Ultrasonography Alone is Not Enough To Exclude Vesicoureteral Reflux in All Small Children After a Urinary Tract Infection

As knowledge on vesicoureteral reflux (VUR) and the limited effectiveness of its treatment has increased, several guidelines have been updated, and no longer recommend extensive routine imaging of all children with urinary tract infection (UTI). We determined the possible consequences of following the most widely used guidelines for imaging children with UTI, in a retrospective cohort of children treated for UTI in Turku University Hospital in the years 2000-2009. Using the same cohort, we identified factors associated with abnormal imaging and UTI recurrence after a first febrile UTI. We also performed a meta-analysis aiming to determine the value of ultrasonography in identifying patients with VUR after UTI. We found that following the guidelines issued by the National Institute for Health and Care Excellence may lead to missing a substantial number of patients with significant urological anomalies, whereas following the guidelines issued by the American Academy of Pediatrics may lead to fewer patients being missed. Both strategies may lead to avoiding a significant number of unnecessary imaging studies. We identified several factors associated with abnormal imaging and UTI recurrence, and determined a risk score system for predicting the risk for VUR and high-grade VUR. This system had high sensitivity in detecting high-grade VUR in our population. In a meta-analysis of 14 studies, we found that ultrasonography is not sufficiently accurate in predicting the presence or absence of VUR. The optimal imaging strategy for imaging children with UTI is controversial, and depends ultimately on the significance of VUR and the effectiveness of its treatment.Ultraäänitutkimus yksin ei riitä poissulkemaan vesikoureteraalista refluksia kaikilla pienillä lapsilla virtsatieinfektion jälkeen Viime vuosikymmenien aikana tieto vesikoureteraalisen refluksista (VUR) ja sen hoidon rajallisesta vaikuttavuudesta on lisääntynyt. Tämän myötä useita suosituksia on päivitetty, eikä kaikkien virtsatieinfektion (VTI) sairastaneiden lasten rutiinikuvantamista enää suositella. Me selvitimme, mitä mahdollisia seurauksia suosituimpien suositusten noudattamisella olisi ollut potilaskohortissa lapsia, joita hoidettiin Turun yliopistollisessa keskussairaalassa VTI:n vuoksi vuosien 2000-2009 aikana. Samaa potilaskohorttia käyttäen selvitimme tekijöitä, jotka ovat yhteydessä poikkeaviin kuvantamistuloksiin sekä infektion uusiutuvuuteen ensimmäisen kuumeisen VTI:n jälkeen. Suoritimme myös meta-analyysin, jonka tarkoitus oli selvittää, miten hyvin ultraäänitutkimus ennustaa VURia VTI:n jälkeen. Totesimme, että National Insitute of Health and Care Excellencen suositusten noudattaminen voi johtaa siihen, että huomattava määrä potilaita, joilla on merkittäviä, hoitotoimenpiteitä vaativia urologisia poikkeavuuksia, jäävät löytymättä, kun taas American Academy of Pediatricsin suositusten noudattaminen voi johtaa selvästi pienemmän määrän potilaita löytymättä jäämiseen. Molemmat kuvantamisstrategiat voivat johtaa turhien tutkimuksien selvään vähenemiseen. Tunnistimme useita tekijöitä, joilla on yhteys poikkeaviin kuvantamistuloksiin sekä VTI:iden uusiutuvuuteen, ja muodostimme riskipisteytysjärjestelmän VURin ja korkea-asteisen VURin riskin ennustamiseksi. Riskipisteytysjärjestelmällä oli korkea sensitiivisyys korkea-asteisen VURin tunnistamiselle. Meta-analyysissä, jossa käsiteltiin 14 tutkimusta, totesimme, ettei ultraäänitutkimus ole riittävän tarkka ennustamaan VURia tai sen puuttumista. Optimaalinen kuvantamisstrategia lapsilla VTI:n jälkeen on ristiriitainen aihe, joka riippuu olennaisesti VURin merkityksestä sekä sen hoidon vaikuttavuudesta.Siirretty Doriast

Iatrogenic pneumothorax after breast reduction surgery caused by local anesthesia infiltration - a case report

We present a case of a 44-year-old woman, who underwent bilateral breast reduction mammoplasty and suffered a unilateral pneumothorax that was detected postoperatively. Infiltration of a local anesthetic was considered the cause of the pneumothorax. We recommend a more tangential direction of needle placement when infiltrating a local anesthetic

Three-decade neurological and neurocognitive follow-up of HIV-1-infected patients on best-available antiretroviral therapy in Finland

