tbuckley/cabot-search huggingface dataset:
Hormonal status and the quality of life of testicular cancer survivors
Authors: P. J. Wiechno, M. A. Sadowska, K. S. Kubiak, T. Demkow, J. Kaminska
Journal: Journal of Clinical Oncology (2006)

4548 Background: Testicular cancer is a highly curable neoplasm and treated patients may potentially survive many decades. The aim of the study was to assess the rate of hormonal abnormalities among testicular cancer survivors and the effect of these changes on patients’ quality of life. Methods: Men with complete remission of testicular cancer lasting over 2 years were eligible. Patients completed State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS), Beck’s Depression Inventory (BDI), International Index of Erectile Dysfunction (IIEF), Sexual Functioning Questionnaire (SFQ) and rated their physical and psychological well-being, quality of life and relationship with partners. Levels of the following hormons were determined: testosterone, estradiol, thyreotropin, folicule stimulating hormone (FSH), luteinizing hormone (LH) and prolactin. Relations between hormone levels and questionaires results were analysed. Results: A total of 326 men were tested from November 2004 till December 2005. Median age was 37 years (range: 18–72). Median disease free survival was 59 months (range: 19–291). Only 24% of patients had all tested hormones within normal ranges. The most common of endocrine abnormalities were gonadotropins over normal (LH - 55% and FSH - 49% of cases) and lowered testosterone (15%). Percentage of patients with abnormal anxiety levels was 27% (STAI) and 28% (HADS), depression rate was 15% (BDI) and 18% (HADS), 40% of patients had erectile disfunction. Hormone levels and scores of the used scales corelated strongly with patients’ age, then a linear regression analysis was performed to exclude the influence of age factor. It was shown that higher depression levels in BDI are found amongst patients with elevated LH (p = 0.010) or FSH (p = 0.017). Men with higher than normal FSH were more anxious in STAI (p = 0.026). Patients with overnormal LH shown more sexual problems in SFQ (p = 0.030). Abnormal gonadotropins levels corelated with a deteriorated physical well-being (p = 0.028). Men with abnormal estradiol were more prone to erectile disfunction (p = 0.009). Conclusions: Hormonal abnormalities are frequent among testicular cancer survivors and have negative impact on the patients’ physical and psychological well-being as well as on their sexual functioning. No significant financial relationships to disclose.
App to help spot acute kidney injury had no clinical benefits, study finds
Authors: Nigel Hawkes
Journal: BMJ (2019)

An alerting tool developed in cooperation with the Google company DeepMind to speed up the diagnosis of acute kidney injury has shown no clinical benefits when it was compared with normal care, a team from University College London and the Royal Free Hospital has concluded.

Although the system worked as intended and led to earlier recognition of the reduced kidney function characteristic of AKI in patients admitted through the hospital’s emergency department, it did not lead to any improvements in the primary outcome measure (renal recovery) or in secondary outcomes, which included survival, length of stay in hospital, and admission to the intensive care unit.

Results from patients who developed AKI during their hospital stay have also been collected but were not included in this study, published in Nature Digital Medicine .1 Unless results are more encouraging, the study will be a serious …
Dipeptidylpeptidase 4 as a Marker of Activated Fibroblasts and a Potential Target for the Treatment of Fibrosis in Systemic Sclerosis
Authors: Alina Soare, Hermina A. Györfi, Alexandru E. Matei, Clara Dees, Simon Rauber, Thomas Wohlfahrt, Chih‐Wei Chen, Ingo Ludolph, Raymund E. Horch, Tobias Bäuerle, Stephan von Hörsten, Carina Mihai, Oliver Distler, Andreas Ramming, Georg Schett, Jörg H. W. Distler
Journal: Arthritis & Rheumatology (2019)

