tbuckley/cabot-search huggingface dataset:
A phase I/IIa study of the safety and efficacy of radium-223 chloride (Ra-223) with docetaxel (D) for castration-resistant prostate cancer (CRPC) patients with bone metastases.
Authors: Michael J. Morris, Hans J. Hammers, Christopher Sweeney, Marianne Bloma, Anne-Kirsti Aksnes, C. Gillies O'Bryan-Tear, Jorge A. Carrasquillo
Journal: Journal of Clinical Oncology (2012)

TPS4694 Background: Ra-223is a first-in-class alpha-pharmaceutical that targets bone metastases (mets) with high energy alpha-particles of short range (&lt; 100 μm). In the ALSYMPCA trial, Ra-223 plus best standard of care (BSC) significantly improved OS vs placebo plus BSC in CRPC patients (pts) with bone mets (Parker et al. ECCO/ESMO 2011), and was shown to have an excellent safety profile. Since D is an approved chemotherapy with demonstrated survival benefit for pts progressing after castrating hormone therapy, it is logical to explore combining Ra-223 plus D in pts with CRPC and bone mets. This study is being conducted in the Prostate Cancer Clinical Trials Consortium with an aim to establish the safe dose of Ra-223 and D when used in combination in pts with bone mets with CRPC. Methods: This ongoing phase I/IIa trial (NCT01106352) is enrolling pts with bone mets from CRPC intended for treatment with D. D naïve pts are preferred, although up to 10 previous infusions of D are acceptable if D was well tolerated and the patient is in good condition and fulfills all eligibility criteria at study entry. Phase I dose-escalation study: minimum of 9 pts (max. 18 pts) will be included if no dose limiting toxicity (DLT) is observed. Dose escalation will follow a ‘3+3’ design, with no intra-patient dose escalation or overlapping of cohorts permitted. Ra-223 doses are 25 or 50 kBq/kg, with number of Ra-223 injections (inj) (2, 4, 5, or 10) and interval between inj (3 or 6 wks) varying by escalation schema; D doses are 60 or 75 mg/m 2 q3wk. DLT will be assessed when 6 wks post-inj safety data are available after 1st Ra-223 +D inj. Phase IIa open-label expanded safety study: pts will be randomized 2:1 to the recommended dose of Ra‑223 to be used with D or to treatment with D alone (approx. 42 pts will be included). Primary endpoint is to assess safety of combining Ra-223 with D. Exploratory efficacy endpoints for the open-label expanded safety portion of the study include change in disease-related biomarkers, time to 1st radiological or clinical progression, CTC and pain assessment. Enrollment in dose-escalation portion of the study is complete; expanded safety cohort to begin enrolling in March 2012.
Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy
Authors: Chiara Maria Giulia De Luca, Antonio Emanuele Elia, Sara Maria Portaleone, Federico Angelo Cazzaniga, Martina Rossi, Edoardo Bistaffa, Elena De Cecco, Joanna Narkiewicz, Giulia Salzano, Olga Carletta, Luigi Romito, Grazia Devigili, Paola Soliveri, Pietro Tiraboschi, Giuseppe Legname, Fabrizio Tagliavini, Roberto Eleopra, Giorgio Giaccone, Fabio Moda
Journal: Translational Neurodegeneration (2019)

Parkinson's disease (PD) is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms. PD is characterized by intraneuronal accumulation of abnormal α-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of either α-synuclein, as in the case of Multiple System Atrophy (MSA) or tau, as in the case of Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP), in other disease-specific brain regions. Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization of α-synuclein or tau aggregates in the brain. Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues, including receptor neurons of the olfactory mucosa (OM).We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion (RT-QuIC) assay for OM analysis. In particular, by using human recombinant α-synuclein as substrate of reaction, we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induce α-synuclein aggregation, and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP.Our results showed that a significant percentage of MSA and PD samples induced α-synuclein aggregation with high efficiency, but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect. Notably, the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination.Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities for α-synuclein. Additional studies are required for (i) estimating sensitivity and specificity of the technique and for (ii) evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms. RT-QuIC analyses of OM and cerebrospinal fluid (CSF) can be combined with the aim of increasing the overall diagnostic accuracy of these diseases, especially in the early stages.
18F-THK5351 PET Can Identify Astrogliosis in Multiple Sclerosis Plaques
Authors: Kenji Ishibashi, Yoshiharu Miura, Kosei Hirata, Jun Toyohara, Kenji Ishii
Journal: Clinical Nuclear Medicine (2019)

