High rate of autonomic neuropathy in Cornelia de Lange Syndrome.

BACKGROUND: Cornelia de Lange Syndrome (CdLS) is a rare congenital disorder characterized by typical facial features, growth failure, limb abnormalities, and gastroesophageal dysfunction that may be caused by mutations in several genes that disrupt gene regulation early in development. Symptoms in individuals with CdLS suggest that the peripheral nervous system (PNS) is involved, yet there is little direct evidence. METHOD: Somatic nervous system was evaluated by conventional motor and sensory nerve conduction studies and autonomic nervous system by heart rate variability, sympathetic skin response and sudomotor testing. CdLS Clinical Score and genetic studies were also obtained. RESULTS: Sympathetic skin response and sudomotor test were pathological in 35% and 34% of the individuals with CdLS, respectively. Nevertheless, normal values in large fiber nerve function studies. CONCLUSIONS: Autonomic nervous system (ANS) dysfunction is found in many individuals with Cornelia de Lange Syndrome, and could be related to premature aging.

A prospective, observational study of the performance of MEWS, NEWS, SIRS and qSOFA for early risk stratification for adverse outcomes in patients with suspected infections at the emergency department.

BACKGROUND: Many patients with suspected infection are presented to the emergency Department. Several scoring systems have been proposed to identify patients at high risk of adverse outcomes. METHODS: We compared generic early warning scores (MEWS and NEWS) to the (SIRS) criteria and quick Sequential Organ Failure Assessement (qSOFA), for early risk stratification in 1400 patients with suspected infection in the ED. The primary study end point was 30-day mortality. RESULTS: The AUROC of the NEWS score for predicting 30-day mortality was 0.740 (95% Confidence Interval 0.682- 0.798), higher than qSOFA (AUROC of 0.689, 95% CI 0.615- 0.763), MEWS (AUROC 0.643 (95% CI 0.583-0.702) and SIRS (AUROC 0.586, 95%CI 0.521 - 0.651). The sensitivity was also highest for NEWS⋝ 5 (sensitivity 75,8% specificity of 67,4%). CONCLUSION: Among patients presenting to the ED with suspected infection, early risk stratification with NEWS (cut-off of ⋝5) is more sensitive for prediction of mortality than qSOFA, MEWS or SIRS, with adequate specificity.

Appearance of Focal Nodular Hyperplasia after Chemotherapy in Two Patients during Follow-Up of Colon Carcinoma.

Surgical liver resection is a treatment option in patients with resectable colorectal liver metastases. We present two cases of focal nodular hyperplasia (FNH) development after treatment with oxaliplatin during follow-up of colon carcinoma. The first case was a 40-year-old male patient who developed multiple liver lesions suspect for metastatic disease four years after he had undergone laparoscopic right-sided hemicolectomy and adjuvant chemotherapy (capecitabine and oxaliplatin). He underwent a metastasectomy of segments three and four and microwave ablation (MWA) of the lesion in segment one. Pathological analysis demonstrated FNH. The second patient was a 21-year-old woman who presented with multiple liver lesions during follow-up for colon carcinoma. She underwent a laparoscopic right-sided hemicolectomy and was adjuvantly treated with capecitabine and oxaliplatin three years ago. Magnetic resonance imaging (MRI) was performed, and the lesions showed no signs of metastatic disease but were classified as FNH. Therefore, the decision was made to follow up the patient. In conclusion, the development of benign liver lesions could occur during follow-up of colon carcinoma and might be caused by oxaliplatin-induced changes to the liver parenchyma. Hence, it is important to distinguish these from metastatic liver disease.

Widespread reforestation before European influence on Amazonia.

An estimated 90 to 95% of Indigenous people in Amazonia died after European contact. This population collapse is postulated to have caused decreases in atmospheric carbon dioxide concentrations at around 1610 CE, as a result of a wave of land abandonment in the wake of disease, slavery, and warfare, whereby the attendant reversion to forest substantially increased terrestrial carbon sequestration. On the basis of 39 Amazonian fossil pollen records, we show that there was no synchronous reforestation event associated with such an atmospheric carbon dioxide response after European arrival in Amazonia. Instead, we find that, at most sites, land abandonment and forest regrowth began about 300 to 600 years before European arrival. Pre-European pandemics, social strife, or environmental change may have contributed to these early site abandonments and ecological shifts.

Broken Mirror Symmetry of Tracer's Trajectories in Turbulence.

Topological properties of physical systems play a crucial role in our understanding of nature, yet their experimental determination remains elusive. We show that the mean helicity, a dynamical invariant in ideal flows, quantitatively affects trajectories of fluid elements: the linking number of Lagrangian trajectories depends on the mean helicity. Thus, a global topological invariant and a topological number of fluid trajectories become related, and we provide an empirical expression linking them. The relation shows the existence of long-term memory in the trajectories: the links can be made of the trajectory up to a given time, with particles positions in the past. This property also allows experimental measurements of mean helicity.

