for the Treatment of Neuroendocrine Tumors
Authors: Bianka Saravana-Bawan, Amandeep Bajwa, John Paterson, Alexander J. B. McEwan, Todd P. W. McMullen
Journal: Clinical Nuclear Medicine (2019)

Objective The purpose of this study was to assess the efficacy of 177 Lu-labeled peptide receptor radionuclide therapy (PRRT) induction treatments for patients with unresectable metastatic neuroendocrine tumors. Methods MEDLINE, EMBASE, and Ovid were systematically searched with keywords “lutetium,” “Lu-177,” “PRRT,” “neuroendocrine,” and “prognosis.” Studies evaluating treatment with 177 Lu-labeled PRRT were assessed for disease response and/or disease control rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 or 1.1, modified RECIST, Southwest Oncology Group (SWOG), or modified SWOG criteria. Pooled proportions of disease response and control rates were calculated for both fixed- and random-effects models. Results Eighteen studies with 1920 patients were included (11 with 1268 patients using RECIST and 6 with 804 patients using SWOG). By RECIST criteria, the pooled disease response rate by random-effects model was 29.1% (95% confidence interval [CI], 20.2%–38.9%), and disease control rate was 74.1% (95% CI, 67.8%–80.0%). By SWOG criteria, the pooled disease response rate by random-effects model was 30.6% (95% CI, 20.7%–41.5%), and disease control rate was 81.1% (95% CI, 76.4%–85.4%). Conclusions Induction therapy, typically 4 treatments, with 177 Lu PRRT is an effective method of treating unresectable metastatic neuroendocrine tumors with significant disease response and control rates.
High-Density, Long-Lasting, and Multi-region Electrophysiological Recordings Using Polymer Electrode Arrays
Authors: Jason E. Chung, Hannah R. Joo, Jiang Lan Fan, Daniel F. Liu, Alex H. Barnett, Supin Chen, Charlotte Geaghan-Breiner, Mattias P. Karlsson, Magnus Karlsson, Kye Y. Lee, Hexin Liang, Jeremy F. Magland, Jeanine A. Pebbles, Angela C. Tooker, Leslie F. Greengard, Vanessa M. Tolosa, Loren M. Frank
Journal: Neuron (2018)
Germline mutations of MLH3 in Korean hereditary nonpolyposis colorectal cancer
Authors: Sung-Hye Hong, Young–kyoung Shin, Byong Chul Yoo, Yong Shin, Il-Jin Kim, Jae-Gahb Park
Journal: Cancer Research (2004)

1324  The autosomal dominantly inherited form of colorectal polyposis and cancer, familial adenomatous polyposis (FAP), is in the large majority of cases caused by germline mutations in the APC gene (5q21-q22). The APC tumour suppressor also has a role in sporadic colorectal tumorigenesis. Mutational screening of the APC gene was carried out on family members of the Swedish polyposis registry with the aim to detect the pathogenic mutations to enable presymptomatic diagnosis and identification of genotype-phenotype correlations. The APC gene (encoding 2843 aminoacids) consists of 15 exons where exon 15 has a size of more than six kilobases. We used an initial RNA and DNA based protein truncation test (PTT) and subsequential sequencing of the PTT-fragments to detect a majority of the disease-causing mutations, which mainly are protein truncating. When no chain terminating mutation was found, exon-specific techniques as well as multiplex ligation-dependent probe amplification (MLPA) were used to search for the presence of in-frame mutation or large deletion/duplication respectively. Seventy-two pathogenic mutations were found in 114 families. The mutation detection rate in families with classic FAP was 75% (69/92). Of the identified mutations, 40 were small (one to five bp) deletion/insertion mutations, 22 were nonsense mutations, four were mutations affecting splice sites, and six were gross deletions, among them four deletions of one or more exons. Thirty-eight of the detected mutations, including gross deletions and introductions of cryptic splice sites, were novel. One of the patients displaying an attenuated form of FAP (AFAP) was a rare case of mosaicism. Another AFAP patient carried a novel nonsense mutation in the first exon of the APC gene. The identified causes of disease in these two AFAP patients are in agreement with the notion that the mild phenotype can arise either as a result of mutations in the first five exons of the APC gene, or as a result of lower expression of the mutated allele. However, a third AFAP patient was shown to carry a mutation causing a premature stop codon in the beginning of exon 15. Six missense mutations were also identified in the material. The APC E1317Q variant, previously reported not to be present among Swedish colorectal cancer patients was identified in three unrelated families.
Irradiation-Related Lymphopenia for Bone Metastasis from Hepatocellular Carcinoma
Authors: Sangjoon Park, Hwa Kyung Byun, Jinsil Seong
Journal: Liver Cancer (2019)