Abstract A 26-year-old woman with relapsing-remitting multiple sclerosis (MS) underwent 18 F-THK5351 PET during a remission period. PET imaging showed that small regions with elevated uptake of 18 F-THK5351 were scattered in the brain and that the foci of 18 F-THK5351 accumulations corresponded anatomically to MS plaques identified by MRI. Because 18 F-THK5351 binds to monoamine oxidase B highly expressed in astrocytes, 18 F-THK5351 accumulates in lesions undergoing astrogliosis. Hence, elevated uptake of 18 F-THK5351 in the present case can represent ongoing astrogliosis in inactive MS lesions (plaques).
Identification of breast cancer (BC) patients (pts) fulfilling NCCN criteria for genetic risk assessment.
Authors: Georgios Lypas, Konstantina Papageorgiou, Georgia Georgiou, Menelaos Zoulamoglou, Nikolaos Tsoukalas, Georgios Zografos, Pavlos Papakostas, Vasileios Barbounis
Journal: Journal of Clinical Oncology (2013)

e12537 Background: Five to 10% of BC pts develop the disease due to an inherited predisposition syndrome; BRCA1/2 germline mutations are most commonly associated. NCCN guidelines help identify a somewhat broad group of pts requiring further genetic evaluation and a narrower one, for whom genetic testing is specifically recommended. Aims: The identification of pts requiring genetic guidance and the description of subgroups fulfilling NCCN criteria for genetic testing, according to family history (FH), demographic and clinical features, in a group of unselected Greek BC pts. Methods: This is a retrospective, medical records analysis of all histologically confirmed, unselected BC pts who who visited our department (Medical Oncology Unit, Hippocratio Hospital) between 2009 and 2012. Demographic, histopathologic and family history data was extracted and analyzed. Results: Among 690 pts eligible for analysis, 682 of which (98.8%) of Greek ethnicity, 233 (33.7% ) had a HER2+ subtype, 311 (45%) ER/PR+, and 69 (10%) triple-negative. Information was incomplete for the remaining 76 (11.1%). General criteria for furthr genetic evaluation were fulfilled by 301 patient (43.6%). Two hundred and eighty-six of them (41.44% ) were diagnosed with BC at age ≤50 and 15 (2.17%) at age older than 50; 12 (1.7%) had at least 2 close relatives with BC and 3 (0.43%) had a personal history of ovarian cancer (OC). BRCA1/2 testing criteria were fulfilled by 259 pts (37.5%). 172 (24.9%) were diagnosed at age ≤45. Seventy-five (10.8%) were diagnosed at age 46-50, 22 of which (3.1%) had one close relative with BC or OC and 16 (2.3% ) had two close relatives with BC or OC. Thirty-six pts (5.2%) with triple negative BC were diagnosed at age &lt;60, 16 of which (2.3%) &lt; 45 years old. No pts had a personal or FamHx of sarcoma, thus did not fulfill the relevant TP53 testing criteria. However 7 (1%) were diagnosed under age 30. Only 11 patients (1.6%) underwent genetic testing, revealing 5 (0.7%) carriers of a deleterious BRCA1 mutation. Conclusions: Almost half pts with BC require further genetic evaluation. The need for genetic counseling services and insurance coverage of genetic testing is highlighted by this study.
Off-Pump Versus On-Pump Bypass Surgery for Left Main Coronary Artery Disease
Authors: Umberto Benedetto, John Puskas, Arie Pieter Kappetein, W. Morris Brown, Ferenc Horkay, Piet W. Boonstra, Gabor Bogáts, Nicolas Noiseux, Ovidiu Dressler, Gianni D. Angelini, Gregg W. Stone, Patrick W. Serruys, Joseph F. Sabik, David P. Taggart
Journal: Journal of the American College of Cardiology (2019)
Randomized phase II study of preoperative concurrent chemoradiotherapy with or without induction chemotherapy with S-1 and oxaliplatin in patients with resectable esophageal cancer.
Authors: Dok Hyun Yoon, Geundoo Jang, Jong Hoon Kim, Yong Hee Kim, Seyoung Son, Jiyoun KIM, Seung-Il Park, Hyeong Ryul Kim, Hwoon-Yong Jung, Gin-Hyug Lee, Kee Don Choi, Ho June Song, Ho Young Song, Ji Hoon Shin, Kyung-Ja Cho, Sung-Bae Kim
Journal: Journal of Clinical Oncology (2012)

