Summary
Exercise training (‘exercise’) and hypocaloric diet (‘diet’) are frequently prescribed for weight loss in obesity. Whilst body weight changes are commonly used to evaluate lifestyle ...interventions, visceral adiposity (VAT) is a more relevant and stronger predictor for morbidity and mortality. A meta‐analysis was performed to assess the effects of exercise or diet on VAT (quantified by radiographic imaging). Relevant databases were searched through May 2014. One hundred seventeen studies (n = 4,815) were included. We found that both exercise and diet cause VAT loss (P < 0.0001). When comparing diet versus training, diet caused a larger weight loss (P = 0.04). In contrast, a trend was observed towards a larger VAT decrease in exercise (P = 0.08). Changes in weight and VAT showed a strong correlation after diet (R2 = 0.737, P < 0.001), and a modest correlation after exercise (R2 = 0.451, P < 0.001). In the absence of weight loss, exercise is related to 6.1% decrease in VAT, whilst diet showed virtually no change (1.1%). In conclusion, both exercise and diet reduce VAT. Despite a larger effect of diet on total body weight loss, exercise tends to have superior effects in reducing VAT. Finally, total body weight loss does not necessarily reflect changes in VAT and may represent a poor marker when evaluating benefits of lifestyle‐interventions.
Context:
Somatic mutations in genes that influence cell entry of calcium have been identified in aldosterone-producing adenomas (APAs) of adrenal cortex in primary aldosteronism (PA). Many adrenal ...glands removed for suspicion of APA do not contain a single adenoma but nodular hyperplasia.
Objective:
The objective of the study was to assess multinodularity and phenotypic and genotypic characteristics of adrenals removed because of the suspicion of APAs.
Design and Methods:
We assessed the adrenals of 53 PA patients for histopathological characteristics and immunohistochemistry for aldosterone (P450C18) and cortisol (P450C11) synthesis and for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations in microdissected nodi.
Results:
Glands contained a solitary adenoma in 43% and nodular hyperplasia in 53% of cases. Most adrenal glands contained only one nodule positive for P450C18 expression, with all other nodules negative. KCNJ5 mutations were present in 22 of 53 adrenals (13 adenoma and nine multinodular adrenals). An ATP1A1 and a CACNA1D mutation were found in one multinodular gland each and an ATP2B3 mutation in five APA-containing glands. Mutations were always located in the P450C18-positive nodule. In one gland two nodules containing two different KCNJ5 mutations were present. Zona fasciculata-like cells were more typical for KCNJ5 mutation-containing nodules and zona glomerulosa-like cells for the other three genes.
Conclusions:
Somatic mutations in KCNJ5, ATP1A1, or CACNA1D genes are not limited to APAs but are also found in the more frequent multinodular adrenals. In multinodular glands, only one nodule harbors a mutation. This suggests that the occurrence of a mutation and nodule formation are independent processes. The implications for clinical management remain to be determined.
Large-scale losses of seagrass beds have been reported for decades and lead to numerous restoration programs. From worldwide scientific literature and 20 years of seagrass restoration research in the ...Wadden Sea, we review and evaluate the traditional guidelines and propose new guidelines for seagrass restoration.
Habitat and donor selection are crucial: large differences in survival were found among habitats and among donor populations. The need to preferably transplant in historically confirmed seagrass habitats, and to collect donor material from comparable habitats, were underlined by our results. The importance of sufficient genetic variation of donor material and prevention of genetic isolation by distance was reviewed. The spreading of risks among transplantation sites, which differed in habitat characteristics (or among replicate sites), was positively evaluated. The importance of ecosystem engineering was shown in two ways: seagrass self-facilitation and facilitation by shellfish reefs. Seagrass self-facilitative properties may require a large transplantation scale or additional measures.
Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing’s syndrome, because there is no recent consensus on ...the management of this rare disorder.
Participants: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing’s syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing’s disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing’s disease, and 5) management of ectopic ACTH syndrome, Nelson’s syndrome, and special patient populations.
