Fetal aortic valvuloplasty for critical aortic stenosis: single-center retrospective study focusing on postnatal outcome.

OBJECTIVE: We aimed to report our experience on fetal aortic valvuloplasty (FAV) for critical aortic stenosis (AS) focusing on the postnatal evolution of the patients. METHODS: This retrospective study was approved by our local Institutional Review Board (n°2002-0128143827). All fetuses with critical AS who underwent FAV in a single center between 01/2011 and 06/2022 were included. FAV were performed under ultrasound guidance. Technical success was based upon balloon inflation across the aortic valve and improvement of the anterograde aortic flow across the aortic valve. At birth, biventricular circulation (BVC) strategy was decided assuming the left ventricle (LV) systolic and diastolic functions would ensure the systemic circulation. RESULTS: Sixty-three FAV were performed on 58 fetuses at 24.6[21.4-32.4] weeks of gestation. The procedure was successful in 52/58(89.6%) fetuses. There were 11/58(19%) in utero demises and 9/58(15.5%) terminations of pregnancy. There were no liveborn patients after the unsuccessful procedures. 38/58(65.5%) infants were delivered at a median gestational age of 38.1[29-40.6] weeks and 21/38(55.3%) of them required prostaglandin. 28/38(73.7%) [28/58(48.3%)] children entered the BVC path at birth. Among them, 20 required an aortic valvuloplasty at birth (11 percutaneous, 9 surgical) and 8 did not require any treatment at birth but of those, 5/8 underwent a surgical valvuloplasty between day 26 and day 1200 of life. 11/28(39.3%) infants with BVC at birth required a second intervention and four of them required a third intervention. Two infants who entered the BVC at birth underwent a conversion to UVC. None of the surviving children with BVC developed pulmonary hypertension. The global survival rate in case of BVC was 22/28(78.6%) at 23.3[8-112] months of life. 10 patients had UVC at birth. Among them, 6 received comfort care from birth and only 4 underwent surgery. 3/10 patients were still alive at the latest assessment (48[22-102] months). CONCLUSION: FAV for critical aortic stenosis led to anterograde aortic flow in 89.6% of the fetuses, with BVC being achieved in 48.3% (73.7% of the live born). Among patients with BVC at birth, the rate of reintervention is high but long-term survival is satisfactory. This article is protected by copyright. All rights reserved.

New N-aryl-N-alkyl-thiophene-2-carboxamide compound enhances intracellular Ca2+ dynamics by increasing SERCA2a Ca2+ pumping.

The type 2a sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) plays a central role in the intracellular Ca2+ homeostasis of cardiac myocytes, pumping Ca2+ from the cytoplasm into the sarcoplasmic reticulum (SR) lumen to maintain relaxation (diastole) and prepare for contraction (systole). Diminished SERCA2a function has been reported in several pathological conditions, including heart failure. Therefore, development of new drugs that improve SERCA2a Ca2+ transport is of great clinical significance. In this study, we characterized the effect of a recently identified N-aryl-N-alkyl-thiophene-2-carboxamide (or compound 1) on SERCA2a Ca2+-ATPase and Ca2+ transport activities in cardiac SR vesicles, and on Ca2+ regulation in a HEK293 cell expression system and in mouse ventricular myocytes. We found that compound 1 enhances SERCA2a Ca2+-ATPase and Ca2+ transport in SR vesicles. Fluorescence lifetime measurements of fluorescence resonance energy transfer between SERCA2a and phospholamban indicated that compound 1 interacts with the SERCA-phospholamban complex. Measurement of endoplasmic reticulum Ca2+ dynamics in HEK293 cells expressing human SERCA2a showed that compound 1 increases endoplasmic reticulum Ca2+ load by enhancing SERCA2a-mediated Ca2+ transport. Analysis of cytosolic Ca2+ dynamics in mouse ventricular myocytes revealed that compound 1 increases the action potential-induced Ca2+ transients and SR Ca2+ load, with negligible effects on L-type Ca2+ channels and Na+/Ca2+ exchanger. However, during adrenergic receptor activation, compound 1 did not further increase Ca2+ transients and SR Ca2+ load, but it decreased the propensity toward Ca2+ waves. Suggestive of concurrent desirable effects of compound 1 on RyR2, [3H]-ryanodine binding to cardiac SR vesicles shows a small decrease in nM Ca2+ and a small increase in µM Ca2+. Accordingly, compound 1 slightly decreased Ca2+ sparks in permeabilized myocytes. Thus, this novel compound shows promising characteristics to improve intracellular Ca2+ dynamics in cardiomyocytes that exhibit reduced SERCA2a Ca2+ uptake, as found in failing hearts.

