tbuckley/cabot-search huggingface dataset:
Pilot evaluation of PD-1 inhibition in metastatic cancer patients with liver transplantations (LT): The Mayo Clinic experience.
Authors: Thomas DeLeon, Marcela Salomao, Bashar A. Aqel, Mohamad B. Sonbol, Alan Haruo Bryce, Mitesh J. Borad
Journal: Journal of Clinical Oncology (2018)

328 Background: Patients with a history of solid organ transplants have been excluded from PD-1/PD-L1 inhibitor clinical trials due to concern for graft rejection. Only 2 case reports of PD-1 inhibitor use in patients with liver transplantation (LT) have been reported thus far. Here, we report our experience with using checkpoint inhibitors in metastatic cancer patients with LT. Methods: A single center pilot evaluation was conducted to evaluate the safety and efficacy of PD-1/PD-L1 inhibitors in patients with LT. PD-L1 staining on both the tumor and allograft were assessed if there was available tissue. The primary endpoint was evaluation of the risk for allograft rejection. Secondary endpoints included RECIST v1.1 and Immune-Related Response criteria (iRC) response rates, progression free survival (PFS) and overall survival (OS). Translational objectives included the relationship of PD-L1/PD-1 staining of tumor/allograft with response and rejection. Results: Six metastatic cancer patients with a history of LT received PD-1 inhibitor therapy (hepatocellular n=5, melanoma n=1). 3 patients were on mTOR inhibitor as immunosuppressive regimen and 3 on calcineurin inhibitor. Overall, allograft rejection was observed in 1/6 patients (on mTOR inhibitor). One patient achieved a CR (melanoma), 3 patients had PD and 2 patients discontinued therapy prior to restaging assessments. A single response (by both RECIST v1.1 and iRC) and rejection were reported in patients who received mTOR inhibitors (1 of 3). Three patients were tested for PD-L1 staining in the allograft tissue and all of them were negative (0% staining) with no graft rejections observed. Four patients had tumor PD-L1 evaluated (2 patients tested positive with 1 patient obtained a CR). The median OS, PFS and duration of therapy were 1.2, 1.8 and 1.2 months respectively. Conclusions: In this pilot evaluation of PD-1/PD-L1 inhibitors in LT patients both preliminary efficacy (1 of 4) and allograft rejection (1 of 6) was exhibited. Larger, prospective trials are needed to elucidate optimal patient and immunosuppressive regimen selection in these patients.
I have been selected for a fellowship in spinal surgery in a prestigious institute in New York for a year. This won't fit into my present curriculum of spinal injuries and rehabilitation. But I don't want to give it a miss or lose my NTN either. Can I take a sabbatical and if so who has to sanction it?
Authors: Sabina Dosani
Journal: BMJ (2007)

Have a career related problem that needs answering? Can9t find the person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site <b>www.bmjcareers.com/advicezone</b>
Abstract P1-01-03: Preclinical evidence that distant metastases occur via the lymphatic route
Authors: PL Leslie, SK Ghosh, A Porrello, BC Cooley, CV Pecot
Journal: Cancer Research (2018)

