The aim of the present systematic review was to evaluate the available evidence on laboratory diagnosis of CDI and to formulate recommendations to optimize CDI testing. In comparison with cell ...culture cytotoxicity assay (CCA) and toxigenic culture (TC) of stools, we analyzed the test characteristics of 13 commercial available enzyme immunoasssays (EIA) detecting toxins A and/or B, 4 EIAs detecting Clostridium difficile glutamate dehydrogenase (GDH), and a real-time PCR for C. difficile toxin B gene. In comparison with CCA and TCA and assuming a prevalence of CDI of 5%, PPV and NPV varied between 0.28–0.77, 0.12–0.65 and 0.98–1.00, 0.97–1.00, respectively. Only if the tests were performed in a population with a CDI prevalence of 50 percent, would PPVs be acceptable (ranging from 0.71 to 1.00).To overcome the problem of a low PPV, we propose a two step approach, with a second test or a reference method in case of a positive first test. Further reducing the number of false negative results would require either retesting of all subjects with a negative first test, or re-testing all subjects with a negative second test, after an initially positive test. This approach resulted in non-significant improvements, and emphasizes the need for better diagnostic tests. Further studies to validate the applicability of two-step testing, including assessment of clinical features, are required.
Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Standard treatment is surgical resection. Following complete resection of the primary tumour, patients with PPGL are at ...risk of developing new tumoural events. The present guideline aims to propose standardised clinical care of long-term follow-up in patients operated on for a PPGL. The guideline has been developed by The European Society of Endocrinology and based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) principles. We performed a systematic review of the literature and analysed the European Network for the Study of Adrenal Tumours (ENS@T) database. The risk of new events persisted in the long term and was higher for patients with genetic or syndromic diseases. Follow-up in the published cohorts and in the ENS@T database was neither standardised nor exhaustive, resulting in a risk of follow-up bias and in low statistical power beyond 10 years after complete surgery. To inform patients and care providers in this context of low-quality evidence, the Guideline Working Group therefore prepared recommendations on the basis of expert consensus. Key recommendations are the following: we recommend that all patients with PPGL be considered for genetic testing; we recommend assaying plasma or urinary metanephrines every year to screen for local or metastatic recurrences or new tumours; and we suggest follow-up for at least 10 years in all patients operated on for a PPGL. High-risk patients (young patients and those with a genetic disease, a large tumour and/or a paraganglioma) should be offered lifelong annual follow-up.
Summary
Background
Chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD) can be used for palliative treatment of malignant pheochromocytoma and paraganglioma. However, the precise ...effect of this chemotherapeutic regimen on tumour volume is unclear. The main objective of this study was to perform a systematic review and meta‐analysis assessing the effect of chemotherapy with CVD on tumour volume in patients with malignant paraganglioma/pheochromocytoma.
Methods
A literature search was performed in October 2013 to identify potentially relevant studies. Main outcomes were the pooled percentages of complete response, partial response and stable disease after chemotherapy with CVD. A meta‐analysis was performed with an exact likelihood approach using a logistic regression. Pooled percentages with 95% confidence intervals (CI) were reported.
Results
Four studies concerning a total of 50 patients with malignant paraganglioma/pheochromocytoma reported on treatment with a combination of CVD chemotherapy. A meta‐analysis of the effect of chemotherapy on tumour volume showed pooled percentages of complete response, partial response and stable disease of, respectively, 4% (95% CI: 1%–15%), 37%(95% CI: 25%–51%) and 14% (95% CI: 7%–27%). Only two studies concerning a total of 35 patients assessed the response on catecholamine excess; pooled percentages for complete, partial and stable hormonal response were 14% (95% CI: 6%–30%), 40% (95% CI: 25%–57%) and 20% (95% CI: 10%–36%), respectively. Duration of response was also reported in only two studies with a median duration of response of 20 months and 40 months.
Conclusions
Data on the effects of a combination of CVD chemotherapy on malignant paraganglioma/pheochromocytoma suggest that a partial response concerning tumour volume can be achieved in about 37% of patients and a partial response on catecholamine excess in about 40% of patients. However, in the included studies, the protocol when to initiate treatment was not well described. Therefore, it cannot be excluded that the reported effect of chemotherapy on tumour volume reflects the natural course of the disease, at least partially.
