Factors associated with adherence to antiretroviral therapy in HIV-infected subjects and the use of indicators to characterize the treatment adhesion profile.

At present, there is no gold standard to assess patient adherence to combination antiretroviral therapy (cART). Therefore, this study aimed to characterize the epidemiological profile, delineate adherence indicators, and identify factors associated with adherence and delays in obtaining medication in patients registered at the Specialized Assistance Service in HIV/AIDS in Brazil. This is a descriptive study based on secondary data obtained from official databases of the Brazilian Ministry of Health. Adherence and delay were measured by the frequency of cART medication acquisition in 24 months, and a multivariate linear regression model was developed to identify the factors associated with non-adherence and delays. In 50.2% of the subjects, the viral load remained undetectable throughout the study period. Only 12.4% of patients were fully adherent to cART. Regarding indicators, a value of 0.83 was found for adherence, 0.09 for delay in days, and 0.21 for the number of times the patient was late to obtain the medication. The multivariate analysis showed that males, age between 20 and 59 years, having not changed the cART, and the presence of ≥1000 HIV RNA copies/mL were predictive factors for adherence and delays (P≤0.01). We demonstrated that monitoring cART medication distribution is possible using health indicators, and identifying the factors associated with poor adherence to cART helps characterize patients at higher risks of unsuccessful therapy.

The new small-angle X-ray scattering beamline for materials research at PETRA†III: SAXSMAT beamline P62.

The SAXSMAT beamline P62 (Small-Angle X-ray Scattering beamline for Materials Research) is a new beamline at the high-energy storage ring PETRA III at DESY. This beamline is dedicated to combined small- and wide-angle X-ray scattering (SAXS/WAXS) techniques for both soft and hard condensed matter systems. It works mainly in transmission geometry. The beamline covers an energy range from 3.5 keV to 35.0 keV, which fulfills the requirements of the user community to perform anomalous scattering experiments. Mirrors are used to reduce the intensity of higher harmonics. Furthermore, the mirrors and 2D compound refracting lenses can focus the beam down to a few micrometres at the sample position. This option with the high photon flux enables also SAXS/WAXS tensor tomography experiments to be performed at this new beamline in a relatively short time. The first SAXS/WAXS pattern was collected in August 2021, while the first user experiment was carried out two months later. Since January 2022 the beamline has been in regular user operation mode. In this paper the beamline optics and the SAXS/WAXS instrument are described and two examples are briefly shown.

Impact of sex on the efficacy and safety of panitumumab plus fluorouracil and folinic acid versus fluorouracil and folinic acid alone as maintenance therapy in RAS WT metastatic colorectal cancer (mCRC). Subgroup analysis of the PanaMa-study (AIO-KRK-0212).

BACKGROUND: Clinical trials in metastatic colorectal cancer (mCRC) are usually conducted irrespective of sex. Sex-associated differences relating to safety and efficacy in the treatment of mCRC, however, are gaining interest. METHODS: PanaMa investigated the efficacy of panitumumab (Pmab) plus fluorouracil and folinic acid (FU/FA) versus FU/FA alone after induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab in patients with RAS wild-type mCRC. In this post hoc analysis, the study population was stratified for sex. Evaluated efficacy endpoints during maintenance treatment were progression-free survival (PFS, primary endpoint of the trial), overall survival (OS) and objective response rate during maintenance therapy. Safety endpoints were rates of any grade and grade 3/4 adverse events during maintenance therapy. RESULTS: In total, 165 male and 83 female patients were randomized and treated. Male and female patients showed numerically better objective response rates with Pmab, without reaching statistical significance. Male patients derived a significant benefit from the addition of Pmab to maintenance treatment with regard to PFS [hazard ratio (HR) 0.63; 95% confidence interval (CI) 0.45-0.88; P = 0.006] that was not observed in female patients (HR 0.85; 95% CI 0.53-1.35; P = 0.491). The better PFS for male patients treated with Pmab did not translate into improved OS (HR 0.85; 95% CI 0.55-1.30; P = 0.452). Female patients showed numerically improved OS when treated with Pmab. There was no difference in the total of grade ≥3 adverse events during maintenance regarding sex (P = 0.791). Female patients, however, had a higher rate of any grade nausea, diarrhea and stomatitis. CONCLUSIONS: In the PanaMa trial, the addition of Pmab to maintenance treatment of RAS wild-type mCRC with FU/FA improved the outcome in terms of the primary endpoint (PFS) particularly in male patients. Female patients did not show the same benefit while experiencing higher rates of adverse events. Our results support the development of sex-specific protocols.