Inhibition of activin-like kinase 4/5 attenuates cancer cachexia associated muscle wasting.

Cancer mediated activation of the ActRIIB-ALK4/5 heterodimer by myostatin is strongly associated with muscle wasting. We investigated in vitro and in vivo the efficacy of ALK4/5 receptor blockers SB431542 and GW788388 in preventing muscle wasting, and explored synergy with IGF-I analogue LONG R3 (LR3) IGF-I. In vitro, C2C12 skeletal muscle cells were treated with vehicle, SB431542, GW788388 and LR3 IGF-I. A C26-CD2F1 cachexia model was used to induce cachexia in vivo. Mice were allocated as non-tumour bearing (NTB) or C26 tumour-bearing (C26 TB) vehicle control, treated with SB431542, LR3 IGF-I, SB431542 and LR3 IGF-I, or GW788388 (intraperitoneally or orally). In vitro, differentiation index and mean nuclei count increased using SB431542, GW788388, LR3 IGF-I. In vivo, GW788388 was superior to SB431542 in limiting loss of bodyweight, grip-strength and gastrocnemius weight. and downregulated Atrogin-1 expression comparable to NTB mice. LR3 IGF-I treatment limited loss of muscle mass, but at the expense of accelerated tumour growth. In conclusion, treatment with GW788388 prevented cancer cachexia, and downregulated associated ubiquitin ligase Atrogin-1.

[Somatic comorbidity in children and adults with intellectual disability and mental health problems.] / Somatische comorbiditeit bij kinderen en volwassenen met een verstandelijke beperking en een psychiatrische aandoening.

BACKGROUND: People with intellectual disability (id) frequently suffer from somatic and psychiatric comorbidity. Somatic morbidity can be the cause and the result of mental health problems. Timely diagnosis and interdisciplinary management are essential for optimal health, development and quality of life.
AIM: To improve interdisciplinary cooperation of professionals involved in care for patients with id, with emphasis on prevalence, diagnosis, and treatment of somatic comorbidity.
METHOD: Literature review and expert opinion.
RESULTS: Epidemiology, diagnostics, and treatment of somatic comorbidity in patients with id are discussed. Additionally, roles and responsibilities of involved professionals are addressed.
CONCLUSION: Somatic comorbidity is highly prevalent in patients with id. People with id should be regularly screened for somatic comorbidity, and re-evaluated in case of behavioral changes. Where available, an id physician can be included in the interdisciplinary care team.

Lipoedema in patients after bariatric surgery: report of two cases and review of literature.

Lipoedema is a disorder of adipose tissue that is characterized by abnormal subcutaneous fat deposition, leading to swelling and enlargement of the lower limbs as well as the trunk. This entity is often misdiagnosed as lymphoedema or obesity and, therefore, may be overlooked and missed in patients scheduled for bariatric surgery. Patients with lipoedema who undergo bariatric surgery may have to continue to have extensive lower extremity and trunk adiposity despite adequate weight loss. In this report, we present two patients who had extensive trunk and lower extremity adiposity, one of them before and the other after the bariatric surgery.

Microbiological outcomes and antibiotic overuse in Emergency Department patients with suspected sepsis.

OBJECTIVE: To study the presence of bacterial disease and antibiotic use in patients in the emergency department (ED) included in the local sepsis protocol. METHODS: An observational retrospective cohort study. Adults aged > 18 years, presenting to the ED of a large teaching hospital, from 1 January to 1 June 2011, with more than two SIRS criteria and a clinical suspicion of sepsis were included. RESULTS: Bacterial disease was suspected or confirmed in only 71% of all the patients with suspected sepsis (2008 definition) and consequently treated with antibiotics. Most of these patients (58%) suffered from systemic inflammatory response syndrome (SIRS) without signs of organ dysfunction, hypotension or hypoperfusion. Despite absence of bacterial disease in 29% of the patients after rigorous diagnostics, median antibiotic treatment in this group was still seven days (IQR 4-10). CONCLUSIONS: Standard sepsis detection using SIRS criteria and clinical suspicion identified patients with suspected or confirmed bacterial disease in 71% of the cases. A significant proportion of patients were exposed to prolonged antibiotic use without proof of bacterial disease. This study illustrates the difficulties in correctly identifying bacterial disease and sepsis, and shows that overuse of antibiotics may be the consequence.

Evaluation of Clinical Manifestations in Patients with Severe Lymphedema with and without CCBE1 Mutations.

