tbuckley/cabot-search huggingface dataset:
Telomere length and its implication as prognostic marker in ovarian cancer patients.
Authors: David M. Atallah, Stephanie Antoun, Malak Moubarak, Nadine EL Kassis, Georges Y. Chahine, George Hilal
Journal: Journal of Clinical Oncology (2019)

e17055 Background: Telomeres are DNA structures protecting the linear ends of eukaryotic chromosomes against degradation and fusion, thereby maintaining genome stability. Telomerase is an enzyme that stabilizes the length of linear chromosomes by de novo synthesizing telomeric repeats during incomplete DNA replication, thus ensuring immortalization. This enzyme is expressed in 80% of cancers, including ovarian carcinoma. The human telomerase reverse transcriptase has been investigated as a detection marker for cancers in early stages, and a prognosis marker in late stages disease. The aim of this study is to investigate telomere length as a marker for survival and recurrence in ovarian carcinoma. Methods: 37 ovarian cancer biopsies have been isolated from Lebanese patients. The biopsies were subjected to DNA extraction, and then telomere length was assayed in cancer cells following the method elaborated by R. Cawthon (2002). The results obtained were expressed as ratios (36B4 is a single copy gene) Ct Telomere/Ct 36B4. Clinical data of each patient have been retrieved, including survival, recurrence, lymph node ratio, age, weight. Results: The results obtained revealed a direct relation between telomere length and survival. In fact, patients with shorter survival rates (less than 1 year) exhibited 30% longer telomeres compared with patients with longer survival rates (3 to 5 years). Moreover, recurrence rates increased with longer telomeres. Higher ratios (35%) were detected in patients with early recurrence (less than 1 year) compared to patients with late or absent recurrence. However, no direct effect between telomere length and the other parameters was spotted. Conclusions: telomere length could be used as a prognostic marker in patients with ovarian cancer by predicting better survival and lower recurrence in case of shorter telomeres. This will be of a great value when making therapeutic decisions in a heterogeneous and aggressive disease as ovarian cancer.
Association of pathologic non-complete response of axillary node with outcome after neoadjuvant chemotherapy in node positive breast cancer.
Authors: Shin-Cheh Chen, Hsien-Kun Chang, Yung-Chang Lin, Yung-Chang Lin, Shih-Che Shen, Wen-Lin Kuo, Chi-Chang Yu, Hsu-Huan Chou, Chia-Hui Chu, Yi-Ting Huang, Shir-Hwa Ueng
Journal: Journal of Clinical Oncology (2019)

e12101 Background: The pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) correlates with better outcome in specific subtype of breast cancer and the axillary nodal pCR (N-pCR) rate are more common than breast pCR (B-pCR). While only a few studies to compare the survival in terms of B-pCR and N-pCR, and no study compare between the outcome for those non pCR either in breast or axillary node. Methods: A cohort of 968 cytologically proved nodal metastatic breast cancer (cT1~4N1~2) received NAC in a single medical center between 2005~2017 were analyzed retrospectively. NAC regimen included anthracycline and taxanes in all patients, Trastuzumab was used in 308(70.3%) HER2(+) patients. The percentage of both breast and axillary pCR (T-pCR) 、B-pCR and N-pCR were compared in different subtypes. The impact of T-pCR、B-pCR and N-pCR to DFS and OS were analyzed using univariate and multivariate Cox proportional hazard model. Results: The median follow-up time was 45 months. The median age was 49 years old, average tumor size was 4.2cm, and 543 (56.1%) patients were N1 disease. 382(39.5%) patients were HR(+) HER2(-), 222(22.9%)were HR(+)HER2(+),216(22.3%) were HR(-)HER2(+) and 148(15.3%) were HR(-)HER2(-). After NAC, T-pCR was found in 213 (22.0%) patients, B-pCR and N non-pCR in 31 patients, N-pCR and B non-pCR in 245 patients and T non-pCR in 479 patients. N-pCR rate(47.3%) were significantly higher than B-pCR(25.2%) and this trend found in all subtypes ( P&lt;0.0001).The predicting factors of N-pCR were N1,HER2(+) and HR(-). In survival analysis the pCR (either T,B or N) patients had significantly better 5-year DFS and OS than non- pCR(T-pCR v.s T non-pCR, DFS,85.1% v.s 58.4%;OS,91.2% v.s 73.6%,p&lt;0.0001). B-non pCR had a significant better DFS than T non Pcr(65.1% v.s 58.4%,p=0.041) and non- significant. Cox better 5-year OS(78.9% v.s73.6%,p=0.059). Cox regression model demonstrated that T4,N2,grade 3, HR(-) and T non-pCR were poor prognostic factors in DFS and OS. Conclusions: The study demonstrated higher N-pCR rates than B-pCR in all subtypes after NAC, either T-pCR;B-pCR or N-pCR were associated with better outcome than non pCR. The worst outcome found in those T non-pCR or N non-pCR.
Патогенетические аспекты коморбидности хронического панкреатита и хронической обструктивной болезни легких
Authors: T.N. Hristich, D.O. Hontsariuk
Journal: GASTROENTEROLOGY (2019)

