Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

PurposeWe compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity.Methods and MaterialsWe reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity.ResultsAt 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742; nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction.ConclusionsSurvival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function

Intrathoracic extensive-stage small cell lung cancer: assessment of the benefit of thoracic and brain radiotherapy using the SEER database

Extensive-stage small cell lung cancer (ESCLC) includes metastatic disease and locally advanced disease confined to the thorax that cannot be encompassed in a typical radiation portal. We assessed and then compared the benefits of thoracic radiotherapy (TRT) and/or brain radiotherapy (BRT) on overall survival (OS) between the intrathoracic (T-ESCLC) and metastatic (M-ESCLC) groups using the Surveillance Epidemiology and End Results database.TRT and BRT data were available for 10150 patients treated from 1988−1997. The T-ESCLC group included 1774 patients. The Kaplan–Meier method was used to estimate OS and the proportional hazards model was used to estimate OS hazard ratios for prognostic factors including age, gender, race, tumor size, T/N stage, TRT, and BRT.The 2-year OS for T-ESCLC was 7.8 % compared to 3 % in the M-ESCLC group (p < 0.001). In the T-ESCLC group, TRT and BRT were delivered to 750 and 102 patients, respectively. The 2-year OS was 13 % in the TRT group compared to 4.1 % in the no-TRT group (p ≤ 0.001) and 22.5 % in the BRT group compared to 7 % in the no-BRT group (p < 0.001). In the M-ESCLC group, TRT and BRT were delivered to 3093 and 1887 patients, respectively. The 2-year OS was 4.4 % in the TRT group compared to 2.8 % in the no-TRT group (p < 0.001) and 4.3 % in the BRT compared to 2.6 % in the no-BRT group (p < 0.001). Age, gender, TRT and BRT were significant OS prognostic factors in both groups.Our study suggests that T-ESCLC is a disease entity distinct from M-ESCLC. Prospective studies to determine whether TRT should be recommended for the thoracic-only subgroup are warranted

Consistent patterns of fungal communities within ant-plants across a large geographic range strongly suggest a multipartite mutualism

In recent decades, multipartite mutualisms involving microorganisms such as fungi have been discovered in associations traditionally thought of as bipartite. Ant-plant mutualisms were long thought to be bipartite despite fungi being noticed in an epiphytic ant-plant over 100 years ago. We sequenced fungal DNA from the three distinct domatium chambers of the epiphytic ant-plant Myrmecodia beccarii to establish if fungal communities differ by chamber type across five geographic locations spanning 675 km. The three chamber types serve different ant-associated functions including ‘waste’ chambers, where ant workers deposit waste; ‘nursery’ chambers, where the brood is kept; and ‘ventilation’ chambers, that allow air into the domatium. Overall, fungi from the order Chaetothyriales dominated the chambers in terms of the proportion of operational taxonomic units (OTUs; 13.4%) and sequence abundances of OTUs (28% of the total); however a large portion of OTUs (28%) were unidentified at the order level. Notably, the fungal community in the waste chambers differed consistently from the nursery and ventilation chambers across all five locations. We identified 13 fungal OTUs as 'common' in the waste chambers that were rare or in very low sequence abundance in the other two chambers. Fungal communities in the nursery and ventilation chambers overlapped more than either did with the waste chambers but were also distinct from each other. Differences in dominance of the common OTUs drove the observed patterns in the fungal communities for each of the chamber types. This suggests a multipartite mutualism involving fungi exists in this ant-plant and that the role of fungi differs among chamber types

Heparin and protamine use in peripheral vascular surgery: A comparison between surgeons of the Society for Vascular Surgery and the European Society for Vascular Surgery

It was the intent of this study to document, in general, the patterns and complications of heparin and protamine usage during carotid endarterectomy, aortic and femoral-popliteal-tibial reconstructions for occlusive disease, elective and emergent abdominal aortic aneurysmectomy, thromboembolectomy, and dialysis arteriovenous (AV) fistula placement by surgeons from North America and Europe. All vascular surgeons from the Society for Vascular Surgery (SVS) and the European Society for Vascular Surgery (ESVS) were surveyed by a voluntary, self-reported questionnaire. Six hundred and forty-six completed questionnaires (284 from SVS and 362 from ESVS), representing a 62% response rate, were returned for evaluation. Systemic and regional administration of heparin was common during vascular procedures performed by both SVS and ESVS surgeons. Use of protamine to reverse heparin anticoagulation varied among SVS and ESVS surgeons, respectively, during: carotid endarterectomy (54% vs. 26%, p p p p &lt; 0.001). Adverse reactions to protamine among the 25 219 and 12 902 cases reported from SVS and ESVS surgeons, respectively, included: hypotension (1209 and 495 cases), pulmonary artery hypertension (65 and eight cases), anaphylaxis (52 and 10 cases), and death (seven and two cases). These adverse responses accounted for 5.3% and 4.0% of the SVS and ESVS cases, respectively. Although this study is subject to the known limitations of a retrospective survey, it is clear that heparin use is common. Protamine reversal of heparin anticoagulation is more common in North America. Severe reactions to protamine occur often enough to support the tenet that a safer compound is needed for heparin anticoagulation reversal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31719/1/0000655.pd

Metabolomics and Lipidomics Signatures of Insulin Resistance and Abdominal Fat Depots in People Living with Obesity

The liver, skeletal muscle, and adipose tissue are major insulin target tissues and key players in glucose homeostasis. We and others have described diverse insulin resistance (IR) phenotypes in people at risk of developing type 2 diabetes. It is postulated that identifying the IR phenotype in a patient may guide the treatment or the prevention strategy for better health outcomes in populations at risk. Here, we performed plasma metabolomics and lipidomics in a cohort of men and women living with obesity not complicated by diabetes (mean [SD] BMI 36.0 [4.5] kg/m2, n = 62) to identify plasma signatures of metabolites and lipids that align with phenotypes of IR (muscle, liver, or adipose tissue) and abdominal fat depots. We used 2-step hyperinsulinemic-euglycemic clamp with deuterated glucose, oral glucose tolerance test, dual-energy X-ray absorptiometry and abdominal magnetic resonance imaging to assess muscle-, liver- and adipose tissue- IR, beta cell function, body composition, abdominal fat distribution and liver fat, respectively. Spearman’s rank correlation analyses that passed the Benjamini–Hochberg statistical correction revealed that cytidine, gamma-aminobutyric acid, anandamide, and citrate corresponded uniquely with muscle IR, tryptophan, cAMP and phosphocholine corresponded uniquely with liver IR and phenylpyruvate and hydroxy-isocaproic acid corresponded uniquely with adipose tissue IR (p −4). Plasma cholesteryl sulfate (p = 0.00029) and guanidinoacetic acid (p = 0.0001) differentiated between visceral and subcutaneous adiposity, while homogentisate correlated uniquely with liver fat (p = 0.00035). Our findings may help identify diverse insulin resistance and adiposity phenotypes and enable targeted treatments in people living with obesity