tbuckley/cabot-search huggingface dataset:
Effect of the use of immediate reconstruction on the rates of bilateral mastectomy and adjuvant radiation therapy use in women with node-positive breast cancer treated with neoadjuvant chemotherapy on ACOSOG Z1071 (Alliance).
Authors: Judy Caroline Boughey, Linda Mackie McCall, Bruce George Haffty, Thomas A. Buchholz, Elizabeth Ann Mittendorf, Karla V. Ballman, Kelly Hunt
Journal: Journal of Clinical Oncology (2015)

1060 Background: Each treatment decision can impact other multidisciplinary treatment recommendations. Herein we evaluate the interaction of surgery, reconstruction and radiation in node-positive breast cancer treated with neoadjuvant chemotherapy in a contemporary clinical trial. Methods: ACOSOG Z1071 (Alliance) was a prospective study evaluating sentinel node surgery after chemotherapy in patients with initial node-positive disease. We reviewed breast operation, use of immediate reconstruction and radiation on all patients who underwent mastectomy. Differences in proportions/rates were assessed with a chi-square test. Results: Of 686 eligible patients with data available, 409 underwent mastectomy (47% bilateral). Bilateral mastectomy rate was higher at 67% (117/176) in women undergoing immediate reconstruction compared to 33% (75/233) in women without reconstruction (p < 0.0001). Use of immediate reconstruction varied by clinical tumor stage at presentation, with reconstruction rates being higher in cT0-1 tumors, similar in T2 tumors and lower in cT3-4 disease (p < 0.0001) compared to no reconstruction. Immediate reconstruction did not vary by approximated tumor subtype, pathological tumor stage or nodal stage after chemotherapy. Adjuvant radiation was used less often in patients with immediate reconstruction (76% vs 88%, p = 0.0002) and those patients with pathologic complete response (72% vs 86%, p = 0.002). On multivariable analysis, use of immediate reconstruction was significantly associated with absence of adjuvant radiation (p = 0.009). Conclusions: A majority of node-positive patients treated with neoadjuvant chemotherapy undergoing mastectomy receive adjuvant radiation. Bilateral mastectomy rates are higher in women electing immediate reconstruction. We found that radiation therapy was less commonly used in patients with immediate reconstruction. Since radiation therapy in node-positive breast cancer may impact local control and survival, multidisciplinary input in surgical and reconstructive planning decisions is recommended. Clinical trial information: NCT00881361.
Allogeneic myeloma GVAX with lenalidomide in near complete remission to enhance progression free survival.
Authors: Ivan Borrello, Kimberly Noonan, Anna K. Ferguson, Amy Sidorski, Lakshmi Rudrarajuraraju, Andrea Casildo, Carol Ann Huff
Journal: Journal of Clinical Oncology (2015)

3082 Background: We have previously shown that lenalidomide (Len) can augment vaccine efficacy to the pneumococcal conjugate vaccine (PCV), Prevnar. We now examine if vaccinating patients on Len in a near complete remission (nCR) (negative M-spike, IFE+) could improve the clinical response and generate myeloma specific immunity. Methods: Patients on a Len-containing regimen were eligible for enrollment if: 1) in stable nCR for at least 4 months; 2) converting from IFE negative to IFE positive; or 3) relapsing from a nCR to an M-spike <0.3g/dL. Patients continued only on single agent Len and received 4 GVAX vaccinations consisting of two allogeneic MM lines: H929, U266 admixed with K562-GM-CSF and PCV (Prevnar). Patients received 3 monthly vaccines and a boost at 6 months. Results: To date 34 patients have been screened. 16 patients initially in a nCR were ineligible for vaccination: 5 (31%) had disease progression and 11 (69%) became IFE negative during the 4 month observation period. 15 patients have enrolled. The table contains patient characteristics. Median follow-up is 33.9 months. Median progression free survival (PFS) of the cohort of vaccinated patients has not been reached. In contrast, PFS in the observation arm that remained on a multidrug Len-containing therapy was 10 months (p=0.0146). Vaccination with a rising M-spike was less likely to induce a durable remission. Laboratory analysis showed that patients achieving a CR had more central memory CD8 T cells at baseline in the BM and blood and greater tumor specific IFNg production in the BM. Conclusions: Vaccination in combination with Len appears to significantly extend the PFS in patients with a minimal disease burden. This enhanced clinical response correlates with the development of myeloma-specific immunity with the bone marrow compartment. Vaccination of MM patients with a poly-antigenic approach such as GVAX in combination with Len in nCR shows promising early clinical activity that warrants further investigation as an approach to maintaining durable clinical remissions. Clinical trial information: NCT01349569. Vaccination (n=15) Observation (n=16) Age 69 (55-81) 66 (40-83) FISH (high risk) 0% 0% ISS Stage III 2 (13%) 3 (19%) IFE negative 0 (0%) 11 (69%) Prior Therapies 1.8 (1-4) 1.8 (1-3)
Heroin Smoking Is Not Common in the United States
Authors: Daniel Ciccarone
Journal: JAMA Neurology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Crypt fusion as a homeostatic mechanism in the human colon
Authors: Ann-Marie Baker, Calum Gabbutt, Marc J Williams, Biancastella Cereser, Noor Jawad, Manuel Rodriguez-Justo, Marnix Jansen, Chris P Barnes, Benjamin D Simons, Stuart AC McDonald, Trevor A Graham, Nicholas A Wright
Journal: Gut (2019)