Objective Expression of dipeptidylpeptidase 4 ( DPP ‐4) identifies a dermal fibroblast lineage involved in scarring during wound healing. The role of DDP ‐4 in tissue fibrosis is, however, unknown. The aim of the present study was to evaluate DPP ‐4 as a potential target for the treatment of fibrosis in patients with systemic sclerosis ( SS c). Methods Expression of DPP ‐4 in skin biopsy samples and dermal fibroblasts was analyzed by real‐time polymerase chain reaction, immunofluorescence, and Western blot analyses. The activity of DPP ‐4 was modulated by overexpression, knockdown, and pharmacologic inhibition of DPP 4 using sitagliptin and vildagliptin. The effects of DPP 4 inhibition were analyzed in human dermal fibroblasts and in different mouse models of SS c (each n = 6). Results The expression of DPP ‐4 and the number of DPP ‐4–positive fibroblasts were increased in the fibrotic skin of SS c patients, in a transforming growth factor β ( TGF β)–dependent manner. DPP ‐4–positive fibroblasts expressed higher levels of myofibroblast markers and collagen (each P &lt; 0.001 versus healthy controls). Overexpression of DPP 4 promoted fibroblast activation, whereas pharmacologic inhibition or genetic inactivation of DPP 4 reduced the proliferation, migration, and expression of contractile proteins and release of collagen (each P &lt; 0.001 versus control mice) by interfering with TGF β‐induced ERK signaling. DPP 4‐knockout mice were less sensitive to bleomycin‐induced dermal and pulmonary fibrosis ( P &lt; 0.0001 versus wild‐type controls). Treatment with DPP 4 inhibitors promoted regression of fibrosis in mice that had received bleomycin challenge and mice with chronic graft‐versus‐host disease, and ameliorated fibrosis in TSK 1 mice (each P &lt; 0.001 versus untreated controls). These antifibrotic effects were associated with a reduction in inflammation. Conclusion DPP ‐4 characterizes a population of activated fibroblasts and shows that DPP ‐4 regulates TGF β‐induced fibroblast activation in the fibrotic skin of SS c patients. Inhibition of DPP 4 exerts potent antifibrotic effects when administered in well‐tolerated doses. As DPP 4 inhibitors are already in clinical use for diabetes, these results may have direct translational implications for the treatment of fibrosis in patients with SS c.
A phase II trial of gemcitabine, irinotecan, and panitumumab in advanced cholangiocarcinoma, with correlative analysis of EGFR, KRAS, and BRAF: An interim report.
Authors: Davendra Sohal, Ursina R. Teitelbaum, Takeshi Uehara, Kristine Mykulowycz, Christopher D. Watt, Nevena Damjanov, Bruce J. Giantonio, Mary Carberry, Paul Stephen Wissel, Mona Jacobs-Small, Peter J. O'Dwyer, Antonia Sepulveda, Weijing Sun
Journal: Journal of Clinical Oncology (2012)

4111 Background: Cholangiocarcinoma is an aggressive neoplasm. Current chemotherapy approaches achieve modest results. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan, in patients with advanced cholangiocarcinoma. Molecular analysis of EGFR pathway genes was planned as well. Methods: Patients with advanced (unresectable or metastatic) cholangiocarcinoma, ECOG PS 0-2, and adequate liver, kidney and bone marrow function were treated with panitumumab (9 mg/kg) on day 1, and gemcitabine (1000 mg/m 2 ) and irinotecan (100 mg/m 2 ) on days 1 and 8 of a 21-day cycle. Tissue specimens were collected at diagnosis for correlative molecular analyses. Primary objective is to evaluate the 5-month progression-free survival (PFS) rate. Secondary objectives include overall response rate (ORR), overall survival (OS) and toxicity of the combination. Mutational analysis of EGFR (del 19; 858), KRAS (codons 12, 13) and BRAF (V600E) was done on samples with adequate material for testing. Results: There have been 26 (of planned 42) patients recruited to the study. A median of 6 (0-30) cycles were administered. There were no treatment related deaths. The most common gr 3 or higher toxicities were neutropenia (10 pts, 38%), thrombocytopenia (10 pts, 38%), skin rash (10 pts, 38%) and diarrhea (3 pts, 12%). During the study, there were 3 CR, 6 PR, 10 SD (disease control rate of 90%), and 2 PD (by RECIST) in 21 evaluable pts. Two pts went on to have surgical resection. Median OS is 12.7 months. Of 13 testable samples, no EGFR or BRAF mutations were identified; however, there were 7 KRAS mutations. Retrospective analysis showed no difference in OS by KRAS mutation status. Conclusions: Interim evaluation of this ongoing study showed encouraging tolerability and efficacy of this regimen. Several patients have KRAS mutations; there appears to be no association with response, however. The pre-specified efficacy criteria to continue enrollment were met.
Controlled study to evaluate physical and psychosocial effects of a standardized in-patient rehabilitation program for patients after allogenic stem cell transplantation
Authors: H. Bartsch, P. Auclair, A. Mumm, J. Weis
Journal: Journal of Clinical Oncology (2006)

