tbuckley/cabot-search huggingface dataset:
mTOR pathway alterations in chromophobe renal cell carcinoma: Impact on metastasis development and overall survival.
Authors: Pablo Maroto, Georgia Anguera, Jose Maria Roldan, E. Caleiras, M. Santos, Jesús García-Donas, Guillermo de Velasco, J. Lanillos, AM Martínez, B. Calsina, R. Leton, Lj Leandro-Garcia, M. Monteagudo, Cristina Montero-Conde, Alberto Cascon, Mercedes Robledo, Cristina Rodríguez-Antona
Journal: Journal of Clinical Oncology (2020)

712 Background: Chromophobe renal cell carcinoma (chRCC) is a histologically and molecularly distinct class of rare renal cancer representing less than 5% of the kidney tumors. Molecular knowledge of this disease is limited, as well as prognostic factors for relapse if localized disease or response in the metastatic setting. Methods: From our database form different Spanish Hospitals, we identified a series of 89 chRCC with a localized stage and 3 patients stage IV at first diagnoses. We performed an in-depth characterization of mTOR pathway alterations, through targeted NGS and immunohistochemistry (IHC) of phospho-S6, tuberin and PTEN, and determined their impact on metastasis development and overall survival. Mutations in mitochondria and telomere maintenance genes were also assessed. TCGA kidney chromophobe project (KICH, n=64) was used for validation. Results: TP53, mTOR pathway ( MTOR, TSC2 or TSC1), telomere-related genes ( ATRX, TERT promoter or DAXX) and respiratory chain complex I, were mutated in 28%, 16%, 15% (26, 14, 12 of 87) and 15% (14 of 73) of primary tumors. PTEN and FLCN were mutated in four and three patients, respectively, two with bilateral tumors. IHC of phospho-S6 revealed positive staining in 37% of primary tumors (21 of 57), in association with MTOR, TSC2 and TSC1 mutations (P=0.009). Negative PTEN staining in 82% of cases (46 of 56) suggested PTEN loss as a chRCC characteristic, and was mutually exclusive with MTOR, TSC2 or TSC1 mutations (P=0.001). Weak or negative tuberin staining correlated with TSC2 mutations (P=0.02). Regarding metastasis development, TP53 mutations were enriched in malignant tumors (P=0.018), while telomere-related mutations showed a trend in the same direction. mTOR pathway mutations were associated with worse outcome. Overall survival in multivariable analysis adjusting for tumor stage gave a Hazard Ratio of 6.5 (P=0.009) This association was confirmed in TCGA-KICH (HR=11.9, P=0.05). Conclusions: Our study provides new genomic knowledge of chRCC and identifies novel markers of poor survival. Furthermore, we identified patients with mutations in mTOR pathway genes that showed high sensitivity to mTOR inhibitors.
IMvigor130 clinical trial in patients (pts) with metastatic urothelial carcinoma (mUC): Analysis of upper tract (UT) and lower tract (LT) subgroups.
Authors: Maria De Santis, Enrique Grande, Marina Mencinger, Jian-Ri Li, Javier Puente, Kouji Izumi, Jae-Lyun Lee, Fatih Kose, Igor Antonyan, Beiying Ding, Himika Patel, Ian D. Davis
Journal: Journal of Clinical Oncology (2020)

551 Background: IMvigor130 demonstrated a statistically significant improvement in PFS in pts receiving atezolizumab (atezo; anti–PD-L1) + platinum-based chemotherapy (plt/gemcitabine [gem]; Arm A) vs placebo + plt/gem (Arm C) as first-line treatment for mUC (Grande et al. 2019). Exploratory analyses examined efficacy outcomes in UT and LT mUC subgroups. Methods: Pts with UT and LT mUC from Arm A and Arm C were included. Chemotherapy was gem + investigator choice of plt (cisplatin or carboplatin). Tumors were assessed at baseline and every 9 wk until investigator-assessed PD per RECIST 1.1 or other events. PFS, OS and ORR in UT and LT subgroups are shown. Results: Baseline characteristics were comparable between Arm A and Arm C in the UT and LT subgroups; however, slight imbalances were noted, such as higher PD-L1–positive status (IC2/3) and lower Bajorin risk score in UT Arm A pts. With a median follow-up of 11.8 mo, median PFS was8.2 vs 6.2 mo in Arm A vs Arm C in UT pts (HR, 0.69 [95% CI: 0.51, 0.94]) and 8.1 vs 6.5 mo, respectively, in LT pts (HR, 0.85 [95% CI: 0.70, 1.02]). Interim median OS was 16.9 vs 13.5 mo in Arm A vs Arm C in UT pts (HR, 0.78 [95% CI: 0.54, 1.12]) and 15.8 vs 13.4 mo, respectively, in LT pts (HR, 0.87 [95% CI: 0.70, 1.08]). See table for additional efficacy results. Conclusions: Exploratorysubgroup analyses suggest activity of atezo + plt/gem in both UT and LT mUC, with outcomes in UT pts comparable to those seen in the LT and ITT populations. Clinical trial information: NCT02807636. [Table: see text]
Natural history of an immediately detectable PSA following radical prostatectomy: A description of a contemporary cohort.
Authors: Peter Eoin Lonergan, Samuel L. Washington, Janet E. Cowan, Hao Nguyen, Matthew R. Cooperberg, Peter Carroll
Journal: Journal of Clinical Oncology (2020)

