PIK3CA‐related overgrowth spectrum (PROS): Diagnostic and testing eligibility criteria,differential diagnosis,and evaluation

Somatic activating mutations in the phosphatidylinositol‐3‐kinase/AKT/mTOR pathway underlie heterogeneous segmental overgrowth phenotypes. Because of the extreme differences among patients, we sought to characterize the phenotypic spectrum associated with different genotypes and mutation burdens, including a better understanding of associated complications and natural history. Historically, the clinical diagnoses in patients with PIK3CA activating mutations have included Fibroadipose hyperplasia or Overgrowth (FAO), Hemihyperplasia Multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal (CLOVES) syndrome, macrodactyly, Fibroadipose Infiltrating Lipomatosis, and the related megalencephaly syndromes, Megalencephaly‐Capillary Malformation (MCAP or M‐CM) and Dysplastic Megalencephaly (DMEG). A workshop was convened at the National Institutes of Health (NIH) to discuss and develop a consensus document regarding diagnosis and treatment of patients with PIK3CA‐associated somatic overgrowth disorders. Participants in the workshop included a group of researchers from several institutions who have been studying these disorders and have published their findings, as well as representatives from patient‐advocacy and support groups. The umbrella term of “PIK3CA‐Related Overgrowth Spectrum (PROS)” was agreed upon to encompass both the known and emerging clinical entities associated with somatic PIK3CA mutations including, macrodactyly, FAO, HHML, CLOVES, and related megalencephaly conditions. Key clinical diagnostic features and criteria for testing were proposed, and testing approaches summarized. Preliminary recommendations for a uniform approach to assessment of overgrowth and molecular diagnostic testing were determined. Future areas to address include the surgical management of overgrowth tissue and vascular anomalies, the optimal approach to thrombosis risk, and the testing of potential pharmacologic therapies. © 2014 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.     

Effect of different doses of iron supplementation during pregnancy on maternal and infant health

Currently, there is no consensus regarding the optimum iron supplementation during pregnancy. The aim of this study is to evaluate the effect of different iron supplementation doses (including no supplementation) during pregnancy on the iron status of the mother and on the health of the neonate. A longitudinal study was conducted involving 358 pregnant women and their newborns. Mothers were classified as non-supplemented, low iron supplemented (<60 mg/day), moderate iron supplemented (between 60 and 100 mg/day) or high iron supplemented (>100 mg/day). General clinical and obstetric histories, haemoglobin (Hb), serum ferritin (SF) and transferrin saturation were evaluated in the first, second, third trimesters, and at partum. SF and Hb decreased less sharply in the iron-supplemented groups compared to the non-supplemented group. The higher the doses of iron supplementation, the lower the percentages of iron depletion at partum (p?<?0.001), iron deficiency anaemia (p?<?0.001) and preterm deliveries (p?=?0.009) as well as a higher birth weight of the newborn. However, the group with high supplementation had a greater percentage (27.6 %) of women at risk of haemoconcentration at partum. Our Mediterranean women began gestation with iron stores close to deficit (SF, 28.1 μg/L; 95 % CI 27.9–28.4). With these iron stores, supplementation with iron at daily doses of between 60 and 100 mg appears to be the most beneficial for the health of mother and child. These findings need to be confirmed in further randomised clinical trials.     

Maxillonasal dysplasia (Binder's syndrome): a critical review and case study

Binder's syndrome (maxillonasal dysplasia) is a disorder of unknown etiology characterized by nasomaxillary hypoplasia and a 40-50% association of an underdeveloped frontal sinus and cervicospinal abnormalities. The midfacial retrusion is similar to that in chondrodysplasia punctata, resulting in confusion regarding diagnosis. This paper outlines the distinguishing features of Binder's syndrome, the treatment considerations, and presents 24 patients seen and treated. The facial and skeletal characteristics and developmental findings are emphasized to affirm the diagnosis of Binder's syndrome. A familial finding of Binder's features in five patients raises the possibility of a genetic mechanism, a previously undisclosed finding.     

