Effects of educational intervention on mortality and patient-reported outcomes in individuals with heart failure: A randomized controlled trial

ObjectiveTo examine the effects of an educational intervention on patient-reported outcomes and all-cause mortality in heart failure (HF) patientsMethodsIn this randomized controlled trial, we enrolled 122 hospitalized patients with HF. The intervention group (n = 60) received an individual nurse-led education session on HF self-management during hospitalization and three telephone calls after discharge. The control group (n = 62) received care as usual. Patient-reported outcomes were measured at baseline and at 3 and 6 months. Mortality status was determined using the National Death Records. Intervention effects were evaluated using the Cox proportional hazards regression model and linear mixed models.ResultsDuring the follow-up (median: 568 days), 7 deaths (12%) in the intervention group and 15 deaths (24%) in the control group occurred (adjusted hazard ratio, 0.40; 95% confidence interval, 0.16–0.98; P = .046). From baseline to 3 and 6 months, the intervention group showed greater improvements in HF knowledge (difference=6.14, P = .03; difference=5.76, P = .02, respectively), self-care (difference=?6.08, P < .001; difference=?6.16, P < .001, respectively), and health-related quality of life (difference=?11.90, P = .01; difference=?14.57, P = .004, respectively) than the control group.ConclusionEducational intervention with telephone follow-up reduced all-cause mortality and improved patient-reported outcomes.Practice implicationEducational intervention should be considered as part of routine care for HF patients.     

The spectrum of rare central nervous system (CNS) tumors with EWSR1‐non‐ETS fusions: experience from three pediatric institutions with review of the literature

The group of CNS mesenchymal (non‐meningothelial) and primary glial/neuronal tumors in association with EWSR1‐non‐ETS rearrangements comprises a growing spectrum of entities, mostly reported in isolation with incomplete molecular profiling. Archival files from three pediatric institutions were queried for unusual cases of pediatric (≤21 years) CNS EWSR1‐rearranged tumors confirmed by at least one molecular technique. Extra‐axial tumors and cases with a diagnosis of Ewing sarcoma (EWSR1‐ETS family fusions) were excluded. Additional studies, including anchored multiplex‐PCR with next‐generation sequencing and DNA methylation profiling, were performed as needed to determine fusion partner status and brain tumor methylation class, respectively. Five cases (median 17 years) were identified (M:F of 3:2). Location was parenchymal (n = 3) and undetermined (n = 2) with topographic distributions including posterior fossa (n = 1), frontal (n = 1), temporal (n = 1), parietal (n = 1) and occipital (n = 1) lobes. Final designation with fusion findings included desmoplastic small round cell tumor (EWSR1‐WT1; n = 1) and tumors of uncertain histogenesis (EWSR1‐CREM, n = 1; EWSR1‐CREB1, n = 1; EWSR1‐PLAGL1, n = 1; and EWSR1‐PATZ1, n = 1). Tumors showed a wide spectrum of morphology and biologic behavior. For EWSR1‐CREM, EWSR1‐PLAGL1 and EWSR1‐PATZ1 tumors, no significant methylation scores were reached in the known brain tumor classes. Available outcome (4/5) was reported as favorable (n = 2) and unfavorable (n = 2) with a median follow‐up of 30 months. In conclusion, we describe five primary EWSR1‐non‐ETS fused CNS tumors exhibiting morphologic and biologic heterogeneity and we highlight the clinical importance of determining specific fusion partners to improve diagnostic accuracy, treatment and monitoring. Larger prospective clinicopathological and molecular studies are needed to determine the prognostic implications of histotypes, anatomical location, fusion partners, breakpoints and methylation profiles in patients with these rare tumors.     

High prevalence of Chlamydia trachomatis,Neisseria gonorrhoeae and particularly Trichomonas vaginalis diagnosed using US FDA‐approved Aptima molecular tests and evaluation of conventional routine diagnostic tests in Ternopil,Ukraine