356 Background: Radical prostatectomy (RP) can provide good long-term oncological outcomes in patients with localized and locally advanced prostate cancer (PCa). After RP, prostate specific antigen (PSA) represents the corner stone for follow-up of patients. A persistently detectable PSA immediately following RP is an unfavourable prognostic factor. We described the natural history of the management and outcomes in men with a detectable PSA in an academic cohort. Methods: A retrospective review of prospectively collected clinical and pathologic data from consecutive patients who underwent RP for non-metastatic PCa between 2000 and 2018 was performed. A detectable PSA was defined as PSA ≥ 0.05 ng/ml between 2-6 months post-surgery. Biochemical recurrence (BCR) was defined as two consecutive PSA values ≥ 0.2 ng/ml after 6 months post-surgery or any salvage treatment for a rising PSA. Second recurrence was defined as additional treatment after post-RP salvage treatment. Outcomes were defined as time to other cause mortality (OCM) or prostate cancer specific mortality (PCSM). Results: We identified 499 men with a detectable PSA within 6 months following RP. Median PSA at diagnosis was 7.95 ng/ml (IQR 5.57-12.97). Median CAPRA-S score was 5 (IQR 2-7). Median follow-up was 41 months (IQR 20-77). 296 (59%) underwent salvage treatment for a rising PSA at a median of 5 months. 33 (23%) of these men required further treatment (10 for bone metastases) at a median of 7 months. 203 (41%) of men with an immediately detectable PSA did not undergo any further treatment after RP. Treatment-free survival after post-RP salvage (31 on ADT and 2 underwent salvage RT) in men with a detectable vs undetectable PSA was 86% vs 92% at 1 year, 78% vs 89% at 3 years, 72% vs 86% at 5 years and 70% vs 76% at 10 years (Log-rank p =0.02). Prostate cancer specific survival in men with a detectable vs undetectable PSA was 100% vs 100% at 1 year, 99% vs 100% at 3 years, 96% vs 100% at 5 years and 91% vs 99% at 10 years (Log-rank p &lt; 0.01). Conclusions: This report describes the natural history of the management and outcomes in men with a detectable PSA following RP. We demonstrate that men with a detectable PSA after RP may have excellent long-term outcomes.
Individual Variation in Functional Topography of Association Networks in Youth
Authors: Zaixu Cui, Hongming Li, Cedric H. Xia, Bart Larsen, Azeez Adebimpe, Graham L. Baum, Matt Cieslak, Raquel E. Gur, Ruben C. Gur, Tyler M. Moore, Desmond J. Oathes, Aaron F. Alexander-Bloch, Armin Raznahan, David R. Roalf, Russell T. Shinohara, Daniel H. Wolf, Christos Davatzikos, Danielle S. Bassett, Damien A. Fair, Yong Fan, Theodore D. Satterthwaite
Journal: Neuron (2020)
Challenges and countermeasures for organ donation during the SARS-CoV-2 epidemic: the experience of Sichuan Provincial People’s Hospital
Authors: Lingai Pan, Jie Zeng, Hongji Yang
Journal: Intensive Care Medicine (2020)

confirmed SARS-CoV-2 (aka 2019-nCoV) cases in China.Sichuan Provincial People's Hospital acts as an organ transplant center in west of China, approximately 200 solid organ transplants performed each year and can perform heart, lung, liver, kidney, small bowel, stem cell transplantation, so it is necessary to establish a hospitalspecific protocol to deal with the SARS-CoV-2 infection for the donor and recipient.
Nasal colonization with Staphylococcus aureus is a risk factor for ventricular assist device infection in the first year after implantation: A prospective, single-centre, cohort study
Authors: Dennis Nurjadi, Katharina Last, Sabrina Klein, Sébastien Boutin, Bastian Schmack, Florian Mueller, Klaus Heeg, Arjang Ruhparwar, Alexandra Heininger, Philipp Zanger
Journal: Journal of Infection (2020)

