Utility of the Addenbrooke's Cognitive Examination III online calculator to differentiate the primary progressive aphasia variants.

The Addenbrooke's Cognitive Examination III is a brief cognitive screening tool that is widely used for the detection and monitoring of dementia. Recent findings suggest that the three variants of primary progressive aphasia can be distinguished based on their distinct profiles on the five subdomain scores of this test. Here, we investigated the utility of the Addenbrooke's Cognitive Examination III to differentiate the primary progressive aphasia variants based on their item-by-item performance profiles on this test. From these results, we created an interactive primary progressive aphasia Addenbrooke's Cognitive Examination III calculator which predicts the variant based on a patient's unique item-by-item profile. Twenty-eight logopenic variant, 25 non-fluent variant and 37 semantic variant primary progressive aphasia patients and 104 healthy controls completed the Addenbrooke's Cognitive Examination III at first clinical presentation. Multinomial regression analyses were conducted to establish performance profiles among groups, and R Shiny from RStudio was used to create the interactive Addenbrooke's Cognitive Examination III diagnostic calculator. To verify its accuracy, probability values of the regression model were derived based on a 5-fold cross-validation of cases. The calculator's accuracy was then verified in an independent sample of 17 logopenic, 19 non-fluent and 13 semantic variant primary progressive aphasia patients and 68 Alzheimer's disease patients who had completed the Addenbrooke's Cognitive Examination III (or an older version of this test: Revised) and had in vivo amyloid-PET imaging and/or brain autopsy pathological confirmation. Cross-validation of cases in the calculator model revealed different rates of sensitivity in classifying variants: semantic = 100%, non-fluent = 80.6% and logopenic = 79.9%; healthy controls were distinguished from primary progressive aphasia patients with 100% sensitivity. Verification of in vivo amyloid and/or autopsy-confirmed patients showed that the calculator correctly classified 10/13 (77%) semantic variant, 3/19 (16%) non-fluent variant and 4/17 (24%) logopenic variant patients. Importantly, for patients who were not classified, diagnostic probability values mostly pointed toward the correct clinical diagnosis. Furthermore, misclassified diagnoses of the primary progressive aphasia cohort were rare (1/49; 2%). Although 22 of the 68 Alzheimer's disease patients (32%) were misclassified with primary progressive aphasia, 19/22 were misclassified with the logopenic variant (i.e. falling within the same neuropathological entity). The Addenbrooke's Cognitive Examination III primary progressive aphasia diagnostic calculator demonstrates sound accuracy in differentiating the variants based on an item-by-item Addenbrooke's Cognitive Examination III profile. This calculator represents a new frontier in using data-driven approaches to differentiate the primary progressive aphasia variants.

Breast and Cervical Cancer Screening in Palau: Have We Improved Early Detection and Survival?

The Breast and Cervical Cancer Early Detection Program (BCCEDP) was first introduced in Palau in 1997. The program's aim is to recruit and screen women for early detection of breast and cervical cancers. An assessment of this screening program was conducted to evaluate its effectiveness, including impact on stage of diagnosis and survival time of patients diagnosed with breast and cervical cancers through both screening and clinical diagnosis. A retrospective cohort study using secondary data from 2004-2013 was conducted. There were 45 women diagnosed with breast or cervical cancer. Due to the small number of cases, a comparison of two time periods was made (2004-2008) and (2009-2013). There were more cancer cases detected through screening (26%) in the earlier time period (2004-2008), as compared to those diagnosed through screening (8%) in the later time period (2009-2013), though this difference was not statistically significant (P=.09). The proportion of breast and cervical cancers diagnosed at an earlier stage (0-3) may have decreased between the two time periods (42% to 23%, P=.3). A greater proportion of women who were diagnosed between 2004-2008 lived longer than 2 years (58%), than women who were diagnosed between 2009-2013 (39%; P=.23). The screening program has not shown improvement over the years despite the measures taken to detect the early onset of breast and cervical cancer, and survival outcomes in Palau remain poor.

Profiles of recent autobiographical memory retrieval in semantic dementia, behavioural-variant frontotemporal dementia, and Alzheimer's disease.