Abstract Cancer that metastasizes beyond the lymph nodes is almost invariably terminal. Therefore, understanding how cancer metastasizes is a critical aspect to understanding and eventually preventing cancer spreading from tissue to tissue. A major question that remains controversial is whether cancer cells that metastasize to the LNs are able to physically leave the LNs to colonize distant tissues. Moreover, whether cancer cell metastasis between different tissues involves unique genes is a question that requires further research. Using the metastatic mouse breast carcinoma line 4T1 in an LN microinjection model, we provide evidence suggesting that cancer cells can indeed metastasize and colonize distant tissues after direct implantation into the LNs. Interestingly, direct comparison of distant tissue metastatic capability comparing LN-microinjected cells and tail vein-injected cells suggests that the lymphatic route of cancer cell spreading may be a more efficient mechanism of metastasis than the hematogenous route. Moreover, our comparative transcriptome analysis results suggest that LN metastases show unique gene expression profiles relative to the primary breast tumors and distant metastases. We identified several genes that are up- or down-regulated in an LN-specific manner and thus may play a role in metastasis to the LNs and beyond. Collectively, our results suggest that LN metastases constitute an active “staging site” from which breast cancer cells can further metastasize to distant sites. Furthermore, we identify a unique set of genes that may be involved in the breast cancer metastatic process, several of which are potentially targetable using currently available inhibitors. Citation Format: Leslie PL, Ghosh SK, Porrello A, Cooley BC, Pecot CV. Preclinical evidence that distant metastases occur via the lymphatic route [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-03.
Long-term outcomes of liver transplantation (LT) for the treatment of neuroendocrine liver metastases (NELM): The Mayo Clinic experience.
Authors: Mohamad Bassam Sonbol, Matthew Buras, Daniel H. Ahn, Mitesh J. Borad, Gregory J. Gores, Amit Mathur, Julie Heimbach, Thomas DeLeon, C.Burcin Taner, Thorvardur Ragnar Halfdanarson, Timothy J. Hobday, Ramesh K. Ramanathan, Kabir Mody, Chee-Chee H. Stucky, Mark J. Truty, Adyr A Moss, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2018)

355 Background: In this study, we sought to determine the prognostic factors impacting survival of patients with NELM who underwent LT at Mayo Clinic. Methods: We performed a three-site retrospective analysis of patients with unresectable NELM treated with LT from 1990 -2017. Cases were identified from clinical databases at Mayo Clinic. Data on demographics, timing of diagnosis and transplant, extent of liver involvement, and tumor grade, were extracted. Extent of liver involvement was calculated using previously validated standardized volumetry with high defined as &gt; 25% increase in the weight of the extracted liver at the time of the transplant as compared to the standard liver volume. Survival was calculated using the Kaplan–Meier method. Results: We identified 37 patients. Median age at LT was 47 (range 17.0-64.0), male: female (73% vs. 27%, respectively). Primary tumor site was in the pancreas in 51.3% and in the small bowels in 43.2%; 78.4% had NELM at presentation. While primary tumor resection was done at the time of LT in 5 (13.9%) cases, most patients (80.6%) had ˃6-months interval between primary tumor resection and LT surgery. Prior to LT, 25 (74.3%) patients received somatostatin analogues and 18 (61.3%) had liver-directed therapy. Median time from diagnosis to transplant was 33.6 months (0-246). High extent of liver involvement was identified in 12 patients (33.3%). Disease-Free Survival (DFS) at 3, 5, and 10 years was 56.8%, 43.1%, and 22.4% respectively. Overall-survival (OS) at 3, 5, and 10 years was 86.9%, 79.6%, and 52.6% respectively. High extent of liver involvement at the time of transplantation was associated with inferior DFS and OS and patients˃45 years-old at the time of transplantation had worse DFS. Patients whose disease met the OPTN (Organ Procurement and Transplantation Network) criteria for NELM transplantation had significantly better DFS and OS with median 10-year OS of 80.7 % vs. 17%. Conclusions: LT is a reasonable therapeutic option for selected patients with unresectable NELM with 10-year OS of 52.6%. High extent of liver involvement was associated with worse long-term outcomes while meeting OPTN criteria resulted in best outcomes.
P023 Smoking is associated with low serum levels of soluble PD-l1 in rheumatoid arthritis
Authors: C Wasén, M Erlandsson, A Bossios, L Ekerljung, C Malmhäll, S Töyrä Silfverswärd, R Pullerits, B Lundbäck, MI Bokarewa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Smoking is a risk factor for the development of rheumatoid arthritis (RA) and associates with positivity for disease specific anti cyclic citrullinated peptide (aCCP) antibodies. It is not known exactly how smoking promotes autoimmunity but we have previously demonstrated that smoking limits the expression of the T cell co-inhibitory receptor programmed death-1 (PD-1).<sup>1</sup> <h3>Objectives</h3> To investigate if smoking can interfere with the interaction between PD-1 and its ligand by influencing the serum levels of soluble PD-1 ligand 1 (sPD-L1). <h3>Methods</h3> Serum samples were collected from 254 RA patients and 168 healthy controls with known smoking status and analysed with ELISA for levels of sPD-L1 and inflammatory cytokines IL-6 and IL-1b. Fc-receptor mRNA expression analysis of peripheral blood monocytes (PBMC) from a group of 10 healthy controls and 15 RA patients was done by qPCR. <h3>Results</h3> In RA patients current smokers had 5 times lower median serum levels of sPD-L1 compared to never smokers (p=0.027). This difference persisted in former smokers that quit smoking &lt;25 years ago (p=0.0086). Expectedly, sPD-L1 were associated with high serum levels of inflammatory markers IL-6 (over 5.5 pg/ml, p=0.0006) and IL-1b (over 4 pg/ml, p=0.0005), however the level of these markers was not affected by the smoking status of the patients. We found 14 times lower sPD-L1 levels in smoking RA patients that did not receive TNF-inhibitors (p=0.0092), but treatment with TNF-inhibitors normalised levels of sPD-L1. Furthermore, aCCP positivity in RA patients was associated with higher levels of sPD-L1 (p=0.0036). We speculate that the presence of antibodies might influence the levels of sPD-L1 through the stimulation of Fc-receptors expressed by PD-L1 producing cells. In PBMC depleted of T cells, we saw that smokers had lower mRNA expression of the stimulatory FcgRIIIA (p=0.028) and predominance of the inhibitory FcgRIIB in the FcgRIIB/FcgRIIIA ratio (p=0.0004). <h3>Conclusions</h3> Smoking decreases the serum levels of the inflammation limiting protein sPD-L1, but levels were restored by treatment with TNF-inhibitors. aCCP positive RA patients had higher levels of sPD-L1, possibly due to activation of Fc-receptors expressed by PD-L1 producing cells. <h3>Reference</h3> . Wasén C, et al. J Autoimmun2017. <h3>Disclosure of interest</h3> None declared
Abstract ES1-3: Advanced technologies to optimize outcomes and minimize toxicities
Authors: R Jagsi
Journal: Cancer Research (2018)