The effect of clinical remount procedures on the comfort and success of complete dentures

Fifteen patients were treated with complete dentures in a routine manner that included a clinical remount. A second group of 15 was treated in the identical manner except that the clinical remount was not performed. The occlusal patterns of all dentures were recorded in the patient's mouths at delivery and again 1 week later by using a photoelastic membrane to provide a permanent record. The presence or absence of soreness was also noted for each patient during the week after delivery. Results indicate that clinical remounts significantly reduced the incidence of soreness, preserved the occlusal force, and reduced the changes in occlusal patterns of the dentures. Although both cusped and flat teeth were used in both treatment groups, no significant differences were noted in relation to either form on the basis of the indices studied.     

Association of atherosclerosis in the descending thoracic aorta with coronary artery disease on multi detector row computed tomography coronary angiography in patients with suspected coronary artery disease

The association between atherosclerosis in the descending thoracic aorta (DTA) visualized on computed tomography coronary angiography (CTA) and coronary artery disease (CAD) has not been extensively explored. Therefore, a comprehensive analysis of DTA atherosclerosis on CTA was performed and the association of DTA atherosclerosis with CAD was evaluated in patients with suspected CAD. A total of 344 patients (54 ± 12 years, 54 % men) with suspected CAD underwent CTA. CTA were classified based on CAD severity in no signs of atherosclerosis or minor wall-irregularities <30 %, non-significant CAD 30–50 %, or significant CAD ≥50 % stenosis. The DTA was divided in segments according the posterior intercostal arteries. Per segment the presence of atherosclerotic plaque (defined as ≥2 mm wall thickness) was determined and maximal wall thickness was measured. Plaque composition was scored as non-calcified or mixed and the percentage of DTA segments with atherosclerosis was calculated. Significant CAD was present in 152 (44 %) patients and 278 (81 %) had DTA atherosclerotic plaque. DTA maximal wall thickness and percentage of DTA segments with atherosclerosis were 2.7 ± 1 mm and 49 ± 36 %. The presence, severity and extent of DTA atherosclerosis significantly increased with increasing CAD severity. Multivariate logistic regression analysis corrected for age and other risk factors demonstrated independent associations of DTA plaque (OR 6.56, 95 % CI 1.78–24.19, p = 0.005) and maximal DTA wall thickness (OR 2.00, 95 % CI 1.28–3.12, p = 0.002) with significant CAD. The presence and severity of DTA atherosclerosis were independently related with significant CAD on CTA in patients with suspected CAD.     

Influence of Procedural Success on Immediate and Long-Term Clinical Outcome of Patients Undergoing Percutaneous Revascularization of Occluded Coronary Artery Bypass Vein Grafts

Objectives. This study sought to determine whether successful recanalization of an occluded vein graft is associated with improvement in long-term clinical outcome.

Background. Coronary angioplasty of occluded vein grafts is associated with a lower initial success rate and a higher complication rate than angioplasty of vein grafts with subtotal stenoses and native coronary arteries. Whether successful angioplasty improves clinical outcome is unknown.

Methods. We analyzed 77 consecutive patients who underwent angioplasty of an occluded saphenous vein coronary artery bypass graft between August 1983 and June 1994. Patients with a myocardial infarction in the previous 24 h were excluded from the study.

Results. The mean age of the study cohort was 65 years; the mean (±SD) age of the treated grafts was 7.5 ± 3.9 years. As an adjunct to balloon angioplasty, stents were used in 9% of procedures, laser in 30%, and atherectomy in 16%, and thrombolytic therapy was administered in 23% of patients. The angioplasty success rate was 71%. Major complications within 30 days of the procedure included death in 5.2% of patients, Q wave myocardial infarction in 1.3% and repeat bypass surgery in 7.8%; these events occurred with similar frequency in patients in whom angiographic success was and was not achieved. Kaplan-Meier analysis comparing patients in whom angioplasty was successful (n = 55) and not successful (n = 22) revealed no differences in survival or occurrence of myocardial infarction or recurrent severe angina between the two groups in the 3 years after the procedure. Univariate analysis identified the age of the graft and use of newer interventional devices as predictors of death or myocardial infarction during this time period; procedural success was not associated with freedom from these adverse events after adjusting for these variables.