The crypt population in the human intestine is dynamic: crypts can divide to produce two new daughter crypts through a process termed crypt fission, but whether this is balanced by a second process to remove crypts, as recently shown in mouse models, is uncertain. We examined whether crypt fusion (the process of two neighbouring crypts fusing into a single daughter crypt) occurs in the human colon.
Efficacy and tolerability of 3- and 6-month depot formulations of leuprorelin acetate for advanced prostate cancer in treatment-naïve and pretreated patients: pooled data from two non-interventional studies.
Authors: Carsten Henning Ohlmann, Marco Gross-Langenhoff, Ulf W. Tunn
Journal: Journal of Clinical Oncology (2015)

e16098 Background: Androgen-deprivation therapy is the current standard therapy for advanced prostate cancer (PCa), primarily consisting of injections of luteinizing hormone-releasing hormone agonists (LHRHa). The LHRHa leuprorelin acetate (LA) is available in several formulations, including 1-, 3-, and 6-month biodegradable polymer matrix depot formulations based on the ATRIGEL[R] technology. These formulations have been shown to effectively reduce testosterone and prostate-specific antigen (PSA) levels. Here we report results from two non-interventional studies to assess efficacy and tolerability of these 3- and 6-month polymer matrix depot formulations in PCa patients in clinical practice. Methods: Two prospective, open-label, non-interventional studies were conducted in Germany. 1906 advanced PCa patients starting treatment with either the 3-month (22.5 mg) or the 6-month (45 mg) LA depot formulation (Eligard[R]) were followed for 12 months by 662 office-based urologists. In both studies, the primary efficacy parameter PSA was measured at baseline and every 3 months (for 22.5 mg dose) or 6 months (for 45 mg dose) until 12 months after treatment initiation. Measurement of testosterone levels was not mandatory and was at the discretion of the treating physician. Results: Overall,median serum PSA levels were reduced by 96% from 12.0 ng/ml to 0.5 ng/ml 12 months after treatment initiation. Median testosterone levels were reduced by 89% from 101.0 ng/dl to 11.5 ng/dl 12 months after treatment initiation. Testosterone reduction below the castration level was achieved both in treatment-naïve patients and in patients pretreated with LHRH agonists (43.2%). Adverse events occurred in 8.8% of patients, with injection site pain and hot flushes being most common. Conclusions: These data indicate that the 3- and 6-month LA depot formulations reduce testosterone and PSA levels to a similar extent in clinical practice as in clinical trials, both in treatment-naïve patients and in patients pretreated with LHRH agonists, with good tolerability.
Abstract 028: Increase in Abdominal Visceral Adipose Tissue Accelerates Two Years Prior to Menopause: The Study of Women’s Health Across the Nation (SWAN) Heart
Authors: Saad Samargandy, Karen A Matthews, Maria M Brooks, Emma Barinas-Mitchell, Jared W Magnani, Imke Janssen, Rasa Kazlauskaite, Samar R El Khoudary
Journal: Circulation (2019)