16519 Background: Allogeneic stem cell transplantation (HSCT) involves somatic restrictions as well as psychosocial problems. We devolped a specific, standardized in-patient rehabilitation program (RP) for pts after HSCT. Main goals of this combined medical and psychosocial RP are the accelerated increase of physical strength and the decrease of psychosocial distress to improve health related quality of life (QoL).The purpose of this study was to evaluate this RP and define prognostic factors to discriminate between groups of pts. who might differentially benefit by the program. Methods: 132 pts. after HSCT were prospectively enrolled in the treatment group and compared to 22 pts. after HSCT who did not receive the specific RP. Besides an elucidated medical and physical assessment all pts. answered different standadized questionaires for evaluation of treatment related symptoms, fatigue (MFI), QoL (QlQ), and psycosocial distress (HADS). All measurements were repeated at different time points. RP-Pts received the first questionnaire at their admission to our center, controls during the first control after HSCT at their respective treatment center (T1). T2 was at discharge from the hospital or four to six weeks after T1. T3 was six months and T4 twelve months after T2. A matched-pairs strategy was chosen to compare the smaller group of 22 control patients with matching partners selected from the treatment group. Results: The analyses reveal that the rehabilitation patients as a group had significant poorer initial values compared to controls, particularly in physical parameters and fatigue. At T2 and T3 both groups did improve significantly compared to T1 in different physical and psychosocial measures. However the matched pair analysis is still ongoing and data will be presented. Conclusions: Our data show that pts who are obviously more impaired following HSCT were preferentially transferred to our in-patient RP and benefit significantly from a standardized RP in physical as well as psychosocial conditions. The improvement increases over time and reaches after one year values comparable to those of healthy people. No significant financial relationships to disclose.
Formulation optimization of an ephrin A2 targeted immunoliposome encapsulating reversibly modified taxane prodrugs
Authors: Zhaohua Richard Huang, Suresh Kumar Tipparaju, Dmitri B Kirpotin, Christine Pien, Tad Kornaga, Charles O Noble, Alexander Koshkaryev, Jimmy Tran, Walid S Kamoun, Daryl C Drummond
Journal: Journal of Controlled Release (2019)
Incidence of thromboembolism in patients receiving vorinostat: Clinical trial and post-marketing data from more than 1,800 patients
Authors: S. Rizvi, J. Lis, K. Boileau, J. Garcia-Vargas
Journal: Journal of Clinical Oncology (2009)