Episodic autobiographical memory (ABM) comprises recollection for events that are grounded within a specific spatiotemporal context, and usually accompanied by perceptual and emotional information. The neural substrates mediating ABM retrieval are those harbouring significant pathology in semantic dementia (SD) and behavioural-variant frontotemporal dementia (bvFTD), the most common subtypes of FTD. Relatively little is known, however, regarding the differential patterns of contextual details during episodic ABM retrieval across these dementia syndromes. This study investigated episodic ABM retrieval under free and probed recall conditions from 4 time periods with the aim to identify disease-specific profiles of episodic ABM contextual details. Episodic ABM was measured in 25 SD and 15 bvFTD patients and their performance contrasted to that of 17 Alzheimer's disease (AD) patients and 19 age-matched controls. Critically, SD patients showed relatively preserved recent ABM in comparison with remote epochs. In contrast, bvFTD and AD patients showed a reduced capacity to recall specific and contextually rich ABMs across all life epochs, in both free and probed recall conditions. Analyses of the recent period (last 12 months) provided evidence for different profiles of contextual episodic details recalled in dementia syndromes. Following probing, SD patients' recall deficits emanated exclusively from compromised Emotion/Thoughts and Spatiotemporal details. In contrast, bvFTD patients were significantly impaired across all categories of contextual details whereas AD patients showed deficits for Event and Emotion/Thoughts details only. As the largest study of ABM in FTD to date, these findings emphasise the differential impairment of recent ABM contextual details contingent on the underlying disease pathology. In addition, these results point towards the importance of investigating the constituent elements of emotion processing and strategic retrieval processes as potential variables mediating recent episodic ABM retrieval.

Assessment of behavioural markers of autonoetic consciousness during episodic autobiographical memory retrieval: a preliminary analysis.

There is ongoing theoretical debate regarding episodic memory and how it can be accurately measured, in particular if the focus should be content-based recall of episodic details or something more experiential involving the subjective capacity to mentally travel back in time and "re-live" aspects of the original event. The autonoetic subscale of the Episodic Autobiographical Memory Interview (EAMI) is presented here as a new test instrument that attempts to redress theoretical and methodological shortcomings in autobiographical memory assessment. The EAMI merges a phenomenological detail-based approach with an assessment of autonoetic consciousness, departing considerably from traditional Remember/Know paradigms used within this field. We present findings from an initial pilot study investigating the potential markers of autonoetic consciousness that may accompany episodic retrieval. Key behavioural indices of autonoetic consciousness, notably those of viewer perspective, visual imagery, and emotional re-experiencing, emerged as being inextricably bound with the level of phenomenological detail recalled and the overall re-living judgment. The autonoetic subscale of the EAMI permits conceptually refined assessment of episodic personal memories and the accompanying subjective experience of mental re-living, characteristic of episodic memory.

Attentional biases in geometric form perception.

This paper reports the operation of robust attentional bias to the top and right during perception of small, single geometric forms. Same/different judgements of successively presented standard and comparison forms are faster when local differences are located at top and right rather than in other regions of the forms. The bias persists when form size is reduced to approximately one degree of visual angle, and it is unaffected by saccadic eye movements and by instructions to attend to other reliably differentiating regions of the forms. Results lend support in various degrees to two of the possible explanations of the bias: (1) a static, skewed distribution of attentional resources around eye fixation; and (2) biased, covert scanning that commences invariably at the top and right of stimulus forms. Origins of the bias in terms of possible left-hemispheric capacity for constructing representations of visual stimuli from parts, as well as in terms of reading experience and prevailing optic flow during locomotion through space are considered. Recent investigations of conditions under which the bias can be maintained or reduced are mentioned.

Bleeding in children caused by gastrointestinal vascular lesions.

Intestinal vascular malformations in infants and children are rare but must be considered in the differential diagnosis of gastrointestinal bleeding. Many vascular malformation syndromes have associated intestinal lesions. Localization of vascular lesions is essential for successful management. A variety of treatment options including laser photoablation, surgical resection, and other nonoperative therapies have been utilized to treat these disorders.

Observation of splenic trauma: when is a little too much?

A 12-year-old boy was treated conservatively for a grade II splenic laceration. On discharge, he was instructed to avoid contact sports, running, and strenuous physical activity. Thirty-eight days later, after diving off the side of a swimming pool, he had abdominal pain, nausea, and diaphoresis. On admission, he was hemodynamically unstable. Results of a diagnostic lavage showed gross blood. At laparotomy, a fractured spleen was found, and splenectomy was performed. He recovered without complication. This case questions the activity restrictions placed on patients with conservatively managed splenic trauma. Avoidance of only contact sports and heavy exertion may be inadequate.

Follow-up imaging studies in children with splenic injuries.