The lymphedema-lymphangiectasia-intellectual disability (Hennekam) syndrome (HS) is characterised by a widespread congenital lymph vessel dysplasia manifesting as congenital lymphedema of the limbs and intestinal lymphangiectasia, accompanied by unusual facial morphology, variable intellectual disabilities and infrequently malformations. The syndrome is heterogeneous as mutations in the gene CCBE1 have been found responsible for the syndrome in only a subset of patients. We investigated whether it would be possible to predict the presence of a CCBE1 mutation based on phenotype by collecting clinical data of patients diagnosed with HS, with or without a CCBE1 mutation. We report here the results of 13 CCBE1 positive patients, 16 CCBE1 negative patients, who were clinically found to have classical HS, and 8 patients in whom the diagnosis was considered possible, but not certain, and in whom no CCBE1 mutation was identified. We found no statistically significant phenotypic differences between the 2 groups with the clinical HS phenotype, although the degree of lymphatic dysplasia tended to be more pronounced in the mutation positive group. We also screened 158 patients with less widespread and less pronounced forms of lymphatic dysplasia for CCBE1 mutations, and no mutation was detected in this group. Our results suggest that (1) CCBE1 mutations are present only in patients with a likely clinical diagnosis of HS, and not in patients with less marked forms of lymphatic dysplasia, and (2) that there are no major phenotypic differences between HS patients with or without CCBE1 mutations.

Adults with Down syndrome have reduced cardiac response after light exercise testing.

OBJECTIVE: Physical fitness is reduced in adults with Down syndrome (DS). The present study was conducted to elucidate the exercise response in adults with DS. DESIGN: Case controlled before-after trial. SETTING: Residential centre for people with intellectual disabilities. PARTICIPANTS: 96 Adults with DS, 25 non-DS adults with an intellectual disability, 33 controls. INTERVENTIONS: Echocardiography to exclude heart defects and to measure cardiac index (CI) in the supine position, supine position with raised legs, and following ten knee bends. MAIN OUTCOME MEASURE: Exercise testing RESULTS: At rest, mean CI was not significantly different between persons with DS and controls (2.3 vs. 2.4 l/min/m(2), p = 0.3). However, mean CI after exercise was significantly lower in DS (2.9 vs. 3.7 l/min/m(2), p < 0.001) and mean CI increase from rest to exercise was more than 50% lower in DS. On the contrary, CI after exercise was similar among controls and non-DS adults with an intellectual disability. Significantly lower stroke volumes in DS were found with insufficient heart rate response. CONCLUSIONS: CI at rest was similar in adults with DS and controls; however persons with DS have a diminished cardiac response to exercise. Stroke volumes were significantly lower in DS during exercise and a compensated heightened heart rate was absent.

Inhibited spontaneous emission of quantum dots observed in a 3D photonic band gap.

We present time-resolved emission experiments of semiconductor quantum dots in silicon 3D inverse-woodpile photonic band gap crystals. A systematic study is made of crystals with a range of pore radii to tune the band gap relative to the emission frequency. The decay rates averaged over all dipole orientations are inhibited by a factor of 10 in the photonic band gap and enhanced up to 2× outside the gap, in agreement with theory. We discuss the effects of spatial inhomogeneity, nonradiative decay, and transition dipole orientations on the observed inhibition in the band gap.

A bridge between the single-photon and squeezed-vacuum states.

The two modes of the Einstein-Podolsky-Rosen quadrature entangled state generated by parametric down-conversion interfere on a beam splitter of variable splitting ratio. Detection of a photon in one of the beam splitter output channels heralds preparation of a signal state in the other, which is characterized using homodyne tomography. By controlling the beam splitting ratio, the signal state can be chosen anywhere between the single-photon and squeezed state.

Reversible cardiac valvular disease in catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS) is a severe form of antiphospholipid syndrome (APS). It frequently leads to multiorgan failure with an approximate mortality rate of 50%. The heart is involved in about 50% of the patients with CAPS. We report two cases with CAPS and severe heart manifestations, documented by echocardiography. Both women show regression of the valvular regurgitation under treatment. Valve replacement therapy was no longer necessary. In earlier studies and case reports, cardiac valve involvement had been characterised by valve thickening and vegetations. We suppose that (sometimes reversible) microvascular disturbances lead to valvular regurgitation via papillary muscle dysfunction and myocardial stunning.

Instant single-photon Fock state tomography.

Heralded single photons are prepared at a rate of approximately 100 kHz via conditional measurements on polarization-nondegenerate biphotons produced in a periodically poled potassium-titanyl phosphate crystal. The single-photon Fock state is characterized using high-frequency pulsed optical homodyne tomography with a fidelity of (57.6+/-0.1)%. The state preparation and detection rates allowed us to perform on-the-fly alignment of the apparatus based on real-time analysis of the quadrature measurement statistics.

Down syndrome: a cardiovascular perspective.

This review focuses on the heart and vascular system in patients with Down syndrome. A clear knowledge on the wide spectrum of various abnormalities associated with this syndrome is essential for skillful management of cardiac problems in patients with Down syndrome. Epidemiology of congenital heart defects, cardiovascular aspects and thyroid-related cardiac impairment in patients with Down syndrome will be discussed.