Cardiac ryanodine receptor N-terminal region biosensors identify novel inhibitors via FRET-based high-throughput screening.

The N-terminal region (NTR) of ryanodine receptor (RyR) channels is critical for the regulation of Ca2+ release during excitation-contraction (EC) coupling in muscle. The NTR hosts numerous mutations linked to skeletal (RyR1) and cardiac (RyR2) myopathies, highlighting its potential as a therapeutic target. Here, we constructed two biosensors by labeling the mouse RyR2 NTR at domains A, B, and C with FRET pairs. Using fluorescence lifetime (FLT) detection of intramolecular FRET signal, we developed high-throughput screening (HTS) assays with these biosensors to identify small-molecule RyR modulators. We then screened a small validation library and identified several hits. Hits with saturable FRET dose-response profiles and previously unreported effects on RyR were further tested using [3H]ryanodine binding to isolated sarcoplasmic reticulum vesicles to determine effects on intact RyR opening in its natural membrane. We identified three novel inhibitors of both RyR1 and RyR2 and two RyR1-selective inhibitors effective at nanomolar Ca2+. Two of these hits activated RyR1 only at micromolar Ca2+, highlighting them as potential enhancers of excitation-contraction coupling. To determine whether such hits can inhibit RyR leak in muscle, we further focused on one, an FDA-approved natural antibiotic, fusidic acid (FA). In skinned skeletal myofibers and permeabilized cardiomyocytes, FA inhibited RyR leak with no detrimental effect on skeletal myofiber excitation-contraction coupling. However, in intact cardiomyocytes, FA induced arrhythmogenic Ca2+ transients, a cautionary observation for a compound with an otherwise solid safety record. These results indicate that HTS campaigns using the NTR biosensor can identify compounds with therapeutic potential.

Accuracy and impact of prenatal diagnosis of common arterial trunk.

OBJECTIVES: Outcome of common arterial trunk (CAT) depends mainly on truncal valve function, presence of coronary artery abnormalities and presence of interrupted aortic arch. The main objective of this study was to evaluate the accuracy of prenatal diagnosis of CAT by analyzing prenatal vs postnatal assessment of: (1) anatomic subtypes and (2) truncal valve function. The secondary objective was to assess the potential impact of prenatal diagnosis of CAT on postnatal mortality and morbidity by comparing prenatally vs postnatally diagnosed patients. METHODS: This was a retrospective analysis of all CAT patients diagnosed either prenatally, with postnatal or fetopsy confirmation, or postnatally, from 2011 to 2019 in a single tertiary center. Cohen's kappa statistic was used to evaluate agreement between pre- and postnatal assessment of anatomic subtypes according to Van Praagh and of truncal valve function. Mortality and morbidity variables were compared between prenatally vs postnatally diagnosed CAT patients. RESULTS: A total of 84 patients (62 liveborn with prenatal diagnosis, 16 liveborn with postnatal diagnosis and six terminations of pregnancy with fetopsy) met the inclusion criteria. The accuracy of prenatal diagnosis of CAT anatomic subtype was 80.3%, and prenatal and postnatal concordance for subtype diagnosis was only moderate (κ = 0.43), with no patient with CAT Type A3 (0/4) and only half of patients with CAT Type A4 (8/17) being diagnosed prenatally. Fetal evaluation of truncal valve function underestimated the presence (no agreement; κ = 0.09) and severity (slight agreement; κ = 0.19) of insufficiency. However, four of five cases of postnatally confirmed significant truncal valve stenosis were diagnosed prenatally, with fair agreement for both presence and severity of stenosis (κ = 0.38 and 0.24, respectively). Mortality was comparable in patients with and those without prenatal diagnosis (log-rank P = 0.87). CAT patients with fetal diagnosis underwent earlier intervention (P < 0.001), had shorter intubation time (P = 0.047) and shorter global hospital stay (P = 0.01). CONCLUSIONS: The accuracy of prenatal diagnosis of CAT is insufficient to tailor neonatal management and to predict outcome. Fetal assessment of truncal valve dysfunction appears unreliable due to perinatal transition. Improvement is necessary in the fetal diagnosis of anatomic subtypes of CAT requiring postnatal prostaglandin infusion. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Can the Hartree-Fock kinetic energy exceed the exact kinetic energy?

