tbuckley/cabot-search huggingface dataset:
Referral for Ophthalmology Evaluation and Visual Sequelae in Children With Primary Brain Tumors
Authors: Yin Liu, Chenue Abongwa, Stephen Ashwal, Douglas D. Deming, Timothy W. Winter
Journal: JAMA Network Open (2019)

Visual impairment in children with brain tumors has received limited attention, as most pediatric neuro-oncology clinical trials neither require ophthalmologic evaluation on enrollment nor monitor effects of treatment on visual function during and after treatment.To investigate ophthalmology referral patterns for children with primary brain tumors, the prevalence of visual sequelae, and the association between tumor characteristics and vision-related diagnoses.This retrospective cohort study included 141 children with primary brain tumors treated at Loma Linda University Children's Hospital and Eye Institute, a university-based tertiary referral center, between January 2013 and September 2017. Data analysis was completed in March 2019.Comprehensive ophthalmologic evaluation for children with primary brain tumors.Percentage of patients with ophthalmology evaluation, prevalence of abnormal ophthalmic findings, and their association with tumor characteristics.A total of 141 children (73 [52%] male; median [range] age, 7 [0-18] years) with primary brain tumors were enrolled in this study. Seventy-three patients (41 [52%] male; median [range] age, 8 [0-17] years) never had formal ophthalmologic evaluation. Sixty-eight patients (32 [48%] male; median [range] age, 7 [0-18] years) were evaluated by 1 of 4 board-certified, fellowship-trained pediatric and/or neuro-ophthalmologists for any visual impairment over a total of 222 visits. Five-year overall survival for patients who had eye examination was not significantly different from those who did not (mean [SD] survival, 78.3% [6.2%] vs 84.9% [4.7%]). Median (range) time from tumor diagnosis to initial ophthalmologic evaluation was 9 (0-94) months. Only 10 of 68 children (15%) presented with visual symptoms at tumor diagnosis, while 61 of 68 (90%) had abnormal findings on examination, including strabismus (41 [60%]), visual acuity impairment (37 [54%]), amblyopia (26 [38%]), papilledema (24 [35%]), visual field defects (13 [19%]), optic atrophy (12 [18%]), and keratopathy (10 [15%]). Strabismus occurred more frequently in patients with posterior fossa tumors (26 of 68 in posterior fossa vs 15 of 68 in other locations; P = .02). The presence of visual field defects in patients with no visual symptoms was 15% (9 of 58). Radiation was significantly associated with amblyopia (odds ratio, 4.5; 95% CI, 1.2-15.7; P = .02).In this study, more than 50% of children with primary brain tumors were not referred for ophthalmologic evaluation. Although visual symptoms were uncommon, visual impairments occurred more frequently than previously reported. Ophthalmologic evaluation is recommended to identify and manage visual impairment and prevent permanent vision loss in children with brain tumors.
Efficacy and safety of hypofractionated preoperative radiotherapy in treatment of localized extremity/trunk wall soft tissue sarcoma (STS): Final results of the study.
Authors: Piotr Rutkowski, Hanna Melania Kosela, Milena Kolodziejczyk, Wirginiusz Dziewirski, Marcin Zdzienicki, Tadeusz Morysinski
Journal: Journal of Clinical Oncology (2013)

10564 Background: The primary treatment of STS is surgical resection combined with pre- or postoperative radiotherapy. Conventional fractionation in neoadjuvant radiotherapy is 50Gy (fractions: 2Gy/day). Radiobiological studies shown that alpha/beta ratios of some sarcoma cells are below 10Gy, what is rationale for hypofractionation. Aim of the study was to assess the efficacy and safety of hypofractionated radiotherapy in preoperative setting in patients with STS treated in one institution. Methods: 220 patients (median age 54years) participated in this prospective study (2006-2010). Median follow up is 34 months. 140 patients (64%) had high grade (G3) tumors, median size -9cm (45% ≥10cm), 68% on lower limb. 137 patients (62.2%) had primary tumors. Preoperative radiotherapy 5x5 Gy per 5 consecutive days was applied, with immediate tumor resection. Results: R0 resection was possible in 79%. 61 patients died (3-year overall survival OS 72%), 91 (41%) had disease relapse. Local recurrence (LR) was found in 20% of the patients (3-year LR-free survival 80%). Negative prognostic factors for LR were: tumor size ≥10cm (p=0.037), grade 3 (p=0.0041) and primary vs. recurrent tumor with borderline significance. LRs had significant impact on OS (p=0.0001). 101 patients (46%) had any kind of complications, majority on lower limb (early: 17.2% prolonged healing of the wound &gt;1month, 12.7% -wound dehiscence, 4% -prolonged punctures of lymph fluid, 2.7% -acute skin toxicity; late: 0.9% -severe fibrosis with contracture, 11% -prolonged edema. 2.7% -bone fracture), but only 6.3% required additional surgery. Conclusions: In this non-selected group of advanced STS use of hypofractionated preoperative radiotherapy was associated with similar local control (80%) when compared to previously published studies. The early toxicity is tolerable, with small rate of late complications. Presented results warrants evaluation in randomized trial.
Pulselessness After Initiation of Cardiopulmonary Resuscitation for Bradycardia in Hospitalized Children
Authors: Rohan Khera, Yuanyuan Tang, Saket Girotra, Vinay M. Nadkarni, Mark S. Link, Tia T. Raymond, Anne-Marie Guerguerian, Robert A. Berg, Paul S. Chan
Journal: Circulation (2019)