ObjectivesTo assess, whether S. aureus nasal colonization is a risk factor for infections in patients with durable ventricular assist device (VAD).MethodsProspective, single-centre, cohort study (i) ascertaining S. aureus nasal colonization status of patients admitted for VAD-implantation and detecting time to first episode of VAD-specific or -related infection according to International Society for Heart and Lung Transplantation criteria during follow-up and (ii) comparing whole genomes of S. aureus from baseline colonization and later infection.ResultsAmong 49 patients (17 colonized, 32 non-colonized), S. aureus VAD-infections occurred with long latency after implantation (inter quartile range 76–217 days), but occurred earlier (log-rank test P = 0.006) and were more common (9/17, 52.9% vs. 4/32, 12.5%, P = 0.005; incidence rates 2.81 vs. 0.61/1000 patient days; incidence rate ratio 4.65, 95% confidence interval 1.30–20.65, P = 0.009) among those nasally colonized with S. aureus before implantation. We found a similar but less pronounced effect of colonization status when analysing its effect on all types of VAD-infections (10/17, 58.8% vs. 7/32, 21.9%, P = 0.01). These findings remained robust when adjusting for potential confounders and restricting the analysis to 'proven infections'. 75% (6/8) of paired S. aureus samples from colonization and VAD-infection showed concordant whole genomes.ConclusionsIn patients with durable VAD, S. aureus nasal colonization is a source of endogenous infection, often occurring months after device-implantation and affecting mostly the driveline. Hygiene measures interrupting the endogenous route of transmission in VAD-patients colonized with S. aureus long-term may about half the burden of infections and require clinical scrutiny.
Abstract 9841: Image-based Patient-specific Analysis Could Accurately Predict Stroke Events in Pediatric Cerebrovascular Disease
Authors: Shaolie S Hossain, Zbigniew Starosolski, Travis Sanders, Michael Wu, Ming-Chen Hsu, Dianna Milewicz, Ananth Annapragada
Journal: Circulation (2019)

Introduction: Pediatric MoyaMoya Disease (MMD) is characterized by progressive narrowing of the major arteries in the circle of Willis (CoW) and rampant collaterization, leading to recurring ischem...
New Fire Exit to Help Parents Flee Smoking
Authors: Jonathan P. Winickoff, Jeremy E. Drehmer, Emara Nabi-Burza
Journal: JAMA Pediatrics (2020)

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 Pediatrics 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 Pediatrics journal
Rapid recovery of postnivolumab vemurafenib-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome after tocilizumab and infliximab administration
Authors: Natalia Maximova, Alessandra Maestro, Davide Zanon, Annalisa Marcuzzi
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immune checkpoint inhibitors such as nivolumab and targeted BRAF inhibitors have dramatically altered the treatment outcomes of metastatic melanoma over the past few years. Skin toxicity is the most common adverse event (AE) related to the commonly used BRAF inhibitor vemurafenib, affecting more than 90% of patients. Vemurafenib-related severe AEs with early onset are reported in patients who were previously treated with anti-programmed cell death-1 (anti PD-1) antibodies. A prolonged administration of systemic steroids is the first-line treatment of severe or life-threatening AEs. We report the case of a woman suffering from vemurafenib-related severe, rapidly worsening Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, resolved in a few hours after single-dose administration of a combination of TNF-α antagonist infliximab with interleukin (IL)-6 receptor antagonist tocilizumab. Case presentation A 41-year-old woman treated with single-agent nivolumab presented with a melanoma progression. Biopsy samples were revised, revealing a BRAF V600E mutation. The patient was started on vemurafenib and cobimetinib treatment only 10 days after the last administration of nivolumab. On the third day of anti-BRAF therapy, profound lymphopenia was detected, and maculopapular eruption appeared afterward. Subsequently, the clinical conditions deteriorated further, and the woman was admitted on an emergency basis with high fever, respiratory and cardiocirculatory failure, diffuse rash, generalized edema, and lymphadenopathy. Diagnosis of DRESS syndrome with overexpressed capillary leakage was made. A single dose of tocilizumab was administered with an improvement of cardiocirculatory and renal function in a few hours. Because of worsening of liver function, skin lesions and mucositis, a single dose of infliximab was prescribed, and dramatic improvement was noted over the next 24 hours. Dabrafenib and trametinib were initiated, and coinciding with washout of infliximab from the patient’s blood, the drug toxicity recurred. Conclusion Anti-IL-6 and anti-TNF-α target treatment of very severe AEs may afford an immediate resolution of potentially life-threatening symptoms and reduce the duration and the costs of hospitalization. Maintenance of therapeutic infliximab blood concentrations permits an early switch to dabrafenib after vemurafenib-related AEs.
Thoracic radiotherapy for renal cell carcinoma metastases.
Authors: Glenn Stewart, William Breen, Brad J. Stish, Sean Sunghun Park, Kenneth R. Olivier, Brian Addis Costello
Journal: Journal of Clinical Oncology (2020)

