Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome

Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

     

Electromagnetic navigation during flexible bronchoscopy

BACKGROUND: Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseases. Nondiagnostic bronchoscopy leads to more invasive interventions, such as transthoracic needle aspiration, mediastinoscopy or even thoracotomy. Electromagnetic navigation is a novel technology that facilitates approaching peripheral lung lesions, which are difficult to sample by conventional means. The navigation system involves creating an electromagnetic field around the chest and localizing an endoscopic tool using a microsensor overlaid upon previously acquired CT images. OBJECTIVES: To determine the practicality, accuracy and safety of real-time electromagnetic navigation, coupled with previously acquired 3D CT images, in locating artificially created peripheral lung lesions in a swine model. METHODS: Peripheral lung lesions were created in four swine models by insertion of a metal tube (1 x 10 mm) via a transthoracic approach. An electromagnetic field was created by placing the animal on an electromagnetic location board. A position sensor incorporated into the distal tip of a dedicated tool was used to navigate to the various target lesions. Information gathered in real time during bronchoscopy was presented on a monitor simultaneously by displaying previously acquired CT images. Upon reaching the target lesion, biopsies were performed and the functionality and safety of the superDimension/Bronchus System was observed and documented. RESULTS: The registration accuracy expressed by the fiducial target registration error, expressing both the registration quality and the stability of fiducial (registration) points, was 4.5 mm on average. No adverse effects, such as pneumothorax or internal bleeding, were encountered in any of the animals in this study. CONCLUSIONS: Real-time electromagnetic positioning technology coupled with previously acquired CT images is an accurate technology added to standard bronchoscopy to assist in reaching peripheral lung lesions and performing biopsies.     

Prognostic impact of renal impairment and sodium imbalance in patients undergoing transjugular intrahepatic portosystemic shunting for the prevention of variceal rebleeding

BACKGROUND/AIM: Kidney function and portal pressure have prognostic relevance in nonshunted patients with cirrhosis. Since insertion of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal pressure and may improve the renal function, the aim of the present study was to investigate the prognostic role of renal impairment and portal hemodynamics in patients with compensated cirrhosis electively shunted due to recurrent variceal hemorrhages. METHODS: Data of 101 consecutive and prospectively followed patients with compensated cirrhosis (bilirubin <5 mg/dl) undergoing elective TIPS due to recurrent variceal bleeding (45 died, and 8 were transplanted during the follow-up period) were evaluated in a multivariate Cox model. RESULTS: Creatinine and sodium were identified as the only independent predictors of survival in this model. The 90th percentile of creatinine (>1.7 mg/dl) defined a subgroup with a similar poor prognosis as the 90th percentile of the model for end-stage liver disease (MELD) score. Neither baseline nor post-TIPS portal pressure correlated with the long-term outcome. CONCLUSIONS: In compensated patients undergoing TIPS due to variceal bleeding, renal impairment indicates a poor prognosis. Portal hemodynamic parameters are not predictive of survival in TIPS patients.     

Percutaneous coronary intervention of or through saphenous vein grafts or internal mammary arteries: the impact of stents, adjunctive pharmacology, and multicomponent distal protection.

We hypothesized that the use of stents and aggressive adjunctive pharmacotherapies has been associated with lower rates of complicating myocardial infarction (MI) and improved long-term outcomes compared to either previous balloon-only percutaneous coronary intervention (PCI) or atheroablative intervention for lesions of or through saphenous vein grafts (SVGs) and/or internal mammary arteries (IMAs). PCI of SVG has been complicated by relatively high rates of procedural MI and less favorable long-term outcomes than native vessel PCI, stimulating the development and application of an array of technologies. This study was based on retrospective review of stent-era (1999-2004) 5-year experience of a single center with 95 SVG procedures in 85 patients and 20 IMA procedures in 20 patients. These cases were compared with the previously published experience of one of the operators during the balloon-only period and literature review of the application of multiple technologies to SVG intervention, as well as consideration of the reoperation alternative. There was one in-hospital death each in the SVG cohort (1%) and in the IMA cohort (5%). There were SIX procedural MIs (6%), defined by total CK > normal, and 19 procedural MIs (20%) based on troponin-I > 1.0. Follow-up has been from 4 months to 5 years (average, 2.5 years), with 91% survival and one late CABG in the IMA group. SVG PCI with stents and adjunctive pharmacotherapies is associated with relatively low rates of procedural MI and favorable long-term outcomes.     

Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia

OBJECTIVE: Newborn screening based on measurement of 17alpha-hydroxyprogesterone (17-OHP) in a dried blood spot on filter paper is an effective tool for early diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Its most important rationale is prevention of a life-threatening salt-wasting (SW) crisis; in moderate forms of CAH, early diagnosis and treatment may prevent permanent negative effects of androgen overproduction. Our target was to analyse if all CAH patients who had been identified clinically before puberty would have been detected by the newborn screening. METHODS: Newborn screening cards of 110 CAH patients born between 1988 and 2000 in five Middle-European countries and diagnosed prior to puberty (77 SW and 33 moderate) and cards from 920 random, healthy newborn controls were analysed. CAH screening had not yet been introduced during this time. The diagnosis was based on clinical and laboratory signs and, in most cases, on CYP21 gene mutation analysis. All 17-OHP measurements in dried blood spots were carried out using a time-resolved fluoroimmunoassay kit. RESULTS: In the newborn screening blood spots, the median of 17-OHP levels was 561 nmol/l (range 91-1404 nmol/l) in subjects with the SW form and 40 nmol/l (4-247 nmol/l) in the moderate form. All 77 SW patients would have been detected by newborn screening using the recommended cut-off limits (30 nmol/l). However, 10 of 33 patients with moderate CAH would have been missed. 17-OHP levels of all controls were below the cut-off. CONCLUSION: Newborn screening is efficient for diagnosing the SW form of CAH, but is inappropriate for identifying all patients with a moderate form of CAH. It appears that the false-negative rate is at least one-third in children with the moderate form of CAH.     

Local conformal autoencoder for standardized data coordinates

We propose a local conformal autoencoder (LOCA) for standardized data coordinates. LOCA is a deep learning-based method for obtaining standardized data coordinates from scientific measurements. Data observations are modeled as samples from an unknown, nonlinear deformation of an underlying Riemannian manifold, which is parametrized by a few normalized, latent variables. We assume a repeated measurement sampling strategy, common in scientific measurements, and present a method for learning an embedding in Rd that is isometric to the latent variables of the manifold. The coordinates recovered by our method are invariant to diffeomorphisms of the manifold, making it possible to match between different instrumental observations of the same phenomenon. Our embedding is obtained using LOCA, which is an algorithm that learns to rectify deformations by using a local z-scoring procedure, while preserving relevant geometric information. We demonstrate the isometric embedding properties of LOCA in various model settings and observe that it exhibits promising interpolation and extrapolation capabilities, superior to the current state of the art. Finally, we demonstrate LOCA’s efficacy in single-site Wi-Fi localization data and for the reconstruction of three-dimensional curved surfaces from two-dimensional projections.     

Risk Factors for Gastrointestinal Complications in Aspirin Users: Review of Clinical and Experimental Data

This paper reviews recent clinical evidence that suggests that aspirin prophylaxis against cardiac and cerebral vascular ischemia is associated with significant gastrointestinal complications. The clinical and experimental evidence to confirm the role of risk factors of concomitant use of nonsteroidal anti-inflammatory drugs (NSAID), tobacco cigarette smoking, and alcohol consumption are discussed. The limitations of long-term acid suppression treatment for the prevention of these complications are considered. Future experimental studies to guide the clinical approach to develop novel and potentially cost-effective management strategies are discussed.