4093 Background: The value of adding induction chemotherapy (ICT) to preoperative chemoradiotherapy followed by surgery has not been delineated well. Methods: Patients with stage II, III or IVA (by AJCC 6 th ed.) esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m 2 on day 1 and S-1 at 40 mg/m 2 bid on days 1-14, every 3 weeks), followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/day with oxaliplatin 130 mg/m 2 on day 1 and 21 and S-1 30 mg/m 2 bid, 5 days/week during radiotherapy) and surgery (arm A, n=48), or the same chemoradiotherapy followed by surgery without ICT (arm B, n=49). Primary outcome was to compare pathologic complete response (pCR). Results: Thirty six and 35 patients underwent surgery with or without ICT, respectively. pCR rate among those who underwent surgery was significantly lower in arm A (30.6% vs. 54.3%, p=0.043). However, no difference in progression-free survival (PFS) and overall survival (OS) was observed with a median follow-up of 19.5 mo (95% CI, 19.1-22.4). Two-year PFS rate was 63.8% in arm A and 55.2% in arm B (p=0.626) and 2-year OS rate was 70.1% and 62.6%, respectively (p=0.515). While 47 (arm A) and 48 (arm B) patients received at least 44 Gy of radiotherapy, relative dose intensity (RDI) for oxaliplatin during CCRT was significantly lower in arm A vs. arm B (92.7% ± 19.6% vs. 99.7 ± 1.8%, p=0.017). RDI for S1 did not significantly differ (94.1% ± 17.3% vs. 98.5% ± 5.9%, p=0.095). G3/4 thrombocytopenia was significantly common in arm A (37.5% vs. 4.1%, p &lt;0.001), which contributed to lower RDI of oxaliplatin. Three patients in arm A, compared to none in arm B, failed to survive for 90 days after surgery. Conclusions: Adding this ICT to preoperative chemoradiotherapy seems to cause lower pCR rate and higher toxicity during CCRT.
Eomes+ T-betint CD8 T Cells Are Functionally Impaired and Associate with Primary Refractory Disease in Patients with Acute Myeloid Leukemia (AML)
Authors: Bei Jia, David F. Claxton, W. Christopher Ehmann, Witold B. Rybka, Shin Mineishi, Liru Wang, Todd D. Schell, Raymond J. Hohl, Hong Zheng
Journal: Blood (2017)
The association of tissue and serum adiponectin levels with the parameters of insulin-resistance in breast cancer patients
Authors: M. Seker, F. Y. Erkal, A. Bilici, T. Salman, B. O. Ustaalioglu, M. Karaduman, B. Sonmez, C. Gezen, M. Gumus, M. Yaylaci
Journal: Journal of Clinical Oncology (2009)

e22172 Background: Adiponectin is a novel adipocyte-secreted proteine and associated with insulin-resistant (IR) status, such as type 2 diabetes mellitus and obesity. The inverse correlation between serum adiponectin levels and breast cancer risk was previously documented. Moreover, the association of high tissue adiponectin levels with breast cancer has been recently reported. In the present study, the relationship among tumor, normal breast tissue and serum adiponectin levels, breast cancer, and the other IR parameters were evaluated. Methods: Fifty-three patients with diagnosed and histologically confirmed breast cancer were included in our study. We analyzed the correlation among the levels of normal and tumor breast tissue adiponectin and serum adiponectin levels. In addition, the association of tissue and serum adiponectin levels with the various classical risk and IR factors, such as body mass index, menopausal status and, tumor size, stage, lymph node status, hormonal status were also studied. Results: Tumor tissue adiponectin levels (56 ± 9.6 ng/ml) were similar with normal breast tissue (56 ± 10 ng/ml) (p&gt;0.05). However, the serum adiponectin levels were significantly lower compared with both normal and tumor tissue (p&lt;0.05). In addition, the inversely association of serum adiponectin levels with tumor tissue adiponectin levels was detected (p=0.001). The inverse correlation between T stage and tumor tissue adiponectin was found (p=0.03). The levels of serum adiponectin were significantly more higher in patients with c- erb-B2 overexpressed (p=0,008). Both nuclear and histologic grade were significantly associated with serum adiponectin levels (p=0.04,p=0.04, respectively). On the other hand, the reverse relationship between nuclear grade and, both tumor (p=0.01) and normal tissue (p=0.009) adiponectin levels was also detected. In subgroup analysis, the correlation among demographic, clinicopathologic, IR parameters, tissue and serum adiponectin levels was not found (p&gt;0.05). Conclusions: Our results suggest that the low serum adiponectin and high normal and tumor tissue adiponectin levels detected in breast cancer patients and serum adiponectin levels inversely associated with tumor tissue adiponectin levels. No significant financial relationships to disclose.
An update on gemcitabine, rituximab, and oxaliplatin in combination for relapsed/refractory non-Hodgkin lymphomas.
Authors: Robert M. Crescentini, Kendra Lynn Sweet, Jijun Liu, Idalia Liboy, Samir Dalia, Julio C. Chavez, Celeste M. Bello, Lubomir Sokol, Eduardo M. Sotomayor, Fernando Cabanillas, Jennifer L. Cultrera
Journal: Journal of Clinical Oncology (2012)