Introduction: Abdominal visceral adipose tissue (VAT) contributes to pathogenesis of cardiometabolic disease through endocrine and paracrine secretion of adipocytokines. Midlife women experience adipose tissue redistribution towards increasing central adiposity. A few studies suggested a contribution of the menopausal transition, but evidence is lacking to characterize the change in VAT relative to time of the final menstrual period (FMP). We hypothesized that VAT would change non-linearly relative to FMP with a significant rise close to FMP. Methods: We evaluated participants with no self-reported CVD from the SWAN Heart Ancillary study. Women had up to two computed tomographic planimetric measurements of VAT over a median of 2.2 years of follow-up and known dates of FMP. LOESS splines were used to determine potential inflection points of VAT change relative to FMP. Piecewise linear mixed-effects models were used to estimate and compare yearly % changes in VAT at LOESS spline-identified time segments. Results: The study included 321 women (at baseline: mean age (SD) of 51.0 (2.8) years; 60% White, 40% Black; 9% premenopausal, 51% early/ 13% late perimenopausal, and 27% postmenopausal). LOESS splines suggested a non-linear association between VAT change and time of FMP with two inflection points demarcating 3 segments: segment 1: &gt; 2 years before FMP, segment 2: 2 years before FMP to the FMP, and segment 3: after FMP (Figure) . Adjusting for covariates listed under the Figure , VAT increased significantly by 10.5% (95% CI: 5.9, 15.3) per year in segment 2, and this increase was greater than changes in segments 1 [1.3% (-2.0, 4.7)] and 3 [3.1% (0.8, 5.4)], both P=0.01. Additional adjustment for concurrent body mass index attenuated difference only between segments 2 and 3 (P=0.07). Conclusions: Women show significantly faster increase in VAT two years prior to menopause, which may place them at greater risk of cardiometabolic outcomes later in life. These results encourage lifestyle modifications early in menopausal transition.
The association of NOX4 mediated nuclear colocalization and overall survival in renal cell carcinoma.
Authors: Dharam Kaushik, Hanzhang Wang, Keith A. Ashcraft, Alia Nazarullah, Michael A. Liss, Deepak Pruthi, Ahmed Mansour, Cooper B. Tye, Wasim Chowdhury, Dean Bacich, Denise O’Keefe, Ronald Rodriguez
Journal: Journal of Clinical Oncology (2019)

639 Background: NOX4 protein are involved in cell differentiation, migration and apoptosis. We recently demonstrated that NOX4 in renal cell carcinoma (RCC) is an energetic sensor and couples energy metabolism to drug-resistance. In this study we demonstrate that enhanced nuclear localization of NOX4 is correlated with poor survival. Methods: We identified 350 RCC patients with (n = 85) and without (n = 265) venous tumor thrombus (VTT) who underwent radical nephrectomy with or without thrombectomy at our institution between 2013-2016. Fifty patients with RCC and VTT were matched 1:1 to patients with RCC and no VTT. Tissue Microarray (TMA) consisting of primary renal tumor, adjacent renal tumor and VTT were created. These matched TMA (n = 174) were stained with NOX4 antibodies; scanned using the Aperio scanning system and analyzed with the ImageScope software. The RCC nucleus was evaluated for roundness, elongation and size. NOX4 nuclear staining was categorized based on intensity as either strong positive, moderate, weak or no localization. Differential protein expression between the primary tumor, adjacent normal parenchyma and VTT was assessed using the Chi-squared test or t-test. Progression-free survival (PFS) and overall-survival (OS), stratified by NOX4 staining intensity, was estimated using the Kaplan-Meier method and compared with the log-rank test. Cox regression model was used to investigate effect of NOX4 staining on survival in multivariate analyses. Results: NOX4 nuclear colocalization was higher in patients who had progression and death from RCC. On univariate analysis, the intensity of NOX4 protein expression in the nucleus was significantly associated with PFS (HR 1.67, 95%CI (1.08-2.57; p = 0.02) and OS (HR 2.31, 95%CI (1.26-4.24; p = 0.007). On multivariate analyses the association between NOX4 protein expression and OS remains statistical significance (HR 2.09, 95%CI (1.05-4.18, p = 0.037). Conclusions: We provide evidence that in high grade/high stage cancer, NOX4 is colocalized within the nucleus of RCC. The prognostic role of NOX4 was determined at the protein level. We provide rationale for further investigation of NOX4, which may serve as a checkpoint in RCC.
Liver toxicity associated with the use of pazopanib in renal cancer patients: UK teaching hospital experience.
Authors: Ankit Jain, Cinzia Canipari, Farzana Haque, Heena Solanki, Abhishek Kumar, Emilio Porfiri
Journal: Journal of Clinical Oncology (2015)