409 Background: For patients with metastatic renal cell carcinoma (RCC), metastasis-directed local therapies can delay progression and need to initiate/switch systemic therapy. We examined our experience treating lung or mediastinal metastases from RCC with radiotherapy (RT). Methods: We reviewed patients with lung or mediastinal metastases from RCC treated with RT. Overall survival (OS) and local control (LC) was measured from the start of RT using the Kaplan-Meier method. Results: Seventy-one patients were treated with RT for 89 lung or mediastinal metastases. Median follow-up was 2.0 years (range 0.02-11.4 years) after RT for surviving patients. Most patients were male (n=53, 74.6%). Median age was 58.4 years at initial diagnosis. Histology was most frequently clear cell carcinoma (n=62, 89.9%). At the time of treatment, 18 patients (25.4%) had 1-3 metastases, and the remainder (74.6%) had 4 or more metastases. Forty-one patients (57.5%) received systemic therapy prior to thoracic radiation. Initial systemic therapy was most commonly sunitinib (45%) or pazopanib (32.5%). Median time from starting systemic therapy to initiation of radiation was 2.0 years. Fifty-eight lung metastases and 31 mediastinal metastases were treated with a median 5 fractions (range 1-40), to a median total dose of 4800 cGy (range 400-7000), with a median fraction size of 500 cGy (range 150-2000). Thirty-three lesions were treated with concurrent systemic therapy, which was most commonly nivolumab (n=16). Of 89 treated lesions, 11 (12%) had local tumor recurrence, at a median of 1.6 years (range 0.4-2.9 years) after initiation of radiation. 1, 3, and 5 year MC (metastasis control) were 96.6%, 83.5% and 67.9%, respectively. Nine patients were treated with radiation in order to delay initiation of systemic therapy. Of these, 3 eventually received systemic therapy, initiated at a median 2.5 years after radiation. At last follow-up, 41 patients (57.7%) had died. Median OS was 2.6 years. Survival at 1, 3, and 5 years was 65.2%, 48.5%, and 38%, respectively. Conclusions: Radiation achieves high metastasis control rates for lung and mediastinal metastases from RCC, potentially delaying the need for systemic therapy.
rhIGF-1 Therapy: A Silver Bullet for Bronchopulmonary Dysplasia Prevention?
Authors: Erin J. Plosa, John T. Benjamin
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

