Regina Riedl

Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial.

IMPORTANCE Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal. OBJECTIVE To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs. DESIGN, SETTING, AND PARTICIPANTS A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243). INTERVENTIONS Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months. MAIN OUTCOMES AND MEASURES The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis. RESULTS A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12). CONCLUSIONS AND RELEVANCE Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01130181.

Are morphological criteria sufficient for the identification of circulating tumor cells in renal cancer

BackgroundSingle circulating tumor cells (CTCs) or circulating tumor microemboli (CTMs) are potential biomarkers of renal cell cancer (RCC), however studies of CTCs/CTMs in RCC are limited. In this pilot study we aimed to evaluate a novel blood filtration technique suited for cytomorphological classification, immunocytochemical and molecular characterization of filtered, so called circulating non-hematologic cells (CNHCs) - putative CTCs/CTMs - in patients with RCC.MethodsBlood of 40 patients with renal tumors was subjected to ScreenCell® filtration. CNHCs were classified according to cytomorphological criteria. Immunocytochemical analysis was performed with antibodies against CD45, CD31 and carbonic anhydrase IX (CAIX, a RCC marker). DNA of selected CNHCs and respective primary tumors was analysed by array-CGH.ResultsCNHC-clusters with malignant or uncertain malignant cytomorphological features - putative CTMs - were negative for CD45, positive for CD31, while only 6% were CAIX positive. Array-CGH revealed that 83% of malignant and uncertain malignant cells did represent with a balanced genome whereas 17% presented genomic DNA imbalances which did not match the aberrations of the primary tumors. Putative single CTCs were negative for CD45, 33% were positive for CD31 and 56% were positive for CAIX.ConclusionsThe majority of CNHC-clusters, putative CTMs, retrieved by ScreenCell® filtration may be of endothelial origin. Morphological criteria seem to be insufficient to distinguish malignant from non-malignant cells in renal cancer.

Assessment of Long-Term Effects of Nanoparticles in a Microcarrier Cell Culture System

Nano-sized materials could find multiple applications in medical diagnosis and therapy. One main concern is that engineered nanoparticles, similar to combustion-derived nanoparticles, may cause adverse effects on human health by accumulation of entire particles or their degradation products. Chronic cytotoxicity must therefore be evaluated. In order to perform chronic cytotoxicity testing of plain polystyrene nanoparticles on the endothelial cell line EAhy 926, we established a microcarrier cell culture system for anchorage-dependent cells (BioLevitatorTM). Cells were cultured for four weeks and exposed to doses, which were not cytotoxic upon 24 hours of exposure. For comparison, these particles were also studied in regularly sub-cultured cells, a method that has traditionally been used to assess chronic cellular effects. Culturing on basal membrane coated microcarriers produced very high cell densities. Fluorescent particles were mainly localized in the lysosomes of the exposed cells. After four weeks of exposure, the number of cells exposed to 20 nm polystyrene particles decreased by 60% as compared to untreated controls. When tested in sub-cultured cells, the same particles decreased cell numbers to 80% of the untreated controls. Dose-dependent decreases in cell numbers were also noted after exposure of microcarrier cultured cells to 50 nm short multi-walled carbon nanotubes. Our findings support that necrosis, but not apoptosis, contributed to cell death of the exposed cells in the microcarrier culture system. In conclusion, the established microcarrier model appears to be more sensitive for the identification of cellular effects upon prolonged and repeated exposure to nanoparticles than traditional sub-culturing.

Fecal carriage and intrafamilial spread of extended-spectrum β-lactamase-producing enterobacteriaceae following colonization at the neonatal ICU.

