tbuckley/cabot-search huggingface dataset:
Colon cancer in patients below age of 50 years: Kuwait cancer control center eight years case series.
Authors: Mohamed Salah Fayaz, Heba El-Sayed Eissa, Gerges Attia Demian, Suzanne Samir, Thomas George, Sadeq Abuzalouf
Journal: Journal of Clinical Oncology (2015)

e14538 Background: This study was undertaken to analyze and evaluate the clinico-patholological profile and the outcome of young patients diagnosed with colon cancer, and to possibly raise the awareness of colon cancer in this population entity. Methods: A retrospective study was designed to review all patients under the age of 50 years with a diagnosis of adenocarcinoma of colon treated at the KCCC from January 2000 to December 2007. Results: One-Hundred thirty patients out of 600 registered colon cancer patients (nearly 22%) were found to be diagnosed below the age of 50. There were 67 females and 63 males. The median age was 43 years (range 24-50). The median follow-up was 61 months (range 5-170). The most common presenting symptoms were abdominal pain (74%), bleeding per rectum (28%), weight loss (17%), constipation (15%) and bowel obstruction (14%). Forty-eight percent of the tumors were located in the right colon, 6% in the transverse colon, 11% in the left colon and 35% in the sigmoid colon. According to the TNM system, 14 patients (10.7%) had T1 & T2 disease, 116 patients (89.3%) had T3 & T4 disease, 71 patients (54.6%) had node negative disease& 59 patients (45.4%) had node positive disease. Patients under the age of 40 years (83 patients) more often presented with T3 & T4 disease (96%). All patients except three underwent surgery. Chemotherapy was given in 106 patients either for adjuvant or palliative intent. Local recurrence was reported in 5 patients. Ten patients developed metastases while twenty patients were metastatic at diagnosis. The 5-year Overall survival (OS) and progression free survival (PFS) were 78% and 75% respectively. Survival was significantly worse in patients presented with positive lymph nodes (94% vs. 65%, P = 0.0005). Subset analysis for patients under age of 40 years showed that the 5-year OS and PFS were 70% & 67% respectively compared to those between 40-50 years which were 80% & 81% respectively with no statistical significance. Conclusions: We confirmed that more than 20% of our colon cancer patients diagnosed in the under 50 population. They also seem to present with higher T and N staging.
NOX5 as a therapeutic target in cerebral ischemic injury
Authors: Luciana Simão do Carmo, Bradford C. Berk, David G. Harrison
Journal: Journal of Clinical Investigation (2019)

In this issue of the JCI, Casas et al. define a previously unknown role of the NADPH oxidase catalytic subunit NOX5 in cerebral infarction. Using a mouse expressing human NOX5 in the endothelium, the investigators show that NOX5 is activated and plays a deleterious role in promoting edema, infarction, and ultimately, worsened neurological function following cerebral ischemia. They provide evidence that this is due to the breakdown of the blood-brain barrier (BBB) and that a unique pharmacological inhibitor of NOX5, ML090, if given early, around the time of reoxygenation, can maintain BBB integrity. Future studies of NOX5 inhibition in humans, particularly in the setting of thrombolysis, are warranted.
Correlation of Ki-67 expression and tumor response to induction chemotherapy (IC) containing cell cycle-specific agents in patients (pts) with head and neck squamous cell carcinoma (HNSCC).
Authors: Jon Chatzkel, James S. Lewis, Jessica C. Ley, Loren S. Michel, Tanya Marya Wildes, Jason Rich, Brian Nussenbaum, Douglas Adkins
Journal: Journal of Clinical Oncology (2015)