A Silver Bullet for Bronchopulmonary Dysplasia Prevention?Advancements in neonatal care over the past two decades have improved survival of extremely premature infants, yet bronchopulmonary dysplasia (BPD) continues to be a vexing problem that plagues these infants.Initially described in the presurfactant era as a disorder associated with lung injury and fibrosis, the "new" BPD is characterized by reduced alveolarization and impaired microvascular development in the immature lung (1).Although it is considered a disease of the neonatal period, infants with BPD continue to suffer from its consequences well into adulthood (2).Both prenatal insults, such as exposure to chorioamnionitis and maternal smoking, and postnatal injury from mechanical ventilation and hyperoxia increase the risk of BPD (3).The multifactorial etiology of BPD has made the development of therapies a unique challenge, and currently no effective treatment exists to prevent or cure this debilitating disease.IGF-1 (insulin-like growth factor-1) is a peptide hormone with structural homology to proinsulin that is expressed in various tissues in the body, including the lung (4).IGF-1 binds to its receptor, IGFR-1 (IGF receptor-1) and promotes cellular growth and differentiation (4).Circulating IGF-1 is bound to one of seven IGFBPs (IGF-binding proteins), of which IGFBP-3 is the most abundant (5).IGF-1 levels are high in the fetus and increase rapidly in the third trimester of pregnancy, a period of rapid growth and development (6, 7).Serum levels of IGF-1 then decrease after birth, in the early neonatal period.The decrease in IGF-1 levels is especially pronounced after preterm birth, which leaves prematurely born infants relatively IGF-1 deficient (5).As in other tissues, IGF-1 regulates numerous functions in the fetal lung that are critical for morphogenesis, including VEGF-dependent endothelial cell proliferation, epithelial cell proliferation and differentiation, and mesenchymal production of extracellular matrix components.IGFR-1-null mice develop pulmonary hypoplasia and diaphragmatic defects and die of respiratory failure (8).In addition, blocking IGF-1 signaling prevents ex vivo branching in human fetal lung explants (9).Thus, IGF-1 is indispensable for normal lung development and its deficiency could contribute to lung disease in preterm infants.Indeed, reduced serum IGF-1 levels in the early postnatal period are associated with later development
FORT-1: Phase II/III study of rogaratinib versus chemotherapy (CT) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) selected based on <i>FGFR1/3</i> mRNA expression.
Authors: David I. Quinn, Daniel Peter Petrylak, Joaquim Bellmunt, Andrea Necchi, Howard Gurney, Jae-Lyun Lee, Michiel Simon Van Der Heijden, Eli Rosenbaum, Nicolas Penel, See-Tong Pang, Jian-Ri Li, Xavier Garcia del Muro, Florence Joly, Zsuzsanna Papai, Peter Ellinghaus, Chengxing Lu, Keiko Nakajima, Tatiane Ishida, Hiroyuki Nishiyama, Cora N. Sternberg
Journal: Journal of Clinical Oncology (2020)

489 Background: Aberrant activation of fibroblast growth receptor (FGFR) signaling plays a role in UC. Rogaratinib, a pan-FGFR1-4 inhibitor, has promising efficacy and safety in pts with advanced muscle-invasive UC, selected based on FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations/translocations. This Phase II/III, randomized, open-label study evaluated the efficacy of rogaratinib vs CT in pts with FGFR-positive advanced or metastatic UC who received prior platinum CT. We present an ORR analysis for rogaratinib vs CT. Methods: FGFR1/3 mRNA was tested by in situ hybridization of archival tissue. Pts were randomized 1:1 to 800 mg rogaratinib p.o. BID continuously or CT Q3W (i.v., docetaxel 75 mg/m 2 , paclitaxel 175 mg/m 2 , or vinflunine 320 mg/m 2 ), and stratified by PIK3CA/ RAS-activating mutations, prior immunotherapy, and modified 4-factor Bellmunt risk score. Results: 87 pts were assigned to rogaratinib and 88 to CT. Overall, 82.9% were male, median age was 69.0 yrs (range: 36-89), 96.6% had stage IV disease, and 2.3% were stage IIIB. PIK3CA/ RAS-activating mutations were present in 11.4% of pts. ORRs of 19.5% and 19.3% (1-sided p=0.56) and disease control rates of 49.4% and 55.7% (p=0.84) were observed for rogaratinib and CT, respectively; median progression-free survival was 2.7 months (95% CI 1.6, 4.2) and 2.9 months (95% CI 2.6, 4.2). Grade 3-4 treatment-emergent adverse events occurred in 40/86 pts (47%) treated with rogaratinib and 46/82 pts (56%) with CT, most commonly anemia (3% vs 15%), neutropenia (1% vs 17%), asthenia (9% vs 1%), lipase increase (8% vs 2%), fatigue (2% vs 6%), and urinary tract infection (2% vs 6%). Exploratory analysis of pts with FGFR3 DNA alterations (4 spot mutations and fusions) showed ORRs of 52.4% with rogaratinib and 26.7% with CT. Conclusions: In pts with FGFR1/3 tumor mRNA-positive UC, rogaratinib had efficacy comparable with standard CT and an acceptable safety profile. Subgroup analysis suggests rogaratinib may be more active in pts with an FGFR3 DNA alteration. Sensitivity analysis of biomarker subgroups is ongoing. Clinical trial information: NCT03410693.
It’s Time to Reevaluate the Apgar Score
Authors: Mario Rüdiger, Henry J. Rozycki
Journal: JAMA Pediatrics (2020)

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 Pediatrics 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 Pediatrics journal