Sexually transmitted infections (STIs) remain major public health problems globally. Appropriate laboratory diagnosis of STIs is rare in Ukraine. We investigated the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) using the US FDA‐approved Aptima Combo 2 and Aptima TV assays and compared the results with the conventional routine diagnostic tests (CDTs) in Ukraine. Urogenital swabs from consecutive mostly symptomatic females (n = 296) and males (n = 159) were examined. The prevalences were as follows: 10% (n = 47) of TV, 5.3% (n = 24) of CT and 1.5% (n = 7) of NG. The specificity of some CDTs was high, for example, 100% for NG culture, TV IgG ELISA, CT IgM ELISA and CT microscopy, but lower for other CDTs, that is, from 44% to 99.8%. The sensitivity of all CDTs was suboptimal, that is, 71% (n = 5) for NG microscopy, 57% (n = 4) for NG culture, 53% (n = 8) for CT IgG ELISA, 33% (n = 1) for TV IgG ELISA, 28% (n = 13) for TV microscopy, 25% (n = 1) for CT IgA ELISA, 20% (n = 3) for CT IgM ELISA and 0% (n = 0) for CT microscopy. The prevalences of particularly TV and CT were high, but substantial also for NG, in Ternopil, Ukraine. The sensitivities of all CDTs were low, and widespread implementation of validated, quality‐assured and cost‐effective molecular diagnostic STI tests in Ukraine is imperative.     

First‐night effect on cardiac autonomic function in different female reproductive states

Decreases in heart rate variability, a marker of autonomic nervous system function, are associated with increased cardiovascular mortality. Heart rate variability increases in non‐rapid eye movement sleep, peaking in slow‐wave sleep. Therefore, decreasing the amount of deep sleep, for example, by introducing patients to a sleep laboratory environment, could decrease heart rate variability, increasing cardiovascular risk. We studied four groups of women with no previous sleep laboratory experience: young [n = 11, 23.1 (0.5) years]; perimenopausal [n = 15, 48.0 (0.4) years]; postmenopausal without hormone therapy [n = 22, 63.4 (0.8) years]; and postmenopausal on hormone therapy [n = 16, 63.1 (0.9) years], using a cross‐sectional design. Polysomnography including electrocardiogram was performed over two consecutive nights. Heart rate variability was assessed overnight, and the first‐night effect on heart rate variability was analysed. Furthermore, correlations between heart rate variability and sleep variables were analysed. Using combined groups, only minor changes were observed in non‐linear heart rate variability, indicating increased parasympathetic tone from the first to the second night. No group differences in first‐night effect were seen. Heart rate variability and sleep variables were not significantly correlated. Heart rate variability decreased with increasing age, and it was lowest in the postmenopausal women on hormone therapy. We conclude that a first night in a sleep laboratory elicits only minimal changes in overnight vagally mediated non‐linear heart rate variability in women irrespective of reproductive state. This finding warrants further analyses in different sleep stages, but suggests that changes in sleep architecture per se do not predict the autonomic strain of a poor night.     

The anatomical society core embryology syllabus for undergraduate medicine

A modified Delphi methodology was used to develop a consensus regarding a series of learning outcome statements to act as the foundation of an undergraduate medical core embryology syllabus. A Delphi panel was formed by recruiting stakeholders with experience in leading undergraduate teaching of medical students. The panel (n = 18), including anatomists, embryologists and practising clinicians, were nominated by members of Council and/or the Education Committee of the Anatomical Society. Following development of an a priori set of learning outcome statements (n = 62) by the authors, panel members were asked in the first of a two‐stage process to ‘accept’, ‘reject’ or ‘modify’ each learning outcome, to propose additional outcomes if desired. In the second stage, the panel was asked to either accept or reject 16 statements which had either been modified, or had failed to reach consensus, during the first Delphi round. Overall, 61 of 62 learning outcome statements, each linked to examples of clinical conditions to provide context, achieved an 80% level of agreement following the modified Delphi process and were therefore deemed accepted for inclusion within the syllabus. The proposed syllabus allows for flexibility within individual curricula, while still prioritising and focusing on the core level of knowledge of embryological processes by presenting the essential elements to all newly qualified doctors, regardless of their subsequent chosen specialty.     

Biology and grading of pleomorphic xanthoastrocytoma—what have we learned about it?

