Hemorrhagic transformation after stroke: inter- and intrarater agreement.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a complication of stroke that can occur spontaneously or after treatment. We aimed to assess the inter- and intrarater reliability of HT diagnosis. METHODS: Studies assessing the reliability of the European Cooperative Acute Stroke Study (ECASS) classification of HT or of the presence (yes/no) of HT were systematically reviewed. A total of 18 raters independently examined 30 post-thrombectomy computed tomography scans selected from the Aspiration versus STEnt-Retriever (ASTER) trial. They were asked whether there was HT (yes/no), what the ECASS classification of the particular scan (0/HI1/HI2/PH1/PH2) (HI indicates hemorrhagic infarctions and PH indicates parenchymal hematomas) was and whether they would prescribe an antiplatelet agent if it was otherwise indicated. Agreement was measured with Fleiss' and Cohen's κ statistics. RESULTS: The systematic review yielded four studies involving few (≤3) raters with heterogeneous results. In our 18-rater study, agreement for the presence of HT was moderate [κ = 0.55; 95% confidence interval (CI), 0.41-0.68]. Agreement for ECASS classification was only fair for all five categories, but agreement improved to substantial (κ = 0.72; 95% CI, 0.69-0.75) after dichotomizing the ECASS classification into 0/HI1/HI2/PH1 versus PH2. The inter-rater agreement for the decision to reintroduce antiplatelet therapy was moderate for all raters, but substantial among vascular neurologists (κ = 0.70; 95% CI, 0.57-0.84). CONCLUSION: The ECASS classification may involve too many categories and the diagnosis of HT may not be easily replicable, except in the presence of a large parenchymal hematoma.

Intravenous thrombolysis and thrombectomy decisions in acute ischemic stroke: An interrater and intrarater agreement study.

PURPOSE: We aimed to assess agreement on intravenous tissue-plasminogen activator (IV tPA) and mechanical thrombectomy (MT) management decisions in acute ischemic stroke (AIS) patients. Secondary objectives were to assess agreement on Diffusion-Weighted-Imaging-Alberta-Stroke-Program-EArly-CT-Score (DWI-ASPECTS), and clinicians' willingness to recruit patients in a randomized controlled trial (RCT) comparing medical management with or without MT. MATERIALS AND METHODS: Studies assessing agreement of IV tPA and MT were systematically reviewed. An electronic portfolio of 41 AIS patients was sent to randomly selected providers at French stroke centers. Raters were asked 4 questions for each case: (1) What is the DWI-ASPECTS? (2) Would you perform IV tPA? (3) Would you perform MT? (4) Would you include the patient in a RCT comparing standard medical therapy with or without MT? Twenty responders were randomly selected to study intrarater agreement. Agreement was assessed using Fleiss' Kappa statistics. RESULTS: The review yielded two single center studies involving 2-5 raters, with various results. The electronic survey was answered by 86 physicians (60 vascular neurologists and 26 interventional neuroradiologists). The interrater agreement was moderate for IV tPA treatment decisions (κ=0.565 [0.420-0.680]), but only fair for MT (κ=0.383 [0.289-0.491]) and for combined treatment decisions (κ=0.399 [0.320-0.486]). The intrarater agreement was at least substantial for the majority of raters. The interrater agreement for DWI-ASPECTS was fair (κ=0.325 [0.276-0.387]). Physicians were willing to include a mean of 14±9 patients (33.1%±21.7%) in a RCT. CONCLUSION: Disagreements regarding the use of IVtPA or MT in the management of AIS patients remain frequent. Further trials are needed to resolve the numerous areas of uncertainty.

Hyperphosphatemic familial tumoral calcinosis secondary to fibroblast growth factor 23 (FGF23) mutation: a report of two affected families and review of the literature.

