BACKGROUND:Transsphenoidal surgery is the standard approach for treating Cushing disease. Evidence is needed to document effectiveness.
OBJECTIVE:To analyze results of transsphenoidal surgery in 276 ...consecutive patients, including 19 children.
METHODS:Medical records were reviewed for patients treated initially with surgery for Cushing disease from 1980 to 2012. Radiographic features, pathology, remissions, recurrences, and complications were recorded. Patients were categorized for statistical analysis based on tumor size (microadenomas, macroadenomas, and negative imaging) and remission type (type 1 = morning cortisol ≤3 μg/dL; type 2 = morning cortisol normal).
RESULTS:Females comprised 78% of patients and were older than men. Imaging showed 50% microadenomas, 13% macroadenomas, and 37% negative for tumor. Remission rates for microadenomas, macroadenomas, and negative imaging were 89%, 66%, and 71%, respectively. Patients with microadenomas were more likely to have type 1 remission. Pathology showed adrenocorticotropic hormone-secreting adenomas in 82% of microadenomas, in 100% of macroadenomas, and in 43% of negative imaging. The incidence of hyperplasia was 8%. The finding of hyperplasia or no tumor on pathology predicted treatment failure. The recurrence rate was 17%, with an average time to recurrence of 4.0 years. Patients with type 1 remission had a lower rate of recurrence (13% type 1 vs 50% type 2) and a longer time to recurrence. Children had similar imaging findings, remission rates, and pathology. There were no operative deaths.
CONCLUSION:Transsphenoidal surgery provides a safe and effective treatment for Cushing disease. For both adults and children, the best outcomes occurred in patients with microadenomas and/or those with type 1 remission.
ABBREVIATIONS:ACTH, adrenocorticotropic hormoneIPSS, inferior petrosal sinus sampling
► Two wet ponds were studied pre- and post-floating treatment wetland (FTW) retrofit. ► No significant improvement in TN concentration was observed with addition of FTWs. ► Results suggested a ...minimum percent coverage of 18% for improvement in TP and TSS. ► Mean and median pond temperature was the same beneath the FTWs versus open water. ► Below mat N, P, and K plant concentrations were higher than above mat concentrations.
Thousands of existing wet retention ponds have been built across the United States, primarily for the mitigation of peak flow and removal of sediment. These systems struggle to mitigate soluble nutrient loads from urban watersheds. A simple retrofit for improvement of pond performance for nitrogen and phosphorus removal could become popular. Floating treatment wetlands (FTWs), one such retrofit, are a hydroponic system that provides a growing medium for hydrophytic vegetation, which obtain nutrients from the stormwater pond. Installation of FTWs does not require earth moving, eliminates the need for additional land to be dedicated to treatment, and does not detract from the required storage volume for wet ponds (because they float). To test whether FTWs reduce nutrients and sediment, two ponds in Durham, NC, were monitored pre- and post-FTW installation. At least 16 events were collected from each pond during both monitoring periods. The distinguishing characteristic between the two ponds post-retrofit was the fraction of pond surface covered by FTWs; the DOT pond and Museum ponds had 9% and 18%, respectively, of their surface area covered by FTWs. A very small fraction of N and P was taken up by wetland plants, with less than 2% and 0.2%, respectively, of plant biomass as N and P. Temperature measurements at three depths below FTWs and at the same depths in open water showed no significant difference in mean daily temperatures, suggesting little shading benefit from FTWs. The two ponds produced effluent temperatures that exceeded trout health thresholds. Both the pre- and post-FTW retrofit ponds performed well from a pollutant removal perspective. One pond had extremely low total nitrogen (TN) effluent concentrations (0.41mg/L and 0.43mg/L) during both pre- and post-FTW retrofit periods, respectively. Floating treatment wetlands tended to improve pollutant capture within both ponds, but not always significantly. Mean effluent concentrations of TN were reduced at the DOT pond from 1.05mg/L to 0.61mg/L from pre- to post-retrofit. Mean total phosphorus (TP) effluent concentrations were reduced at both wet ponds from pre- to post-retrofit 0.17mg/L to 0.12mg/L (DOT pond) and 0.11mg/L to 0.05mg/L (Museum pond). The post-retrofit effluent concentrations were similar to those observed for bioretention cells and constructed stormwater wetlands in North Carolina. The DOT pond showed no significant differences between pre- and post-retrofit effluent concentrations for all nine analytes. The Museum pond had a statistically significant improvement post-retrofit (when compared to the pre-retrofit period) for both TP and total suspended solids (TSS). Wetland plant root length was measured to be approximately 0.75m, which had the benefit of stilling water flow, thereby increasing sedimentation. Results suggested that greater percent coverage of FTWs produced improved pollutant removal.