Abstract Advances in radiation technology offer substantial promise for improving the therapeutic ratio in breast cancer management, both by improving tumor control and by reducing toxicity. Multiple historical randomized trials and their meta-analysis have demonstrated that the benefits of radiation therapy have been accompanied by toxicity to incidentally irradiated structures, including the heart. However, the past two decades have witnessed a dramatic revolution in technological capabilities to allow greater sparing of normal tissues while simultaneously improving the ability to identify and target areas at greatest risk. Intended for the general audience, this presentation will provide an overview of transformative technological advances in radiation oncology in recent years, including three-dimensional conformal treatment planning, intensity modulation, prone positioning, and devices that allow reproducible deep inspiration to facilitate cardiac sparing. It will review the evidence from historical trials that have established the importance of minimizing dose to normal tissues and the heart in particular, as well as more recent data demonstrating excellent dose distributions and promising outcomes with new technologies, motivating their increased utilization. The presentation will include consideration of advances such as the development of contouring atlases to facilitate greater consistency and quality of care. It will also reflect on cost considerations and concerns about rapid uptake of certain technologies prior to studies establishing evidence of benefit, along with a description of ongoing endeavors to assess value. After summarizing new professional society guidelines on whole breast irradiation, it will identify the current consensus recommendations regarding the most appropriate uses of technology to optimize outcomes of whole breast and boost radiotherapy in the modern era. Finally, it will close with a mention of ongoing and future trials evaluating the potential role of even more advanced technologies, such as proton therapy, true inverse-planned intensity modulated radiotherapy, and stereotactic body radiotherapy, in the management of breast cancer. Citation Format: Jagsi R. Advanced technologies to optimize outcomes and minimize toxicities [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES1-3.
How many lives are at stake? Assessing 2030 sustainable development goal trajectories for maternal and child health
Authors: John W McArthur, Krista Rasmussen, Gavin Yamey
Journal: BMJ (2018)