Cardiopulmonary resuscitation (CPR) is initiated in hospitalized children with bradycardia and poor perfusion. However, their rate of progression to pulseless cardiac arrest despite CPR and the differences in survival compared with initially pulseless arrest are unknown. We examined the prevalence and predictors of survival of children who progress from bradycardia to pulseless in-hospital cardiac arrest despite CPR.Pediatric patients >30 days and <18 years of age who received CPR at hospitals participating in Get With The Guidelines-Resuscitation during 2000 to 2016 were included. Each CPR event was classified as bradycardia with pulse, bradycardia with subsequent pulselessness, and initial pulseless cardiac arrest. We assessed risk-adjusted rates of survival to hospital discharge using multilevel Poisson regression models.Overall, 5592 pediatric patients were treated with CPR, of whom 2799 (50.1%) received CPR for bradycardia with poor perfusion and 2793 (49.9%) for initial pulseless cardiac arrest. Among those with bradycardia, 869 (31.0%, or 15.5% of cohort) became pulseless after a median of 3 minutes of CPR (interquartile range, 1-9 minutes). Rates of survival to discharge were 70.0% (1351 of 1930) for bradycardia with pulse, 30.1% (262 of 869) for bradycardia progressing to pulselessness, and 37.5% (1046 of 2793) for initial pulseless cardiac arrest (P for difference across groups <0.001). Children who became pulseless despite CPR for bradycardia had a 19% lower likelihood (risk ratio, 0.81 [95% CI, 0.70, 0.93]; P=0.004) of surviving to hospital discharge than those who were initially pulseless. Among children who progressed to pulselessness despite CPR for bradycardia, a longer interval between CPR and pulselessness was a predictor of lower survival (reference, <2 minutes; for 2-5 minutes, risk ratio, 0.54 [95% CI, 0.41-0.70]; for >5 minutes, risk ratio, 0.41 [95% CI, 0.32-0.53]).Among hospitalized children in whom CPR is initiated, half have bradycardia with poor perfusion at the initiation of chest compressions, and nearly one-third of these progress to pulseless in-hospital cardiac arrest despite CPR. Survival was significantly lower for children who progress to pulselessness despite CPR compared with those who were initially pulseless. These findings suggest that pediatric patients who lose their pulse despite resuscitation attempts are at particularly high risk and require a renewed focus on postresuscitation care.
Fibroblast growth factor receptor 1 (FGFR1) and SRY-related HMG-box (SOX2) amplification in squamous cell carcinoma (SCC) of the lung.
Authors: Amaya Gasco, Pedro Mendez, Jose Luis Ramirez, Santiago Viteri Ramirez, Teresa Moran, Enric Carcereny Costa, Carlota Costa, Ana Gimenez Capitan, Irene Sansano, Maria Perez, Montserrat Tierno, Monica Botia, Miquel Taron, Harry J.M. Groen, Rafael Rosell
Journal: Journal of Clinical Oncology (2013)