Objectives: Is it possible to live without neurocognitive or neurological symptoms after being infected with HIV for a very long time? These study patients with decades-long HIV infection in Finland were observed in this follow-up study during three time periods: 1986-1990, in 1997 and in 2013. Setting: Patients from greater Helsinki area were selected from outpatient's unit of infectious diseases. Participants: The study included 80 HIV patients. Patients with heavy alcohol consumption, central nervous system disorder or psychiatric disease were excluded. Primary and secondary outcome measures: The patients underwent neurological and neuropsychological examinations, MRI of the brain and laboratory tests, including blood CD4 cells and plasma HIV-1 RNA. Neuropsychological examination included several measures: subtests of Wechsler Adult Intelligence Scale, Wechsler Memory Scale-Revised, list learning, Stroop and Trail-Making-B test. The Beck Depression Inventory and Fatigue Severity Scale were also carried out. The obtained data from the three time periods were compared with each other. Results: Owing to high mortality among the original 80 patients, eventually, 17 participated in all three examinations performed between 1986 and 2013. The time from the HIV diagnosis was 27 (23-30) years. Blood CD4 cells at the diagnosis were 610 (29-870) cells/mm(3), and the nadir CD4 168 (4-408) cells/mm(3). The time on combined antiretroviral treatment was 13 (5-17) years. 9 patients suffered from fatigue, 5 had polyneuropathy and 3 had lacunar cerebral infarcts. There was a subtle increase of brain atrophy in 2 patients. Mild depressive symptoms were common. The neuropsychological follow-up showed typical age-related cognitive changes. No HIV-associated dementia features were detected. Conclusions: Polyneuropathy, fatigue and mild depression were common, but more severe neurological abnormalities were absent. These long-term surviving HIV-seropositive patients, while on best-available treatment, showed no evidence of HIV-associated neurocognitive disorder in neuropsychological and neuroradiological evaluations.Peer reviewe

Easy and accurate reconstruction of whole HIV genomes from short-read sequence data

Abstract Next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of rapid between- and within-host evolution may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions. De novo assembly avoids this bias by effectively aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the tool shiver to preprocess reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We use shiver to reconstruct the consensus sequence and minority variant information from paired-end short-read data produced with the Illumina platform, for 65 existing publicly available samples and 50 new samples. We show the systematic superiority of mapping to shiver ’s constructed reference over mapping the same reads to the standard reference HXB2: an average of 29 bases per sample are called differently, of which 98.5% are supported by higher coverage. We also provide a practical guide to working with imperfect contigs

Comparative analysis of Neph gene expression in mouse and chicken development

Neph proteins are evolutionarily conserved members of the immunoglobulin superfamily of adhesion proteins and regulate morphogenesis and patterning of different tissues. They share a common protein structure consisting of extracellular immunoglobulin-like domains, a transmembrane region, and a carboxyl terminal cytoplasmic tail required for signaling. Neph orthologs have been widely characterized in invertebrates where they mediate such diverse processes as neural development, synaptogenesis, or myoblast fusion. Vertebrate Neph proteins have been described first at the glomerular filtration barrier of the kidney. Recently, there has been accumulating evidence suggesting a function of Neph proteins also outside the kidney. Here we demonstrate that Neph1, Neph2, and Neph3 are expressed differentially in various tissues during ontogenesis in mouse and chicken. Neph1 and Neph2 were found to be amply expressed in the central nervous system while Neph3 expression remained localized to the cerebellum anlage and the spinal cord. Outside the nervous system, Neph mRNAs were also differentially expressed in branchial arches, somites, heart, lung bud, and apical ectodermal ridge. Our findings support the concept that vertebrate Neph proteins, similarly to their Drosophila and C. elegans orthologs, provide guidance cues for cell recognition and tissue patterning in various organs which may open interesting perspectives for future research on Neph1-3 controlled morphogenesis

The extent of B-cell activation and dysfunction preceding lymphoma development in HIV-positive people

OBJECTIVES: B-cell dysfunction and activation are thought to contribute to lymphoma development in HIV-positive people; however, the mechanisms are not well understood. We investigated levels of several markers of B-cell dysfunction [free light chain (FLC)-κ, FLC-λ, immunoglobulin G (IgG), IgA, IgM and IgD] prior to lymphoma diagnosis in HIV-positive people. METHODS: A nested matched case–control study was carried out within the EuroSIDA cohort, including 73 HIV-positive people with lymphoma and 143 HIV-positive lymphoma-free controls. Markers of B-cell dysfunction were measured in prospectively stored serial plasma samples collected before the diagnosis of lymphoma (or selection date in controls). Marker levels ≤ 2 and > 2 years prior to diagnosis were investigated. RESULTS: Two-fold higher levels of FLC-κ [odds ratio (OR) 1.84; 95% confidence interval (CI) 1.19, 2.84], FLC-λ (OR 2.15; 95% CI 1.34, 3.46), IgG (OR 3.05; 95% CI 1.41, 6.59) and IgM (OR 1.46; 95% CI 1.01, 2.11) were associated with increased risk of lymphoma > 2 years prior to diagnosis, but not ≤ 2 years prior. Despite significant associations > 2 years prior to diagnosis, the predictive accuracy of each marker was poor, with FLC-λ emerging as the strongest candidate with a c-statistic of 0.67 (95% CI 0.58, 0.76). CONCLUSIONS: FLC-κ, FLC-λ and IgG levels were higher > 2 years before lymphoma diagnosis, suggesting that B-cell dysfunction occurs many years prior to lymphoma development. However, the predictive value of each marker was low and they are unlikely candidates for risk assessment for targeted intervention

Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens

Objectives: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. Methods: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. Results: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95–1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37–2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84–1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90–1.61) and 0.83 (95% CI 0.70–0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47–1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65–1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53–1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76–1.72 for RALvs. CONC). Conclusions: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.Peer reviewe

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA

Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P <0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.Peer reviewe