Evidence: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking.
Consensus Process: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority.
Conclusions: ACTH-dependent Cushing’s syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing’s syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing’s disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing’s syndrome, early diagnosis and prompt therapy are warranted.
Seagrasses are well-known ecosystem engineers. They reduce water dynamics and sediment resuspension, and trap fine sediments. However, exceptions of this paradigm have been reported. To test whether ...these exceptions could be related to plant cover and environmental conditions, we investigated sediment modification under influence of seagrass presence in various annual eelgrass (
Zostera marina) beds with varying plant cover and sediment composition.
At the relatively wave-exposed, sandy sites, dense vegetation caused muddification (increase in fine sediments and organic content) of the sediments. Sparse vegetation (<35% cover) had no effect, as such confirming the classical sediment trapping paradigm. In contrast, at the sheltered sites with muddy sediments, dense vegetation had no effect on the sediment composition, and in sparse vegetation sandification (decrease in fine sediments and organic content) was recorded. Sandification was never recorded before and was probably related to turbulence enhancement.
Both, muddification and sandification are likely to provide a feedback on seagrass performance. Muddification may increase the nutrient input and, depending on the nutrient status of the system, either stimulate or reduce seagrass development. Similarly, sandification may postpone and even prevent extinction of seagrass beds when it occurs in areas that may have become too muddy for seagrass growth.
Context and Objective:
Pheochromocytomas and paragangliomas (PGLs) are neuroendocrine tumors of sympathetic or parasympathetic paraganglia. Nearly 40% of PGLs are caused by germline mutations. The ...present study investigated the effect of genetic alterations on metabolic networks in PGLs.
Design:
Homogenates of 32 sporadic PGLs and 48 PGLs from patients with mutations in SDHB, SDHD, SDHAF-2, VHL, RET, and NF-1 were subjected to proton (1H) nuclear magnetic resonance (NMR) spectroscopy at 500 MHz for untargeted and HPLC tandem mass spectrometry for targeted metabolite profiling.
Results:
1H NMR spectroscopy identified 28 metabolites in PGLs of which 12 showed genotype-specific differences. Part of these results published earlier reported low complex II activity (P < .0001) and low ATP/ADP/AMP content (P < .001) in SDH-related PGLs compared with sporadics and PGLs of other genotypes. Extending these results, low levels of N-acetylaspartic acid (NAA; P < .05) in SDH tumors and creatine (P < .05) in VHL tumors were observed compared with sporadics and other genotypes. Positive correlation was observed between NAA and ATP/ADP/AMP content (P < .001) and NAA and complex II activity (P < .0001) of PGLs. Targeted purine analysis in PGLs showed low adenine in cluster 1 compared with cluster 2 tumors (SDH P < .0001; VHL P < .05) whereas lower levels (P < .05) of guanosine and hypoxanthine were observed in RET tumors compared with SDH tumors. Principal component analysis (PCA) of metabolites could distinguish PGLs of different genotypes.
Conclusions:
The present study gives a comprehensive picture of alterations in energy metabolism in SDH- and VHL-related PGLs and establishes the interrelationship of energy metabolism and amino acid and purine metabolism in PGLs.
The relation between vegetable and fruit consumption and colorectal cancer risk was comprehensively assessed in the Netherlands Cohort Study on Diet and Cancer using a validated 150-item food ...frequency questionnaire. After 6.3 years of follow-up (1986-1992), over 1,000 incident cases of colorectal cancer were registered. Using case-cohort analysis, the authors calculated rate ratios and 95% confidence intervals adjusted for age, alcohol intake, and family history of colorectal cancer. For colon cancer, no statistically significant associations with total vegetable intake or total fruit intake were found. However, among women, an inverse association was observed with vegetables and fruits combined (for the highest quintile vs. the lowest, the rate ratio was 0.66 (95% confidence interval: 0.44, 1.01)). Brassica vegetables and cooked leafy vegetables showed inverse associations for both men and women. Among women and, to a lesser extent, among men, inverse associations were stronger for distal colonic tumors than for proximal colonic tumors. For rectal cancer, no statistically significant associations were found for vegetable consumption or fruit consumption or for specific groups of vegetables and fruits; only Brassica vegetables showed a positive association in women. As in other cohort studies, the observed inverse relation between vegetable and fruit consumption and occurrence of colorectal cancer was less strong than relations reported in case-control studies.