Factors associated with adherence to antiretroviral therapy in HIV-infected subjects and the use of indicators to characterize the treatment adhesion profile

At present, there is no gold standard to assess patient adherence to combination antiretroviral therapy (cART). Therefore, this study aimed to characterize the epidemiological profile, delineate adherence indicators, and identify factors associated with adherence and delays in obtaining medication in patients registered at the Specialized Assistance Service in HIV/AIDS in Brazil. This is a descriptive study based on secondary data obtained from official databases of the Brazilian Ministry of Health. Adherence and delay were measured by the frequency of cART medication acquisition in 24 months, and a multivariate linear regression model was developed to identify the factors associated with non-adherence and delays. In 50.2% of the subjects, the viral load remained undetectable throughout the study period. Only 12.4% of patients were fully adherent to cART. Regarding indicators, a value of 0.83 was found for adherence, 0.09 for delay in days, and 0.21 for the number of times the patient was late to obtain the medication. The multivariate analysis showed that males, age between 20 and 59 years, having not changed the cART, and the presence of ≥1000 HIV RNA copies/mL were predictive factors for adherence and delays (P≤0.01). We demonstrated that monitoring cART medication distribution is possible using health indicators, and identifying the factors associated with poor adherence to cART helps characterize patients at higher risks of unsuccessful therapy.

Real-World Efficacy of Nintedanib Plus Docetaxel After Progression on Immune Checkpoint Inhibitors: Results From the Ongoing, Non-interventional VARGADO Study.

AIMS: To evaluate the efficacy and safety of nintedanib plus docetaxel in patients with advanced adenocarcinoma non-small cell lung cancer (NSCLC) who progressed after chemotherapy and immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: VARGADO (NCT02392455) is an ongoing, prospective, non-interventional, real-world study of nintedanib plus docetaxel after first-line chemotherapy in the routine clinical treatment of patients with locally advanced, metastatic or locally recurrent adenocarcinoma NSCLC. Data were collected during routine visits. We report the results from cohort B (n = 80), who received third-line nintedanib plus docetaxel after first-line chemotherapy and second-line ICI therapy. RESULTS: The median duration of follow-up was 12.4 months. Median progression-free survival from initiation of third-line nintedanib plus docetaxel was 6.4 months (95% confidence interval 4.8, 7.3); median overall survival was 12.1 months (95% confidence interval 9.4, 13.5). The 1-year overall survival rate after initiation of third-line nintedanib plus docetaxel treatment (primary end point) was 52% (95% confidence interval 38.0%, 64.4%). Among 64 patients with a documented response, the objective response rate was 50% (n = 32; one complete response and 31 partial responses) and the disease control rate was 86% (n = 55). There were no new safety signals or unexpected toxicities. Among all treated patients, 74% (n = 59) experienced drug-related adverse events, most commonly (nintedanib-related/docetaxel-related) diarrhoea (34%/24%), a decreased white blood cell count (11%/19%) and nausea (13%/16%). CONCLUSIONS: Nintedanib plus docetaxel demonstrated a high response rate and disease stabilisation in the third-line setting after failure of prior chemotherapy and ICI treatment, with a manageable safety profile. These results suggest that nintedanib plus docetaxel represents an efficient treatment option after failure of prior ICIs. The ongoing VARGADO study provides valuable real-world data to inform clinical decision-making regarding treatment sequencing after chemotherapy and ICI failure in patients with adenocarcinoma NSCLC.

Cardiac output and peripheral vascular resistance during normotensive and hypertensive pregnancy - a systematic review and meta-analysis.