Hyperphosphatemic familial tumoral calcinosis (HFTC), secondary to fibroblast growth factor 23 (FGF23) gene mutation, is a rare genetic disorder characterized by recurrent calcified masses. We describe young Lebanese cousins presenting with HFTC, based on a retrospective chart review and a prospective case study. In addition, we present a comprehensive review on the topic, based on a literature search conducted in PubMed and Google Scholar, in 2014 and updated in December 2017. While the patients had the same previously reported FGF23 gene mutation (homozygous c.G367T variant in exon 3 leading to a missense mutation), they presented with variable severity and age of disease onset (at 4 years in patient 1 and at 23 years in patient 2). A review of the literature revealed several potential patho-physiologic pathways of HFTC clinical manifestations, some of which may be independent of hyperphosphatemia. Most available treatment options aim at reducing serum phosphate level, by stimulating renal excretion or by inhibiting intestinal absorption. HFTC is a challenging disease. While the available medical treatment has a limited and inconsistent effect on disease symptomatology, surgical resection of calcified masses remains the last resort. Research is needed to determine the safety and efficacy of FGF23 replacement or molecular therapy, targeting the specific genetic aberration. Hyperphosphatemic familial tumoral calcinosis is a rare genetic disorder characterized by recurrent calcified masses, in addition to other visceral, skeletal, and vascular manifestations. It remains a very challenging disease.

Application of the DAWN clinical imaging mismatch and DEFUSE 3 selection criteria: benefit seems similar but restrictive volume cut-offs might omit potential responders.

BACKGROUND AND PURPOSE: An external validation of the selection criteria of diffusion-weighted imaging or computerized tomography perfusion assessment with clinical mismatch in the triage of wake-up and late-presenting strokes undergoing the Neurointervention with Trevo (DAWN) and the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE3) trials was conducted in a cohort of unknown onset stroke (UOS) patients treated with thrombectomy. METHODS: A validation cohort of UOS patients was selected from a prospectively collected thrombectomy database to match the inclusion criteria of DAWN and DEFUSE 3. Patients with an initial National Institutes of Health Stroke Scale (NIHSS) ≥10 were stratified according to the DAWN selection criteria. Patients ≤90 years old with an initial NIHSS ≥6 were stratified according to the DEFUSE 3 selection criteria. The proportions of patients with a modified Rankin Scale (mRS) ≤2 at 3 months follow-up were compared between DAWN-eligible patients and the DAWN trial thrombectomy group, and between DEFUSE 3-eligible patients and the DEFUSE 3 trial thrombectomy group. RESULTS: Of the 60/102 (59%) DAWN-eligible patients, 26 patients (43%) reached a mRS ≤2 at 3 months follow-up [versus 52/107 patients (49%) in the DAWN trial thrombectomy group; P = 0.52]. Of the 100/117 (85%) DEFUSE 3-eligible patients, 48 patients (48%) reached a mRS ≤2 at 3 months follow-up [versus 41/92 patients (45%) in the DEFUSE 3 trial thrombectomy group; P = 0.67]. Of the DAWN-ineligible and DEFUSE 3-ineligible patients who underwent thrombectomy, 38% (16/42) and 41% (7/17) of patients reached a mRS ≤2, respectively. CONCLUSION: The results of the DAWN and DEFUSE 3 trials were externally validated in a UOS cohort where the trials' selection criteria identified a similar proportion of responders to thrombectomy.

Coeliac disease presenting as severe hypoglycaemia in youth with type 1 diabetes.

BACKGROUND: Coeliac disease is an autoimmune disorder classically characterized by gastrointestinal symptoms and poor growth. The disease can be difficult to recognize in patients with Type 1 diabetes mellitus. Some clinicians find treatment of the disease in asymptomatic individuals controversial. CASE REPORTS: Two adolescent female patients with Type 1 diabetes experienced recurrent hypoglycaemic seizures. Neither patient reported gastrointestinal symptoms or poor growth. After diagnosis and treatment of coeliac disease, hypoglycaemia resolved. CONCLUSION: These cases illustrate how frequent unexplained severe hypoglycaemia can be an atypical presentation of coeliac disease in youth with Type 1 diabetes. Furthermore, they emphasize the importance of screening and treatment of coeliac disease in asymptomatic patients with Type 1 diabetes. Although controversial, management of coeliac disease in these asymptomatic patients can prevent the vicious cycle of recurrent hypoglycaemia and decrease risk for morbidity and death.

Structural bases for central nervous system malfunction in the quaking mouse: dysmyelination in a potential model of schizophrenia.