В обзоре литературы освещается вопрос участия некоторых механизмов в развитии коморбидного течения хронического панкреатита с хронической обструктивной болезнью легких. Внимание обращается на то, что общность механизмов развития может раскрыть суть адаптационных процессов или служить для их использования в разработке стратегии и тактики лечения, профилактики и реабилитации больных при полиморбидности с учетом индивидуального подхода. Авторы попытались осветить вопросы развития и прогрессирования заболеваний с точки зрения теории синтропических и интерференционных механизмов. С учетом данного подхода рассматривается значение окислительного стресса, хронического системного воспаления (в том числе С-реактивного белка в развитии инсулинорезистентности), эндотелиальной дисфункции, микроциркуляторных нарушений и гипоксии. Акцентируется внимание на том, что микроциркуляторные нарушения и гипоксия, а также влияние С-реактивного белка на формирование инсулинорезистентности можно трактовать в качестве транссиндромальных и интерференционных механизмов при коморбидном течении хронического панкреатита с хронической обструктивной болезнью легких. Это важно для тактики и стратегии лечебных и медицинских реабилитационных мероприятий, проводимых с пациентами, страдающими хроническим панкреатитом с хронической обструктивной болезнью легких, поскольку предотвращает полипрагмазию.
Assessing the risk of chemotherapy toxicity and hospital admission due to toxicity.
Authors: Samuel Robert Malton
Journal: Journal of Clinical Oncology (2019)

e14508 Background: Acute chemotherapy toxicity can have negative effects for the patient and the health economy. Finding overall toxicity incidence for a typical teaching hospital population proved difficult, although the 2008 report in to deaths within 30 days of chemotherapy found that 43% of patients who died reported a grade 3 or 4 toxicity 1 . At Nottingham University Hospitals (NUH) a Cancer Admissions and Triage Team was established, who undertake a proactive telephone toxicity assessment 24 hours following the administration of a first cycle of chemotherapy. This had the aim of reducing hospital admission due to toxicity through timely advice and intervention and allowed the accrual of data regarding reported toxicity. Methods: Data was obtained from the telephone assessment of acute toxicity 24 hours after administration of a first cycle of chemotherapy, once the service had been in use for 1 year. Descriptive statistics were produced to establish toxicity incidence and severity and hospital admission rates as well as length of stay. Regression modelling was used to identify predictors of the four outcome measures. The commonest toxicities were explored as secondary outcome measures. Results: 1539 patients were studied and the overall incidence of toxicity was 35.6%. Disease site and number of chemotherapy agents given were shown to predict toxicity, with breast and upper gastrointestinal cancers having a higher likelihood of toxicity. The more anticancer agents used, the higher the risk of toxicity. Disease was predictive of toxicity grade, with urology, gynaecology and lung patients experiencing higher grades of toxicity than other tumour sites. The rate of hospital admission due to toxicity was 13.1% and median length of stay 3 days. The risk of admission had some risk factors in common with toxicity. Disease and the number of drugs in the regimen affected the risk of admission, with gynaecology, head and neck and lung patients and patients who received 3 drugs having a higher likelihood of admission. No predictors could be reliably identified for length of stay. Predictors in the sub-groups of breast, lower gastrointestinal and lung cancers did not differ greatly from the whole population and the number of drugs was shown to be a predictor of nausea, vomiting and fatigue when explored as secondary outcomes. Conclusions: Predictors were identified for occurrence of toxicity, severity of toxicity, risk of hospital admission but not for length of stay. Sub-group analyses were undertaken. The overall burden of acute chemotherapy toxicity of a heterogeneous population was elucidated.
Pathologic complete response and serial circulating tumor cell monitoring during neoadjuvant therapy in nonmetastatic triple-negative breast cancer patients.
Authors: Carolyn S. Hall, Kenneth R. Hess, Elizabeth Ravenberg, Alyson Clayborn, Salyna Meas, Stacy L. Moulder, Alastair Mark Thompson, Anthony Lucci
Journal: Journal of Clinical Oncology (2019)