BACKGROUND: In-depth insight into haemodynamic changes during normotensive pregnancy may help identify women at risk for gestational hypertensive complications. OBJECTIVES: To determine the magnitude of changes in cardiac output and its determinants stroke volume and heart rate, and total peripheral vascular resistance during singleton normotensive and hypertensive pregnancies. SEARCH STRATEGY: PubMed (NCBI) and Embase (Ovid) databases were searched from their inception up to November 2019. SELECTION CRITERIA: Studies reporting original measurements of haemodynamic parameters during pregnancy together with a non-pregnant reference measurement. Studies including women using antihypertensive medication were excluded. DATA COLLECTION AND ANALYSIS: Pooled mean differences between pregnant and non-pregnant women, and absolute values of haemodynamic parameters were calculated for predefined gestational intervals using a random-effects model in normotensive and hypertensive pregnancy. Meta-regression analysis was used to analyse group differences in adjustments and absolute values during pregnancy. MAIN RESULTS: In normotensive pregnancies, cardiac output increased from the first weeks on, reaching its highest level early in the third trimester (mean difference, 1.41 l·min1 ; 95% CI 1.18-1.63 l·min). In parallel, vascular resistance decreased progressively until its nadir in the early third trimester (mean difference, -331 dyn·sec-1 ·cm-5 ; 95% CI -384 to -277 dyn·sec-1 ·cm-5 ) and then increased slightly at term. In hypertensive pregnancies, the initial cardiac output increase was higher and vascular resistance did not change throughout gestation compared with reference values. CONCLUSIONS: Hemodynamic changes in women who eventually develop hypertensive complications are substantially different. Serial monitoring and plotting against developed normograms can identify women at risk and may allow timely intervention. TWEETABLE ABSTRACT: Monitoring haemodynamic changes in pregnancy helps identify women at risk for hypertensive complications.

Recommendations for the diagnosis and management of vaccine-induced immune thrombotic thrombocytopenia.

There have recently been safety concerns regarding an increased risk of vaccine-induced immune thrombotic thrombocytopenia (VITT) following administration of SARS-CoV-2 adenoviral vector vaccines. The Southern African Society of Thrombosis and Haemostasis reviewed the emerging literature on this idiosyncratic complication. A draft document was produced and revised by consensus agreement by a panel of professionals from various specialties. The recommendations were adjudicated by independent international experts to avoid local bias. We present concise, practical guidelines for the clinical management of VITT.

Performance of the Ionospheric Kappa-Correction of Radio Occultation Profiles Under Diverse Ionization and Solar Activity Conditions.

The kappa-correction is an easy-to-use method to correct for residual ionospheric errors in radio occultation (RO) data. It is a simple empirical model term that only depends on readily available data. While its basic utility was well proven in previous studies, including a recent predecessor study on RO climatologies under solar cycle variations, its performance for individual RO profile correction under diverse and extreme ionization conditions is unclear so far. Here we tackle this gap and focus on investigating (extremely) low and high solar activity and ionization conditions of individual RO events, including inspection of ionospheric symmetry between inbound and outbound raypaths. Using a global multi-year ensemble of MetOp-A and GRACE-A RO events over 2008-2015 as basis, we applied a sampling approach leading to six characteristic condition cases. These cases also relate to day and night time variations and geographic variations from the equatorial to the high latitude region. We inspected the kappa-correction and its performance relative to the standard bending angle correction for RO-retrieved stratospheric profiles and found mean deviations in temperature of near -0.3 K in the upper stratosphere (40-45 km) for high ionization conditions, with extreme deviations exceeding -2 K for strong inbound/outbound asymmetry. The kappa-correction term itself reaches a mean value near 0.05 µrad under these high conditions. Low solar activity and ionization conditions lead to a mean correction smaller than 0.005 µrad and mean temperature deviations smaller than 0.02 K. An intercomparison to other quality datasets, predominantly showed a decrease in mean temperature difference when applying the kappa-correction.

Linking language features to clinical symptoms and multimodal imaging in individuals at clinical high risk for psychosis.