<b>John W McArthur</b>, <b>Krista Rasmussen</b>, and <b>Gavin Yamey</b> examine how far countries have to go to meet the targets for maternal and child mortality and what needs to be done to help them
Working with midwives (a midwife's view)
Authors: Nicola Miller
Journal: BMJ (2005)

Midwives working in a hospital environment practise in two distinct ways—as autonomous professionals striving to offer women a positive maternity experience with minimal intervention, and as companion professionals to obstetricians, who are invited to review patients when the midwife feels labour isn't going “normally.” Where appropriate the midwife will then take responsibility for delivering the obstetrician's plan …
FDG PET/CT and N0 mediastinal nodal status in early stage non-small cell lung cancer: A single institution retrospective experience.
Authors: Shashank Reddy Cingam, Sean Connor, Abhishek Harshad Patel, Samip R. Master, Amol Takalkar
Journal: Journal of Clinical Oncology (2017)

11570 Background: The increasing use of CT and now low-dose screening CT scans for at-risk patients have led to increasing detection of lung cancer at early stages. FDG PET/CT is used as an adjunct to conventional imaging to assess loco-regional lymph node spread. However, there is a potential for false-negative results, especially in smaller lesions or early nodal involvement. The main objective of this study was to study the value of PET/CT scan to evaluate for true negative mediastinal nodes in patients with early stage NSCLC. Accurate determination of N0 status can have a significant impact on the cost-effectiveness and timely management of early stage NSCLC. Methods: Of a total of 404 patients with NSCLC managed at our facility between 2008 to 2015, 29 adult patients whose PET scan showed no or equivocal mediastinal nodal involvement and subsequently underwent surgical exploration of mediastinal lymph nodes were included in the study. Data variables that were collected included the cancer site, date of PET, node status on PET, type and date of surgery, cancer histology, and the tissue diagnosis of the sampled nodes. SAS software was used for the analysis of the data. Results: Of the 29 patients with N0 or equivocal nodes on FDG PET/CT, 7 (24.13%) had evidence of malignancy on biopsy of the surgically resected lymph nodes. No statistically significant differences were noted between the site of the neoplastic lesion, cancer histology, duration between the date of PET and the date of surgery in the true negative (TN) and false negative (FN) groups. The recurrence rate was higher in the FN group 60 % (3/5) compared to 21 % (4/19) in the TN group who had follow up for atleast 2 years. Conclusions: Our findings suggest incidence of false negative results of FDG PET/CT for evaluation of N0 nodes in early stage NSCLC is 24.13%. This is comparatively higher than false negatives rates with mediastinoscopy (5-10%) reported in other studies. Although our sample size is small, if confirmed, such a relatively high incidence of false negative results on FDG PET/CT for N0 disease supports the current recommendations for exploratory mediastinoscopy and/or surgery for definitive staging in early stage NSCLC.
Evaluation of self-reported symptoms and interference issues in prostate cancer patients.
Authors: Mahdi Taha
Journal: Journal of Clinical Oncology (2018)