8084 Background: Relapsed/refractory non-Hodgkin lymphomas (NHL) have no standard of care. A variety of salvage chemotherapy options are available. We previously reported results of our phase II trial using gemcitabine, rituximab and oxaliplatin (GROC) in the salvage setting for relapsed/refractory NHL in which we observed an overall response rate of 58% with an incidence of grade 3-4 thrombocytopenia of 9% and neutropenic fever of 3.5%, but no grade 3-4 non-hematologic toxicities. Here we update progression free survival (PFS) and overall survival (OS) data. Methods: This phase II, single-arm, multicenter study evaluated safety and efficacy of GROC in patients with relapsed/refractory NHL. Patients were treated on a 14 day cycle. On day 1, patients with CD20+ NHL received rituximab (375 mg/m 2 ). On day 2, patients received gemcitabine (1000 mg/m 2 ) and oxaliplatin (100 mg/m 2 ). Granulocyte colony stimulating factor was given. Stem cell transplant (SCT) was considered after a minimum of 6 cycles. Results: A total of 58 patients were enrolled from the H. Lee Moffitt and the Auxilio Mutuo Cancer Centers. Ages ranged from 24 to 88 years (median 72 years). The majority of patients had an ECOG performance status of 0-1 (89%). Lymphoid neoplasms included large B-cell (79%), follicular (7%), lymphoblastic (1.8%), Burkitt (1.8%), primary mediastinal large B-cell (3.5%), and peripheral T-cell lymphoma (7%). Eighty-one percent of patients had stage III-IV disease, median IPI was 3, 40% had B-symptoms, 43% had bulky disease and 74% had an elevated LDH. Anthracycline-based therapy had been used in 91% of patients and 66% had received rituximab. Median PFS was 134 days (95% CI 115-153) and median OS was 296 days (95% CI 164-428). No difference in response was observed based on age &gt;60, IPI, LDH or albumin levels. Prior therapy with rituximab (p=0.02) and initial response to front-line therapy (p=0.04) appear to correlate with improved outcomes. Nine patients went on for SCT. Conclusions: GROC is a useful salvage regimen for relapsed/refractory NHL with minimal toxicities and good clinical efficacy. Several patients were able to be successfully mobilized, collected and transplanted post GROC therapy.
Long-Term Interactions with Bone Marrow Stromal Cells Alter the Molecular Dependencies of Myeloma Cells: Insights from Genomewide CRISPR-Based Functional Genomic Screens
Authors: Sara Gandolfi, Olga Dashevsky, Ricardo De Matos Simoes, Geoffrey Matthews, Ryosuke Shirasaki, Michal Sheffer, Constantine S. Mitsiades
Journal: Blood (2017)
David Oliver: Fighting phantom policies in hospitals
Authors: David Oliver
Journal: BMJ (2019)

Much has been written about the informal “hidden curriculum” in clinical training that can influence our behaviours, perceptions, and values.12 Hospital medicine has a parallel problem of hidden or “phantom” policies, which aren’t formally written but become accepted custom and practice.

I’m aware of this from working in older people’s acute care, but readers in other specialties will have their own bugbears. This is no exhaustive list, but I’ll give some examples.

Contrary to popular belief, patients discharging themselves against medical advice (for whatever reason) can still be offered transport and medication. And people who aren’t self discharging shouldn’t have to wait for medicine to be dispensed before they leave the ward if someone can pick it up later or it can be sent after them.