The dysmyelinating mouse mutant quaking (qk) is thought to be a model of schizophrenia based on diminution of CNS myelin (Andreone et al., 2007) and downregulation of the Qk gene (Haroutunian et al., 2006) in the brains of schizophrenic patients. The purpose of this study was to identify specific structural defects in the qk mouse CNS that could compromise physiologic function and that in humans might account for some of the cognitive defects characteristic of schizophrenia. Ultrastructural analysis of qk mouse CNS myelinated fibers shows abnormalities in nodal, internodal, and paranodal regions, including marked variation in myelin thickness among neighboring fibers, spotty disruption of paranodal junctions, abnormal distribution of nodal and paranodal ion channel complexes, generalized thinning and incompactness of myelin, and on many axonal profiles complete absence of myelin. These structural defects are likely to cause abnormalities in conduction velocity, synchrony of activation, temporal ordering of signals, and other physiological parameters. We conclude that the structural abnormalities described are likely to be responsible for significant functional impairment both in the qk mouse CNS and in the human CNS with comparable myelin pathology.

Three-dimensional radiographic assessment of the mandibular interforaminal donor site in different vertical facial growth types.

PURPOSE: To assess volumetrically, the impact of vertical facial growth types (VFGT) on the mandibular interforaminal region as a potential bone donor site. MATERIAL AND METHODS: 60 cone beam computed tomography (CBCT) scans of adult individuals were classified in three groups according to their SN-GoGn angle: hypodivergent group (hG) (N=20), normodivergent group (NG) (N=19) and hyperdivergent group (HG) (N=21). Total harvestable bone volume (TBV), cortico-cancellous bone volume (CBV-cBV), and cortical bone surface (CBS) were evaluated. ANOVA test followed by Tukey post hoc tests were used to compare the mean continuous outcomes according to their VFGT. RESULTS: The whole sample showed a mean TBV of 1376.32±541.01mm3, CBV of 468.52±121.54mm3 and cBV of 908.73±474.71mm3. The mean CBS amounted to 782.58±146.80mm2. The comparison between the groups stated a significantly different mean TBV and cBV (-p-value<0.001). The mean CBS was significantly different (-p-value=0.015): the smallest for the NG, but not significantly different (-p-value<0.001): the highest for the HG, intermediate for the NG and the smallest for the hG. CONCLUSION: Hypodivergent individuals have the thickest cancellous bone suitable for an onlay bone graft, while hyperdivergent individuals have the thinnest bone ideal for a 3D grafting approach.

Periodontal Inflammation Primes the Systemic Innate Immune Response.

The presence of periodontal diseases (PDs) often strongly correlates with other severe chronic inflammatory conditions, including cardiovascular disease, diabetes, and arthritis. However, the mechanisms through which these diseases interact are unclear. In PD, tissue and bone destruction in the mouth is driven by elevated recruitment of polymorphonuclear neutrophils (PMNs), which are primed and recruited from the circulation to sites of inflammation. We predicted that systemic effects on PMN mobilization or priming could account for the interaction between PD and other inflammatory conditions. We tested this using a mouse model of ligature-induced PD and found elevated PMN counts specifically in bone marrow, supporting a systemic effect of periodontal tissue inflammation on PMN production. In contrast, mice with induced peritonitis had elevated PMN counts in the blood, peritoneum, and colon. These elevated counts were further significantly increased when acute peritonitis was induced after ligature-induced PD in mice, revealing a synergistic effect of multiple inflammatory events on PMN levels. Flow cytometric analysis of CD marker expression revealed enhanced priming of PMNs from mice with both PD and peritonitis compared to mice with peritonitis alone. Thus, systemic factors associated with PD produce hyperinflammatory PMN responses during a secondary infection. To analyze this systemic effect in humans, we induced gingival inflammation in volunteers and also found significantly increased activation of blood PMNs in response to ex vivo stimulation, which reverted to normal following resolution of gingivitis. Together, these results demonstrate that periodontal tissue inflammation has systemic effects that predispose toward an exacerbated innate immune response. This indicates that peripheral PMNs can respond synergistically to simultaneous and remote inflammatory triggers and therefore contribute to the interaction between PD and other inflammatory conditions. This suggests larger implications of PD beyond oral health and reveals potential new approaches for treating systemic inflammatory diseases that interact with PD.

Crohn's disease: A retrospective analysis between computed tomography enterography, colonoscopy, and histopathology.