The Hartree-Fock (HF) approximation has been an important tool for quantum-chemical calculations since its earliest appearance in the late 1920s and remains the starting point of most single-reference methods in use today. Intuition suggests that the HF kinetic energy should not exceed the exact kinetic energy; but no proof of this conjecture exists, despite a near century of development. Beginning from a generalized virial theorem derived from scaling considerations, we derive a general expression for the kinetic energy difference that applies to all systems. For any atom or ion, this trivially reduces to the well-known result that the total energy is the negative of the kinetic energy and, since correlation energies are never positive, proves the conjecture in this case. Similar considerations apply to molecules at their equilibrium bond lengths. We use highly precise calculations on Hooke's atom (two electrons in a parabolic well) to test the conjecture in a nontrivial case and to parameterize the difference between density functional and HF quantities, but find no violations of the conjecture.

[Neurodevelopmental Disorders, Psychiatric Comorbidities and Associated Pathologies in Patients with Childhood-Onset Schizophrenia and Premorbid Autistic Symptoms.] / Atteintes Neurodéveloppementales, Comorbidités Psychiatriques Et Pathologies Associées Chez Des Patients Atteints de Schizophrénie Très Précoce Avec Symptômes Autistiques Prémorbides.

INTRODUCTION: Childhood-Onset Schizophrenia (COS) is a rare (1/40000), severe and neurodevelopmental form of schizophrenia beginning before 13 years of age. Little is known about comorbidities and specific COS-related disorders. Thus, the objective of our study was to evaluate them from a psychiatric, neurodevelopmental and somatic perspective. METHOD: This is an ancillary study of the GenAuDiss protocol. A standardized psychiatric interview (K-SADS-PL DSM5) and a neuropsychological assessment (WISC-V/WAIS-IV) were carried out in outpatients with COS as well as a medical history collection concerning pregnancy, perinatal period, development, biography and medical and psychiatric, personal, and family history. RESULTS: 20 outpatients were included. The mean age of onset of COS was 8.90 years (+/- 2.30). Psychiatric comorbidities (DSM5) were Attention Deficit Hyperactivity Disorder (15/20 patients), Anxiety Disorders (14/20) and Autism Spectrum Disorder (13/20). The average IQ was 70.26 (+/- 18.09). A language delay and a break in school career were noted in 18/20 patients. Finally, the main associated somatic disorder was asthma (15/20 patients). DISCUSSION: We highlighted in our patients with COS a high frequency of comorbidities including at least one systematic psychiatric disorder. However, although COS is a severe condition impacting the patient, his family and society, its management remains essentially symptomatic. In clinical practice, it is necessary to look for all these comorbidities and to manage them in order to improve the overall quality of care.