e12111 Background: ARTEMIS (A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival) is a randomized trial to determine if precision guided neoadjuvant chemotherapy (NAC) influences rates of pathologic complete response in the breast and axillary nodes (pCR). We hypothesized that blood circulating tumor cell (CTC) identification before and/or after NAC (just before surgery) would be associated with pCR in non-metastatic TNBC patients. Methods: Blood was assessed for CTCs at baseline (pre-NAC) and after NAC (post-NAC), as part of an IRB approved study, ARTEMIS (2014 – 0185/PA15-1050). CTCs (per 7.5 ml blood) were identified using the Cell Search System (Menarini Silicon Biosystems). Samples &gt; one cell having morphologic criteria for malignancy were deemed CTC+. Fisher exact test was used to evaluate associations between CTC detection and clinicopathologic characteristics, and Chi 2 test was used to analyze associations between CTC detection pre- and post- NAC, and pCR. Results: Fifty-nine patients had pre-NAC and 43 patients had post-NAC CTC assessments. One or more CTC was detected in 13/59 (22%) patients pre-NAC and in 16/43 (37%) of post NAC samples. CTC detection was not associated with patient stage, tumor androgen receptor expression, vimentin expression, Ki-67 staining, or tumor-infiltrating lymphocyte levels. Pre-NAC CTC detection was not (chi 2 P = 0.98), but post-NAC (chi 2 P = 0.0017) CTC identification was negatively associated with pCR. Conclusions: CTC detection post-NAC was negatively associated with pCR in non-metastatic TNBC patients. These findings warrant larger studies studying serial CTC detection throughout treatment to assess response to NAC.
Relationship between underlying causes of HCC and its complications.
Authors: Daniel Kyung, Stuthi Perimbeti, Bolanle Adepoju, Shaun Bryan Hanson, Michael Joseph McCormack, Kristine Marie Ward, Maneesh Rajiv Jain, Michael Styler
Journal: Journal of Clinical Oncology (2019)

e13123 Background: Hepatocellular carcinoma (HCC) remains the 4th leading cause of cancer mortality in the US. While mortality varies by stage, the presence of certain HCC-related complications contribute to increased mortality. In this study, we assessed whether the underlying cause for HCC influenced the frequency of common complications. Methods: The National Inpatient Sample between 1999 and 2014 was analyzed using ICD-9 codes. The ICD-9 code for HCC was used to extract all admissions from the years 1999-2014 and weighted to approximate the full inpatient population of the US over the 16 year interval. The prevalence of HCC-related complications were calculated for portal vein thrombosis (PVT), erythrocytosis, peritonitis, esophageal variceal bleeding (EVB), portal hypertension (Portal HTN) and hepatic encephalopathy (HE). Bivariate analysis using Chi square test was performed to compare the percentages of each complication with underlying risk factors for HCC (HBV, HCV, NASH and alcohol). Results: Total of 131,115 admissions (weighted = 648,732) was identified to have HCC. Conclusions: Portal HTN was the most common complication associated with HCV and NASH, whereas hepatic encephalopathy was most frequently seen with alcohol and PVT with HBV, respectively. Alcohol was associated with the highest rate of HCC-complications with the exception of portal vein thrombosis. HBV was associated with the lowest frequencies of complications except for PVT, for which it was the highest. Future studies might look at whether disease modifying measures such as cessation of alcohol and eradication of active HBV, HCV would impact the natural history of HCC.[Table: see text][Table: see text]
Addition of docetaxel or abiraterone to androgen deprivation therapy in metastatic castration-naive prostate cancer in South Asian population.
Authors: Neha Sonthwal, Shaik Maheboob Hussain, Devavrat Arya, Sandeep Batra, Harit Kumar Chaturvedi, Alok Gupta
Journal: Journal of Clinical Oncology (2019)