e17077 Background: We hypothesized that highly proliferative tumors, reflected by increased Ki-67 expression, may be more responsive to an IC regimen containing cell cycle-specific agents (taxane, antimetabolite, and EGFR inhibitor) used to treat HNSCC. Methods: 61 pts with HNSCC were treated with 3 cycles of IC followed by chemoradiation with cisplatin. Primary tumor site response (PTSR) was evaluated by visual assessment after 2 cycles of IC by experienced otolaryngologists. Two IC regimens were employed. The nab-paclitaxel-based group (APF-C: nab-paclitaxel, cisplatin, 5-FU, and cetuximab) included 29 pts and the docetaxel-based group (TPF-C: docetaxel, cisplatin, 5-FU) included 32 pts. Pts with a complete PTSR by visual assessment were classified as positive visual responders. Pts in the APF-C group also underwent FDG-PET/CT scans to assess PTSR which was assessed both categorically (as either Complete, Partial, stable, or progressive) and as the average percent change in up to three selected tumor target lesions (percent PET response). Pre-treatment tumor specimens were assessed for the percent of tumor cells staining for Ki-67 by IHC (percent Ki-67 staining as a continuous variable) by digital image analysis. Regression analyses were used to determine whether there was an association between percent Ki-67 staining and PTSR- visual, categorical PET response, percent PET response, or relapse status; p16+ oropharyngeal tumors were denoted with a dummy variable. Significance was assessed at the p < .05 level. Results: Percent Ki-67 staining was significantly associated with a high percent PET response (Odds Ratio [OR] for Ki-67 7.8, p = .02). However, percent Ki-67 staining was not significantly associated with categorical PET response (OR .14, p = .38), visual response (OR 1.1, p = 0.96), or relapse status (OR .16, p = .29). Conclusions: Although the link between percent Ki-67 staining and a high percent PET response is intriguing, the overall analysis argues against an association between Ki-67 expression and clinical outcomes following IC regimens containing cell cycle-specific agents.
Abstract 5789: Prevention of Peripheral Arterial Disease With Calcium Channel Blockers in Patients With Hypertension: A Meta-analysis of Randomized Trials
Authors: Harm H Feringa, Usha R Emani, Afrooz Ardestani, Shilpa Shetty, William N Pearson
Journal: Circulation (2009)

Background: Peripheral arterial disease (PAD) is a manifestation of atherosclerosis and associated with increased morbidity and mortality. Several preclinical studies suggest that calcium channel blockers (CCB) may prevent the development of atherosclerosis in high-risk patients. Aim : This study sought to evaluate the effect of CCB treatment for the primary prevention of PAD in patients with hypertension. Methods : We searched the published literature (MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE) for trials published after 1990 reporting the effect of CCB on the development of PAD. Criteria for inclusion included a study duration &gt;6 months, use of a randomized control group not receiving CCB, and availability of outcome data on PAD. We conducted a meta-analysis with random and fixed effects models to combine the results of these studies. Results: Of 2,006 potentially relevant studies, a total of 7 studies (65,925 patients) met our inclusion criteria. Patients randomized to the control group received either placebo or active treatment with ACE-inhibitors, beta-blockers or diuretics. In patients receiving CCB, 535 of 24,678 (2.2%) developed PAD versus 1,249 of 39,833 (3.1%) in the control group. CCB reduced the relative risk for PAD development by 25% (95% confidence interval 33% to 17%, p&lt;0.001). In the subset of 6 studies with 64,511 participants taking dihydropyridines vs control, dihydropyridines were associated with a significant risk reduction in PAD of 26% (95% CI 33% to 18%, p&lt;0.001). Conclusion: Based on the results of this study, calcium-channel blockers appear to be effective in the prevention of PAD in patients with hypertension.
Genetic screening for patients with pancreatic cancer: Frequency of high-risk mutations.
Authors: Jenny Geurts, Douglas B. Evans, Susan Tsai
Journal: Journal of Clinical Oncology (2015)

e12526 Background: There is currently no accurate test for the early diagnosis of pancreatic cancer (PC). In an effort to identify patients at high risk for the development of PC, we have integrated genetic evaluation into our PC program. Methods: All patients seen in our Pancreas Clinic over a 44 month period were reviewed by a team of surgeons, APPs, and a senior genetic counselor; those with a concern for hereditary cancer were offered genetic testing when appropriate. Results: A total of 114 patients with PC underwent detailed pedigree analysis and genetic counseling, of which 70 (61%) pursued gene testing. Genetic analysis identified 10 (14%) patients harboring a total of 11 different hereditary cancer gene mutations: ATM(4), BRCA2(1), CDKN2A(2), CHEK2(2), NBN(1), PALB2(1). An additional 13 (17%) patients were identified as having a genetic variant of uncertain significance. PC screening was offered to all family members who harbored a gene mutation. An additional 29 (48%) of the patients without mutations identified were members of families which fulfilled the clinical diagnosis of Familial PC; unaffected family members were also offered PC screening. Conclusions: Our data suggests a high yield for the identification of PC-associated mutations when surgeons partner with an experienced genetic counselor; in fact, the genetic diagnostic yield for hereditary PC was similar to that of hereditary breast cancer. Families with identified gene mutations are then provided opportunities for cancer prevention and early detection.
Parathyroid Function in Primary Osteoporosis
Authors: B. Lawrence Riggs, Claude D. Arnaud, Jenifer Jowsey, Ralph S. Goldsmith, Patrick J. Kelly
Journal: Journal of Clinical Investigation (1973)