INTRODUCTION: La schizophrénie très précoce (STP) est une forme rare (1/40000), grave et neurodéveloppementale de schizophrénie débutant avant 13 ans. Les comorbidités et atteintes associées spécifiques des STP étant peu étudiées, l'objectif de notre étude a été de les évaluer sur le plan psychiatrique, neurodéveloppemental et somatique. MÉTHODE: Il s'agit d'une étude ancillaire du protocole GenAuDiss. Un entretien psychiatrique standardisé (K-SADS-PL DSM5) et un bilan neuropsychologique (WISC-V/WAIS-IV) ont été effectués chez les patients atteints de STP ainsi qu'une anamnèse concernant la grossesse, la périnatalité, le développement, la biographie et les antécédents médicaux et psychiatriques, personnels et familiaux. RÉSULTATS: 20 sujets ont été inclus. L'âge moyen de début du trouble était de 8,90 ans (+/−2,30). Les comorbidités psychiatriques (DSM5) étaient le Trouble Déficitaire de l'Attention avec Hyperactivité (15/20 patients), les troubles anxieux (14/20) et le Trouble du Spectre de l'Autisme (13/20). Le QI moyen était de 70,26 (+/−18,09). Un retard de langage et une rupture de parcours scolaire étaient notés chez 18/20 patients. Enfin, l'affection somatique principale associée était l'asthme (15/20 patients). DISCUSSION: Nous avons mis en évidence chez nos patients atteints de STP une fréquence élevée de comorbidités dont au moins un trouble psychiatrique systématique. Or, bien que la schizophrénie infantile soit une pathologie de pronostic sévère impactant le patient, sa famille et la société, sa prise en charge demeure essentiellement symptomatique. En pratique clinique, il apparaît nécessaire de rechercher systématiquement ces comorbidités et de les prendre en charge pour améliorer la qualité globale des soins.

[COVID-19 in children: SARS-CoV-2-related inflammatory multisystem syndrome mimicking Kawasaki disease]. / COVID-19 chez l'enfant : syndrome inflammatoire multi-systémique lié à SARS-CoV-2 mimant un syndrome de Kawasaki.

SARS-CoV-2 pandemics is characterized by a high level of infectivity and a high mortality among adults at risk (older than 65 years, obesity, diabetes, systemic hypertension). Following a common viral pneumonia, a multisystem inflammatory syndrome sometimes occurs, including an Acute Respiratory Distress Syndrome (ARDS) carrying a high mortality. Unlike most common respiratory viruses, children seem less susceptible to SARS-CoV-2 infection and generally develop a mild disease with low mortality. However, clusters of severe shock associated with high levels of cardiac biomarkers and unusual vasoplegia requiring inotropes, vasopressors and volume loading have been recently described. Both clinical symptoms (i.e., high and persistent fever, gastrointestinal disorders, skin rash, conjunctivitis and dry cracked lips) and biological signs (e.g., elevated CRP/PCT, hyperferritinemia) resembled Kawasaki disease. In most instances, intravenous immunoglobin therapy improved the cardiac function and led to full recovery within a few days. However, adjunctive steroid therapy and sometimes biotherapy (e.g., anti-IL-1Ra, anti-IL-6 monoclonal antibodies) were often necessary. Although almost all children fully recovered within a week, some of them developed coronary artery dilation or aneurysm. Thus, a new 'Multisystem Inflammatory Syndrome associated with SARS-CoV-2' has been recently described in children and helps to better understand Kawasaki disease pathophysiology.

Ivermectin safety in infants and children under 15 kg treated for scabies: a multicentric observational study.

