Despite advances in medical and cardiac resynchronization therapy (CRT), individuals with chronic congestive heart failure (CHF) have persistent symptoms, including exercise intolerance. Optimizing ...cardio-locomotor coupling may increase stroke volume and skeletal muscle perfusion as previously shown in healthy runners. Therefore, we tested the hypothesis that exercise stroke volume and cardiac output would be higher during fixed-paced walking when steps were synchronized with the diastolic compared with systolic portion of the cardiac cycle in patients with CHF and CRT.
Ten participants (58±17 years of age; 40% female) with CHF and previously implanted CRT pacemakers completed 5-minute bouts of walking on a treadmill (range, 1.5-3 mph). Participants were randomly assigned to first walking to an auditory tone to synchronize their foot strike to either the systolic (0% or 100±15% of the R-R interval) or diastolic phase (45±15% of the R-R interval) of their cardiac cycle and underwent assessments of oxygen uptake (V̇o
; indirect calorimetry) and cardiac output (acetylene rebreathing). Data were compared through paired-samples
tests.
V̇o
was similar between conditions (diastolic 1.02±0.44 versus systolic 1.05±0.42 L/min;
=0.299). Compared with systolic walking, stroke volume (diastolic 80±28 versus systolic 74±26 mL;
=0.003) and cardiac output (8.3±3.5 versus 7.9±3.4 L/min;
=0.004) were higher during diastolic walking; heart rate (paced) was not different between conditions. Mean arterial pressure was significantly lower during diastolic walking (85±12 versus 98±20 mm Hg;
=0.007).
In patients with CHF who have received CRT, diastolic stepping increases stroke volume and oxygen delivery and decreases afterload. We speculate that, if added to pacemakers, this cardio-locomotor coupling technology may maximize CRT efficiency and increase exercise participation and quality of life in patients with CHF.
Proximal (duodenal) small bowel adenocarcinomas have a worse prognosis than distal (jejuno-ileal) tumors, but differences in patient, tumor, and treatment factors between locations remain unclear.
...Patients in the National Cancer Database with surgically resected pathologic stage I-IV small bowel adenocarcinomas between 2004 and 2015 were analyzed. Clinical stage IV patients were excluded.
Proximal tumors (n = 3767) were more likely to be higher grade (OR 1.52, CI 1.22-1.85 for moderately; OR 1.83, CI 1.49-2.33 for poorly differentiated, P < 0.01 for both) and have positive lymph nodes (OR 2.04, CI 1.30-3.23, P < 0.01), while distal tumors (n = 3252) were likely to be larger (OR 1.31, CI 1.07-1.60 for size > 5 cm, P < 0.01). Proximal tumors were associated with worse overall survival (OS) and stage-specific survival compared with distal tumors (all P < 0.01). Cox regression analysis of the entire cohort showed worse survival with community versus academic cancer programs, higher comorbidity scores, pathologic stage IV, poorly differentiated histology, positive nodal or margin status, and proximal location, while female gender, larger tumor size, and chemotherapy predicted better survival. On separate Cox regression analyses of each location, neoadjuvant chemotherapy was associated with better OS in the proximal cohort (HR 0.70, CI 0.55-0.88, P < 0.01), while adjuvant chemotherapy was associated with better OS for both proximal (HR 0.49, CI 0.42-0.57, P < 0.01) and distal tumors (HR 0.68, CI 0.57-0.81, P < 0.01).
Proximal small bowel adenocarcinomas are associated with worse overall and stage-specific survival. This may be due to tumor biologic differences as proximal tumors were more likely to have higher grade. Future studies should further investigate differences between proximal and distal tumors to guide targeted treatment algorithms.
In semantic dementia (SD), asymmetric degeneration of the anterior temporal lobes is associated with loss of semantic knowledge and alterations in socioemotional behavior. There are two clinical ...variants of SD: semantic variant primary progressive aphasia (svPPA), which is characterized by predominant atrophy in the anterior temporal lobe and insula in the left hemisphere, and semantic behavioral variant frontotemporal dementia (sbvFTD), which is characterized by predominant atrophy in those structures in the right hemisphere. Previous studies of behavioral variant frontotemporal dementia, an associated clinical syndrome that targets the frontal lobes and anterior insula, have found impairments in baseline autonomic nervous system activity that correlate with left-lateralized frontotemporal atrophy patterns and disruptions in socioemotional functioning. Here, we evaluated whether there are similar impairments in resting autonomic nervous system activity in SD that also reflect left-lateralized atrophy and relate to diminished affiliative behavior. A total of 82 participants including 33 people with SD (20 svPPA and 13 sbvFTD) and 49 healthy older controls completed a laboratory-based assessment of respiratory sinus arrhythmia (RSA; a parasympathetic measure) and skin conductance level (SCL; a sympathetic measure) during a two-minute resting baseline period. Participants also underwent structural magnetic resonance imaging, and informants rated their current affiliative behavior on the Interpersonal Adjective Scale. Results indicated that baseline RSA and SCL were lower in SD than in healthy controls, with significant impairments present in both svPPA and sbvFTD. Voxel-based morphometry analyses revealed left-greater-than-right atrophy related to diminished parasympathetic and sympathetic outflow in SD. While left-lateralized atrophy in the mid-to-posterior insula correlated with lower RSA, left-lateralized atrophy in the ventral anterior insula correlated with lower SCL. In SD, lower baseline RSA, but not lower SCL, was associated with lower gregariousness/extraversion. Neither autonomic measure related to warmth/agreeableness, however. Through the assessment of baseline autonomic nervous system physiology, the present study contributes to expanding conceptualizations of the biological basis of socioemotional alterations in svPPA and sbvFTD.
