Duration of type 2 diabetes strongly predicts all-cause and cardiovascular mortality in people referred for coronary angiography

ObjectiveType 2 diabetes represents a major cardiovascular risk factor. However, few studies have addressed the impact of the disease duration on mortality. Thus, we aimed to investigate the predictive value of diabetes duration for all-cause and cardiovascular mortality in subjects undergoing coronary angiography.MethodsWe studied 2455 participants of the LUdwigshafen RIsk and Cardiovascular health study (1768 males/687 females). They had a mean ± standard deviation (SD) age of 63.1 ± 9.0 years (range: 40.0–79.9) and a mean ± SD body mass index of 27.7 ± 4.0 kg/m². 704 subjects were newly diagnosed with type 2 diabetes according to the 2010 criteria of the American Diabetes Association and 446 subjects had a known history of type 2 diabetes. The mean ± SD duration of the follow-up for all-cause and cardiovascular mortality was 7.4 ± 2.3 years.ResultsA total of 543 deaths occurred during the follow-up. Among these, 343 were accounted for by cardiovascular diseases. The duration of type 2 diabetes was strongly and positively correlated with all-cause and cardiovascular mortality (both P < 0.001). The multivariate adjusted hazard ratios (95% confidence intervals) for cardiovascular mortality compared to subjects without diabetes were 1.76 (1.34–2.32), 2.86 (2.00–4.08), 2.96 (1.85–4.74), and 4.55 (3.24–6.39) for subjects with new onset type 2 diabetes and subjects with known type 2 diabetes (duration ≤5, >5 and ≤10, >10 years), respectively.ConclusionsThe data emphasise the need to consider the diabetes duration for the prediction of mortality in subjects at intermediate to high cardiovascular risk.     

Tonic postganglionic sympathetic inhibition induced by afferent renal nerves?

Other than efferent sympathetic innervation, the kidney has peptidergic afferent fibers expressing TRPV1 receptors and releasing substance P. We tested the hypothesis that stimulation of afferent renal nerve activity with the TRPV1 agonist capsaicin inhibits efferent renal sympathetic nerve activity tonically by a neurokinin 1 receptor-dependant mechanism. Anesthetized Sprague-Dawley rats were instrumented as follows: (1) arterial and venous catheters for recording of blood pressure and heart rate and drug administration; (2) left-sided renal arterial catheter for selective intrarenal administration of the TRPV1 agonist capsaicin (3.3, 6.6, 10, 33*10(-7) m; 10 μL; after 15, 30, 45, and 60 minutes, respectively) to stimulate afferent renal nerve activity; (3) right-sided bipolar electrode for continuous renal sympathetic nerve recording; and (4) specialized renal pelvic and renal artery catheters to separate pelvic from intrarenal afferent activity. Before and after intrarenal capsaicin application, increasing intravenous doses of the neurokinin 1 receptor blocker RP67580 were given. Intrarenal capsaicin decreased integrated renal sympathetic activity from 65.4±13.0 mV*s (baseline) to 12.8±3.2 mV*s (minimum; P<0.01). This sustained renal sympathetic inhibition reached its minimum within 70 minutes and was not directly linked to the transient electric afferent response to be expected with intrarenal capsaicin. Suppressed renal sympathetic activity transiently but completely recovered after intravenous administration of the neurokinin 1 blocker (maximum: 120.3±19.4 mV*s; P<0.01). Intrarenal afferent activity could be unequivocally separated from pelvic afferent activity. For the first time we provide direct evidence that afferent intrarenal nerves provide a tonically acting sympathoinhibitory system, which seems to be rather mediated by neurokinin release acting via neurokinin 1 receptor pathways rather than by electric afferent effects on central sympathetic outflow.     