BACKGROUND: Scabies is a frequent condition seen in infants and children. Only topical treatments have been approved in infants, but some of them are poorly tolerated. Oral ivermectin is approved for the treatment of scabies in several countries, but its use in infants and children weighing < 15 kg is off label. OBJECTIVES: To assess the safety of ivermectin in infants and young children, and to collect data on ivermectin efficacy in these age groups. METHODS: This study was performed in the dermatology and paediatric dermatology departments of 28 French centres between July 2012 and November 2015. Physicians treating an infant or child weighing < 15 kg for scabies with oral ivermectin were asked to send back a completed standardized and anonymous questionnaire, and the data were analysed. RESULTS: Data were collected on 170 infants and children aged 1-64 months, with a body weight of 4-14·5 kg, who were treated with oral ivermectin. The mean dose received was 223 µg kg-1 and 89% of the patients received a systematic second dose. Concomitant topical treatment was administered to 73% of patients. Adverse events were reported in seven patients (4%) and were not severe. At the follow-up visit, 139 (85%) patients had achieved healing. Factors significantly associated with healing were an ivermectin dose > 200 µg kg-1 (P < 0·001), and a delay between those two doses of < 10 days (P = 0·025). CONCLUSIONS: Our findings suggest the safety and efficacy of ivermectin for the treatment of scabies in infants and young children. What's already known about this topic? Scabies is a frequent condition in small children and infants, but the therapeutic options are limited. Ivermectin has been approved for the treatment of scabies in adults and children > 15 kg, but its use is off-label in infants and children weighing < 15 kg. Safety data on the use of ivermectin in children weighing < 15 kg are limited. What does this study add? Of 170 infants and children weighing < 15 kg who were treated for scabies with oral ivermectin, there were only seven reported mild adverse events and no serious ones. Our results show that ivermectin is effective in treating scabies in 85% of patients. Efficacy is higher when the received dose exceeds 200 µg kg-1 and when the delay between the two doses is < 10 days. Respond to this article.

[Toward a preventive management Alzheimer's disease]. / Pour une prise en charge préventive de la maladie d'Alzheimer.

Dementias, and Alzheimer's disease (AD) in particular, will increasingly become a public health issue. However, three major data may change the severity of these pathologies: in young adults, simple measures of healthy lifestyle (control of vascular risk factors, physical activity and cognitive stimulation), have an impact on a future cognitive decline; the same lifestyle interventions may delay the start of the disease for elderly people potentially at-risk; finally, and for the first time, a monoclonal antibody directed against amyloid lesions has just shown a significant effect on the progression of AD in patients at an early stage of the disease. According to these results, we will have to reconsider the strategy for managing minor or severe cognitive disorders and particularly AD. Nowadays, patients start the care process too late. The solution is to act earlier, even preventively. It is necessary to improve a care offer adapted to this new situation in order to impact on the disease as soon as possible, even before the onset of symptoms, based on: 1) predictive algorithms aimed at establishing whose cognitively unimpaired individuals may further develop the disease; these algorithms will be based on demographic, family, cognitive, genomic and biological data, such as in the "Santé Cerveau" project developed in partnership with the Health Regional Agency (ARS) and the general practitioners; 2)and on some expert centers which must become "dementia prevention clinics" to test prevention measures, initiate and validate multi-domain therapeutic education programs; to disclose about the risk in response to the request of worried patients; and to propose early pharmacological treatments if these individuals are on the way to declare AD in the coming months, taking into account competition between risks. This will allow to prepare to make use of new pharmacological treatments that might be discovered.

Circulating tumor DNA as a biomarker in metastatic colorectal carcinoma case report.

INTRODUCTION: Colorectal cancer (CRC) is the third most common malignant disease worldwide. The stage of the disease at the time of diagnosis and the capture of an early recurrence have a direct impact on long-term survival. Existing control screening methods often do not reflect real-time metastatic disease. In patients with detectable circulating tumor DNA (ctDNA), liquid biopsy can be an effective monitoring tool. CASE REPORT: In 2012, we performed sigmoid resection in a 57 years old patient for advanced CRC. The follow-up assessments included: blood samples for CA 19-9 and CEA, endoscopy and imaging methods. We also sampled peripheral blood to determine the level of ctDNA. Its value corresponded to the development of the disease throughout the period. Twice it outperformed imaging methods. CEA showed some degree of unreliability, especially after prolonged illness. CA 19-9 was in the normal range at all times. CONCLUSION: Circulating tumor DNA is an effective tool in the diagnosis of recurrent metastatic CRC. In patients with detectable ctDNA, its level correlates with the tumoral mass in real time. It has a predictive value in monitoring the treatment response. Its implementation in the follow-up of patients with CRC may have an impact on the choice of treatment strategy and consequently on patient survival.