BACKGROUND: Abnormalities in the semantic and syntactic organization of speech have been reported in individuals at clinical high-risk (CHR) for psychosis. The current study seeks to examine whether such abnormalities are associated with changes in brain structure and functional connectivity in CHR individuals. METHODS: Automated natural language processing analysis was applied to speech samples obtained from 46 CHR and 22 healthy individuals. Brain structural and resting-state functional imaging data were also acquired from all participants. Sparse canonical correlation analysis (sCCA) was used to ascertain patterns of covariation between linguistic features, clinical symptoms, and measures of brain morphometry and functional connectivity related to the language network. RESULTS: In CHR individuals, we found a significant mode of covariation between linguistic and clinical features (r = 0.73; p = 0.003), with negative symptoms and bizarre thinking covarying mostly with measures of syntactic complexity. In the entire sample, separate sCCAs identified a single mode of covariation linking linguistic features with brain morphometry (r = 0.65; p = 0.05) and resting-state network connectivity (r = 0.63; p = 0.01). In both models, semantic and syntactic features covaried with brain structural and functional connectivity measures of the language network. However, the contribution of diagnosis to both models was negligible. CONCLUSIONS: Syntactic complexity appeared sensitive to prodromal symptoms in CHR individuals while the patterns of brain-language covariation seemed preserved. Further studies in larger samples are required to establish the reproducibility of these findings.

Injection of freshly collected autologous adipose tissue into non-healing wounds after closed incision pilonidal surgery.

BACKGROUND: Chronic non-healing wounds are a major problem after closed incision pilonidal surgery. Freshly collected autologous adipose tissue injected into perianal fistulas in patients with Crohn's disease seems to promote healing. We investigated this technique in patients with non-healing wounds after cleft-lift surgery for pilonidal sinus disease (PSD). METHOD: In a prospective interventional pilot study conducted at our institution autologous adipose tissue from the abdominal wall was harvested, and injected into chronic non-healing PS wounds after surgical revision, healing rate being the primary outcome. The wounds were left open. Patients were followed every 2 to 3 weeks until complete healing (skin coverage, no undermining). RESULTS: 7 male patients were included (mean age 24 ± 0,6 SD years) and complete healing was achieved in 6 patients (86%). Median time to healing was 90 days (range 36-403 days ) and mean follow-up time was 388± 45 days. All patients reported major symptom relief shortly after the procedure. The mean operation time was 80 ± 23 minutes and the mean amount of freshly collected adipose tissue injected was 27.4± 12 ml. There were no complications. CONCLUSIONS: Freshly collected autologous adipose tissue injected into chronic non-healing pilonidal wounds seems safe and efficient.

Cortical processing to anorectal stimuli after rectal resection with and without radiotherapy.

BACKGROUND: Bowel dysfunction is common after surgery for rectal cancer, especially when neoadjuvant radiotherapy is used. The role of sensory function in the pathogenesis remains obscure, and the aim of the present study was to characterize the sensory pathways of the brain-gut axis in rectal cancer patients treated with resection ± radiotherapy compared with healthy volunteers. METHODS: Sensory evaluation by (neo)rectal distensions was performed and sensory evoked potentials (SEPs) were recorded during rapid balloon distensions of the (neo)rectum and anal canal in resected patients with (n = 8) or without (n = 12) radiotherapy. Twenty healthy volunteers were included for comparison. (Neo)rectal latencies and amplitudes of SEPs were compared and spectral band analysis from (neo)rectal and anal distensions was used as a proxy of neuronal processing. RESULTS: Neorectal sensation thresholds were significantly increased in both patient categories (all p < 0.008). There were no differences in (neo)rectal SEP latencies and amplitudes between groups. However, spectral analysis of (neo)rectal SEPs showed significant differences between all groups in all bands (all p < 0.01). On the other hand, anal SEP analyses only showed significant differences between the delta (0-4 Hz), theta (4-8 Hz) and, gamma 32-50 Hz) bands (all p < 0.02) between the subgroup of patients that also received radiotherapy and healthy volunteers. CONCLUSIONS: Surgery for rectal cancer leads to abnormal cortical processing of neorectal sensation. Additional radiotherapy leads to a different pattern of central sensory processing of neorectal and anal sensations. This may play a role in the functional outcome of these patients.

International survey of neurosurgical anesthesia (iSonata) : An international survey of current practices in neurosurgical anesthesia.