283 Background: Prostate cancer is a leading cause of global morbidity and mortality and in the next few years is expected to be the leading cause of death among men in the United States. Both the disease and its treatments produce a variety of symptoms that impact prostate cancer outcomes, of which the more common symptoms are in relation to sexual dysfunction. A large body of literature has established that systematic patient reporting of symptoms during routine oncology care leads to clinical benefits. At our comprehensive community cancer center we evaluate patients’ reported symptoms using the Symptom Inventory Tool (SIT), an assessment tool that captures the patients' perceived symptom burden for real-time clinical intervention taken at the point of no intervention and every ≥ 21 days thereafter. Methods: The 27-question SIT is comprised of the M.D. Anderson Symptom Inventory Tool (MDASI), a validated assessment instrument, with 8 supplementary questions and a free-text box added by Cancer Treatment Centers of America. Symptoms are rated “at the worst” on a numeric scale ranging from 0 to 10, as experienced by pts in the past 24 hours. The SIT became an integral part of patient care at CTCA beginning in 2012. Results: Over a 45 month period (9/1/2012 to 05/31/2016), prostate cancer pts at CTCA completed the SIT at intake and again ≥ 21 days after. A total of 2,937 assessments were analyzed. The assessments consisted of 1,065 completed at baseline, 1,065 completed at the 2nd follow up (FU), and 807 completed at 3rd FU or greater. Further analysis of baseline SIT identified the pts who rated the above symptoms as “very burdensome” with a score of ≥ 5. 2nd SIT results from these PC patients revealed that those with a heavier symptoms burden at baseline would be more likely to experience a significant decrease in their symptoms burden than the average PC patient population. Conclusions: The SIT was successful in identifying symptoms burden and interference with life issues in prostate cancer patients. Sexual dysfunction and disturbed sleep were the most common reported symptoms. Early identification of patients with heavy symptom-burden allowed immediate intervention and improvement in approximately a one-fourth to two-thirds of patients.
ASSESSMENT OF RIGHT VENTRICULAR SYSTOLIC FUNCTION BY GLOBAL LONGITUDINAL STRAIN WITHIN 1 MONTH AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Michael Tanoue, Brian West, Heajung Nguyen, Dhananjay Chatterjee, Troy Sekimura, Gabriel Vorobiof, Eric H. Yang, Olcay Aksoy
Journal: Journal of the American College of Cardiology (2018)
Most FY1s feel supported by senior doctors, survey shows
Authors: Abi Rimmer
Journal: BMJ (2015)

The majority (91%) of foundation year 1 trainees feel supported by senior doctors, a survey by MPS (the Medical Protection Society) has found.

The survey received 586 responses from MPS members who had just completed their first year of foundation training. It found that overall 89% of foundation year 1 doctors …
Tumour growth pattern and degree of thymidine phosphorylase expression are strongly related to metastasis risk in Dukes B colorectal cancer.
Authors: H.K. van Halteren, H. Peters, A. Vreugdenhil, J.J. Keuning, R.M.H. Roumen, F.A.A.M. Croiset van Uchelen, J.W.W. Coebergh, E. van der Worp, J.H.J.M. van Krieken, D.J.T. Wagener
Journal: Annals of Oncology (2000)
How many clinical attachments do overseas doctors need to do?
Authors: Romeh Gupta
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
OUTCOME OF TRANSCATHETER AORTIC VALVE REPLACEMENT USING SAPIEN3 IN PATIENTS WITH EXTRA LARGE AORTIC ANNULUS
Authors: Masaki Miyasaka, Rahul Sharma, Jaideep Sandhu, Sung-Han Yoon, Takahiro Nomura, Tomoki Ochiai, Tanya Rami, Tarun Chakravarty, Mamoo Nakamura, Wen Cheng, Raj Makkar
Journal: Journal of the American College of Cardiology (2018)
Push for seven day services risks losing doctors’ goodwill, experts warn
Authors: Abi Rimmer
Journal: BMJ (2016)

The government could lose the goodwill of junior doctors and damage their morale if it continues to push forward plans for seven day NHS services, experts have warned.

The topic of NHS seven day services was discussed at a Royal Society of Medicine conference on Tuesday 15 March.

Panellists responded to a question from Vimal Gokani, past president of the Association of Surgeons in Training, on what effect the introduction of seven day services would have on doctors’ morale, given the ongoing dispute over the junior doctors’ contract in England.

Charles Easmon, emeritus professor of health policy at the University of West London, said that the …
How do I apply for clinical attachments—to the dean, consultant, or medical staffing?
Authors: Shaaz Mahboob
Journal: BMJ (2006)

<b>www.bmjcareers.com/advicezone</b> Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.