INTRODUCTION: To investigate the spectrum of computed tomography enterography (CTE) findings of active Crohn's disease (CD) in comparison to endoscopic, histopathologic and inflammatory markers. METHODS: Hospital records of 197 patients with known or suspected CD who underwent CTE over a period of 5 years were reviewed. Eighty-nine patients fulfilled the inclusion criteria. Three-point severity scores for endoscopy, pathology, and haematologic inflammatory markers were recorded. The findings on CTE were identified by three readers and correlated with endoscopic, pathologic, and haematologic severity scores. Statistical analysis was carried out employing a Pearson Chi square test and Fisher exact test. Receiver operating characteristic (ROC), visual grading characteristic (VGC) and Cohens' kappa analyses were performed. RESULTS: The CTE findings which were significantly correlated with the severity of active disease on endoscopy include bowel wall thickening, mucosal hyperenhancement, bilaminar stratified wall enhancement, transmural wall enhancement, and mesenteric fluid adjacent to diseased bowel (p < 0.05). Only bowel wall thickening and bilaminar stratified wall enhancement correlated with the pathological severity of active CD. ROC and VGC analysis demonstrated significantly higher areas under the curve (p < 0.0001) together with excellent inter-reader agreement (k = 0.86). CONCLUSION: CTE is a reliable tool for evaluating the severity of active disease and helps in the clinical decision pathway.

Oral bisphosphonates in treatment of transient osteoporosis.

Transient osteoporosis is a rare clinical syndrome of unknown etiology. It is believed that this syndrome is self-limiting; however, the data in the literature support the use of anti-resorptive agents that may reduce pain and decrease the duration of the illness. Herein, we describe two cases of transient osteoporosis of the hip and one case of transient osteoporosis of the knee where the use of oral bisphosphonates provided successful objective and subjective outcome.

Reversible encephalopathy associated with cholesterol embolism syndrome: magnetic resonance imaging and pathological findings.

We describe a patient found to have acute diffuse and reversible encephalopathy on magnetic resonance imaging (MRI) associated with cholesterol emboli syndrome (CES). The initial MRI showed extensive white matter, basal ganglia and cortical damage without evidence of brain infarction. Dramatic clinical and MRI improvement was observed with corticosteroids. Pathologically, cholesterol crystal emboli were found in the lumen of skin and brain arteries and were associated with varying degrees of inflammation of the arteriole wall. This case suggests that CES may be responsible for extensive, acute and reversible encephalopathy underlined by an inflammation of brain arteries.

[A case of alcohol-induced ketoacidosis?]. / Une acidocétose alcoolique?

We report a case of severe ketoacidosis. Initially the patient showed metabolic acidosis, the anion gap was positive and there was neither hyperlactatemia nor intoxication with acid substances. As the rate of glycemia was high (17.8 mmol/L), the diagnosis of diabetic ketoacidosis was proposed. Under treatment with continuous IV injection of insulin, hypoglycemia (1.8 mmol/L) appeared rapidly, while urine bioreactive test was positive for ketonuria, but negative for glycosuria. We finally concluded that it was an alcoholic ketoacidosis. The history of the patient confirmed the diagnosis : chronic alcoholism with recent increased of alcohol intake which provoked vomiting and fasting. This case report shows the difficulty in distinguishing between alcoholic ketoacidosis and diabetic ketoacidosis. We discuss the diagnostic strategy and particularly biologic data in the light of pathophysiologic mechanism of alcoholic ketoacidosis.

Response of human immunodeficiency virus-infected adults to measles-rubella vaccination.

Measles-mumps-rubella vaccine (MMR) is recommended for human immunodeficiency virus-infected (HIV+) adults. Data concerning MMR vaccination of HIV+ patients are limited to children. We evaluated 39 HIV+ (97% with > 200 CD4+ lymphocytes) and 17 non-HIV+ control adults receiving measles-rubella vaccine (MR). Clinical adverse events did not differ between groups. Prevaccination, three HIV+ and two control vaccinees were measles seronegative; no HIV+ and one control vaccinee seroconverted. No initially measles-seropositive vaccinee had a significant antibody elevation. Four HIV+ and three control vaccinees were rubella seronegative prevaccination; three HIV+ and two control vaccinees seroconverted. Among those initially rubella seropositive, two HIV+ and one control vaccinee had significant antibody elevations. There were no significant percentage CD4+ or CD8+ lymphocyte changes between groups. Three HIV+ vaccinees were p24 antigen positive pre- and postvaccination. Although MR vaccination appears safe in HIV+ adults, questions remain about the response of measles and rubella antibody-negative HIV+ adults and those with < 200 CD4+ lymphocytes.

Hypercalcemia in Langerhans' cell granulomatosis with elevated 1,25 dihydroxyvitamin D (calcitriol) level.