To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary ...adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly.
Growing evidence suggests that liana competition with trees is threatening the global carbon sink by slowing the recovery of forests following disturbance. A recent theory based on local and regional ...evidence further proposes that the competitive success of lianas over trees is driven by interactions between forest disturbance and climate. We present the first global assessment of liana–tree relative performance in response to forest disturbance and climate drivers. Using an unprecedented dataset, we analysed 651 vegetation samples representing 26,538 lianas and 82,802 trees from 556 unique locations worldwide, derived from 83 publications. Results show that lianas perform better relative to trees (increasing liana‐to‐tree ratio) when forests are disturbed, under warmer temperatures and lower precipitation and towards the tropical lowlands. We also found that lianas can be a critical factor hindering forest recovery in disturbed forests experiencing liana‐favourable climates, as chronosequence data show that high competitive success of lianas over trees can persist for decades following disturbances, especially when the annual mean temperature exceeds 27.8°C, precipitation is less than 1614 mm and climatic water deficit is more than 829 mm. These findings reveal that degraded tropical forests with environmental conditions favouring lianas are disproportionately more vulnerable to liana dominance and thus can potentially stall succession, with important implications for the global carbon sink, and hence should be the highest priority to consider for restoration management.
Des preuves de plus en plus nombreuses suggèrent que la competition entre lianes et les arbres menace le puits de carbone mondial en ralentissant la récupération des forêts après une perturbation. Une théorie récente, fondée sur des observations locales et régionales, propose en outre que le succès compétitif des lianes sur les arbres est dû aux interactions entre la perturbation forestière et le climat. Nous présentons la première évaluation mondiale de la performance relative des lianes par rapport aux arbres en réponse aux perturbations forestières et aux facteurs climatiques. En utilisant un ensemble de données sans précédent, nous avons analysé 651 échantillons de végétation représentant 26,538 lianes et 82,802 arbres, issus de 556 emplacements uniques dans le monde entier, tirés de 83 publications. Les résultats montrent que les lianes ont de meilleure performances par rapport aux arbres (augmentation du ratio liane‐arbre) lorsque les forêts sont perturbées, sous des zones chaudes aves précipitations faibles, et vers les basses altitudes tropicales. Nous avons également constaté que les lianes peuvent être un facteur critique entravant la récupération des forêts dans les forêts perturbées connaissant des climats favorables aux lianes, car les données de chronoséquence montrent que le succès compétitif élevé des lianes sur les arbres peut persister pendant des décennies après les perturbations, surtout lorsque la température annuelle moyenne dépasse 27.8°C, que les précipitations sont inférieures à 1614 mm et que le déficit hydrique climatique est supérieur à 829 mm. Ces découvertes révèlent que les forêts tropicales dégradées avec des conditions environnementales favorables aux lianes sont disproportionnellement plus vulnérables à la dominance des lianes, et peuvent ainsi potentiellement entraver la succession, avec d'importantes implications pour le puits de carbone mondial et devraient donc être la plus haute priorité à considérer pour la gestion de la restauration.
In a meta‐analysis, we use an unprecedented dataset, representing 556 unique locations worldwide, distributed across 44 countries and six continents to show for the first time that lianas (woody vines) thrive relatively better than trees when forests are disturbed, temperature increase, precipitation decrease, and particularly in tropical lowlands. We demonstrate that liana dominance can persist for decades post‐disturbance and hinder the recovery of disturbed forests, especially when climate favours lianas. With implications for the global carbon sink, our findings suggest that degraded tropical forests with environmental conditions favouring lianas should be the highest priority to consider for restoration management.
Synopsis
The fourth known occurrence of ductal carcinoma in situ found in ectopic breast tissue of the vulva successfully treated with wide‐excision biopsy and anastrozole.
Purpose
Approximately 25 % of cases of clinically active acromegaly cases treated in our academic center between 1996 and 2000, were diagnosed in patients who had elevated plasma IGF-1 levels, but ...apparently “normal” 24-h mean plasma GH levels. The current study served to update the data for patients with acromegaly referred to our facility, after increasing awareness of this “normal” GH subpopulation throughout the medical community.
