Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted “Shotgun” Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period,a Single-Center Observational Study

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.     

Bladder-outlet obstruction — assessment of symptoms

Summary Assessment of symptoms plays a central role in the evaluation of men with suspected bladder-outflow obstruction (BOO) secondary to benign prostatic hyperplasia (BPH). It is on the basis of symptoms that treatment designed to relieve outflow obstruction is recommended. However, a variety of studies have suggested that a considerable proportion of men presenting with suspected outflow obstruction are not obstructed as determined by pressure-flow criteria. The relationship between many so-called obstructive symptoms and BOO has not yet been defined. Furthermore, all previous studies have defined BOO on the basis of urethral resistance factors, which are now regarded as outdated. Using current concepts of urethral pressure-flow relationships, we studied in detail the relationship between the obstructive symptoms of BPH, objective evidence of abormal voiding and BOO. Only the symptoms of hesitancy and poor flow were found to be significantly related to BOO. The symptoms of straining to void, intermittency, terminal dribbling and feeling of incomplete bladder emptying were not specific for BOO. Objective evidence of an intermittent flow pattern and of terminal dribbling do, however, have a high specificity and positive predictive value for BOO. The assessment of men with lower-urinary-tract symptoms must include objective tests of voiding function. A better understanding of the pathophysiology of lower-urinary-tract symptoms should lead to an improved symptomatic outcome of prostatectomy.     

Using stable isotopes to assess mineral absorption and utilization by children

Adequate mineral intake is a crucial part of a healthy diet for children-it supports appropriate growth and development and provides protection against childhood conditions like anemia and helps to prevent future adult diseases such as osteoporosis. Challenges in performing and interpreting studies in infants and children have hampered the accurate assessment of their mineral utilization. Many of the most powerful techniques used in adults, such as radioisotope testing, are not appropriate for use in children. In recent years, advanced mineral stable-isotope techniques have been developed to fill this gap. Pediatric applications include studies of calcium absorption and kinetics during puberty and evaluation of the calcium-iron interaction in infants and toddlers. The effects of genetics in determining calcium absorption and bone turnover may become an important research area. The goals and methods of ongoing mineral stable-isotope research in infants and children are examined in this report. In the past, the cost and difficulties in obtaining isotopes have limited such research. This situation has improved considerably, although relatively few nutrition research laboratories are prepared to perform sample analyses.     

Pleckstrin homology domains and phospholipid-induced cytoskeletal reorganization

At the moment of hemostasis, the platelet must be able to reorganize its cytoskeleton through a complexly orchestrated signaling cascade that is regulated, in part, by polyphosphoinositides. In the past 6 years, evidence has accumulated that PH domains bind these polyphosphoinositides and play a role in cytoskeletal changes. Work to date implies that the amino-terminal PH domain of pleckstrin induces a shift of F-actin towards the cell cortex and participates in the production of lamellipodia. The effect of pleckstrin on actin is, in turn, regulated by the phosphorylation of pleckstrin by PKC. Evidence also suggests that PH domains of Dbl family exchange factors play a role in the PI3K-stimulated activation of Rac. It is likely that the PH domains of pleckstrin, as well as the PH domains of the Dbl family of exchange factors, are only a few examples of PH domains that are able to influence the organization of the cytoskeleton.     

Psychological impact of predicting individuals' risks of illness: a systematic review