Two major species of serum immunoreactive parathyroid hormone (iPTH) were measured in 47 untreated patients with primary osteoporosis by using two highly specific radioimmunoassays. Mean iPTH was normal with one antiserum but was lower than normal (P < 0.001) with the other, iPTH values did not correlate with biochemical parameters or with the proportion of bone-resorbing surfaces in iliac crest bone biopsy specimens. These data suggest that the increased bone resorption is not due to increased parathyroid function in most osteoporotic patients. However, seven of our patients (15%) appear to represent a separate population because they had increased values with one or the other of the antisera.
Keynote 057: Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG).
Authors: Arjun Vasant Balar, Girish S. Kulkarni, Edward M. Uchio, Joost Boormans, Loic Mourey, Laurence Eliot Miles Krieger, Eric A. Singer, Dean F. Bajorin, Ashish M. Kamat, Petros Grivas, Ho Kyung Seo, Hiroyuki Nishiyama, Badrinath R. Konety, Kijoeng Nam, Ekta Kapadia, Tara L. Frenkl, Ronald De Wit
Journal: Journal of Clinical Oncology (2019)

350 Background: The PD-1 inhibitor pembro has durable antitumor activity in pts with metastatic urothelial carcinoma. Upregulation of the PD-1 pathway has been observed in BCG-resistant NMIBC, suggesting pembro may benefit. Efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study; updated results for pts with carcinoma in situ (CIS) with or without papillary tumor (cohort A) are reported. Methods: Pts with histologically confirmed HR, BCG-unresponsive CIS with or without papillary disease, who received adequate BCG therapy and were unable/unwilling to undergo radical cystectomy received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Pts with HR NMIBC or progressive disease during treatment were required to discontinue. Primary end point: complete response rate (CRR); key secondary end points: duration of response and safety. Results: 103 pts (median age 73 years; CIS alone 71.8%; median number of prior BCG instillations 12) have enrolled in cohort A. 3-mo CRR rate was 38.8% (95% CI 29.4%-48.9%) by central assessment. Among 40 pts who achieved CR at 3 mo, 72.5% maintained CR at last follow-up (median 14.0 mo; range 4.0-26.3) and median CR duration has not been reached (range 0+ to 14.1+ mo). 80.2% of pts had a CR duration of ≥6 mo (Kaplan-Meier method). 10 (25.0%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle invasive or metastatic disease. Treatment-related adverse events (AEs) occurred in 65 (63.1%) pts; most frequent were pruritus (10.7%), fatigue (9.7%), diarrhea (8.7%), hypothyroidism (5.8%), and maculopapular rash (5.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.6%) pts; 1 death was considered treatment-related (colitis in patient inadequately treated with steroids). Immune-mediated AEs occurred in 19 (18.4%) pts. Conclusions: Pembro had encouraging activity in pts with HR, BCG-unresponsive CIS with or without papillary tumors and a safety profile consistent with that of previous experience. Updated data using additional follow-up will be presented. Clinical trial. Clinical trial information: NCT02625961.
Proliferation and Molecular Risk Score of Low Risk Myeloma Cells Are Increased in High Risk Microenvironment Via Augmented Bioavailability of Growth Factors
Authors: Syed J. Mehdi, Sarah K Johnson, Sharmin Khan, Wen Ling, Randal Shelton, Joshua Epstein, Frits van Rhee, Maurizio Zangari, Carolina D. Schinke, Sharmilan Thanendrarajan, Brian A Walker, Cody Ashby, Faith E. Davies, Gareth Morgan, Shmuel Yaccoby
Journal: Blood (2018)
Investigation of IMPDH2 overexpression in renal cell carcinoma (RCC) &amp; its association with oncologic outcomes.
Authors: Arun Sendilnathan, Ramya Krishna Velagapudi, Alejandro Marinos Velarde, Roman Jandarov, Zheng Zhu, Jaskirat Singh Randhawa, Kelsey Dillehay McKillip, Hirofumi Yoshino, Satoshi Kofuji, Koichi Okumura, Rand Naffouje, Matthew Koch, Xiang Ao, Kara Finley, Atsuo Sasaki
Journal: Journal of Clinical Oncology (2019)