The determinants that cause impaired quality of life (QOL) in patients in long-term remission of Cushing's syndrome (CS) are unknown. The aim of this study was to get more insight into the patient ...and disease characteristics related to impaired QOL in these patients.
Cross-sectional study.
The QOL of 123 patients in remission of CS (age 52.2 ± 12.0 years, 106 women, duration of remission 13.3 ± 10.4 years, 80% pituitary CS), assessed with seven validated questionnaires, was compared with the QOL of an age- and sex-matched control group (n=105). To investigate the influence of the aetiology of CS on QOL, patients in remission of pituitary and adrenal CS were compared. Furthermore, the influence of hormonal deficiencies, treatment strategy, duration of remission, gender and age on QOL was investigated.
QOL in the total patient group and each patient subgroup was significantly worse on practically all dimensions of questionnaires compared with the control group (P<0.05), except for patients in remission of pituitary CS without hormonal deficiencies who had an impaired QOL on 50% of the QOL dimensions. Subgroup analysis revealed no difference in QOL between different patient groups, especially no difference between patients in remission of adrenal and pituitary CS. Female gender and a shorter duration of remission had a negative influence on QOL in the patient group.
QOL remains impaired in patients in long-term remission of CS regardless of aetiology, presence of hormonal deficiencies and treatment strategies. More research is needed to establish the causes.
Although the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated ...long-term recurrence rates. This is the largest endoscopic series published till now.
To gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas.
Retrospective cohort study.
The medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤ 50 nmol/l either basal or after 1 mg dexamethasone.
The remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71 ± 39 months of follow-up (mean ± S.D., range 10-165 months).
Endoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.
Context:
Venous thrombosis has frequently been reported in patients with endogenous Cushing's syndrome (CS).
Objective:
The aim of this study was to evaluate the incidence of venous thromboembolism ...(VTE) in patients with CS prior to treatment and after surgery.
Design and Setting:
We conducted a multicenter cohort study at all university medical centers in The Netherlands.
Patients:
Consecutive patients diagnosed with endogenous CS of benign origin between January 1990 and June 2010 were eligible for inclusion. Patients surgically treated for nonfunctioning pituitary adenoma served as controls for the incidence of postoperative VTE in ACTH-dependent CS.
Main Outcome Measures:
We documented all objectively confirmed VTE during 3 yr prior to, and 3 yr after treatment onset. The incidences of VTE were expressed as incidence rates.
Results:
A total of 473 patients (mean age 42 yr, 363 women) were included (360 ACTH-dependent pituitary CS). The total number of person-years was 2526. Thirty-seven patients experienced VTE during the study period, resulting in an incidence rate of 14.6 95% confidence interval (CI) 10.3–20.1 per 1000 person-years. The incidence rate for first-ever VTE prior to treatment was 12.9 (95% CI 7.5–12.6) per 1000 person-years (17 events). The risk of postoperative VTE, defined as risk within 3 months after surgery, was 0% for ACTH-independent and 3.4% (95% CI 2.0–5.9) for ACTH-dependent CS (12 events in 350 patients); most events occurred between 1 wk and 2 months after surgery. Compared with the controls, the risk of postoperative VTE in patients undergoing transsphenoidal surgery was significantly greater (P = 0.01).
Conclusions:
Patients with CS are at high risk of VTE, especially during active disease and after pituitary surgery. Guidelines on thromboprophylaxis are urgently needed.
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