We undertook a retrospective study of pediatric blunt splenic injuries treated nonoperatively at our institution from 1990 to 1995 (n = 72) to assess the impact of serial computed tomography (CT) scans on the outcome. Median number of studies per child was three. The result showed that the appearance of the splenic injury remained unchanged or improved in 95% of the imaging studies obtained (116 of 122). Only one of five patients with an image suggesting a worsening splenic injury required operative intervention. There were no instances of missed injuries, delayed ruptures, or readmissions. We conclude that serial CT scans have limited follow-up value and should be used selectively.

Tracheal ligation and mechanical ventilation do not improve the antioxidant enzyme status in the lamb model of congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: The antioxidant enzyme (AOE) system is the primary intracellular defense system of the lung against oxygen toxicity. The authors recently demonstrated depressed levels of catalase, glutathione peroxidase, and superoxide dismutase in congenital diaphragmatic hernia (CDH) lambs compared with controls. The aim of this study was to determine whether tracheal ligation (TL) or mechanical ventilation (recently shown to stimulate growth and surfactant metabolism, respectively) could induce an elevation in AOE activity. METHODS: Four nonventilated lambs with surgically created CDH and TL and five CDH lambs ventilated for 4 hours were studied. Lung tissue was analyzed for AOE and the results compared with untreated CDH lambs. RESULTS: Both ventilation and TL failed to elevate AOE activity above that of untreated CDH lambs. CONCLUSIONS: The data provide further evidence that TL does not improve lung metabolism or maturation. Mechanical ventilation, which often involves high oxygen delivery, is a necessary and often beneficial therapeutic modality. In the CDH neonate compromised not only by low baseline levels of the AOE, but also by an inability to induce enzyme synthesis in response to hyperoxia, mechanical ventilation may, by causing lung injury, be contributing to the high morbidity and mortality rate associated with CDH.

Lung physiological and metabolic changes in lambs with congenital diaphragmatic hernia after administration of prenatal maternal corticosteroids.

BACKGROUND/PURPOSE: Improved outcomes of preterm infants born to mothers treated prenatally with corticosteroids have been documented. The authors investigated the role of prenatal maternal corticosteroid therapy in congenital diaphragmatic hernia (CDH). METHODS: Five CDH lambs of ewes given 0.5 mg/kg betamethasone intravenously 24 hours before delivery (single-dose), four CDH lambs of ewes similarly dosed at 48 and 24 hours before delivery (double-dose), five untreated CDH lambs and five control lambs were studied. After 2 hours of ventilation, compliance, arterial oxygen (PO2) and carbon dioxide (pCO2) concentrations were recorded. Lavage protein and phospholipid levels were measured, and lung tissue was analyzed for antioxidant enzyme activity (AOE). RESULTS: No improvement in gas exchange was noted in either treatment group. Significant increases in compliance (P = .02) were noted in the double-dose steroid group, which were different from that of untreated CDH lambs or controls. Minimal changes in AOE activities were seen with steroid administration. CONCLUSIONS: Although the metabolic changes were not significant, the marked improvement in compliance seen in the double-dosed steroid group suggests a potential role for prenatal maternal corticosteroids in CDH. Further timing and dosage studies are warranted in this model.

The approach to common abdominal diagnosis in infants and children.

This article focuses on salient points in the evaluation of abdominal pain in infants and children. Specifically, the authors address appendicitis and abdominal pain associated with either vomiting, constipation, or gastrointestinal bleeding. A discussion of common abdominal masses, urologic, and gynecologic problems, and considerations in the evaluation of immunologically suppressed or neurologically impaired children, and children with recurrent abdominal pain is also presented. The authors establish logical, focused approaches to the initial evaluation and management of abdominal pain and suggest criteria for timely surgical referral.

Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Pulmonary hypertension plays a significant role in the pathophysiology of congenital diaphragmatic hernia (CDH). Although there has been an intensive research effort directed at mediators that may cause pulmonary vasoconstriction, no single agent has been identified. The authors hypothesize that there may be an alteration in the cGMP-nitric oxide (NO) pathway of vasodilatation contributing to the pulmonary hypertension observed in CDH. The purpose of these studies is to begin to elucidate vasoactive properties of pulmonary vessels with particular attention to the cGMP-NO pathway of vasodilatation in fetal lambs with CDH. METHODS: Fourth-generation pulmonary arteries and pulmonary veins were dissected from both right and left lungs of eight, 139-day gestational fetuses with surgically created CDH. Vessels were studied with standard isolated tissue bath techniques. Experiments examined basal release of NO in endothelium-intact PVs and PAs of both right and left lungs by measuring the contractile force of vessels constricted with norepinephrine (NE) in the presence and absence of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine (L-NA). Concentration-response curves to the vasodilating agents zaprinast and A23187 were also obtained in vessels contracted by NE. RESULTS: Left and right pulmonary artery responses to NE are enhanced over those of historic controls. Pretreatment of left pulmonary arteries with L-NA enhances the vasoconstrictor response to NE, whereas right PAs show no increased response. Relaxation responses to A23187 and zaprinast, in both left and right pulmonary arteries were not different from control lambs. Relaxation responses of both left and right pulmonary veins to A23187 and zaprinast are blunted compared with controls. This blunting is significantly more in left pulmonary veins than right. Further, right but not left pulmonary veins display enhanced vasoconstrictive response to NE after L-NA pretreatment. CONCLUSIONS: The NO-cGMP pathway of vasodilatation is abnormal in the near term, fetal lamb with CDH. These abnormalities were most apparent in pulmonary veins and may reflect abnormal NOS activity or content between left and right lungs of the fetal lamb with CDH. Pulmonary arteries from CDH lambs have basal and stimulated NO release equal to that of historic controls but appear to be hypersensitive to exogenous vasoconstrictors.

Cervical ECMO cannula placement in infants and children: recommendations for assessment of adequate positioning and function.

BACKGROUND/PURPOSE: Cervical extracorporeal membrane oxygenation (ECMO) cannula position is often difficult to confirm by chest x-ray alone. Malposition requires a second surgery to rectify the problem. Reoperation places the patient at risk for infection, bleeding, or death. This study analyzes indications for cannula repositioning and suggests an alternative standard for intraoperative evaluation of catheter function as it relates to position. METHODS: The authors reviewed charts of 73 patients placed on arterio-venous ECMO through cervical vascular access. Reasons for repositioning of either cannula at the initial surgery or postoperatively were recorded. RESULTS: Of 73 patients, 18 (24.6%) required either arterial cannula or venous cannula repositioning. In 10 (55%) of these patients, cannula malposition was not detected by chest x-ray during the initial cannulation, and they therefore required a second cervical exploration for repositioning. CONCLUSIONS: Chest x-ray is not sensitive in demonstrating malpositioned cervical ECMO cannulae. Two-dimensional ECHO before wound closure, may be a superior, more cost effective means of assessing cannula placement and function than x-ray alone. Confirmation of cannula position and function, before wound closure, would reduce the risks involved with cervical reexploration.

The approach to common abdominal diagnoses in infants and children. Part II.

Part I (August 1998 issue, Pediatric Clinics), discussed appendicitis and common abdominal diagnoses in infants and in children associated with vomiting, as well as special considerations in the evaluation of immunologically suppressed and neurologically impaired pediatric patients. In this article, the authors continue to discuss the evaluation of constipation, gastrointestinal bleeding, common abdominal masses, and recurrent abdominal pain.

Care of the surgical intensive care nursery graduate. The primary care pediatrician's perspective.

Care of the intensive care nursery graduate may be quite challenging. It is important that primary care pediatricians become familiar with the complications unique to surgical patients so that they may properly prepare and educate parents and provide appropriate long-term follow-up for these often complex patients. Maintenance of a close relationship with the pediatric surgeon with an open line of communication regarding the approach to various surgical problems facilitates the effective integration of the intensive care nursery graduate into the primary care pediatrician's practice and provides the foundation for a successful clinical outcome.

Prenatal diagnosis of the fetus with cystic fibrosis and meconium ileus.

The sonographic finding of hyperechoic or dilated fetal bowel raises suspicion of a number of prenatal disorders including meconium ileus (MI), meconium peritonitis, congenital infection, neoplasm, or chromosomal trisomy. These findings may also represent transient normal variants. The following case report details the evaluation of one pregnancy with abnormal intestinal echogenic findings on serial sonograms (US), to demonstrate inherent diagnostic difficulties in such a case. A diagnostic algorithm is presented to aid in the proper use of US and DNA mutation analysis for cystic fibrosis (CF), so that the cause of an abnormal abdominal US can be established earlier and more accurately than suggested by previous management schemes. Earlier fetal diagnosis may help to anticipate postnatal problems associated with CF/MI, and therefore provide more optimal clinical management of the affected fetus.