594 Background: Approximately 40% of locoregional RCC patients relapse after nephrectomy leading to lower 5 year survival rates of 53% (stage III) &amp; 8% (metastatic). No biomarkers of prognostic significance are in clinical use at this time. It is important to identify biomarkers that can better inform clinicians the nature of disease &amp; personalize treatment. It is even better if the biomarkers are targetable with drugs. Inosine 5”-mono-phosphate dehydrogenase type II (IMPDH2), a rate limiting enzyme in the de novo guanine nucleotide biosynthesis is upregulated in many tumor types. Work by Sasaki laboratory showed increased GTP synthesis by IMPDH2 upregulation is important for cell growth, metastasis &amp; cell maintenance in Gliobastoma Multiforme cell lines. Hypothesis: We are investigating the feasibility of using IMPDH2 expression in RCC as a diagnostic &amp; prognostic biomarker. Methods: 45 cases of clear cell RCC (all stages) were identified by chart review. Slides reviewed to identify blocks with carcinoma, normal tissue &amp; interface. Tissue microarray (TMA) was constructed using the fully automated TMA Master. TMA sectioned and stained with H &amp;E &amp; IMPDH2 antibody. Staining interpretation: TMA stained with IMPDH2 were reviewed based on IRS scoring system (PP x SI) - percentage positive(PP) cells (Negative-0, ≤ 10% -1, ≥ 11%- ≤ 50%- 2, ≥ 51%-≤ 80% -3, and ≥ 81%-4) &amp; staining intensity (SI) (Negative-0, Weak-1, Moderate-2, and Strong-3). The scoring pathologist was blinded to the clinical data &amp; outcomes of patients. Results: Preliminary results show IMPDH2 is overexpressed in RCC and tumor-normal interface compared to normal kidney. Further analyses are ongoing if IMPDH2 overexpression correlates with pertinent clinical &amp; pathological variables including TNM stage, histologic grade (Fuhrman Grade) &amp; oncologic outcomes including overall survival (OS) &amp; risk of relapse. Conclusions: In the era of Sunitinib being approved as an adjuvant therapy (but not widely used due to lack of OS data), the above data will be important to verify if IMPDH2 can be used as a clinically useful test &amp; may give insight to future personalized &amp; targeted treatment strategies (IMPDH2 inhibitors like mycophenolate) for RCC.
Real-world treatment patterns, healthcare resource utilization (HRU), and costs of initial line of therapy (LOT1) in multiple myeloma (MM).
Authors: Stacey DaCosta Byfield, Tim Bancroft, Esprit Ma, Vijayveer Bonthapally, April H. Teitelbaum
Journal: Journal of Clinical Oncology (2015)

6603 Background: MM is the second most common hematologic malignancy in adults. Few studies have evaluated the economic impact associated with MM treatment. Methods: This retrospective study identified patients (pts) aged ≥ 18 yrs with ≥ 2 claims for MM (ICD-9 203.00) and ≥ 1 claim for anti-cancer systemic therapy (A-CST) in a large national US claims database between Jan 2008 and Aug 2013; first MM claim date was the index date. Pts required continuous enrollment (CE) in the health plan for 6 mos pre- and ≥ 6 mos post-index date ( < 6 mos if due to death), and no evidence of any cancers or A-CST in the pre-index period. Treatment patterns, HRU (inpatient, office, outpatient, and ER visits), and costs (drug and medical costs) during LOT1 were examined. LOT1 started with first A-CST; regimens included all agents received in the first 30 d. LOT1 ended at the earliest of: start of a new drug, ≥ 60-d gap after run-out of initial regimen drugs, death, or end of CE/study period (these censored LOTs were included). Results: Of 2053 pts, median age was 67 yrs (42% ≥ 70 yrs), 55% were male, and 638 (31%) had hematopoietic cell transplant (HCT) after LOT1 start. Median length of LOT1 was 4.3 mos (mean 6 mos). During LOT1, 96%, 90%, 43%, and 38% pts had ≥ 1 office, hospital outpatient, ER visit, and inpatient stay, respectively. Most common regimens were bortezomib ± dexamethasone (V±d, 25%), lenalidomide ±d (R±d, 17%), and VR±d (14%); in HCT pts, most common regimens were VR±d (25%), V±d (25%), and R±d (16%). Unadjusted per-pt per-month (PPPM) costs in HCT pts were $24,290 (SD $16,619; range $16,401–30,929 depending on initial regimen) and in non-HCT pts were $14,610 (SD $24,875; range $10,214–24,492). Drug and administration costs accounted for 37% of LOT1 costs and varied by initial regimen. 1-year costs after LOT1 initiation were $171,513 (SD $142,511; range $97,076–259,531). Adjusted (by initial regimen, pt characteristics, HCT, and baseline comorbidities) LOT1 costs were not significantly different with V±d and R±d; VR±d costs were higher vs V±d. Conclusions: HRU and costs were high during LOT1. Overall healthcare costs for LOT1 ranged from $10,214 to $30,909 PPPM depending on initial regimen and receipt of HCT.
Abstract P243: Impact of Menopausal Hormone Therapy on Association Between Heart Fat and Carotid Artery Atherosclerosis Progression in Recently Postmenopausal Women: the KEEPS Trial
Authors: Samar R El Khoudary, Vidya Venugopal, JoAnn E Manson, Maria M Brooks, Nanette Santoro, Dennis M Black, Mitchell Harman, Howard N Hodids, Eliot Brinton, Virginia M Miller, Hugh S Taylor, Matthew J Budoff
Journal: Circulation (2019)