Markers for endothelial dysfunction,but not markers for oxidative stress correlate with classical risk factors and the severity of coronary artery disease

Objective. Endothelial dysfunction and oxidative stress are involved in atherogenesis. In the search for predictors of vascular disease markers for endothelial dysfunction and oxidative stress were analyzed. Methods. Of 208 consecutive patients 22% were controls (CO) without coronary artery disease (CAD), 52% presented with stable angina (SAP) and 26% had acute coronary syndromes (ACS). Nitric oxide (NO), thrombomodulin (TM), von Willebrand factor (vW), sVCAM-1, sICAM-1, sP-selectin, sE-selectin, sL-selectin and C-reactive protein (CRP) were determined as markers for endothelial dysfunction, glutathione (GSH), glutathione peroxidase (Gpx), myeloperoxidase (Mpx), lipid peroxides (Lpx), 8-isoprostane (Iso), superoxide dismutase (SOD), total antioxidant capacity (TAC) and homocysteine (Hc) as markers for oxidative stress. Results. The increases of TM, vW, sVCAM-1, CRP, SOD and Mpx correlated with the CAD status in the order CO?<?SAP?<?ACS, whereas NO and sL-selectin were inversely correlated (p?<?0.05, resp.). The other markers remained unchanged. For several markers a significant relationship to risk factors was detected. Conclusions. Markers for endothelial dysfunction rather than those for oxidative stress may serve as indicators for the presence and severity of CAD.     

Prevention of symptomatic vasospasm after SAH by constant venous infusion of nimodipine

Sixty-one patients with SAH due to rupture of a cerebral aneurysm, classified in Grades I to IV according to Hunt and Hess, received a constant venous infusion of Nimodipine in a dose of 2mg/h for at least 14 days, followed by an oral administration of 60 mg/6 h for at least 4 days. Patients admitted after the 6th day of SAH, patients with SAH but without aneurysm on the angiogram and patients in Grade V were excluded. Mortality in 30 patients of Grades I-II was 3.3%, in 31 patients of Grades III-IV 42%. In the latter group 1 patient died due to cerebral vasospasm. Transient vasospasm occurred in 2 patients of Grades I-II. Recovery was complete in both cases. Thus, incidence of cerebral vasospasm was 4.9%, the incidence of poor-outcome-vasospasm even only 1.6%. The syndrome of cerebral vasospasm seems to be more than only constriction of cerebral vessels. The deleterious effects of Ca²⁺ shift into vascular cells and into neural cells which causes irreversible damage are discussed. Early administration of a specific 'cerebral' calcium antagonist like Nimodipine after SAH will prevent the intracellular Ca²⁺ overloading, thus protecting the neural cells and preventing Ca²⁺-induced smooth-muscle contraction of cerebral vessels, which encourages ischaemic deficits after SAH. The preventive use of Nimodipine has markedly reduced the incidence of symptomatic vasospasm in our clinic.     

Seroprevalence of anti-N-methyl-d-aspartate receptor antibodies in women with ovarian teratoma

Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.     

Chondrocyte cultures from human proximal interphalangeal finger joints

Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described. Chondrocyte culture has been essential to understand cartilage degeneration, which is a hallmark of OA. We investigated the feasibility of human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints. Hyaline cartilage of the PIP and knee joints was obtained from human cadavers. Chondrocytes harvested up to 236 h after death of the donors were viable and expressed chondrocyte‐specific genes. Gene expression comparing chondrocytes from PIP and knee joints using Affymetrix GeneChip arrays resulted in a unique PIP‐specific gene expression pattern. Genes involved in developmental processes including the WNT pathway were differentially expressed between the joints. These findings suggest that our knowledge on chondrocyte biology derived mainly from knee and hip joints may not apply to chondrocytes of the PIP joints and some of the distinctive features of HOA may be caused by the specific properties of PIP chondrocytes. Chondrocyte culture of PIP cartilage is a novel tool to study cartilage degeneration in HOA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1569–1575, 2016.     

Potential role of <Superscript>68</Superscript>Ga-DOTATOC PET/CT in screening for pancreatic neuroendocrine tumour in patients with von Hippel-Lindau disease

Purpose

Neuroendocrine tumours of the pancreas (pNET) are observed in 8 – 17 % of patients with von Hippel-Lindau disease (vHLD), and 11 – 20 % of these patients develop metastatic disease. MRI and CT have a very high resolution; however, their sensitivity and specificity for the detection of pNET amongst cystic lesions in the pancreas of vHLD patients are generally considered insufficient. In contrast, ⁶⁸Ga-DOTATOC PET/CT demonstrates a high sensitivity for the diagnosis and staging of neuroendocrine tumours. In this study we investigated the potential role of ⁶⁸Ga-DOTATOC PET/CT in screening of patients with vHLD.