In the era of immunotherapy, treatment-related lymphopenia (TRL) is gaining attention. In this study, TRL was investigated in patients with bone metastasis from hepatocellular carcinoma (HCC) treated with radiotherapy (RT).Clinical data of 302 patients receiving RT for 511 bone metastases from HCC between 2005 and 2018 were reviewed. Data on absolute lymphocyte count (ALC) from pre-RT to 12 months post-RT were collected. Severe TRL was defined as ALC <500 cells/mm3 and evaluated using ALC 2 months after initiating RT. Factors associated with TRL were analyzed, which include the amount of active bone marrow within the RT field. The amount of active bone marrow included in the RT field was calculated as the product of the percentage of the bone compartment included in the RT field and the active bone marrow percentage of the bone compartment.Overall, 33.4% of patients developed TRL 2 months after initiating RT. The mean ALC decreased after initiating RT and remained persistently low during 12 months of observation. Overall survival (OS) was significantly worse in patients with TRL than in those without (median OS: 3.7 vs. 6.5 months, p < 0.001). In the prognostic factor analysis, TRL was an independent prognostic factor of OS (p = 0.036), along with known prognostic factors of HCC. The percentage of active bone marrow within the RT field was the only significant factor associated with TRL (p < 0.001).TRL was observed in patients receiving RT for bone metastasis from HCC, and it was associated with poor survival. The percentage of active bone marrow within the RT field significantly affected TRL development. The results suggest that a new strategy is required to prevent TRL.
THU0662 THE FREQUENCY OF MULTIPLE MYELOMA IN PATIENTS WITH ELEVATED ACUTE PHASE RESPONSE AND LOW BACK PAIN IN A RHEUMATOLOGY OUTPATIENT CLINIC
Authors: Fulya Cosan, Yavuz Furuncuoglu, Meis Timuroglu, Mohammed Raid Oyiwe, Osman Kara
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Multiple myeloma (MM), is a malignant hematological monoclonal neoplasm of plasma cells. Main clinical findings of MM are anemia, bone pain, elevated erythrocyte sedimentation rate and CRP levels, M-spike on protein electrophoresis, monoclonal protein in serum or urine. Anemia, low back pain and elevated acute phase reactants are frequently seen symptoms of patients who admit to a rheumatology outpatient. <h3>Objectives</h3> We aimed in this study to evaluate the frequency of plasma cell malignancies in patient with elevated acute phase reactants and low back pain. <h3>Methods</h3> 4100 rheumatology patients from rheumatology outpatient clinic are screened retrospective for &gt;50 age, elevated ESR, anemia and back pain or hip pain. 548 patients (312 female and 236 male, mean age: 61±6) fulfilled these criteria and these patients are screened with protein electrophoresis for monoclonal gammopathies. If M-spike is seen in protein electrophoresis, patients are evaluated for lambda and kappa chains in serum and urine. <h3>Results</h3> 3 patients were diagnosed for multiple myeloma. All three patients had moderate to severe anemia (Hgb&lt;8 g/dl) and ESR&gt;70 mm/h. Two patients are classified as rheumatoid arthritis and one patient had no inflammatory rheumatological diseases. 7 patients were diagnosed as MGUS and 5 patients from this group is diagnosed as rheumatoid arthritis and 2 patient polymyalgia rheumatica. In MGUS patient group mean ESR level was 44±9 mm/h and mean Hgb level was 10,8±6 g/dl. <h3>Conclusion</h3> We found no increased frequency for MM in rheumatology outpatient clinic. Patients &gt;50 years with high ESR and moderate to severe anemia should be screened with protein electrophoresis for monoclonal gammopathies. <h3>References</h3> [1] A population study to define the incidence and survival of multiple myeloma in a National Health Service Region in UK. Phekoo KJ et al. Br J Haematol. (2004) <h3>Disclosure of Interests</h3> None declared
PF246 PERSONALIZED FOLLOW‐UP OF ACUTE MYELOID LEUKEMIA THROUGH MULTIPARAMETER FLOW CYTOMETRY: A PROOF OF CONCEPT
Authors: H. Jacqmin, Q. Louveaux, B. Chatelain, P. Jacqmin, C. Chatelain, J.‐M. Dogné, C. Graux, F. Mullier
Journal: HemaSphere (2019)