Despite a regulatory impetus for patients to be reviewed by a senior clinician,3 it’s not the case on clinical …
Stereotactic hypofracionated radiotherapy for prostate cancer patients.
Authors: Monika Rucinska, Marta Stefanczyk, Joanna Minczewska, Sergiusz Nawrocki
Journal: Journal of Clinical Oncology (2013)

e16097 Background: 3D conformal radiotherapy (78Gy in 2Gy per fraction) is the standard treatment for prostate cancer patients. It is a very long treatment, not comfortable both for patients and radiotherapy departments. Stereotactic radiotherapy has recently been recognized as an alternative technique. Prostate cancer has probably a low α/β ratio (1.5Gy) and 33.5Gy in 5 fractions has the predicted efficacy of 78Gy in 39 fractions. The objective of the study was to investigate the effectiveness and safety of stereotactic radiotherapy for localized prostate cancer. Methods: This is a prospective one-center clinical study. The treatment was done with IMRT. PTV received 33.5Gy in 5 fractions twice a week. Three gold fiducial markers were placed in the prostate under transrectal ultrasound guidance for image-guided positioning and motion tracking. Treatment planning CT and MRI scans were performed. IMRT plans were done. Before each treatment MV Cone Beam CT and portal imagines for markers were performed. Results: In this analysis 32 patients were included (age 65-83 years, median 73 years) with localized low- and intermediate-risk (according to NCCN) adenocarcinoma of prostate T2-T3N0M0. Combined Gleason scores were 5 to 7, the prostate-specific antigen (PSA) was 4.7-20.0ng/ml (median 10.2ng/ml). The median prostate volume calculated during treatment planning (on CT and MR) was 40.5cc (15.8cc to 113.6cc). Acute genitourinary toxicity Grade 1–2 was observed in about 50% patients and only Grade 1 acute gastrointestinal toxicity in 25% patients. No Grade 3 or higher toxicity was reported. Only 3 patients reported rectal bleeding after radiotherapy (Grade 1 late toxicity). PSA level were systematically decreased to 1.08ng/ml 3 months, 0.91ng/ml 6 months and 0.56ng/ml 9 months after treatment end. Conclusions: Stereotactic hypofractionated radiotherapy for prostate cancer patients is an effective and safe treatment in short term analysis.
Health-related quality of life in family members of cancer survivors: A comparison with general population norms.
Authors: Sun Min Lim, Hyeon Chang Kim, Soohyeon Lee
Journal: Journal of Clinical Oncology (2012)

e16529 Background: Family caregiver burden is emerging as an important issue as number of cancer survivors increase. We hypothesized that presence of cancer survivor may influence the health-related quality of life (HRQL) of family members. Thus, we examined the HRQL of family members with cancer survivors in comparison with general population norms. Methods: Using the Fourth Korea National Health and Nutrition Examination Surveys (KNHANES IV) (2007–2009) data, we performed matching analysis to compare characteristics of cancer family vs. non-cancer family. The primary outcomes were EQ-5D and EQ-visual analogue scale (VAS) scores and generalized linear model was used. Results: Compared with general population norms, cancer family members were less employed (57.9% vs. 63.0%, P&lt;0.001) and had higher functional limitation (20.2% vs. 16.5%, P=0.032). Moreover, cancer family members had higher level of stress (70.5% vs. 65.4%, P=0.008) and history of depression (12.9% vs. 10.2%, P=0.035). The mean EQ-5D and EQ-VAS scores were similar between the two groups. In multilevel models, EQ-5D was significantly associated with household income and education level (all P&lt;0.001). EQ-VAS was associated with presence of cancer survivor (β=3.393, 95% confidence interval [CI] 1.018~5.769, P=0.052) along with household income (β=3.815, 95% CI 0.662~6.696, P=0.018), education level (β=5.663, 95% CI 2.663~8.662, P&lt;0.001), employment status (β=5.624, 95% CI 2.858~8.390, P&lt;0.001), functional limitation (β=-10.83, 95% CI -13.509~-8.151, P&lt;0.001), and level of stress (β=-4.555, 95% CI -7.030~-2.080, P=0.003). Conclusions: EQ-VAS was significantly associated with presence of cancer survivor in a family. More attention should be given to family caregivers of cancer survivors and dynamic approaches to evaluate cancer survivorship and its influence on family members are required in the future.
A painful shoulder after a seizure
Authors: Tobenna Jerris Oputa, Ronnie Davies
Journal: BMJ (2019)

A 25 year old man presented to the emergency department with pain and reduced movement in his left shoulder following a generalised tonic clonic seizure. He had no medical history and no history of seizures. On examination, his level of consciousness was 15/15 on the Glasgow coma scale, and he had no neurological abnormalities. His left shoulder was notably deformed, with a posterior prominence, anterior flattening, rounding of the shoulder, and prominence of the coracoid process anteriorly. He held his left arm in internal rotation at the …