e14547 Background: Thromboembolic events (TEEs) occur in approximately 10–15% of advanced cancer patients. Risk factors include cancer therapy and extent and type of malignancy. Vorinostat, a histone deacetylase inhibitor, has been licensed in the USA for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent, or recurrent disease on or following two systemic therapies. TEEs were observed in 6/86 patients (7.0%) enrolled in vorinostat CTCL clinical trials at licensure. To gain further insight into the association between TEEs and vorinostat treatment, we analyzed data from vorinostat clinical trials and post-marketing surveillance (PMS) reports. Methods: Serious adverse events (SAEs) reported through November 3, 2008, among patients receiving vorinostat in completed and ongoing clinical trials, PMS reports, and published literature were reviewed for terms consistent with TEEs. A committee of independent (non-Merck employees) academic experts evaluated these reports. Although no safety signals were observed, the committee recommended that d-dimer and/or plasmin-antiplasmin assays should be conducted. This recommendation has been implemented in three ongoing studies ( NCT00486720 , NCT00632931 , NCT006429542) and will provide further information on clotting parameters among patients being treated with vorinostat. Results: During the reporting period, data from &gt;1,845 cancer patients who received vorinostat were reviewed. Irrespective of causality, 107 patients (&lt;5.8%) reported TEE SAEs (Table). Of these, 47 (&lt;2.6%) had TEE SAEs that were rated as related to vorinostat, four of which were fatal. As of the data cut off, review of the special assays in the three studies did not result in any conclusive correlation. Conclusions: The incidence rate of TEEs observed in vorinostat studies is similar to reported rates of TEEs for advanced cancer patients. [Table: see text] [Table: see text]
Ibritumomab tiuxetan combined with high-dose chemotherapy and autologous stem-cell transplantation (SCT) in patients with chemo-refractory aggressive non-Hodgkin’s lymphoma
Authors: A. Shimoni, T. Zwass, Y. Oksman, I. Hardan, N. Shem-Tov, R. Yerushalmi, A. Nagler
Journal: Journal of Clinical Oncology (2006)

6538 Background: High-dose chemotherapy and autologous SCT have an established role in the treatment of patients with first chemo-sensitive relapse of aggressive lymphoma. However, autologous SCT has only limited success when performed in refractory or progressive stage of the disease and the expected 1-year progression-free survival (PFS) in this setting is &lt; 20%. Methods: This study was designed to explore the safety and outcome following inclusion of ibritumomab tiuxetan (IT) in the conditioning regimen given prior to autologous SCT. Patients were eligible for this study only if they had refractory lymphoma and a positive PET-CT prior to SCT. The primary end-point was 1-year PFS. Rituximab 250 mg/m 2 followed by IT 0.4 mCi/kg were given on day -14. Chemotherapy according to standard BEAM was started on day -6. Results: The study included 20 pts, median age 55 years (range, 35–66). Histology was diffuse large cell (n=14), transformed follicular (n=5) and mantle cell lymphoma (n=1). Patients had active lymphoma at SCT, either primary refractory (n=11) or refractory relapse (n=9) and 12 had bulky disease at SCT. The median number of prior therapies was 3 (range, 1–6). There were no early infusion reactions associated with IT. Fourteen patients achieved CR, 4 achieved PR and 2 died early after SCT. With a median follow-up of 9 months (range, 1–20), 14 patients are alive and 6 have died with an estimated 1-year survival of 58% (95% C.I., 31–85). All surviving patients are progression-free. Only 2 patients relapsed with a 1-year cumulative incidence of only 14% (5–51). Two patients died of multi-organ toxicities and 2 of late occurring infections. These rates of non-relapse mortality are expected in heavily pretreated patients with refractory lymphoma and there was no additional toxicity related to IT. Conclusions: The inclusion of IT in the conditioning regimens given prior to autologous SCT may reduce the risk of relapse following autologous SCT and improve the poor outcome of patients with refractory lymphoma given SCT with standard conditioning regimens. This observation merits further study in larger comparative trials. No significant financial relationships to disclose.
Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology
Authors: Robert A. Swarm, Judith A. Paice, Doralina L. Anghelescu, Madhuri Are, Justine Yang Bruce, Sorin Buga, Marcin Chwistek, Charles Cleeland, David Craig, Ellin Gafford, Heather Greenlee, Eric Hansen, Arif H. Kamal, Mihir M. Kamdar, Susan LeGrand, Sean Mackey, M. Rachel McDowell, Natalie Moryl, Lisle M. Nabell, Suzanne Nesbit, Nina O’Connor, Michael W. Rabow, Elizabeth Rickerson, Rebecca Shatsky, Jill Sindt, Susan G. Urba, Jeanie M. Youngwerth, Lydia J. Hammond, Lisa A. Gurski
Journal: Journal of the National Comprehensive Cancer Network (2019)

In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.
Evidence of Prostate-Specific Membrane Antigen Expression in Hepatocellular Carcinoma Using 68Ga-PSMA PET/CT
Authors: Serkan Kuyumcu, Duygu Has-Simsek, Raim Iliaz, Yasemin Sanli, Fikret Buyukkaya, Filiz Akyuz, Cuneyt Turkmen
Journal: Clinical Nuclear Medicine (2019)