Tidal wetlands produce long-term soil organic carbon (C) stocks. Thus for carbon accounting purposes, we need accurate and precise information on the magnitude and spatial distribution of those ...stocks. We assembled and analyzed an unprecedented soil core dataset, and tested three strategies for mapping carbon stocks: applying the average value from the synthesis to mapped tidal wetlands, applying models fit using empirical data and applied using soil, vegetation and salinity maps, and relying on independently generated soil carbon maps. Soil carbon stocks were far lower on average and varied less spatially and with depth than stocks calculated from available soils maps. Further, variation in carbon density was not well-predicted based on climate, salinity, vegetation, or soil classes. Instead, the assembled dataset showed that carbon density across the conterminous united states (CONUS) was normally distributed, with a predictable range of observations. We identified the simplest strategy, applying mean carbon density (27.0 kg C m
), as the best performing strategy, and conservatively estimated that the top meter of CONUS tidal wetland soil contains 0.72 petagrams C. This strategy could provide standardization in CONUS tidal carbon accounting until such a time as modeling and mapping advancements can quantitatively improve accuracy and precision.
The CBFA2T3-GLIS2 (C/G) fusion is a product of a cryptic translocation primarily seen in infants and early childhood and is associated with dismal outcome. Here, we demonstrate that the expression of ...the C/G oncogenic fusion protein promotes the transformation of human cord blood hematopoietic stem and progenitor cells (CB HSPCs) in an endothelial cell coculture system that recapitulates the transcriptome, morphology, and immunophenotype of C/G acute myeloid leukemia (AML) and induces highly aggressive leukemia in xenograft models. Interrogating the transcriptome of C/G-CB cells and primary C/G AML identified a library of C/G-fusion-specific genes that are potential targets for therapy. We developed chimeric antigen receptor (CAR) T cells directed against one of the targets, folate receptor α (FOLR1), and demonstrated their preclinical efficacy against C/G AML using in vitro and xenograft models. FOLR1 is also expressed in renal and pulmonary epithelium, raising concerns for toxicity that must be addressed for the clinical application of this therapy. Our findings underscore the role of the endothelial niche in promoting leukemic transformation of C/G-transduced CB HSPCs. Furthermore, this work has broad implications for studies of leukemogenesis applicable to a variety of oncogenic fusion-driven pediatric leukemias, providing a robust and tractable model system to characterize the molecular mechanisms of leukemogenesis and identify biomarkers for disease diagnosis and targets for therapy.
The potential bioavailability of toxic chemicals from oil spills to water column organisms such as fish embryos may be influenced by physical dispersion along an energy gradient. For example, a ...surface slick with minimal wave action (low energy) could potentially produce different toxic effects from high energy situations such as pressurized discharge from a blown wellhead. Here we directly compared the toxicity of water accommodated fractions (WAFs) of oil prepared with low and high mixing energy (LEWAFs and HEWAFs, respectively) using surface oil samples collected during the 2010 Deepwater Horizon spill, and embryos of a representative nearshore species, red drum (Sciaenops ocellatus). Biological effects of each WAF type was quantified with several functional and morphological indices of developmental cardiotoxicity, providing additional insight into species-specific responses to oil exposure. Although the two WAF preparations yielded different profiles of polycyclic aromatic hydrocarbons (PAHs), cardiotoxic phenotypes were essentially identical. Based on benchmark thresholds for both morphological and functional cardiotoxicity, in general LEWAFs had lower thresholds for these phenotypes than HEWAFs based on total PAH measures. However, HEWAF and LEWAF toxicity thresholds were more similar when calculated based on estimates of dissolved PAHs only. Differences in thresholds were attributable to the weathering state of the oil samples.
•Low and high energy water accommodated fractions of crude oil were compared.•Toxic effects were assessed using cardiotoxicity endpoints in red drum embryos.•The biological effects of both WAF types were virtually identical.•Differences in toxic threshold levels based on ∑PAH measures were observed.