Objective: Fecal carriage of extended-spectrum &bgr;-lactamase-producing enterobacteriaceae may contribute to the spread of extended-spectrum &bgr;-lactamase-producing enterobacteriaceae into the community. The objective of this study was to assess the duration of fecal carriage after discharge and the occurrence of intrafamilial transmission. Design: Case series. Setting: Quaternary care children’s hospital. Patients: Patients colonized with extended-spectrum &bgr;-lactamase-producing enterobacteriaceae at the neonatal ICU and the respective household members. Interventions: Screening for intestinal extended-spectrum &bgr;-lactamase-producing enterobacteriaceae colonization was done at 1, 2, 4, 6, 9, and 12 months after discharge. Genetic relatedness of isolated extended-spectrum &bgr;-lactamase-producing enterobacteriaceae strains was determined using automated rep-PCR. Results: Twenty-five neonates (case-patients) colonized with extended-spectrum &bgr;-lactamase-producing enterobacteriaceae (one extended-spectrum &bgr;-lactamase-Escherichia coli; six extended-spectrum &bgr;-lactamase-Klebsiella pneumoniae; 11 extended-spectrum &bgr;-lactamase-Klebsiella oxytoca; and seven extended-spectrum &bgr;-lactamase-Serratia marcescens) were included. Duration of fecal carriage was longer (up to 1 yr) in case-patients colonized with Klebsiella species than in case-patients colonized with Serratia marcescens (<4 months). During follow-up, strains and species of extended-spectrum &bgr;-lactamase-producing enterobacteriaceae different from the primary strain were found in four and three case-patients, respectively. In nine of 49 (18.4%) included household members, extended-spectrum &bgr;-lactamase-producing enterobacteriaceae were found during the follow-up period. In two of nine colonized household members, the isolated extended-spectrum &bgr;-lactamase-producing enterobacteriaceae was identical to the primary strains of the respective case-patients. Conclusions: After intestinal colonization with extended-spectrum &bgr;-lactamase-producing enterobacteriaceae at the neonatal ICU, infants potentially remain carriers during the first year after discharge. Intrafamilial spread has been proven.

Ocular Trauma Scores in paediatric open globe injuries

Background/aims To assess the predictive value and the applicability of Ocular Trauma Score (OTS) for paediatric injuries. Methods Retrospective case series of 71 open globe injuries in children less than 18 years of age with a minimum follow-up period of 1 year. The variables of the OTS, the Paediatric Penetrating OTS (POTS), lens injuries and anterior versus posterior segment injuries were analysed for their predictive values in terms of visual outcome. The applicability and the predictive values of OTS and POTS as a whole were then evaluated. Results Initial visual acuities, retinal detachments, wound locations (p<0.001 each), lens injuries (p=0.001), posterior segment injuries (p=0.002), traumatic cataracts (p=0.010), hyphaema (p=0.011) and vitreous haemorrhages (p=0.026) had significant impacts on visual outcome. The application of OTS proved difficult, as the presence of a mild degree of a relative afferent pupillary defect (RAPD) could not accurately be evaluated in all of our patients. Calculating the OTS without evaluation of RAPD renders it easily applicable for the initial examinations while remaining significantly prognostic (p<0.001). The predictions of the POTS correlated with the actual final visual acuities (p<0.001), but several POTS variables (ie, iris prolapse, age, organic injuries and delay of surgery >48 h) had only limited impacts on visual outcome. Conclusions The OTS has a high predictive value for visual outcome after open globe injuries in children, even without evaluation of RAPD.

Induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy with cetuximab for locally advanced squamous cell carcinoma of the head and neck☆

PURPOSE To determine the efficacy and feasibility of induction chemotherapy (ICT) with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy and cetuximab (C) in patients with locally advanced head and neck cancer. PATIENTS AND METHODS Forty-nine previously untreated patients with local advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) received three courses of ICT consisting of docetaxel 75mg/m(2) day 1, cisplatin 75mg/m(2) day 1 and infusional 5-fluorouracil 750mg/m(2)/day on days 1-5 followed by radiotherapy plus C at 250mg/m(2)/week (after an initial loading dose of 400mg/m(2)). RESULTS After completion of ICT 44 of 49 patients received radiotherapy plus C. Three months after therapy completion tumour response was observed in 33 patients and after two years, 25 patients were in complete remission (CR). The most common grade 4 toxicity during the whole treatment period was dermatitis (30%), followed by mucositis (27%) and neutropenia (17%) without fever. One toxic related death was observed during ICT. Two-year progression-free survival (PFS) rate was 59% and two-year overall survival (OS) rate was 63%, respectively. CONCLUSION Concurrent radiotherapy plus C after three courses of ICT was feasible and was associated with promising CR, PFS and OS rates. Further optimisation of dose and sequence is warranted.