BACKGROUND: No standardized recommendations have been currently defined for anesthesia management of patients undergoing elective intracranial surgery. It can therefore be assumed that international clinical institutions have diverging approaches or standard operating procedures (SOP) which determine the type of general anesthesia, hemodynamic management, neuromuscular blockade, implementation of hypothermia and postoperative patient care. OBJECTIVE: This international survey aimed to assess perioperative patient management during elective intracranial procedures. This survey was performed from February to October 2018 and 311 neurosurgical, maximum care centers across 19 European countries were contacted. The aim was to evaluate the anesthesia management to provide relevant data of neuroanesthesia practices across European centers. The survey differentiated between vascular and non-vascular as well as supratentorial and infratentorial procedures. RESULTS: A total of 109 (35.0%) completed questionnaires from 15 European countries were analyzed. The results illustrated that total intravenous anesthesia was most commonly implemented during elective intracranial procedures (83.8%). All centers performed endotracheal intubation prior to major intracranial surgery (100%). Central venous lines were placed in 63.3% of cases. Moderate intraoperative hypothermia was carried out in 12.8% of the procedures, especially during vascular supratentorial and infratentorial surgery. A neuromuscular blockade during surgery was implemented in 74.1% of patients. Assessment of the neuromuscular junction was performed in 59.2% of cases, 76.7% of patients were immediately extubated in the operating room. 84.7% of these patients were directly transferred to a monitoring ward or an intensive care unit (ICU) and 55.1% of ventilated patients were transferred directly to an ICU. CONCLUSION: The data demonstrate that many aspects of anesthesia management during elective intracranial surgery vary between European institutions. The data also suggest that a broad consensus exists regarding the implementation of total intravenous anesthesia, airway management (endotracheal intubation), the implementation of urinary catheters, large bore peripheral venous lines and the broad availability of cross-matched red blood cell concentrates. Nevertheless, anesthesia management (e.g. central venous catheterization, moderate hypothermia, neuromuscular monitoring) is still handled differently across many European institutions. A lack of standardized guidelines defining anesthetic management in patients undergoing intracranial procedures could explain this variability. Further studies could help establish optimal anesthesia management for these patients. This in turn could help in the development of national and international guidelines and SOPs which could define optimal management strategies for intracranial procedures.

SAXS-CT: a nanostructure resolving microscopy for macroscopic biologic specimens.

SAXS-CT is an emerging powerful imaging technique which bridges the gap between information retrieved from high-resolution local techniques and information from low-resolution, large field-of-view imaging, to determine the nanostructure characteristics of well-ordered tissues, e.g., mineralized collagen in bone. However, in the case of soft tissues, features such as poor nanostructural organization and high susceptibility to radiation-induced damage limit the use of SAXS-CT. Here, by combining the freeze-drying the specimen, preceded by formalin fixation, with the nanostructure survey we identified and monitored alterations on the hierarchical arrangement of triglycerides and collagen fibrils three-dimensionally in breast tumor specimens without requiring sample staining. A high density of aligned collagen was observed precisely on the invasion front of the breast carcinoma, showing the direction of cancer spread, whereas substantial content of triglycerides was identified, where the healthy tissue was located. Finally, the approach developed here provides a path to high-resolution nanostructural probing with a large field-of-view, which was demonstrated through the visualization of characteristic nanostructural arrangement and quantification of content and degree of organization of collagen fibrils in normal, benign and malignant human breast tissue.

Organoleptic excipients used in pediatric antibiotics.

Taste is a crucial factor that determines the palatability of the oral dosage form and patient compliance. OBJECTIVE: The aim of this work was to evaluate the organoleptic excipients in oral antibiotics for pediatric use marketed in Brazil. METHODS: The information was obtained from the GuidetoPharmacy, a reference for the pharmaceutical trade. The analysis included dosage forms for oral administration and drugs and their combination with antibacterial action. After this survey, we identified the constitution of the flavoring, sweetening, and coloring agents of each medicine. The results are presented in a descriptive form. RESULTS: Twelve drugs or associations are distributed in 70medicines. Oral suspension was the most common pharmaceutical dosage form. Sweeteners were sucrose, sodium saccharin, and sodium cyclamate. All the coloring agents observed are synthetic and the most frequent ones were yellow twilight no. 6, yellow tartrazine no. 5, and red ponceau 4R. The presence of two or more types of flavorings per medicine was observed. CONCLUSION: Antibacterials use coloring agents, flavorings, and sweeteners to facilitate the administration of medicines for children, using up to six different substances per formulation. No natural coloring agent was observed, demonstrating an issue to be explored in the future. It is important to note that, although necessary, these excipients are responsible for a high incidence of allergic reactions in children.