11025 Background: SOX2 is a key transcription factor that is amplified in lung SCC. FGFR1 is a receptor tyrosine kinase that promotes cell proliferation, survival and apoptotic resistance through the PLCγ/PKC, RAS/MAPK and PI3K-AKT pathways, respectively. FGFR1 is amplified in 15-25% of lung SCC. Pre-clinical studies of targeted inhibitors showed a growth dependency on FGFR1 amplification both in vitro and in vivo. A European, multicenter clinical trial of second-line treatment with BIBF1120, an FGFR1 inhibitor, will be performed in p with lung SCC with FGFR1 amplification. Methods: We have examined FGFR1 and SOX2 gene copy number (GCN) in 76 lung SCC p by multiplex ligation-dependent probe amplification (MLPA). Genomic DNA (gDNA) was isolated from enriched tumor cells by laser capture microdissection from formalin-fixed paraffin embedded (FFPE) tumor tissue. 50-100 ng of gDNA was analyzed in each of three independent replicates per tumor sample. Two independent probe sets were used for each gene analyzed. For inter-patient GCN comparisons, the results from each patient were normalized against the GCN values derived from FFPE peripheral blood leukocytes. In order to study intra-tumor heterogeneity (TH), we examined FGFR1 and SOX2 GCN in different areas of 4 tumors. In 2 p, TH was examined in serial tumor biopsies and/or resections obtained at different points of disease progression. Results: High FGFR1 amplification was detected in 13/76 (17.10%) and low amplification in 7/76 (9.21%) p. High SOX2 amplification was observed in 38/63 (60.32%) and low amplification in 9/63 (14.28%) p. 46.15% of the FGFR1-amplified tumors were also co-amplified for SOX2. Intra-TH was observed in 2/4 tumors. Survival according to FGFR1 and SOX2 GCN will be presented. In addition, GCN changes in FGFR1, SOX2, PIK3CA, PDGFRA, KDR, EGFR and MET over 10 years of follow-up will be presented for one surgically resected SCC lung p. Conclusions: FGFR1 and SOX2 co-amplification could represent a novel therapeutic target and warrants further research.
Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac‐1
Authors: Gautam Sule, William J. Kelley, Kelsey Gockman, Srilakshmi Yalavarthi, Andrew P. Vreede, Alison L. Banka, Paula L. Bockenstedt, Omolola Eniola‐Adefeso, Jason S. Knight
Journal: Arthritis & Rheumatology (2019)

Objective While the role of antiphospholipid antibodies in activating endothelial cells has been extensively studied, the impact of these antibodies on the adhesive potential of leukocytes has received less attention. This study was undertaken to investigate the extent to which antiphospholipid syndrome ( APS ) neutrophils adhere to resting endothelial cells under physiologic flow conditions and the surface molecules required for that adhesion. Methods Patients with primary APS (n = 43), patients with a history of venous thrombosis but negative test results for antiphospholipid antibodies (n = 11), and healthy controls (n = 38) were studied. Cells were introduced into a flow chamber and perfused across resting human umbilical vein endothelial cells ( HUVEC s). Surface adhesion molecules were quantified by flow cytometry. Neutrophil extracellular trap release ( NET osis) was assessed in neutrophil‐ HUVEC cocultures. Results Upon perfusion of anticoagulated blood through the flow chamber, APS neutrophils demonstrated increased adhesion as compared to control neutrophils under conditions representative of either venous (n = 8; P &lt; 0.05) or arterial (n = 15; P &lt; 0.0001) flow. At the same time, APS neutrophils were characterized by up‐regulation of CD 64, CEACAM 1, β 2 ‐glycoprotein I, and activated Mac‐1 on their surface (n = 12–18; P &lt; 0.05 for all markers). Exposing control neutrophils to APS plasma or APS IgG resulted in increased neutrophil adhesion (n = 10–11; P &lt; 0.0001) and surface marker up‐regulation as compared to controls. A monoclonal antibody specific for activated Mac‐1 reduced the adhesion of APS neutrophils in the flow‐chamber assay ( P &lt; 0.01). The same monoclonal antibody reduced NET osis in neutrophil– HUVEC cocultures ( P &lt; 0.01). Conclusion APS neutrophils demonstrate increased adhesive potential, which is dependent upon the activated form of Mac‐1. In patients, this could lower the threshold for neutrophil–endothelium interactions, NET osis, and possibly thrombotic events.
Clinicopathologic and survival analysis of patients with lung cancer treated at a tertiary care centre in India.
Authors: Vinod Raina, Prabhat Singh Malik, B. K Mohanti, Mehar C Sharma, Anant Mohan, S. V. S Deo, N. K Shukla
Journal: Journal of Clinical Oncology (2012)