In 2009 the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnosing Clostridium difficile infection (CDI) was launched. Since then newer tests for ...diagnosing CDI have become available, especially nucleic acid amplification tests. The main objectives of this update of the guidance document are to summarize the currently available evidence concerning laboratory diagnosis of CDI and to formulate and revise recommendations to optimize CDI testing. This update is essential to improve the diagnosis of CDI and to improve uniformity in CDI diagnosis for surveillance purposes among Europe. An electronic search for literature concerning the laboratory diagnosis of CDI was performed. Studies evaluating a commercial laboratory test compared to a reference test were also included in a meta-analysis. The commercial tests that were evaluated included enzyme immunoassays (EIAs) detecting glutamate dehydrogenase, EIAs detecting toxins A and B and nucleic acid amplification tests. Recommendations were formulated by an executive committee, and the strength of recommendations and quality of evidence were graded using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. No single commercial test can be used as a stand-alone test for diagnosing CDI as a result of inadequate positive predictive values at low CDI prevalence. Therefore, the use of a two-step algorithm is recommended. Samples without free toxin detected by toxins A and B EIA but with positive glutamate dehydrogenase EIA, nucleic acid amplification test or toxigenic culture results need clinical evaluation to discern CDI from asymptomatic carriage.
Patients with polycystic ovary syndrome (PCOS) are at risk of arterial disease. We examined the risk of (non)fatal coronary heart disease (CHD) or stroke in patients with PCOS and ovulatory women ...without PCOS, and assessed whether obesity might explain a higher risk of CHD or stroke.
We performed a systematic review and meta-analysis of controlled observational studies. Four definitions of PCOS were considered: World Health Organization type II anovulation, National Institutes of Health criteria, Rotterdam consensus and Androgen-excess criteria. Obesity was defined as BMI > 30 kg/m(2) and/or waist circumference >88 cm. Study quality was assessed using the Newcastle-Ottawa Scale. Primary outcome was fatal/non-fatal CHD or stroke. Definitions of CHD and stroke were based on criteria used by the various authors. The effect measure was the pooled relative risk in a random effects model. Risk ratios and rate ratios were combined here.
After identifying 1340 articles, 5 follow-up studies published between 2000 and 2008 were included. The studies showed heterogeneity in design, definitions and quality. In a random effects model the relative risk for CHD or stroke were 2.02 comparing women with PCOS to women without PCOS (95% confidence interval 1.47, 2.76). Pooling the two studies with risk estimates adjusted for BMI showed a relative risk of 1.55 (1.27, 1.89).
This meta-analysis showed a 2-fold risk of arterial disease for patients with PCOS relative to women without PCOS. BMI adjustment did not affect this finding, suggesting the increased risk for cardiovascular events in PCOS is not completely related to a higher BMI in patients with PCOS.
Objective Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis. Many publications in ACC report on risk factors for a poor outcome; one risk factor studied is hormonal hypersecretion ...(cortisol, sex-hormones, steroid precursors or aldosterone). The aim of this systematic review was to study the association between hormonal secretion and recurrence or mortality in ACC. Design Systematic review and meta-analysis. We searched PubMed, EMBASE and The Cochrane library (January 2018) for cohort studies examining the association between hormonal secretion on overall or recurrence-free survival in ACC. Methods A random-effects model meta-analysis was performed to obtain a weighted relative risk comparing cortisol-secreting and/or androgen-secreting ACCs to non-secreting tumours regarding overall and recurrence-free survival. Risk of bias assessment was performed for all studies included. Results Nineteen publications were included representing a total of 3814 patients. Most studies were generally considered low/intermediate risk of bias. Meta-analysis showed higher mortality risk for cortisol-secreting ACCs, weighted relative risk 1.71 (95% CI: 1.18-2.47) combining studies that adjusted for tumour stage; also a higher recurrence risk was found for cortisol producing ACCs, relative risk 1.43 (95% CI: 1.18-1.73). Androgen secretion was not clearly associated with survival (RR: 0.82, 95% CI: 0.60-1.12). Conclusion This systematic review and meta-analysis show that cortisol-secreting ACCs are associated with a worse overall survival; future research is needed to establish whether this association points to negative effects of cortisol action, whether it signifies a more aggressive ACC subtype or whether cortisol is merely a prognostic marker.
Mortality in Acromegaly: A Metaanalysis Dekkers, O. M; Biermasz, N. R; Pereira, A. M ...