A 48-year-old woman presented with a history of premature menopause, polyuria, polydipsia, fever, and diffuse bony tenderness. Her evaluation revealed central diabetes insipidus, hypothalamic amenorrhea, an elevated free calcium on multiple occasions with an elevated 1,25 dihydroxyvitamin D level, and osteoporosis by densitometry. Skeletal series revealed multiple lytic lesions involving the long bones. The diagnosis of Langerhans' cell granulomatosis was made. She was treated with hormone replacement therapy, radiotherapy, and vinblastine, with a dramatic improvement in her pain and a near normalization of her free calcium. Whereas hypercalcemia has been described in several granulomatous disorders and is secondary to unregulated extrarenal production of 1,25 dihydroxyvitamin D, it is, however, extremely rare in Langerhans' cell granulomatosis. This is the first case report of Langerhans' cell granulomatosis with hypercalcemia and documented elevated increased 1,25 dihydroxyvitamin D level that responded to the treatment of her primary disease.

A comparative immunohistochemical study of peritoneal and ovarian serous tumors, and mesotheliomas.

The distinction between serous neoplasms of the peritoneum in women and conventional mesothelioma can be difficult. In order to determine any significant immunohistochemical differences, formalin-fixed, paraffin-embedded sections of 10 peritoneal serous tumors (PST), 10 ovarian serous tumors (OST), and 10 epithelial mesotheliomas were evaluated with a panel of 10 antibodies directed against carcinoembryonic antigen (CEA: polyclonal, monoclonal), high molecular weight keratin (34 beta E12), low molecular weight keratin (35 beta H11), Leu-M1, TAG-72 (monoclonal antibody B72.3), human milk fat globulin (HMFG-2), vimentin, placental alkaline phosphatase (PLAP), and S-100 protein. The antibodies CEA, Leu-M1, and B72.3 had the most discriminatory value in differentiating serous tumors from mesothelioma. Eighty-five percent of PSTs and OSTs (17 of 20) were positive with CEA, Leu-M1, and/or B72.3. None of the mesotheliomas stained for CEA or Leu-M1; three mesotheliomas had very focal positivity with B72.3 (1% or less). Vimentin, PLAP, HMGF-2, keratin, and S-100 had no significant discriminatory value. Epithelial mucin was present in 80% of serous tumors, while the mesotheliomas lacked epithelial mucin. Leu-M1, CEA, and/or B72.3 positivity in a peritoneal tumor supports a diagnosis of serous tumor. However, since some PST do not stain for any of the three antibodies and the focal nature of positive reactions in some cases may be difficult to interpret, exclusion of mesotheliomas is enhanced by the use of mucin stains.

Lidocaine cardioplegia for prevention of reperfusion ventricular fibrillation.

Lidocaine addition to crystalloid cardioplegic solution for prevention of reperfusion ventricular fibrillation after the release of the aortic cross-clamp was studied in 50 patients undergoing coronary artery bypass grafting and in 30 patients undergoing mitral or aortic valve replacement. Twenty-six of the patients undergoing coronary artery bypass grafting received lidocaine, 100 mg/L of cardioplegia, whereas a control group of 24 patients received cardioplegia without lidocaine. In the group undergoing valve replacement, 14 patients received lidocaine cardioplegia and 16 patients served as control. In the coronary artery bypass grafting group, lidocaine cardioplegia reduced significantly the incidence of reperfusion ventricular fibrillation from 100% to 42%. In the valve group, lidocaine cardioplegia also reduced significantly the incidence of reperfusion ventricular fibrillation from 93% to 42%. In both groups, lidocaine cardioplegia decreased the number of direct-current countershocks required to defibrillate the heart, with no significant increase in the incidence of high-grade atrioventricular block.

Ductal cysts of the accessory lacrimal glands: CT findings.

Benign ductal cysts of the accessory lacrimal glands are uncommon lesions of the orbit, arising from the glands of Wolfring and Krause. We report two patients with histopathologically proved cysts in whom CT scans revealed well-circumscribed extraconal cystic lesions adjacent to the globe, involving both eyelids. Radiologists should be aware of these rare lesions so as to include them in the differential diagnosis of orbital cysts.

Use of military antishock trousers in the hospital.

The military antishock trouser (MAST) suit has demonstrated its versatility in a number of situations. A method of inflation and monitoring for use in hospitalized patients using an oxygen flowmeter is described. This technique is simple to use and gives the physician more flexibility in controlling the inflation pressures of the suit.