The aim of this review is to determine the frequency and circumstances under which predicting individuals' risk of illness has adverse psychological effects. Using systematic review methodology, the literature was searched for studies that had assessed the adverse psychological outcomes of risk assessment programmes. The outcomes investigated are emotional (anxiety, depression, distress) cognitive (intrusive thoughts, perceptions of health) and behaviour (work absenteeism). The impact of both positive and negative test results are summarised in terms of the number of studies showing significant effects between and within groups in the short (one month or less) and longer term (more than one month). Where sufficient data were available, a meta-analysis was conducted to assess effect size. Fifty-four studies met the criteria for inclusion. The studies assessed the impact of informing individuals about cardiovascular risk (21), risk of AIDS (eight), risk of cancer (10), risk of Huntington's disease (10), risk of diabetes (two), risk of spinocerebellar ataxia (one) and risk of osteoporosis (two). Overall, the quality of studies assessed was limited, with only two using a randomised design to determine the psychological impact of risk assessment. Receiving a positive test result was associated in the short term in the great majority of studies with depression, anxiety, poorer perceptions of health and psychological distress. Data were available for a quantitative synthesis of results on three outcomes, anxiety, depression and distress. Anxiety and depression were significantly higher in those tested positive compared with those tested negative in the short term but not the longer term. Distress could only be assessed in the longer term: there was no evidence of an increase for those receiving positive test results. The five experimental studies that reported interventions aimed at preventing some of these adverse effects all reported favourable results. There was little evidence of any adverse psychological effects of receiving an unfavourable test result. Adverse psychological effects are a common immediate consequence of positive test results following risk assessment. Results from the few experimental studies reviewed suggest that these adverse outcomes should not be seen as inevitable.     

Spindle cell carcinoma of the breast,a mimicker of benign lesions: case report and review of the literature

The clinical and pathologic features of a breast tumor with unusual morphology in a 69-year-old woman are presented. Spindle cell carcinoma is considered one of the variants of metaplastic carcinoma and is commonly described in the upper aerodigestive tract, but it is relatively rare in the breast. This case is uniquely different from the usual cases of spindle cell carcinoma because of the lack of squamous differentiation or a recognizable infiltrating ductal component at the light microscopic level. With immunohistochemical stains using keratin and actin, a rather prominent network of infiltrating compressed ductal structures became apparent. These immunohistochemical features are consistent with the current concept of myoepithelial origin for metaplastic carcinomas. Although mention has been made in the literature of cases in which this "bland" carcinoma could be confused with benign nonneoplastic conditions, few illustrated examples exist. The prognosis for this particular subgroup of metaplastic carcinoma may be somewhat better than that for ordinary ductal carcinoma. For prognostic purposes, this entity should be distinguished from other metaplastic carcinomas and sarcomas, but more importantly, it should be differentiated from lesions such as nodular fasciitis, reactive granulation tissue, and fibromatosis, with which it may be confused histologically.     

Hand Infections: Treatment Recommendations for Specific Types

Hand infections can be associated with considerable morbidity. Expeditious treatment is needed to minimize permanent dysfunction, loss of work, and medical cost. Hand infections can affect the skin, subcutaneous tissues, fascia, subfascial and synovial spaces, joints, and bone. Pathogens include a variety of bacteria, viruses, yeasts, fungi, and mycoplasmata. Management frequently involves rest, elevation, incision and drainage, and appropriate antibiotic therapy. The orthopaedic surgeon must be knowledgeable about the pertinent anatomy and how this influences the behavior of specific types of infections, the role of immunocompromise, and the importance of early mobilization.     

Harvard community health plan's mental health redesign project: A managerial and clinical partnership

Harvard Community Health Plan, founded in 1969 as a staff model HMO, is currently a staff and group model HMO with 521,000 members, 19 health centers and 12 independently owned group practices with 26 locations. In 1987, the Plan initiated a review of its mental health benefit and program because its costs were rising, member and clinician dissatisfaction was increasing and many believed the problem was the nature and scope of the benefit. After two years of study, surveys, interviews, cost and utilization analysis, the Plan identified its professional staff as its key asset but recognized many problem areas, including problems with access, variation from site to site, inconsistent service delivery, lack of consistent utilization management and the need for greater diversity along the spectrum of care available to members. From 1989 to 1990, more than 200 clinicians and support staff were engaged in the process of developing a variety of components to the mental health redesign program. Three simultaneous efforts included developing a method of categorizing patients, restructuring the delivery system and redesigning the benefit. A Mental Health Patient Assessment Tool was created which assists clinicians in performing comprehensive evaluations, administers the benefit, measures progress and supports outcomes research. Delivery system changes included the implementation of self-referral, access standards, intake triage functions by non-clinical staff, program development and an outpatient utilization management function.