Improved outcomes of islet autotransplant after total pancreatectomy by combined blockade of IL-1ß and TNFα.

The efficacy of islet transplant is compromised by a significant loss of islet mass posttransplant due to an innate inflammatory reaction. We report the use of a combination of etanercept and anakinra (ANA+ETA) to block inflammatory islet damage in 100 patients undergoing total pancreatectomy with islet autotransplant. The patients were divided into 3 groups: no treatment (control [CTL]), etanercept alone (ETA), or a combination of etanercept and anakinra (ANA+ETA). Peritransplant serum samples were analyzed for protein markers of islet damage and for inflammatory cytokines. Graft function was assessed by fasting blood glucose, basal C-peptide, secretory unit of islet transplant objects (SUITO) index, and hemoglobin A1c . Administration of both antiinflammatory drugs was well tolerated without any major adverse events. Reductions in interleukin-6, interleukin-8, and monocyte chemoattractant protein 1 were observed in patients receiving ANA+ETA compared with the CTL group, while also showing a modest improvement in islet function as assessed by basal C-peptide, glucose, hemoglobin A1c , and SUITO index but without differences in insulin dose. These results suggest that double cytokine blockade (ANA+ETA) reduces peritransplant islet damage due to nonspecific inflammation and may represent a promising strategy to improve islet engraftment, leading to better transplant outcomes.

MOG encephalomyelitis: international recommendations on diagnosis and antibody testing.

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation.

Evaluation of the basophil activation test and skin prick testing for the diagnosis of sesame food allergy.

BACKGROUND: The prevalence of sesame food allergy (SFA) has increased over recent years, with the potential of anaphylactic reactions upon exposure. Oral food challenge (OFC) remains the diagnostic standard, yet its implementation may be risky. Commercial skin prick tests (SPT) have a low sensitivity. Investigation of alternate diagnostic methods is warranted. OBJECTIVE: To evaluate the utility of SPT and the basophil activation test (BAT) for SFA diagnosis. METHODS: Eighty-two patients with suspected SFA completed an open OFC to sesame or reported a recent confirmed reaction. Patients were administered skin prick tests (SPT) with commercial sesame seed extract (CSSE) and a high protein concentration sesame extract (HPSE) (100 mg/mL protein). Whole blood from 80 patients was stimulated with sesame seed extract (40-10 000 ng/mL protein) for BAT), assessing CD63 and CD203c as activation markers. RESULTS: Sixty patients (73%) had IgE-mediated reactions to sesame, and 22 (27%) did not react. Receiver operating characteristic (ROC) curve analysis demonstrated an area under the curve (AUC) of 0.87 for HPSE-SPT and 0.66 for CSSE-SPT. At 1000 ng/mL of sesame protein, induction of CD63 and CD203c was weakly but significantly associated with OFC eliciting dose by rank (Spearman's rho = -.42 (P < .01) and -.35 (P < .05) for CD63 and CD203c, respectively). By ROC analysis, the AUC was 0.86 for CD63 and was 0.81 for CD203c sesame-induced basophil expression. Using HPSE-SPT as a first test to definitively diagnose (n = 24) or rule-out (n = 5) SFA and BAT as a second test to diagnose the remainder results in the correct classification of 73 of 80 (91%) patients, leaving one false negative and 4 false positive patients. Two BAT non-responders remain unclassified by this algorithm. CONCLUSIONS & CLINICAL RELEVANCE: While prospective cohort validation is necessary, joint utilization of BAT and SPT with HPSE extract may obviate the need for OFC in most SFA patients.

NUT Co Reactivity - ACquiring Knowledge for Elimination Recommendations (NUT CRACKER) study.