e16514 Background: Clinical trials have shown that addition of Docetaxel or Abiraterone to androgen deprivation therapy (ADT) achieves superior survival outcome in metastatic castration naive prostate cancer (mCNPC) in predominantly western population. We sought to evaluate treatment outcomes of adding Docetaxel or Abiraterone to ADT in South Asian population. Methods: 90 mCNPC patients who received treatment between January 2015 and June 2018 were prospectively followed. Diagnosis was established by TRUS guided prostate biopsy and staging was done by Ga 68 PSMA PET CT scan in all patients. Patients who were unfit for combination therapy received ADT alone. Patients diagnosed before June 2017 &amp; fit to receive chemo-hormonal therapy, received ADT+Docetaxel. Patients diagnosed after June 2017 and fit to receive combination were offered ADT+Docetaxel or ADT+Abiraterone and therapy selected based on patient’s choice. Monthly clinical evaluation and PSA measurement was done. Outcome measures analyzed included PSA decline &gt; 90%, serological complete response (PSA &lt; 0.2 ng/ml) and progression to CRPC. 76 patients with atleast 6 months follow-up were included in outcome analysis. Results: Patients received ADT alone (N = 37) or ADT+Docetaxel (N = 31) or ADT+Abiraterone (N = 22). Median age was 72, 64 &amp; 70 years, median PSA was 88, 95 &amp; 38 ng/ml, Gleason score was ≥8 in 57%, 71% &amp; 77% patients in ADT alone, ADT+Docetaxel &amp; ADT+Abiraterone group, respectively. Bone &amp; visceral metastasis were present in 62% &amp; 24%, 74% &amp; 26%, 68% &amp; 23% patients in ADT alone, ADT+Docetaxel &amp; ADT+Abiraterone group, respectively. Outcome analysis in 76 evaluable patients is shown in Table. Conclusions: ADT+Docetaxel &amp; ADT+Abiraterone achieve deeper serological response and reduced progression to CRPC compared to ADT alone in metastatic castration naive prostate cancer patients with South Asian ethnicity. Longer follow up is required to comment on overall survival and also to determine which combination (ADT+Docetaxel or ADT+Abiraterone) is superior to other, if at all.[Table: see text]
Clinical genomic profiling to identify actionable alterations for very early relapsed triple-negative breast cancer patients in Chinese population.
Authors: Ruoxi Hong, Zhai Qinglian, Zhongyu Yuan, Wen Xia, Fei Xu, Shusen Wang
Journal: Journal of Clinical Oncology (2019)

e13031 Background: Triple negative breast cancer (TNBC) represents about 19% of all breast cancers in Chinese population. Compared with other breast cancer subtypes, TNBC tend to be more aggressive and is associated with early relapse and worse survival. In this study, we performed comprehensive genomic profiling to explore the clinical relevant genomic alterations (CRGAs) and potential therapeutic targets in very early relapsed TNBCs, regarding as tumor recurrences within 24 months. Methods: Formalin-fixed paraffin-embedded (FFPE) tumor tissue specimens from 23 very early relapsed TNBC patients were tested by FoundationOne CDx (F1CDx), a next generation sequencing based diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB). Results: In total, 137 CRGAs were detected in all the 23 TNBC patients, averaging 6 alterations per sample. The mean TMB was 4 Muts/Mb, and only one patient was MSI-Intermediate. The top ranked altered genes were TP53 (83%), PTEN (35%), RB1 (30%), PIK3CA (26%), BRCA1 (22%), NOTCH1 (13%), MYC (13%) and CCND1 (13%). Notable co-segregating amplifications included KAS-KDM5A and FGF3-FGF4-FGF19. Importantly, we detected one patient with ERBB2 amplification and one patient with ERBB2 exon20 insertion, both of them were missed by immunohistochemistry (IHC). We also detected novel alterations of ROS1-EPHA7 fusion and EGFRvIVa in the first time, which has not been reported in breast cancer before. Furthermore, we also found EGFR amplification with copy number equal to 126 in one TNBC patient. In addition, 61%, 52%, 43%, 22% and 17% TNBC patients have at least one CRGA in pathways involving PI3K/mTOR, Cell cycle, DNA repair, Growth factor receptors (GFRs) and RAS/MAPK signaling pathways, respectively. Importantly, alterations in RAS/MAP tended to occur in very early-stage, such as IA-IIB tumors, and GFRs tended to occurr in IIIA-IIIC tumors. Furthermore, 100% of these patients have at least one CRGA and 87% patients have at least one actionable alteration. Conclusions: This study demonstrated that most of TNBCs have at least one actionable alteration. In conclusion, incorporating F1CDx into TNBC may shed light on novel therapeutic opportunities for these very early relapsed TNBC patients.
Single agent ONC201 in adult recurrent H3 K27M-mutant glioma.
Authors: Isabel Arrillaga, Sylvia Kurz, Ashley Sumrall, Nicholas A. Butowski, Rebecca A. Harrison, John Frederick De Groot, Nicole A. Shonka, Frank S. Lieberman, Yazmin Odia, Rohinton Tarapore, Krystal Merdinger, Joshua E. Allen, Wolfgang Oster, Minesh P. Mehta, Timothy Francis Cloughesy, Andrew S. Chi, Andrew B. Lassman, Tracy Batchelor, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2019)