Background: Standardization, machine learning techniques and comparison to normality are concepts that are changing the landscape of multiparameter flow cytometry data analysis in clinical hematology. We applied these concepts to the follow‐up of acute myeloid leukemia (AML), which remains challenging due to the heterogeneity of the disease. Aims: To evaluate a new flow cytometry data analysis approach for the follow‐up of measurable residual disease in AML. Methods: Based on retrospective flow cytometry data, we developed a strategy for personalized monitoring of AML. This strategy is an evolution of the “leukemia associated immunophenotype” or “LAIP”‐approach that has been used the last decades in specialized flow cytometry laboratories. It relies on new concepts, comparing simultaneously the patient's follow‐up and diagnosis results to control group samples. We named these concepts the “leukemic cloud” and the “abnormality ratio”. To evaluate this approach, flow cytometry data of 6 AML patients and 20 control patients was used. All samples were analyzed with the same 10‐parameter (FSC‐A, SSC‐A, CD45, CD34, CD117, CD13, CD33, CD19, CD3, HLA‐DR) FACS Canto II flow cytometry assay. The “abnormality ratio” results over time were compared with morphology and molecular biology results. Results: The “Abnormality Ratio” results over time were in line with the clinical evolution of the patients (see example on image below) and were overall more sensitive for detecting residual disease than morphology and molecular biology, excepted for NPM1‐mutated AML. The “Abnormality Ratio” did not consider phenotypic switches of the malignant cell population identified at diagnosis. However, the discrepancy between the “abnormality ratio” results and morphology or molecular biology results could be used to objectify these phenotypic switches. Summary/Conclusion: We developed a quasi‐fully automatable flow cytometry data analysis algorithm. It could be used as a basis for the development of “next generation” flow cytometry assays for monitoring of hematological malignancies such as AML. Prospective studies are needed to confirm the applicability and limitations of our concepts. image
AB1264 THE RELATIONSHIP BETWEEN SERUM URIC ACID AND PULMONARY FUNCTION IN KOREAN ADULT POPULATION: DATA FROM THE KOREA NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY:
Authors: Hyemin Jeong, Yeoung Hee Eun, In-Young Kim, Eun-Jung Park, Hyungjin Kim, Jaejoon Lee, Chan Hong Jeon
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Hyperuricemia is associated with several comorbidities. The association between uric acid and pulmonary function is still controversial. <h3>Objectives:</h3> The aim of this study was to evaluate the relationship between serum uric acid and pulmonary function in Korean adult population. <h3>Methods:</h3> A total of 3,177 (weighted n = 19,770,902) participants aged 40 years or older from the 2016 Korean National Health and Nutrition Examination Survey were included and performed cross-sectional study. <h3>Results:</h3> Participant with hyperuricemia was older than participants with normouricemia in females. Body mass index, Mean arterial pressure, and hemoglobin A1c, and estimated glomerular filtration rate (eGFR) were significantly associated with uric acid levels in both sex. Hyperuricemia was significantly associated with decreased FEV1 and FVC in females after adjustment for age, income, region, education, marital status, alcohol consumption, smoking, body mass index, mean arterial pressure, hemoglobin A1c, and eGFR (β = -0.143, P-value = 0.002 and β = -0.159, P-value = 0.001, respectively). There was no significant association between uric acid levels and lung function in males. After additional adjustment for respiratory disease including pulmonary tuberculosis, asthma, and lung cancer, hyperuricemia was associated with decreased FEV1 and FVC in females (β = -0.142, P-value = 0.001 and β = -0.161, P-value &lt; 0.001, respectively) <h3>Conclusion:</h3> Hyperuricemia was associated with decreased FVE1 and FVC in female general population. <h3> Disclosure of Interests:</h3> None declared
Cilia, mitochondria, and cardiac development
Authors: Bill Chaudhry, Deborah J. Henderson
Journal: Journal of Clinical Investigation (2019)

Motile cilia provide propulsion, and immotile ones are enriched with receptors. Both are required to establish left-right identity in the developing embryo and are also implicated in a wide range of human diseases. Abnormalities in cilial function underlie heterotaxy congenital heart disease (CHD) occurring in individuals with laterality disturbance. Mitochondrial function and cellular energetics, through mTOR and autophagy, are now linked with cilial function, revealing new mechanisms and candidate genes for syndromic human disease. In the current issue of the JCI, Burkhalter et al. ask the question: Can mitochondrial disturbances produce ciliopathy and does this explain some cases of heterotaxy?