ICU at home, with the use of mobile IC unit services:intensive care goes that extra mile

In this report we describe a patient with a long ICU stay because of severe Guillain Barré syndrome. Treatment was patient-centred and Mobile ICU facilities were used to facilitate an ICU at home for one day. Early focus on individual needs and wishes and close communication with and within ICU treatment teams can help to improve the long-term consequences of ICU admission. Research on which interventions are effective and most cost-effective need to be performed

Influence of sensitization and allergen provocation procedures on the development of allergen-induced bronchial hyperreactivity in conscious, unrestrained guinea-pigs

The effects of different sensitization and allergen provocation regimens on the development of allergen-induced bronchial hyperreactivity (BHR) to histamine were investigated in conscious, unrestrained guinea-pigs. Similar early and late phase asthmatic reactions, BHR for inhaled histamine after the early (6 h) as well as after the late reaction (24 h), and airway inflammation were observed after a single allergen provocation in animals sensitized to produce mainly IgG or IgE antibodies, respectively. Repeating the allergen provocation in the IgE-sensitized animals after 7 days, using identical provocation conditions, resulted in a similar development of BHR to histamine inhalation. Repetition of the allergen provocation during 4 subsequent days resulted in a decreased development of BHR after each provocation, despite a significant increase in the allergen provocation dose necessary to obtain similar airway obstruction. The number of inflammatory cells in the bronchoalveolar lavage was not significantly changed after repeated provocation, when compared with a single allergen provocation. Finally, we investigated allergen-induced bronchial hyperreactivity by repetition of the sensitization procedure at day 7 and 14 (booster), followed by repeated allergen provocation twice a week for 5 weeks. Surprisingly, no BHR to histamine could be observed after either provocation, while the number of inflammatory cells in the bronchoalveolar lavage fluid after 5 weeks was enhanced compared with controls. These data indicate that both IgE and IgG sensitized guinea-pigs may develop bronchial hyperreactivity after a single allergen provocation. Repeated allergen exposure of IgE sensitized animals causes a gradual fading of the induced hyperreactivity despite the on-going presence of inflammatory cells in the airways, indicating a mechanism of reduced cellular activation

Rectification of thermal fluctuations in ideal gases

We calculate the systematic average speed of the adiabatic piston and a thermal Brownian motor, introduced in [Van den Broeck, Kawai and Meurs, \emph{Microscopic analysis of a thermal Brownian motor}, to appear in Phys. Rev. Lett.], by an expansion of the Boltzmann equation and compare with the exact numerical solution.Comment: 18 page

Prescription of the first prosthesis and later use in children with congenital unilateral upper limb deficiency: A systematic review

Background: The prosthetic rejection rates in children with an upper limb transversal reduction deficiency are considerable. It is unclear whether the timing of the first prescription of the prosthesis contributes to the rejection rates. Objective: To reveal whether scientific evidence is available in literature to confirm the hypothesis that the first prosthesis of children with an upper limb deficiency should be prescribed before two years of age. We expect lower rejection rates and better functional outcomes in children fitted at young age. Methods: A computerized search was performed in several databases (Medline, Embase, Cinahl, Amed, Psycinfo, PiCarta and the Cochrane database). A combination of the following keywords and their synonyms was used: "prostheses, upper limb, upper extremity, arm and congenital''. Furthermore, references of conference reports, references of most relevant studies, citations of most relevant studies and related articles were checked for relevancy. Results: The search yielded 285 publications, of which four studies met the selection criteria. The methodological quality of the studies was low. All studies showed a trend of lower rejection rates in children who were provided with their first prosthesis at less than two years of age. The pooled odds ratio of two studies showed a higher rejection rate in children who were fitted over two years of age ( pooled OR 3.6, 95% CI 1.6-8.0). No scientific evidence was found concerning the relation between the age at which a prosthesis was prescribed for the first time and functional outcomes. Conclusion: In literature only little evidence was found for a relationship between the fitting of a first prosthesis in children with a congenital upper limb deficiency and rejection rates or functional outcomes. As such, clinical practice of the introduction of a prosthesis is guided by clinical experience rather than by evidence-based medicine

Thrombin Generation in Vitreous and Subretinal Fluid of Patients with Retinal Detachment