e17505 Background: Lung cancer ranks among the most common and lethal malignancies worldwide and also in India. There are geographic and ethnic variations in incidences, clinical and pathological profile of lung cancer. There is paucity of data of changing trend of pathological and clinical profile from this part of the world. Methods: A total of 434 patients with lung cancer were analyzed who were registered at All India Institute of Medical Sciences, over a 3 year period, from July 2008 till June2011, based on information in hospital records. Survival analysis was performed on 310 patients who have received at least one modality of treatment. Results: Median age of the whole cohort was 55 years (23-84 years). There were 357 (82.26%) males and 77 (17.74%) females, 295(69.91%) smokers and 127 (30.09%) non smokers. 370 (85.25%) patients had NSCLC and 64 (14.74%) had SCLC. Among NSCLC, adenocarcinoma was the commonest histology (45.41%) followed by squamous cell carcinoma (29.46%) and unclassified NSCLC (20.54%). Majority (66.13%) of the diagnosis were based on biopsy (needle or bronchoscopic). Among NSCLC, 26.3% patients were of stage 1-3A and 73.7% were of stage 3B and 4. Among SCLC 25% patients were of limited stage and 75% patients were of extensive stage. 73.18% of NSCLC patients received chemotherapy, 19.15% received TKI and 5.75% received RT as first line treatment modality. Among SCLC 93.88% received chemotherapy and 6.12% received RT as first line treatment. Median PFS and OS of patients with NSCLC were 7.8 months and 13.2 months respectively while that of SCLC were 6.1 months and 9.2 months respectively. Conclusions: Pathological profile of lung cancer has changed in India. Adenocarcinoma has become the commonest histology, contrary to the older reports when squamous cell carcinoma was more common. Majority of the patients are diagnosed in advanced stage and survival of these patients remains poor.
Neoadjuvant paclitaxel plus carboplatin followed by concomitant radiochemotherapy in stage IVb nasopharyngeal carcinoma: Preliminary results
Authors: H. Jouhadi, N. Tawfiq, S. Sahraoui, A. Benider
Journal: Journal of Clinical Oncology (2006)

15521 Background: Nasopharyngeal cancer Is the first head and neck cancer in Morocco. undifferentiated carcinoma (WHO 3)is dominant. Loco regional advanced stages IVa and IVb (AJCC/UICC 1997) represents 60 to 78%. Classical treatment is neoadjuvant chemotherapy (3 courses of BEP protocol) followed by radiotherapy. Therapeutic results are characterised by a high rate of failure. For stage IVb failure is due to distant metastasis wich occur in 30 to 40% of cases needing more systemic therapy. The aim of this prospective study is to analyse for stage IVb the benefit of introducing paclitaxel associated to carboplatin as a neoadjuvante chemotherapy followed by chemoradiation in terms of reducing distant metastasis and improving local control. Tolerance of this protocol was also analysed. Methods: Between September 2003 and January 2004, a total of 33 previously untreated, histologically confirmed NPC adults, were enrolled in this study. The new protocol is based on 1-Four courses of neoadjuvant chemotherapy (1 course = paclitaxel: 175 mg/m 2 day 1 + carboplatin: 300 mg/m 2 day 1; 1 course every 21 days) 2-followed by a concomitant radiochemotherapy: -radiotherapy to a total dose of 65 gray -and low dose of cisplatine (30 mg/m 2 ) delivered on a weekly schedule. Eligibility criteria were: histologically confirmed NPC, stage IVb, no prior treatment, and informed consent of patients. There were 21 male and 12 female patients and their ages ranged from 19 to 58 years. Results: The minimal follow up was 2 years. The 2 year DFS was 85% and the 2 year loco regional free survival was 91%. All patients completed radiotherapy. Neutropenia grade III-IV was observed in 6% without fever. According to NCI toxicity criteria, acute mucositis (due to radiation) grade 3 was observed in 15% and grade 2 in 24%. Xerostomia grade 1 was observed in 70%. Conclusion: This protocol is very effective with less toxicity. Radiation dose is reduced without decreasing local control rate. The 2 years DFS is increased with this protocol to 85%. No significant financial relationships to disclose.
Image Gallery: An atypical form of bacillary angiomatosis as the presenting illness of AIDS
Authors: J. Reis, J. Fragoso, R. Amorim, I. Fernandes, M. Selores
Journal: British Journal of Dermatology (2019)