The journal of clinical endocrinology and metabolism,
01/2008, Letnik:
93, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Context: Several studies have assessed mortality risk in patients treated for acromegaly. All studies found a mortality that was higher than expected for the general population, but most of these ...increases were not statistically significant. For this reason, it is not formally established whether mortality in acromegaly is different from the general population.
Objective: The objective of the study was to address the all-cause mortality risk in patients with acromegaly.
Design: The study was a metaanalysis.
Methods: Sixteen studies on mortality in patients with acromegaly were included. The principal outcome of the metaanalysis was the weighted average of the standardized mortality ratio (SMR) of all studies. In addition, we performed a subgroup analysis of studies in which more than 80% of the patients were treated by transsphenoidal approach.
Results: The weighted mean of the SMR from all 16 studies was 1.72 (95% confidence interval 1.62–1.83). In studies with transsphenoidal surgery as the primary therapy, the weighted mean of the SMR was 1.32 (95% confidence interval 1.12–1.56).
Conclusions: This metaanalysis shows increased all-cause mortality in acromegalic patients, compared with the general population, even after transsphenoidal surgery.
Context: Increased mortality in patients with pituitary tumors after surgical treatment has been reported. However, it is unknown to what extent excess mortality is caused by pituitary tumors and ...their treatment in general and to what extent by previous exposure to hormonal overproduction.
Objective: The aim of the study was to compare mortality between patients treated for Cushing’s disease and nonfunctioning pituitary macroadenomas (NFMAs).
Design: This was a follow-up study.
Patients: We included 248 consecutive patients with pituitary adenomas treated by transsphenoidal surgery in our hospital for NFMAs (n = 174) and ACTH-producing adenomas (n = 74). The mean duration of follow-up after surgery was 10.1 ± 7.2 yr for the whole cohort.
Outcome Measures: The standardized mortality ratio (SMR) was calculated for the whole cohort and also for the two diseases separately. Cox regression analysis was used to compare mortality in patients with Cushing’s disease with NFMA patients.
Results: Patients with Cushing’s disease (39.1 ± 16.1 yr) were significantly younger at time of operation than NFMA patients (55.3 ± 13.4 yr). The SMR for the whole cohort was 1.41 95% confidence interval (CI), 1.05–1.86. The SMR in NFMA patients was 1.24 (95% CI, 0.85–1.74) vs. 2.39 (95% CI, 1.22–3.9) in patients with Cushing’s disease. In patients with Cushing’s disease, compared with NFMAs, the age-adjusted mortality was significantly increased: hazard ratio 2.35 (95% CI, 1.13–4.09, P = 0.008).
Conclusions: Mortality in patients previously treated for Cushing’s disease is increased, compared with patients treated for NFMAs. This implies that previous, transient overexposure to cortisol is associated with increased mortality.
Aims/hypothesis This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. Methods PubMed, EMBASE and Web of Science were searched for ...articles assessing the association between genes and diabetic nephropathy. All genetic variants statistically associated with diabetic nephropathy in an initial study, then independently reproduced in at least one additional study, were selected. Subsequently, all studies assessing these variants were included. The association between these variants and diabetic nephropathy (defined as macroalbuminuria/proteinuria or end-stage renal disease ESRD) was calculated at the allele level and the main measure of effect was a pooled odds ratio. Pre-specified subgroup analyses were performed, stratifying for type 1/type 2 diabetes mellitus, proteinuria/ESRD and ethnic group. Results The literature search yielded 3,455 citations, of which 671 were genetic association studies investigating diabetic nephropathy. We identified 34 replicated genetic variants. Of these, 21 remained significantly associated with diabetic nephropathy in a random-effects meta-analysis. These variants were in or near the following genes: ACE, AKR1B1 (two variants), APOC1, APOE, EPO, NOS3 (two variants), HSPG2, VEGFA, FRMD3 (two variants), CARS (two variants), UNC13B, CPVL and CHN2, and GREM1, plus four variants not near genes. The odds ratios of associated genetic variants ranged from 0.48 to 1.70. Additional variants were detected in subgroup analyses: ELMO1 (Asians), CCR5 (Asians) and CNDP1 (type 2 diabetes). Conclusions/interpretation This meta-analysis found 24 genetic variants associated with diabetic nephropathy. The relative contribution and relevance of the identified genes in the pathogenesis of diabetic nephropathy should be the focus of future studies.
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