Introduction Prostate specific membrane antigen (PSMA) expression has been demonstrated in tumor neovasculature of many solid tumors, including hepatocellular carcinoma (HCC). The purpose of this study is to evaluate PSMA expression in patients with HCC. Materials and Methods Nineteen HCC patients who underwent 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) as part of restaging procedure also underwent 68 Ga-PSMA PET. 18 F-FDG PET and 68 Ga-PSMA findings were compared visually as well as quantitatively using maximized standardized uptake values (SUV max ). Results FDG was positive in 15 patients while 16 patients demonstrated PSMA expression. The only extrahepatic finding was one metastatic lymph node detected by both tracers. Mean SUV max of liver lesions on FDG PET/CT was 8.3 ± 2.3 and mean tumor to background ratio was 2.3 ± 1.5. Respective values for 68 Ga-PSMA PET/CT were 17.4 ± 9 and 3.3 ± 2.2. On visual and quantitative evaluation uptake was higher with PSMA in nine patients and higher with FDG in four patients. PSMA and FDG activity were similar in three patients. One of the FDG positive patients was PSMA negative whereas two patients were PSMA positive but FDG negative. Heterogeneous uptake pattern was observed in three patients. Comparison of mean SUV max and T/B values between PET studies revealed no statistically significant difference ( P &gt; 0.1). The mean survival was 25 months (range: 18–32 months) and SUV max of PSMA ( P = 0.05) and FDG ( P = 0.012) showed medium strength of correlation with overall survival. Conclusion PSMA expression in advanced HCC can be demonstrated by 68 Ga-PSMA PET but is not superior to FDG PET however it could be useful for identifying patients with limited therapeutic options.
Referral for Kidney Transplantation in Canadian Provinces
Authors: S. Joseph Kim, John S. Gill, Greg Knoll, Patricia Campbell, Marcelo Cantarovich, Edward Cole, Bryce Kiberd
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement In Canada, access to kidney transplantation requires referral to a transplant center, and selection of patients for transplant is in part a subjective process. The authors determined the incidence of transplant referral among incident patients with ESKD in Canada. Only 17% of incident patients with ESKD were referred within 12 months of starting dialysis, and transplant referral varied more than three-fold between provinces. Factors associated with a lower likelihood of referral included older age, female sex, and receiving dialysis &gt;100 km from a transplant center, but not median household income or nonwhite race. The findings highlight the need to educate health care providers about the medical criteria for kidney transplantation and implement standards for referral, as well as the need for ongoing reporting of referral for transplantation in national registries. Background Patient referral to a transplant facility, a prerequisite for dialysis-treated patients to access kidney transplantation in Canada, is a subjective process that is not recorded in national dialysis or transplant registries. Patients who may benefit from transplant may not be referred. Methods In this observational study, we prospectively identified referrals for kidney transplant in adult patients between June 2010 and May 2013 in 12 transplant centers, and linked these data to information on incident dialysis patients in a national registry. Results Among 13,184 patients initiating chronic dialysis, the cumulative incidence of referral for transplant was 17.3%, 24.0%, and 26.8% at 1, 2, and 3 years after dialysis initiation, respectively; the rate of transplant referral was 15.8 per 100 patient-years (95% confidence interval, 15.1 to 16.4). Transplant referral varied more than three-fold between provinces, but it was not associated with the rate of deceased organ donation or median waiting time for transplant in individual provinces. In a multivariable model, factors associated with a lower likelihood of referral included older patient age, female sex, diabetes-related ESKD, higher comorbid disease burden, longer durations (&gt;12.0 months) of predialysis care, and receiving dialysis at a location &gt;100 km from a transplant center. Median household income and non-Caucasian race were not associated with a lower likelihood of referral. Conclusions Referral rates for transplantation varied widely between Canadian provinces but were not lower among patients of non-Caucasian race or with lower socioeconomic status. Standardization of transplantation referral practices and ongoing national reporting of referral may decrease disparities in patient access to kidney transplant.