Method

⁶⁸Ga-DOTATOC PET/three-phase contrast-enhanced CT was performed according to guidelines in all consecutive vHLD patients between January 2012 and November 2015. All patients underwent additional MRI imaging of the abdomen, spine, and head. Chromogranin A (CgA) was determined at the time of the PET/CT examination. A lesion seen on ⁶⁸Ga-DOTATOC PET in the pancreas was defined as positive if the uptake was visually higher than in the surrounding tissues. Lesions were quantified using maximum SUV.

Results

Overall, 20 patients (8 men, 12 women; mean age 44.7?±?11.1 years) were prospectively examined. Genetically, 12 patients had type 1 vHLD and 8 had type 2 vHLD. ⁶⁸Ga-DOTATOC PET/CT detected more pNET than morphological imaging (CT or MRI): 11 patients (55 %; 8 type 1, 3 type 2) vs. 9 patients (45 %; 6 type 1, 3 type 2). The concentration of CgA was mildly elevated in 2 of 11 patients with pNET. The mean SUVmax of the pancreatic lesions was 18.9?±?21.9 (range 5.0 – 65.6). Four patients (36.4 %) had multiple pNETs. The mean size of the lesions on CT and/or MRI was 10.4?±?8.3 mm (range 4 – 38 mm), and 41.1 % were larger than 10 mm. In addition, somatostatin receptor-positive cerebellar and spinal haemangioblastomas were detected in three patients (SUVmax 2.1 – 10.1). One patient presented with a solitary somatostatin receptor-positive lymph node metastasis. pNETs were observed more frequently in vHLD type 1 than type 2 (66.7 % vs. 37.5 %, p?=?0.089). None of the patients showed progressive disease during follow-up.

Conclusion

In this study, ⁶⁸Ga-DOTATOC PET detected pNETs in a higher proportion of patients with vHLD than found in previous studies with ¹¹¹In-octreoscan, the imaging method recommended by the NCCN. We therefore suggest ⁶⁸Ga-DOTATOC PET/CT as the more sensible screening tool.

     

Management of bloodstream infections by infection specialists: an international ESCMID cross-sectional survey

Bloodstream infections (BSIs) are common, however international guidelines are available only for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and candidaemia. This international ESCMID cross-sectional survey, open from December 2016 to February 2017, explored the management of BSIs by infection specialists. All infection specialists (senior or trainees) giving at least weekly advice on positive blood cultures could participate. Their practices were evaluated using six clinical vignettes presenting uncomplicated BSI cases. A total of 616 professionals from 56 countries participated [333/616 (54%) infectious diseases specialists, 188/616 (31%) clinical microbiologists], of whom 76% (468/616) were members of an antimicrobial stewardship team. Large variations in practice were noted, in particular for the Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa vignettes. Echocardiography was considered standard of care by 81% (373/459) of participants for MRSA, 78% (400/510) for methicillin-susceptible S. aureus and 60% (236/395) for Candida albicans. Antimicrobial combination therapy was recommended by 2% (8/360) of respondents for C. albicans, 11% (43/378) for E. coli, 27% (114/420) for MRSA and 39% (155/393) for E. faecalis. Intravenous-to-oral switch was considered in 68% (285/418) for MRSA, 79% (306/388) for E. faecalis, 72% (264/366) for P. aeruginosa and 75% (270/362) for C. albicans. In multivariable analysis, IDSA guideline-compliant practice was more frequent among participants belonging to an antimicrobial stewardship team (aOR?=?1.7, P?=?0.018 for the MRSA vignette; and aOR?=?2.0, P?=?0.008 for the candidaemia vignette). This survey showed large variations in practice among infection specialists. International guidelines on management of BSI are urgently needed.