Characterization of opioid consumption and disposal patterns after total knee arthroplasty.

AIMS: The aim of this study was to determine the general postoperative opioid consumption and rate of appropriate disposal of excess opioid prescriptions in patients undergoing primary unilateral total knee arthroplasty (TKA). PATIENTS AND METHODS: In total, 112 patients undergoing surgery with one of eight arthroplasty surgeons at a single specialty hospital were prospectively enrolled. Three patients were excluded for undergoing secondary procedures within six weeks. Daily pain levels and opioid consumption, quantity, and disposal patterns for leftover medications were collected for six weeks following surgery using a text-messaging platform. RESULTS: Overall, 103 of 109 patients (94.5%) completed the daily short message service (SMS) surveys. The mean oral morphine equivalents (OME) consumed during the six weeks post-surgery were 639.6 mg (sd 323.7; 20 to 1616) corresponding to 85.3 tablets of 5 mg oxycodone per patient. A total of 66 patients (64.1%) had stopped taking opioids within six weeks of surgery and had the mean equivalent of 18 oxycodone 5 mg tablets remaining. Only 17 patients (25.7%) appropriately disposed of leftover medications. CONCLUSION: These prospectively collected data provide a benchmark for general opioid consumption after uncomplicated primary unilateral TKA. Many patients are prescribed more opioids than they require, and leftover medication is infrequently disposed of appropriately, which increases the risk for illicit diversion. Cite this article: Bone Joint J 2019;101-B(7 Supple C):98-103.

Maternal kidney function during pregnancy: systematic review and meta-analysis.

OBJECTIVES: To review systematically current literature on kidney function changes during pregnancy, in order to estimate the extent of adaptation over the course of both healthy physiological and complicated singleton pregnancies, and to determine healthy pregnancy reference values. METHODS: PubMed (NCBI) and EMBASE (Ovid) electronic databases were searched, from inception to July 2017, for studies on kidney function during uncomplicated and complicated pregnancies. Included studies were required to report a non-pregnant reference value of kidney function (either in a non-pregnant control group or as a prepregnancy or postpartum measurement) and a pregnancy measurement at a predetermined and reported gestational age. Kidney function measures assessed were glomerular filtration rate (GFR) measured by inulin clearance, GFR measured by creatinine clearance and serum creatinine level. Pooled mean differences between pregnancy measurements and reference values were calculated for predefined intervals of gestational age in uncomplicated and complicated pregnancies using a random-effects model described by DerSimonian and Laird. RESULTS: Twenty-nine studies met the inclusion criteria and were included in the analysis. As early as the first trimester, GFR was increased by up to 40-50% in physiological pregnancy when compared with non-pregnant values. Inulin clearance in uncomplicated pregnancy was highest at 36-41 weeks, with a 55.6% (53.7; 95% CI, 44.7-62.6 mL/min) increase when compared with non-pregnant values, and creatinine clearance was highest at 15-21 weeks' gestation, with a 37.6% (36.6; 95% CI, 26.2-46.9 mL/min) increase. Decrease in serum creatinine level in uncomplicated pregnancy was most prominent at 15-21 weeks, with a 23.2% (-0.19; 95% CI, -0.23 to -0.15 mg/dL) decrease when compared with non-pregnant values. Eight studies reported on pregnancies complicated by a hypertensive disorder. Meta-regression analysis showed a significant difference in all kidney function parameters when comparing uncomplicated and hypertensive complicated pregnancies. CONCLUSIONS: In healthy pregnancy, GFR is increased as early as the first trimester, as compared with non-pregnant values, and the kidneys continue to function at a higher rate throughout gestation. In contrast, kidney function is decreased in hypertensive pregnancy. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of blood pressure monitoring by applanation tonometry and invasively assessed blood pressure in cardiological patients.