e15610 Background: Hepatotoxicity has been observed in about 40-50% renal cancer patients treated with Pazopanib in clinical trials. We have analysed the incidence of Pazopanib induced liver toxicity in real world setting. Methods: A retrospective analysis was conducted on metastatic renal cancer patients treated with Pazopanib between December 2010 and September 2014, within two cancer centres from Birmingham, UK. Data was collected on baseline demographics, liver toxicity and overall survival. Results: A total of 89 patients were identified (59 male, 30 female). Median age was 65 (range 17-91). 59 (66%) patients had prior nephrectomy. 75% of patients had PS 0-1 whereas 25% had PS 2-3. 25% patients had liver metastases. Median duration of treatment was 25.14 weeks. 34 (38%) patients were still on treatment and 50 (56%) were still alive at the time of analysis. Median OS for all patients was 17 months. 27 (30%) patients developed hepatotoxicity. 10 and 23 patients had all grades rise in bilirubin and ALT respectively whereas 4 and 6 patients had grade 3 or 4 rise in bilirubin and ALT respectively. 20 patients continued Pazopanib whereas 2 discontinued treatment temporarily and 5 discontinued Pazopanib permanently. Median duration of treatment for patients with hepatotoxicity was 34.4 weeks. Median duration of treatment before hepatotoxicity was 5.86 weeks (range 1.8 – 53.5). Median duration of hepatotoxicity was 7.71 weeks. 10 (37%) patients with hepatotoxicity were still on treatment. Median OS for patients with hepatotoxicity was 17.5 months. 53/89 (59.5%) patients stopped Pazopanib- 36 (40.5%) disease progression, 10 (11.2%) non-hepatic toxicity, 5 (5.6%) hepatotoxicity, 2 (2.2%) other reasons. Due to advanced age/ co-morbidities, 35 (39.3%) patients commenced treatment at a reduced dose (16 at 600mg, 19 at 400mg od). In these patients, incidence of liver toxicity did not differ from those treated with full dose. Conclusions: Our data shows lower hepatotoxicity rates as compared to clinical trials. Reassuringly most of the cases were mild and settled without treatment modifications. Frequency of hepatotoxicity was not affected by age, PS or presence of liver metastases.
Small but Mighty: Prenatal Ultrafine Particle Exposure Linked to Childhood Asthma Incidence
Authors: Rosalind J. Wright, Brent A. Coull
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

the detrimental modifications observed with omega-6 consumption appeared to be more robust across outcomes than the beneficial effects of omega-3 consumption.This might have implications for the type of intervention that could be successful.In addition, although the authors discuss two modifiable risk factors, diet and indoor particulate matter, they did not present any information regarding the potential sources of particulate matter, which would be necessary to design an intervention in this community.In short, the study by Brigham and colleagues potentially provides novel insight into the intersection of environmental and dietary factors affecting asthma exacerbation that may be relevant to the as-of-yet unmitigated disproportionate burden of asthma morbidity in lowincome urban communities in the United States.The important next steps include validation in other populations and demonstrating the efficacy of dietary modifications and/or particulate matter reduction to reduce the burden of asthma in these communities.
Limitations in using <sup>68</sup>Ga-PSMA-PET/CT for detection of recurrent disease following radical prostatectomy in patients with prostate cancer.
Authors: Volker Mueller-Mattheis, Hubertus Hautzel, Jovana Boskovic, Lino Morris Sawicki, Gerald Antoch, Peter Albers
Journal: Journal of Clinical Oncology (2015)