A mixing model derived from first principles describes the bulk density (BD) of intertidal wetland sediments as a function of loss on ignition (LOI). The model assumes that the bulk volume of ...sediment equates to the sum of self‐packing volumes of organic and mineral components or BD = 1/LOI/k1 + (1‐LOI)/k2, where k1 and k2 are the self‐packing densities of the pure organic and inorganic components, respectively. The model explained 78% of the variability in total BD when fitted to 5075 measurements drawn from 33 wetlands distributed around the conterminous United States. The values of k1 and k2 were estimated to be 0.085 ± 0.0007 g cm−3 and 1.99 ± 0.028 g cm−3, respectively. Based on the fitted organic density (k1) and constrained by primary production, the model suggests that the maximum steady state accretion arising from the sequestration of refractory organic matter is ≤ 0.3 cm yr−1. Thus, tidal peatlands are unlikely to indefinitely survive a higher rate of sea‐level rise in the absence of a significant source of mineral sediment. Application of k2 to a mineral sediment load typical of East and eastern Gulf Coast estuaries gives a vertical accretion rate from inorganic sediment of 0.2 cm yr−1. Total steady state accretion is the sum of the parts and therefore should not be greater than 0.5 cm yr−1 under the assumptions of the model. Accretion rates could deviate from this value depending on variation in plant productivity, root:shoot ratio, suspended sediment concentration, sediment‐capture efficiency, and episodic events.
Key Points
Sediment bulk density can be largely explained by its organic matter concentration
Bulk volume approximates the summed volumes of the mineral and organic fractions
Upper bound of steady‐state accretion defines sustainability of coastal marshes under SLR
IMPORTANCE: Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant ...recipients (OTRs), no study has estimated the posttransplant population–based incidence in the United States. OBJECTIVE: To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective cohort study examined 10 649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years. MAIN OUTCOMES AND MEASURES: Incident skin cancer was determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100 000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR). RESULTS: Overall, 10 649 organ transplant recipients (mean SD age, 51 12 years; 3873 women 36% and 6776 men 64%) contributed 59 923 years of follow-up. The incidence rates for posttransplant skin cancer was 1437 per 100 000 person-years. Specific subtype rates for SCC, MM, and MCC were 812, 75, and 2 per 100 000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (HR, 4.69; 95% CI, 3.26-6.73), male sex (HR, 1.56; 95% CI, 1.34-1.81), white race (HR, 9.04; 95% CI, 6.20-13.18), age at transplant 50 years or older (HR, 2.77; 95% CI, 2.20-3.48), and being transplanted in 2008 vs 2003 (HR, 1.53; 95% CI, 1.22-1.94). CONCLUSIONS AND RELEVANCE: Posttransplant skin cancer is common, with elevated risk imparted by increased age, white race, male sex, and thoracic organ transplantation. A temporal cohort effect was present. Understanding the risk factors and trends in posttransplant skin cancer is fundamental to targeted screening and prevention in this population.
Between a rock and a soft place Stephens, Tiffany A.; Hughes, Brent B.; Kroeker, Kristy J. ...
Ecology (Durham),
11/2019, Letnik:
100, Številka:
11
Journal Article
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a formidable operation associated with considerable morbidity. It is unclear how often these patients require ...reoperation for postoperative complications and if the need for reoperations leads to worse long-term outcomes.
The Peritoneal Surface Malignancy Database at a single center was retrospectively queried. Out of 149 entries, 141 HIPECs performed between 2012 and 2018 met inclusion criteria. Patients were categorized based on early reoperation (<60 d after HIPEC), and demographic and tumor factors were compared using univariate analyses. Recurrence was calculated for patients with complete cytoreduction and overall survival analyzed using the Kaplan-Meier method.
There were 15 reoperations after 141 HIPECs (10.6%). Median duration between HIPEC and reoperation was 18 d. Indications for reoperation included intra-abdominal infection (n = 5), bowel obstruction (n = 4), wound infection (n = 3), bleeding (n = 2), and evisceration (n = 1). There were no identified patient- or tumor-related risk factors for reoperation. Reoperations were associated with longer hospital length of stay (19 versus 9 d, P = 0.005) and 30-d readmissions (46.7% versus 12.8%, P = 0.003). There was no significant difference in 3-year recurrence-free survival, but there was a significant association between reoperation and 3-year overall survival (38.0% versus 71.9%, P = 0.03).
Complications requiring reoperation after HIPEC lead to increased short-term morbidity, longer hospital length of stay, and most importantly, reduced overall survival. Further studies investigating interventions to decrease complications and reduce reoperation rates are needed to improve outcomes after HIPEC.
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