Methods
A retrospective chart review was conducted on 157 patients with acromegaly who underwent resection of a confirmed somatotroph pituitary adenoma at the University of Michigan Health System between the dates of 1 Jan 2001 to 23 Sept 2015.
Results
Overall prevalence of acromegalic patients with “normal” GH levels, defined as GH <4.7 ng/mL, was 31 %. Over time, the percentage of patients with “normal” GH at diagnosis did not decline: 26 % from 2001 to 2005, 19 % from 2006 to 2010, and 47 % from 2011 to 2015. Mean pituitary tumor size was 1.8 ± 0.1 cm for the group with elevated GH, and 1.2 ± 0.1 cm for the group with “normal” GH (
p
< 0.001). Percent microadenomas was higher in a group with “normal” GH as compared to those with elevated GH (48 vs. 12 %,
p
< 0.001), and tumors >2 cm in the maximal diameter were encountered more frequently in the group with elevated GH (43 vs. 14 %,
p
< 0.001).
Conclusions
Our data show that a substantial percentage of patients with clinical acromegaly have “normal” GH, and therefore strengthens the growing body of evidence which supports the leading role of IGF-1 levels in diagnostic evaluation. At the present time, questions about the natural course of “micromegaly” and treatment benefits compared to the subpopulation with elevated GH levels remain unanswered, but research continues to build on our understanding of the heterogeneous population of individuals.
Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on the ...subcutaneous adipose tissue from patients with Cushing's disease (n=5) compared to patients with nonfunctioning pituitary adenomas (n=11). We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids.
Several reports suggest that spine surgery has experienced rapid growth in the past decade. Limited data exist, however, documenting the increase in spinal fusion. The objective of this work was to ...quantify and characterize the contemporary practice of spinal fusion in the United States.
Clinical data were obtained from the Nationwide Inpatient Sample for the years from 1993 to 2003. All patients with International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes indicating cervical fusion, thoracolumbar fusion, lumbar or unspecified fusion were identified (n = 471,990). Primary ICD-9-CM diagnosis codes were used to determine the rationale for surgical fusion. Population-based utilization rates overall and for each procedure were calculated from United States census data. Rank order of spinal fusion compared with other inpatient procedures from the Nationwide Inpatient Sample was reported for the years 1997 to 2003.
Overall utilization increased during the time period for cervical, thoracolumbar, and lumbar fusions by 89, 31, and 134%, respectively. Patients aged 40 to 59 years experienced the rapid rise in utilization for cervical fusions (60-110 per 100,000) and lumbar fusions (35-84 per 100,000). For patients 60 years and older, utilization also increased for cervical (30-67 per 100,000), thoracolumbar (4-9 per 100,000), and lumbar (42-108 per 100,000). Spinal fusion rose from the 41st most common inpatient procedure in 1997 to the 19th in 2003.
Cervical, thoracolumbar, and lumbar spinal fusion have experienced a rapid increase in utilization in isolation and compared with other surgical procedures in contemporary practice. These changes are most pronounced for patients over 40 years of age, and degenerative disc disease seems to account for much of this increase.
The Adirondack Mountain region is an extensive geographic area (26,305 km2) in upstate New York where acid deposition has negatively affected water resources for decades and caused the extirpation of ...local fish populations. The water quality decline and loss of an established brook trout (Salvelinus fontinalis Mitchill) population in Brooktrout Lake were reconstructed from historical information dating back to the late 1880s. Water quality and biotic recovery were documented in Brooktrout Lake in response to reductions of S deposition during the 1980s, 1990s, and 2000s and provided a unique scientific opportunity to re-introduce fish in 2005 and examine their critical role in the recovery of food webs affected by acid deposition. Using C and N isotope analysis of fish collagen and state hatchery feed as well as Bayesian assignment tests of microsatellite genotypes, we document in situ brook trout reproduction, which is the initial phase in the restoration of a preacidification food web structure in Brooktrout Lake. Combined with sulfur dioxide emissions reductions promulgated by the 1990 Clean Air Act Amendments, our results suggest that other acid-affected Adirondack waters could benefit from careful fish re-introduction protocols to initiate the ecosystem reconstruction of important components of food web dimensionality and functionality.
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