e16110 Background: Patients with rising PSA levels after radical prostatectomy (RP) often present a diagnostic dilemma. A local recurrence or metastatic lymph node lesions would be amenable to additional local therapy. In this single centre prospective study the effectiveness of 68 Ga-PSMA-PET/CT in patients with PSA relapse was evaluated. Methods: 29 patients (mean age 63.8 years) with histologically confirmed adenocarcinoma of the prostate were enrolled in this study because of rising PSA values following RP. Whole-body PET/CT images were obtained after iv-administration of 220 MBq 68Ga-PSMA. By using attenuation corrected PET data, standardized uptake value was calculated, cut-off 2. Results: Out of 29 patients n = 13 were PSMA-PET positive. PSA level in 4 of this subset was between 1.3 and 5.0 ng/mL, in 3 patients between 5.2 and 10.3 ng/mL, and 6 patients had a PSA distribution between 15.1 and 40 ng/mL, respectively. The PSA levels of the n = 16 PSMA-PET negative patients were between 0.3 and 7.8 ng/mL. In 4 out of the 16 PET negative patients an additionally perfomed MRT detected pelvic lymph node metastases (n = 2) and local recurrence (n = 2). In 3 patients, who were operated, the extirpated metastatic lesions were histopathologically clearly confirmed, in 1 patient radiotherapy was perfomed followed by decreasing PSA level. 7/13 PSMA-PET positive patients underwent dissection of hypermetabolic lymph node lesions (n = 3) or radiotherapy (n = 4), respectively. Histopathology confirmed metastases of a prostate cancer in each case, the response of patients after radiotherapy was decreasing PSA levels in each case. 6/13 received hormone manipulation. Conclusions: In contrary to published data, the sensitivity in detection of recurrent prostate cancer using 68Ga-PSMA as tracer seems to be considerably worse than expected.
Abi1 loss drives prostate tumorigenesis through activation of EMT and noncanonical WNT signaling.
Authors: Disharee Nath, Xiang Li, Claudia Mondragon, Dawn Post, Ming Chen, Anita Hryniewicz-Jankowska, Tiffany Caza, Julie White, Vladimir Kuznetsov, Heidi Hehnly, Rakesh Khanna, Stephanie Gleicher, Tamara Jamaspishvili, David Monty Berman, Fan Zhang, Sonia H.Y. Kung, Ladan Fazli, Gennady Bratslavsky, Pier Paolo Pandolfi, Leszek Kotula
Journal: Journal of Clinical Oncology (2019)

280 Background: Prostate cancer is characterized by heterogeneity of mechanisms which are poorly understood but pointing to epithelial plasticity as the key mechanism in progression to metastatic disease. ABI1, a member of WAVE complex and actin cytoskeleton regulator and adaptor protein, is proposed to act as tumor suppressor in prostate cancer, but the mechanism of tumor progression due to Abi1 loss is not clear. Methods: To address Abi1’s role in prostate cancer we used CRISPR-based gene editing and retroviral expression to manipulate Abi1 levels in prostate cancer cell lines. Levels of Abi1 expression in prostate organoid tumor cell lines were evaluated by Western blotting and/or RNA sequencing. Association of Abi1 loss with tumor grade was evaluated by immunohistochemistry. Results: Abi1 expression is downregulated in tumor organoid cell lines from metastatic bone and lymph node biopsies. Moreover, low Abi1 expression is associated with high-grade prostate tumors (GG3 or higher, p &lt; 0.001). Disruption of Abi1 gene in a benign prostate epithelial cell line RWPE-1 resulted in a gain of invasive phenotype, which is characterized by loss of cell-cell adhesion markers and increased migratory ability of RWPE-1 Abi1 KO spheroids. Through RNA sequencing and protein expression analysis we discovered that Abi1 loss leads to activation of non-canonical WNT signaling and EMT pathways, which are rescued by re-expression of Abi1. Furthermore, increase in STAT3 phosphorylation upon Abi1 inactivation and evidence for high affinity interaction of FYN-SH2 domain with Abi1 pY421 support the model that Abi1 acts as a gatekeeper of the non-canonical WNT-EMT pathway activation downstream from FZD2 receptor. The gene expression profile of Abi1-EMT-WNT pathway overlaps with the reported gene signature of high-risk prostate tumors. Conclusions: Abi1 contributes to prostate cancer progression and epithelial plasticity through regulation of EMT-WNT pathways. Understanding of Abi1’s role may provide more mechanistic understanding of prostate cancer tumor progression.
First experience of ribavirin postexposure prophylaxis for Nipah virus, tried during the 2018 outbreak in Kerala, India
Authors: Sayantan Banerjee, Vettakkara Kandy Muhammed Niyas, Manish Soneja, Areekkare Purayil Shibeesh, Muhammed Basheer, Rajeev Sadanandan, Naveet Wig, Ashutosh Biswas
Journal: Journal of Infection (2019)