Evaluation of ocular surface and tear film function following modified Hughes tarsoconjunctival flap procedure

Purpose:  To evaluate ocular surface characteristics and tear film function following modified Hughes flap for eyelid reconstruction.

C reactive protein: impact on peripheral tissue oxygenation and perfusion in neonates

Objective C reactive protein (CRP) is a sensitive marker of acute inflammation of infectious and non-infectious origin. Aim was to use near-infrared spectroscopy (NIRS) to analyse peripheral oxygenation and perfusion in term and preterm neonates with elevated CRP levels, at a time when routine haemodynamic variables are still normal. Design Prospective observational study. Settings Peripheral-muscle NIRS was performed in the first week of life. Tissue-oxygenation index (TOI), mixed venous oxygenation (SvO2), fractional oxygen extraction (FOE), haemoglobin flow (Hbflow), oxygen delivery (DO2) and oxygen consumption (VO2) were assessed. Blood samples were taken within 3 h of the NIRS measurements. Patients Cardiocirculatory stable term and preterm neonates with infection-related and infection-unrelated CRP elevations >10 mg/l were compared with neonates without CRP elevation. The two groups were matched for gestational and postnatal age. Results 33 neonates with CRP elevation (gestational age 37.7±2.9 weeks) were compared with 33 controls (gestational age 37.3±2.9 weeks). In neonates with CRP elevation, TOI (68.9±6.6%), SvO2 (66.9±7.3%) DO2 (39.2±16.1 µmol/100ml/min) and VO2 (10.9±3.4 µmol/100ml/min) were significantly lower compared with controls (TOI 72.9±3.8%, SvO2 70.2±4.7%, DO2 48.8±18.4 µmol/100ml/min, VO2 12.3±3.8 µmol/100ml/min). There was no significant difference in any other NIRS or routine haemodynamic parameter between the two groups. Conclusion Inflammatory processes with CRP elevation cause impaired peripheral oxygenation and perfusion in neonates even when routine haemodynamic variables are still normal. NIRS might offer a new non-invasive tool for the early recognition and diagnosis of infectious and non-infectious inflammatory processes.

Blood transfusions and the subsequent risk of cancers in the United States elderly

Blood transfusions are common in older adults and also may modulate the immune system. However, the impact of transfusion on cancer risk in the elderly has not been studied.

‘Multi-associations’: predisposed to misinterpretation of peripheral tissue oxygenation and circulation in neonates

Interpretation of peripheral circulation in ill neonates is crucial but difficult. The aim was to analyse parameters potentially influencing peripheral oxygenation and circulation. In a prospective observational cohort study in 116 cardio-circulatory stable neonates, peripheral muscle near-infrared spectroscopy (NIRS) with venous occlusion was performed. Tissue oxygenation index (TOI), mixed venous oxygenation (SvO(2)), fractional oxygen extraction (FOE), fractional tissue oxygen extraction (FTOE), haemoglobin flow (Hbflow), oxygen delivery (DO(2)), oxygen consumption (VO(2)), and vascular resistance (VR) were assessed. Correlation coefficients between NIRS parameters and demographic parameters (gestational age, birth weight, age, actual weight, diameter of calf, subcutaneous adipose tissue), monitoring parameters (heart rate, arterial oxygen saturation (SaO(2)), mean blood pressure (MAP), core/peripheral temperature, central/peripheral capillary refill time) and laboratory parameters (haemoglobin concentration (Hb-blood), pCO(2)) were calculated. All demographic parameters except for Hbflow and DO(2) correlated with NIRS parameters. Heart rate correlated with TOI, SvO(2), VO(2) and VR. SaO(2) correlated with FOE/FTOE. MAP correlated with Hbflow, DO(2), VO(2) and VR. Core temperature correlated with FTOE. Peripheral temperature correlated with all NIRS parameters except VO(2). Hb-blood correlated with FOE and VR. pCO(2) levels correlated with TOI and SvO(2). The presence of multiple interdependent factors associated with peripheral oxygenation and circulation highlights the difficulty in interpreting NIRS data. Nevertheless, these findings have to be taken into account when analysing peripheral oxygenation and circulation data.