Funding sources: none. Conflicts of interest: none to declare. Dear Editor, A 31‐year‐old man, born in Cape Verde and living in Portugal for 11 years, presented with a 7‐cm, 3‐week‐old bosselated and exulcerated plaque with rapid growth and bleeding, associated with weight loss, fatigue and occasional coughing (a). Anatomopathological study showed morphological aspects favouring bacillary angiomatosis (b; Warthin–Starry stain).1,2 Detection of Bartonella spp DNA by polymerase chain reaction was positive in the skin biopsy and blood. The patient tested positive for HIV (7 CD4+ cells mm−3). He was initiated on intravenous gentamicin (14 days) and oral doxycycline (3 months), as well as antiretroviral therapy, with improvement of the lesion at 14 days (c) and resolution at 60 days (d).
The relationship between serum and tumoral CRP, Akt, MAPK, and survival in patients undergoing potentially curative resection for colorectal cancer.
Authors: Arfon Powell, Scott Shepherd, Clare Orange, Donald C. Mcmillan, Paul G Horgan, Joanne E. Edwards
Journal: Journal of Clinical Oncology (2012)

e14110 Background: Serum CRP was previously reported in myeloma to activate membrane bound Fcγ receptors which in turn activated Akt, and MAP kinase and inhibited caspase cascade activation resulting in increased tumour cell proliferation and inhibition of apoptosis. This study investigated the hypothesis that serum C-reactive protein (CRP) may activate signalling pathways in colorectal tumour cells. Methods: A cohort of 147 colorectal tumours was established and immunohistochemistry performed to assess protein expression of CRP, MAP kinase and Akt phosphorylated at serine 473 (pAkt). In addition, reverse transcriptase PCR for CRP mRNA expression was performed on 31 malignant colorectal specimens, 20 non-malignant colorectal specimens and 30 liver specimens. Results: No association between patient survival and tumour expression of CRP, pAkt and MAPK was observed, but serum CRP was independently associated with cancer-specific survival (p&lt;0.001). When analysed according to tumour site, cytoplasmic CRP expression was associated with cancer specific survival in left sided tumours (p=0.022) and cytoplasmic pAkt was associated with cancer specific survival (p=0.029) in rectal tumours. No correlations were observed between serum CRP and tumour expression of CRP, pAkt and MAPK in the cohort as a whole or when subdivided by site. Conclusions: No link was established between serum CRP and signalling within the tumour. However, our results do support the concept of colorectal tumour heterogeneity, as different proteins were associated with patient survival depending on site. Further work is therefore required to elucidate the mechanisms underlying colorectal development and progression in tumour subtypes.
A phase II trial of amrubicin (AMR) for recurrent or refractory small cell lung cancer (SCLC)
Authors: S. Kudoh, N. Yoshimura, T. Kimura, S. Mitsuoka, K. Hirata
Journal: Journal of Clinical Oncology (2006)

17053 Background: AMR, a totally synthetic 9-amino-anthracycline, demonstrated excellent single-agent activity for previously untreated extensive stage SCLC (Yana et al., Proc. ASCO, 1998, abstr.No.1734). The aim of this trial was to evaluate clinical activity of AMR in the treatment of patients with recurrent or refractory SCLC. Methods: Eligibility criteria were patients having histologically or cytologically proven measurable SCLC, had relapsed after one or two previous systemic chemotherapies, an Eastern Cooperative Oncology Group performance status (PS) of 0–2 and adequate organ function. AMR (40 mg/m 2 ) was administered on days 1–3 every 3 weeks. This study, with a planned sample size of 25, had 80% power to support the hypothesis that the true response rate was &gt;30%, and 5% significance to deny the hypothesis is the true RR was &lt;10%. Results: Between July 2003 and October 2005, 19 patients were enrolled with the following characteristics: male/female, 15/4; median age, 66 years (range 47–78); PS 0/1/2, 0/16/3; sensitive relapse/refractory case, 7/12. Median number of treatment cycles was 3. A total of 59 courses were assessable for safety. The principle toxicity was myelosuppression. Grade 3/4hematologic toxicities were leukopenia (53/32%), neutropenia (32/53%), thrombocytopenia (32/0%) and anemia (42/0%). Non-hematologic toxicities weremild with no grade 4 toxicities; grade 3neutropenic fever (16%), infection (11%), diarrhea (5%), constipation (5%), and AST/ALT (11%) were observed.Responses included 7PR (3 sensitive cases and 4 refractory cases) and 8SD; for an objective RR of 37% (95% CI 16–59%). Conclusions: AMR is well tolerated and promising for treatment of recurrent or refractory SCLC. This regimen warrants further evaluation in a phase III trial. No significant financial relationships to disclose.