Conclusions. Angioplasty of occluded vein grafts is associated with a low initial success rate and a high complication rate. Successful angioplasty does not appear to reduce the occurrence of adverse events in the 3 years after the procedure.

(J Am Coll Cardiol 1996;28:1732–7)>     

Exploring prevalence of wound infections and related patient characteristics in homecare using natural language processing

We aimed to create and validate a natural language processing algorithm to extract wound infection-related information from nursing notes. We also estimated wound infection prevalence in homecare settings and described related patient characteristics. In this retrospective cohort study, a natural language processing algorithm was developed and validated against a gold standard testing set. Cases with wound infection were identified using the algorithm and linked to Outcome and Assessment Information Set data to identify related patient characteristics. The final version of the natural language processing vocabulary contained 3914 terms and expressions related to the presence of wound infection. The natural language processing algorithm achieved overall good performance (F-measure = 0.88). The presence of wound infection was documented for 1.03% (n = 602) of patients without wounds, for 5.95% (n = 3232) of patients with wounds, and 19.19% (n = 152) of patients with wound-related hospitalisation or emergency department visits. Diabetes, peripheral vascular disease, and skin ulcer were significantly associated with wound infection among homecare patients. Our findings suggest that nurses frequently document wound infection-related information. The use of natural language processing demonstrated that valuable information can be extracted from nursing notes which can be used to improve our understanding of the care needs of people receiving homecare. By linking findings from clinical nursing notes with additional structured data, we can analyse related patients' characteristics and use them to develop a tailored intervention that may potentially lead to reduced wound infection-related hospitalizations.     

Inducing System-1-type diagnostic reasoning in second-year medical students within 15 minutes

Abstract

Purpose: Diagnostic reasoning literature debates the significance of “dual-process theory” and the importance of its constituent types of thinking: System-1and System-2. This experimental study aimed to determine whether novice medical students could be trained to utilize System-1 thinking when making diagnoses based on chest X-rays.

Method: Second-year medical students were recruited and presented with a series of eight online chest X-rays cases. Participants were shown half of the cases repeatedly during a training phase and the other half only twice. During the final test phase, they were shown all eight cases, providing a diagnosis as a free text answer. Dependent variables were diagnostic accuracy and response time.

Results: Thirty-two students participated. During the test phase, students responses were significantly more accurate and faster for cases which had been seen repeatedly during the training phase (mean score?=?3.56/4, mean time?=?2.34?s) compared with cases which had been seen only twice (mean score?=?1.59/4, mean time?=?7.50?s).

Conclusion: This study demonstrates that it is possible to induce in novice students the speed-to-diagnosis and diagnostic accuracy typical of System-1-type reasoning. The full experimental design and the chest X-rays used may provide new opportunities to explore some of the issues surrounding dual-process theory.     

Regulation of male rat copulatory behavior by preoptic incertohypothalamic dopamine neurons

The role of dopaminergic terminals in the medial preoptic area (MPO) in the regulation of male rat copulatory behavior was investigated. A 6-hydroxydopamine (6-OHDA) injection into the MPO of animals pretreated with desipramine resulted in a small (23%) depletion of DA, and no impairment of copulatory activity. Further depletion of catecholamines with alpha-methyl p-tyrosine (AMPT) produced several deficits in the copulatory behavior of 6-OHDA-treated males, at a dose of AMPT that did not adversely affect copulation prior to 6-OHDA administration. The dose-related effects of intracranial apomorphine (APO) injections were also altered by 6-OHDA injections into the MPO. The inhibition previously found with 0.2 microgram of APO into the lateral ventricle of normal males was abolished by 6-OHDA treatment. A facilitation of copulatory behavior was observed following the injection of 0.2 microgram of APO into the MPO of 6-OHDA-treated animals, whereas this treatment did not affect the copulatory behavior of intact animals. Finally, inhibitory effects observed following an injection of 0.1 microgram of APO into the MPO of normal males were blocked by 6-OHDA administration. The relative roles of presynaptic autoreceptors and postsynaptic DA receptors in the MPO in mediating the dose-related effects of APO on copulatory behavior are discussed.