BACKGROUND: Ambiguities exist regarding the diagnosis of tree-nut allergy, necessitating either their elimination or the performance of oral food challenges (OFCs). OBJECTIVE: To examine the coincidences of allergies among tree-nuts and improve diagnostic testing to minimize the need for OFC. METHODS: Eighty-three patients prospectively evaluated for walnut, pecan, cashew, pistachio, hazelnut, and almond allergy. A history of previous reactions was obtained, and standardized skin prick tests (SPTs) using finely ground tree-nut solution and basophil activation tests (BAT) were performed. Patients underwent OFC for each tree-nut they eliminated and to which a reaction in the previous 2 years was not documented. RESULTS: While most patients were sensitized to 5-6 tree-nuts, over 50% were allergic to only 1-2 tree-nuts. The highest rate of allergy in sensitized patients was observed for walnut (74.6%) and cashew (65.6%). The rate of co-allergy for most tree-nuts was <30%. Two-thirds of walnut- and cashew-allergic patients were also allergic to pecan and pistachio, respectively, while all pecan- and pistachio-allergic patients were allergic to walnut and cashew, respectively. Receiver-operating characteristic analysis for SPT and BAT was tree-nut dependent and yielded area under the curve (AUC) values ranging from 0.75 to 0.94. Knowledge of coincident allergies in these pairs along with the combination of SPT and BAT correctly distinguished allergic from tolerant patients for walnut (87%), pecan (66%), cashew (71%), and pistachio (79%). CONCLUSION: The data presented here should assist in differentiating between allergic and tolerant patients, decrease the need for OFC, and allow for appropriate elimination recommendations.

Utility of routine use of breast ultrasound following contrast-enhanced spectral mammography.

AIM: To evaluate whether breast ultrasound (US) is routinely indicated following contrast-enhanced spectral mammography (CESM). MATERIALS AND METHODS: Consecutive screening and diagnostic CESM examinations with concurrent breast US were collected retrospectively (May 2012 to February 2016). Radiologists assigned a separate Breast Imaging-Reporting and Data System (BIRADS) score for CESM and for US. BIRADS scores were grouped into three categories: normal/benign appearing (BIRADS 1, 2); probably benign, short-term follow-up (BIRADS 3); or suspicious appearing (BIRADS 0, 4, 5). Patients with a suspicious-appearing lesion in either US or CESM underwent biopsy. The associations between malignant pathology with either suspicious-appearing CESM or suspicious-appearing US were calculated. The sensitivities and specificities of CESM and US were analysed. RESULTS: Eighty-seven lesions were biopsied, 37 (43%) biopsies were malignant and 50 (57%) were benign. Although suspicious-appearing CESM was associated with malignant biopsies (p<0.0001), suspicious-appearing US was not (p=0.985). Among 37 malignant biopsies, CESM had a sensitivity of 97% (36/37 lesions), compared to 92% (34/37 lesions) with US. None of the malignant biopsies were normal/benign appearing with CESM. One case of follow-up CESM was suspicious-appearing at US and proved to be malignant on biopsy. The specificity of CESM was 40%, which was significantly higher than US at 8%. CONCLUSION: When CESM is suspicious appearing, subsequent US and biopsy is appropriate. With a CESM BIRADS 3, correlation with US is suggested. If the CESM is benign appearing, the routine use of US is questionable, as it may lead to unnecessary benign biopsies.

Salivary scintigraphy for Sjögren's syndrome in patients with xerostomia: A retrospective study.

OBJECTIVES: The value of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome remains controversial. The primary aim of this study was to estimate the diagnostic accuracy of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome among 237 patients with xerostomia. METHODS: We retrospectively compared eight scintigraphy parameters between 106 Sjögren patients and 131 non-Sjögren patients. RESULTS: Seven of the eight parameters were significantly decreased in patients with Sjögren; however, their diagnostic accuracy was low, with areas under the curves (AUCs) ranging from 0.58 (95% CI 0.50-0.65) to 0.63 (95% CI: 0.55-0.70). The prestimulatory oral activity index allowed discrimination between primary and secondary Sjögren's syndrome (AUC 0.73, 95% CI: 0.62-0.84), and the secretion velocity for parotid glands allowed discrimination between patients with Sjögren and burning mouth syndrome (AUC 0.71, 95% CI 0.59-0.82). CONCLUSION: The accuracy of scintigraphy parameters for the diagnosis of Sjögren's syndrome among patients with xerostomia was low; however, some functional indices appeared to assist discrimination between primary and secondary SS patients and between subgroups of patients with different causes of xerostomia.