The aim of this study was to evaluate the accuracy and precision of non-invasive continuous blood pressure measurement by applanation tonometry (AT) in awake or anaesthetised cardiological intensive care patients. Patients suffering from highly impaired left ventricular function atrial fibrillation or severe aortic valve stenosis were included into the study. Arterial blood pressure was recorded by applanation tonometry (T-Line 400, Tensys Medical®, USA) and an arterial line in awake or anaesthetised patients. Discrepancies in mean (MAP), systolic (SAP), and diastolic (DAP) arterial pressure between the two methods were assessed as bias, limits of agreement and percentage error respectively. In 31 patients a total of 27,900 measurements were analyzed. The concordance correlation coefficient was 0.23, 0.45 and 0.06 for MAP, SAP and DAP, respectively. For all patients bias for MAPAT compared to MAPAL was 14.96 mmHg (SAPAT 4.51 mmHg; DAPAT 19.12 mmHg) with limits of agreement for MAPAT of 46.25 and - 16.33 mm Hg (SAPAT 48.00 and - 38.98 mmHg; DAPAT 50.12 and - 11.89 mmHg). Percentage error for MAPAT was 56.8% (42.7% for SAPAT; 75.2% for DAPAT). We conclude that the AT method is not reliable in ICU patients with severe cardiac comorbidities.

Microstructural white matter brain abnormalities in patients with idiopathic fecal incontinence.

BACKGROUND: Abnormal central nervous system processing of visceral sensation may be a part of the pathogenesis behind idiopathic fecal incontinence (IFI). Our aim was to characterize brain differences in patients with IFI and healthy controls by means of structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: In 21 female patients with IFI and 15 female healthy controls, whole-brain structural differences in gray matter volume (GMV), cortical thickness, and white matter tracts fractional anisotropy (FA) were quantified. For this purpose, we used voxel-based morphometry, surface based morphometry and tract-based spatial statistic, respectively. Furthermore, associations between structural brain characteristics and latencies of rectal sensory evoked electroencephalography potentials were determined. KEY RESULTS: Compared to healthy controls, IFI patients had significantly reduced FA values, reflecting reduced white matter tract integrity, in the left hemisphere superior longitudinal fasciculus (SLF), posterior thalamic radiation, and middle frontal gyrus (MFG), all P<.05. No differences were observed in GMV or in cortical thickness. The reduced FA values in the SLF and MFG were correlated with prolonged latencies of cortical potentials evoked by rectal stimuli (all P<.05). CONCLUSIONS & INFERENCES: This explorative study suggests that IFI patients have no macrostructural brain changes, but exhibit microstructural changes in white matter tracts relevant for sensory processing. The clinical relevance of this finding is supported by its correlations with prolonged latencies of cortical potentials evoked by rectal stimulation. This supports the theories of central nervous system changes as part of the pathogenesis in IFI patients.

Effect of intravenous immunoglobulin administration on erythrocyte and leucocyte parameters.

BACKGROUND: Intravenous immunoglobulins (IVIG) are an attractive therapeutic tool for therapy of toxic epidermal necrolysis and severe forms of certain autoimmune diseases, including dermatomyositis, autoimmune blistering diseases, systemic vasculitis and lupus erythematodes. OBJECTIVES: Prompted by a case of IVIG-associated haemolytic anaemia, the effects of IVIG administrations on haematological parameters in patients with dermatological conditions were investigated. METHODS: Erythrocyte and leucocyte parameters were retrospectively analysed in 16 patients who had received IVIG at doses from 1 to 3 g/kg bodyweight (n = 35 cycles). The influence of IVIG on leucocyte survival was determined in vitro. RESULTS: Decreased absolute erythrocyte numbers, haemoglobin and haematocrit levels and a case of haemolytic anaemia were linked to transfusion of high-, but not low-dose IVIG. In contrast, leucopenia post-IVIG occurred in the vast majority of the recipients, unrelated to the administered IVIG amounts. In vitro investigations revealed a dose-dependent impairment of cell survival by IVIG in the neutrophil and monocyte, but not in the lymphocyte subpopulations. In several IVIG preparations, substantial amounts of blood group anti-A/anti-B antibodies were detected which could have accounted for the observed changes in the haematological parameters in our study cohort. CONCLUSIONS: IVIG products should be administered strictly according to indications. Commercially available IVIG products can contain blood group-specific antibodies that may induce haemolysis in some recipients. Monitoring of blood counts during applied IVIG therapy, especially when high doses are administered, is recommended.