[Dyspnoea and dysphagia in an adult caused by a tracheo-esophageal fistula]. / Dyspnoe en dysfagie door een tracheo-oesofageale fistel bij een volwassene.

In a 64-year-old man who was suffering from chronic obstructive pulmonary disease, recurrent airway infections, dysphagia, and weight loss, achalasia was diagnosed on the basis of endoscopic and radiological examinations. Afterwards he underwent flexible bronchoscopy, which revealed a benign looking fistula between trachea and oesophagus. This appeared to be a congenital tracheo-oesophageal fistula. The fistula was closed surgically. Three months later breathlessness and a sputum-producing cough were the only remaining symptoms. This rare anomaly is mostly diagnosed during childhood, but can also manifest itself in adulthood. If a tracheo-oesophageal fistula is suspected, the diagnostic procedures of choice are a barium oesophagogram in a forward-sitting or supine position or endoscopy of the trachea. Treatment consists of division and closure of the fistula. The prognosis is good.

The effect of age on treatment choice and survival in elderly breast cancer patients.

To investigate the effect of age on treatment choice and survival in patients with breast cancer, data from the cancer registry of the Netherlands Cancer Institute (NKI, Amsterdam, The Netherlands) on 611 women have been analyzed. All patients 55 years and older admitted to the NKI for primary treatment of breast cancer between 1981 and 1986 were selected. For women 75 years and older, physicians were less likely to use treatment of adjuvant radiation therapy after a mastectomy and more often employed primary hormonal therapy only for local stage disease than for younger patients. Life-table analysis showed that disease-specific survival at 7 years for patients 65 through 74 years of age was significantly better (65%) than that of the youngest (55%) and the oldest age group (50%). In multivariate regression analysis (Cox), age older than 74 years was significantly and independently associated with a shorter disease-specific survival as compared with patients younger than 75 years. This difference in survival, however, does not seem to be the result of the difference in treatment between the age groups, but suggests an influence of age-related factors such as comorbid diseases and weak physical condition, which manifest themselves most strongly in the oldest age category and make the older woman more vulnerable to the course of malignant disease.

Long-term venous access with a Hickman catheter: complications and patient satisfaction.

Hickman catheters can be used to secure prolonged access to the venous system. We have retrospectively analysed the incidence of complications, risk factors for the occurrence of complications and patient satisfaction in 120 catheters. The total number of complications was 30, leading to the removal of 15 catheters. The majority of complications were infectious, occurring 28 times and leading to catheter removal in 13 patients. Other complications (i.e. catheter thrombosis) were rare. The only identifiable risk factor for the occurrence of complications was the male gender, associated with a higher rate of catheter infection. Patient satisfaction after catheter insertion, assessed by a questionnaire to which 24 of the 30 patients responded, was high. This report indicates that the use of Hickman catheters is associated with an acceptable complication rate and a high level of patient satisfaction.

Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease.

The risk of second cancers (SCs) was assessed in 744 patients with Hodgkin's disease (HD) admitted to The Netherlands Cancer Institute from 1966 to 1983. Sixty-nine SCs were observed one month or more after start of first treatment. These included 14 cases of lung cancer, nine cases of non-Hodgkin's lymphoma (NHL), 16 cases of leukemia, and six cases of the myelodysplastic syndrome (MDS). The median interval between the diagnosis of HD and that of second lung cancer, NHL, and leukemia was 8.1, 13.3, and 5.7 years, respectively. The overall relative risks (RR) (observed/expected [O/E] ratios) of developing lung cancer, NHL, and leukemia were 4.9 (95% confidence limit [CL], 2.7 to 8.2), 31.0 (95% CL, 14.2 to 58.9) and 45.7 (95% CL, 26.1 to 74.2), respectively. At 15 years the cumulative risk of developing an SC amounted to 20.6% +/- 2.9%. The 15-year estimates of lung cancer, NHL, and leukemia were 6.2% +/- 1.9%, 5.9% +/- 2.1% and 6.3% +/- 1.7%, respectively. Increased lung cancer risk following HD has not frequently been clearly demonstrated before; that we were able to demonstrate such risk may be due to the completeness of follow-up over long periods that could be achieved in this study. Excess lung cancer risk was only noted in treatment regimens with radiotherapy (RT); also, all lung cancers arose in irradiation fields. Excess risk of leukemia was only found in treatment regimens involving chemotherapy (CT). For NHL, combined modality treatment was shown to be the most important risk factor. Risk of lung cancer and NHL increased with time since diagnosis. A time-dependent covariate analysis (Cox model) performed on leukemia and MDS showed an increasing risk with intensity of CT, age (greater than 40 years), and a splenectomy.