Purpose: To measure prothrombin fragments (F1+2) and thrombin-antithrombin complex (TAT) in vitreous and subretinal fluid (SRF) of rhegmatogenous retinal detachment (RRD) patients and to validate and further specify our earlier finding of increased thrombin activity in patients with proliferative vitreoretinopathy (PVR). Methods: F1+2 and TAT were measured in 31 vitreous and 16 SRF samples using the Enzygnost® immunoassays. Results: We found significant levels of F1+2 and TAT in the vitreous of all patients with RRD compared to patients with macular hole or macular pucker. However, there was no significant difference between patients who would develop PVR in the future, had established PVR, and patients with uncomplicated RRD both in vitreous concentrations of F1+2 (Kruskal-Wallis p = 0.963) and TAT (p = 0.516). Conclusion: The analysis of F1+2 and TAT confirmed significant thrombin generation in both vitreous and SRF of patients with RRD. An imbalance between the thrombin regulation mechanisms TAT and α2-macroglobulin possibly explains the difference from our previous findings

Incidence, timing and outcome of AKI in critically ill patients varies with the definition used and the addition of urine output criteria

Background: Acute kidney injury (AKI) is a serious complication of critical illness with both attributed morbidity and mortality at short-term and long-term. The incidence of AKI reported in critically ill patients varies substantially with the population evaluated and the definitions used. We aimed to assess which of the AKI definitions (RIFLE, AKIN or KDIGO) with or without urine output criteria recognizes AKI most frequently and quickest. Additionally, we conducted a review on the comparison of incidence proportions of varying AKI definitions in populations of critically ill patients. Methods: We included all patients with index admissions to our intensive care unit (ICU) from January 1(st), 2014 until June 11th, 2014 to determine the incidence and onset of AKI by RIFLE, AKIN and KDIGO during the first 7 days of ICU admission. We conducted a sensitive search using PubMed evaluating the comparison of RIFLE, AKIN and KDIGO in critically ill patients Results: AKI incidence proportions were 15, 21 and 20% respectively using serum creatinine criteria of RIFLE, AKIN and KDIGO. Adding urine output criteria increased AKI incidence proportions to 35, 38 and 38% using RIFLE, AKIN and KDIGO definitions. Urine output criteria detected AKI in patients without AKI at ICU admission in a median of 13 h (IQR 7-22 h; using RIFLE definition) after admission compared to a median of 24 h using serum creatinine criteria (IQR24-48 h). In the literature a large heterogeneity exists in patients included, AKI definition used, reference or baseline serum creatinine used, and whether urine output in the staging of AKI is used. Conclusion: AKIN and KDIGO criteria detect more patients with AKI compared to RIFLE criteria. Addition of urine output criteria detect patients with AKI 11 h earlier than serum creatinine criteria and may double AKI incidences in critically ill patients. This could explain the large heterogeneity observed in literature

Gender specific effects of the calcium channel TRPV4 on osteoporotic fracture risk and osteoblast-osteoclast coupling

TRPV4 is a member of the transient receptor potential (TRP) superfamily and responds to an array of stimuli, including osmolarity, pH and pressure. Recent findings showing that TRPV4 deficiency leads to reduced sensing of mechanical stimuli led us to explore the role of TRPV4 in bone. TRPV4 mRNA was abundantly expressed in both osteoblasts and osteoclasts as assessed by qPCR. Femoral cortical and trabecular bone mass as assessed by microcomputed tomography was higher in male TRPV4 knockout mice compared to wild type mice. Despite thicker bone structures, cortical porosity was increased in the male TRPV4 knockout mice leading to reduced bone strength as assessed by 3-point bending. Osteoclast and osteoblast differentiation and function was studied, using bone marrow cultures from wildtype and TRPV4 knockout mice. Osteoclast numbers as well as the formation of resorption pits were significantly reduced in cultures of TRPV4 knockout mice compared to wildtype littermates. In contrast, osteoblast differentiation and matrix mineralization was significantly increased in TRPV4 knockout bone marrow cultures. None of these parameters were significantly different in bones and bone marrow cultures of female knock out mice. These data implicate a gender-specific osteoblast–osteoclast uncoupling and support the observed increase in bone mass in male TRPV4 deficient mice. To assess the possible impact of TRPV4 on osteoporotic outcome in humans, we extracted data from the genome-wide association study within the Rotterdam Study. Two single nucleotide polymorphisms (SNPs) in the TRPV4 gene showed strong associations with osteoporotic fracture risk fragility fracture risk and hip fracture risk in men, but not in women. This was not affected after adjusting for height, weight, age and bone mineral density (BMD). In conclusion, TRPV4 plays an important role in male but not female bone biology. Apparently, the increased periosteal bone apposition fails to overcome the increased cortical porosity, leading to reduced bone strength in TRPV4 deficient male mice. In line with the gender-specific findings in mice, variations in the TRPV4 gene are predicting fracture risk in men but not in women