Objective: Heart fat depots, within [epicardial adipose tissue (EAT)] and outside [paracardial adipose tissue (PAT)] the pericardium, have been linked to carotid atherosclerosis in various populations. Postmenopausal women have greater volumes of heart fat than premenopausal women. Our previous work suggests that lower endogenous estrogen may contribute to heart fat accumulation, although possibly limited to PAT, while postmenopausal oral hormone therapy (HT) may slow its progression. We evaluated the effect modification of HT use over 48 months on associations between heart fat accumulation and carotid artery intima-media thickness (CIMT) progression in recently postmenopausal women. Methods: The Kronos Early Estrogen Prevention Study (KEEPS) was a multi-center, randomized, double-blind placebo-controlled trial to investigate effects over 48 months of oral conjugated equine estrogens (o-CEE) and transdermal 17β-estradiol (t-E2), both given with cyclic progesterone, compared to placebo, on progression of CIMT in recently postmenopausal women. EAT and PAT volumes, and CIMT were measured at baseline and at 48 months. Associations between the absolute changes in heart fat volumes and CIMT as well as effect modification by HT type were tested using linear regression, adjusting for age, race, study site, employment status, diastolic and systolic blood pressure, anti-hypertensive medications, insulin resistance index, lipids, body-mass index, smoking, alcohol consumption, C-reactive protein, and adipokines. Results: Of 727 randomly assigned women, 467 [mean age (SD): 52.7(2.5); 78.2% Caucasian] had heart fat volumes and CIMT measured at both time points. Overall, changes in EAT and PAT were not associated with CIMT progression; however, assigned treatment significantly modified the association between changes in PAT, but not EAT, and CIMT progression in unadjusted model, P=0.04. In o-CEE group, CIMT progression was 0.028mm (SE:0.01mm) lower, per 1 unit increase in log PAT, than in t-E2 group, P=0.01, and trended 0.017mm (SE:0.01mm) lower than in placebo group, P=0.09. Although adjusted analysis attenuated these findings (P-value for interaction 0.09), differences between o-CEE and t-E2 groups remained significant, P=0.03. Conclusion: HT use modified the association between PAT accumulation, but not EAT, and CIMT progression. Our results suggest a potential beneficial impact of o-CEE (but not transdermal E2) on the relationship between adverse changes in PAT and CIMT. The current findings support the notion that EAT and PAT are distinct fat depots and suggest a complex role of HT in the association between heart fat and CIMT progression in recently postmenopausal women.
Brain networks require a network-conscious psychopathological approach
Authors: Achille Pasqualotto
Journal: Behavioral and Brain Sciences (2019)

Abstract In experimental psychology and neuroscience, technological advances and multisensory research have contributed to gradually dismiss a version of reductionism. Empirical results no longer support a brain model in which distinct “modules” perform discrete functions, but rather, a brain of partially overlapping networks. A similarly changed brain model is extending to psychopathology and clinical psychology, and partly accounts for the problems of reductionism.