3005 Background: H3 K27M-mutant glioma is associated with a poor prognosis and there is no effective therapy following radiation. We report the clinical experience with single agent ONC201, the first small molecule DRD2 antagonist in oncology, in adults with recurrent H3 K27M-mutant glioma. Methods: Twenty-nine adult patients with recurrent H3 K27M-mutant glioma have been treated with single agent ONC201 as of January 20, 2019: 19 patients on NCT03295396; 8 patients on NCT02525692; 2 patients on compassionate use protocols under the Sponsor’s IND. Median age was 57 years old (range: 17-74), median prior lines of therapy was 2 (range: 1-4) and all patients received prior radiation (median 8.5 months from radiation completion to ONC201 initiation). ONC201 was orally administered at 625 mg weekly, except for one patient dosed once every 3 weeks. Results: As of February 5, 2019, 13 of 29 patients remain on-trial within median follow up of 6.5 months (range: 0.6-33.6), 8 patients are alive but off-trial with median follow up of 2.4 months (range: 0.2-9), and 8 patients have expired. Nine of 29 patients (31%) remain progression-free on ONC201 with a median follow up of 6.5 months (range 0.6-33.6). No dose-limiting toxicities or treatment discontinuations due to toxicity occurred. Three patients have experienced durable partial responses by RANO (4.3-28.5 months). In addition, one patient experienced complete regression that continues for &gt; 14 months of all &lt; 1 cm tumor lesions that are not measurable by RANO. Furthermore, 10 patients had a best response of stable disease by RANO, 12 patients experienced progressive disease, and 3 patients are not yet evaluable. Among the patients with a best response of stable disease by RANO, one patient had &gt; 50% tumor regression in the basal ganglia that did not qualify as a partial response by RANO due to a new lesion on a confirmatory scan. Another patient with stable disease by RANO has had 37% tumor regression so far in the brainstem and remains on-treatment for 6 months. All tumor regressions remain durable to date and some were associated with improvements in disease-associated neurological symptoms. Conclusions: Single agent ONC201 is well tolerated and clinically active in adult recurrent H3 K27M-mutant glioma patients. Clinical trial information: NCT03295396; NCT02525692.
Case 40-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, David J. Wyler, Joan R. Butterton, Jana C. Sullinger
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 40-year-old man was admitted to the hospital because of fever, headache, and a rash.The patient was well until two days earlier, near the end of a two-week visit to St. Thomas in the Virgin Islands, when he awoke with a pruritic, erythematous rash over the proximal portions of the arms and legs that soon spread to the trunk, sparing the face, palms, and soles. That evening he returned to Boston on schedule in an airliner and began to experience pain around his waist, a bitemporal headache with mild photophobia, and fever and chilliness while en . . .
Clinical and molecular analysis of TAC3 and TACR3 genes in Brazilian patients with isolated hypogonadotropic hypogonadism
Authors: Cintia Tusset, Ericka Trarbach, Letícia Gontijo Silveira, Berenice Bilharinho de Mendonça, Margaret de Castro, Gil Guerra, Adriana Lofrano, Ana Claudia Latronico
Journal: Endocrine Reviews (2011)
SP0100 US OF THE HAMSTRING – CLINICAL APPLICATION + DEMO
Authors: David Andrew Bong
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Ultrasound of the Hamstring Muscle Complex-Clinical Application + DEMO The hamstring muscle complex (HMC) are the "brakes" of human bipedal ambulation and are susceptible to injury during concentric contraction. Although common in sports medicine practice, a recent systematic review of severe hamstring injuries (grade II-III) suggests that greater than 10% of these severe injuries are non-sports related and disproportionately affect older women. Musculoskeletal ultrasound (MSKUS) is one of the basic imaging techniques utilized to detect and define these injuries and eliminate other potential causes of posterior thigh pain. This presentation will discuss the clinical application of MSKUS of the HMC in rheumatology/musculoskeletal medicine and offer a systematic anatomically-based method of examining this important non-articular region. <h3>Disclosure of Interests:</h3> None declared