Genetic population structure of the convict surgeonfish Acanthurus triostegus: a phylogeographic reassessment across its range.

This study investigates the genetic population structure and connectivity of Acanthurus triostegus in five Indo-Pacific biogeographic regions (western and eastern Indian Ocean, western, central and eastern Pacific Ocean), using a mitochondrial DNA marker spanning the ATPase8 and ATPase6 gene regions. In order to assess the phylogeography and genetic population structure of A. triostegus across its range, 35 individuals were sampled from five localities in the western Indian Ocean and complemented with 227 sequences from two previous studies. Results from the overall analysis of molecular variance (AMOVA) without a priori grouping showed evidence of significant differentiation in the Indo-Pacific, with 25 (8.3%) out of 300 pairwise ΦST comparisons being significant. However, the hierarchical AMOVA grouping of Indian and Pacific Ocean populations failed to support the vicariance hypothesis, showing a lack of a genetic break between the two ocean basins. Instead, the correlation between pairwise ΦST values and geographic distance showed that dispersal of A. triostegus in the Indo-Pacific Ocean follows an isolation-by-distance model. Three haplogroups could be deduced from the haplotype network and phylogenetic tree, with haplogroup 1 and 2 dominating the Indian and the Pacific Ocean, respectively, while haplogroup 3 exclusively occurring in the Hawaiian Archipelago of the central Pacific Ocean.

[MOG encephalomyelitis: international recommendations on diagnosis and antibody testing]. / MOG-Enzephalomyelitis: Internationale Empfehlungen zu Diagnose und Antikörpertestung.

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation, and propose for the first time diagnostic criteria for MOG-EM.

High burden of metabolic comorbidities in a citywide cohort of HIV outpatients: evolving health care needs of people aging with HIV in Washington, DC.

OBJECTIVES: With the increasing impact of cardiovascular disease among populations aging with HIV, contemporary prevalence estimates for predisposing metabolic comorbidities will be important for guiding the provision of relevant lifestyle and pharmacological interventions. We estimated the citywide prevalence of hypertension, type 2 diabetes, dyslipidaemia, and obesity; examined differences by demographic subgroups; and assessed clinical correlates. METHODS: Utilizing an electronic medical record (EMR) database from the DC Cohort study - a multicentre prospective cohort study of HIV-infected outpatients - we assessed the period prevalence of metabolic comorbidities between 2011 and 2015 using composite definitions that incorporated diagnoses, pharmacy records, and clinical/laboratory results. RESULTS: Of 7018 adult patients (median age 50 years; 77% black), 50% [95% confidence interval (CI) 49-51] had hypertension, 13% (95% CI: 12-14) had diabetes, 48% (95% CI: 47-49) had dyslipidaemia, and 35% (95% CI: 34-36) had obesity. Hypertension was more prevalent among black patients, diabetes and obesity were more prevalent among female and black patients, dyslipidaemia was more prevalent among male and white patients, and comorbidities were more prevalent among older patients (all P < 0.001). For many patients, evidence of treatment for these comorbidities was not available in the EMR. Longer time since HIV diagnosis, greater duration of antiretroviral treatment, and having controlled immunovirological parameters were associated with metabolic comorbidities. CONCLUSIONS: These findings underscore the pervasive burden of metabolic comorbidities among HIV-infected persons, serve as the basis for future analyses characterizing their impact on subsequent adverse cardiovascular outcomes, and highlight the need for an increased focus on the prevention and control of comorbid complications in this population.