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a cohort of 67 patients with histologically defined PXA (n = 53, 79%) or anaplastic PXA (A‐PXA, n = 14, 21%), including copy number analysis (ThermoFisher Oncoscan, n = 67), methylation profiling (Illumina EPIC array, n = 43) and targeted next generation sequencing (n = 32). The most frequent alterations were CDKN2A/B deletion (n = 63; 94%) and BRAF p.V600E (n = 51, 76.1%). In 7 BRAF p.V600 wild‐type cases, alternative driver alterations were identified involving BRAF, RAF1 and NF1. Downstream phosphorylation of ERK kinase was uniformly present. Additional pathogenic alterations were rare, with TERT, ATRX and TP53 mutations identified in a small number of tumors, predominantly A‐PXA. Methylation‐based classification of 46 cases utilizing a comprehensive reference tumor allowed assignment to the PXA methylation class in 40 cases. A minority grouped with the methylation classes of ganglioglioma or pilocytic astrocytoma (n = 2), anaplastic pilocytic astrocytoma (n = 2) or control tissues (n = 2). In 9 cases, tissue was available from matched primary and recurrent tumors, including 8 with anaplastic transformation. At recurrence, two tumors acquired TERT promoter mutations and the majority demonstrated additional non‐recurrent copy number alterations. Methylation class was preserved at recurrence. For 62 patients (92.5%), clinical follow‐up data were available (median follow‐up, 5.4 years). Overall survival was significantly different between PXA and A‐PXA (5‐year OS 80.8% vs. 47.6%; P = 0.0009) but not progression‐free survival (5‐year PFS 59.9% vs. 39.8%; P = 0.05). WHO grade remained a strong predictor of overall survival when limited to 38 cases defined as PXA by methylation‐based classification. Our data confirm the importance of WHO grading in histologically and epigenetically defined PXA. Methylation‐based classification may be helpful in cases with ambiguous morphology, but is largely confirmatory in PXA with well‐defined morphology.     

Challenges in investigating patients with isolated decreased serum IgM: The SIMcal study

The clinical consequences of isolated decreased serum immunoglobulin (Ig)M are not sufficiently known. Therefore, it is difficult to determine the clinical policy following such a finding. Only few reported IgM‐deficient patients fulfil the European Society for Immunodeficiencies (ESID) diagnostic criteria for selective IgM deficiency (true sIgMdef), or their diagnosis is uncertain due to insufficient laboratory data (possible sIgMdef). Decreased serum IgM is often incidentally found in asymptomatic adults. The objective of our study was to further characterize true sIgMdef and to compare the European data collected through the ESID Registry community (tertiary centres) to our previously published Dutch cohort (secondary centre). Fifteen centres (12 countries) participated with 98 patients. Patients were excluded if serum IgM was only determined once (n = 14), had normalized (n = 8), or if they also had other immunological abnormalities (n = 15). Ten patients (5 adults) completely fulfilled the ESID criteria for true sIgMdef. Age‐matched cut‐off values varied widely between centres; when using the ESID diagnostic protocol reference values, only six patients (five adults) had true sIgMdef. Because of these small numbers, further analyses were performed in patients with true or possible sIgMdef (13 adults, 48 children). Respiratory infections were commonly reported at presentation (adults 54%, children 60%). Symptomatic adults had lower serum IgM levels (mean 0.27 g/L, 95% CI 0.22‐0.31) than those without symptoms (mean 0.33 g/L, 95% CI 0.30‐0.36; P = 0.02). To be able to explore the clinical consequences of true sIgMdef, we should fully analyse and accurately describe those patients in whom a decreased serum IgM is found.     

Magnetic resonance imaging of the upper airway in patients with quadriplegia and obstructive sleep apnea

The aim of this study was to investigate upper airway anatomy in quadriplegics with obstructive sleep apnea. Fifty subjects were recruited from three hospitals in Australia: people with quadriplegia due to spinal cord injury and obstructive sleep apnea (n = 11), able‐bodied people with obstructive sleep apnea (n = 18), and healthy, able‐bodied controls (n = 19). All underwent 3‐Tesla magnetic resonance imaging of their upper airway. A subgroup (n = 34) received a topical vasoconstrictor, phenylephrine and post‐phenylephrine magnetic resonance imaging. Mixed‐model analysis indicated no significant differences in total airway lumen volume between the three groups (P = 0.086). Spinal cord injury–obstructive sleep apnea subjects had a significantly larger volume of soft palate (P = 0.020) and retroglossal lateral pharyngeal walls (P = 0.043) than able‐bodied controls. Able‐bodied–obstructive sleep apnea subjects had a smaller mandible volume than spinal cord injury–obstructive sleep apnea subjects and able‐bodied control subjects (P = 0.036). No differences were seen in airway length between groups when controlling for height (P = 0.055). There was a marginal increase in velopharyngeal volume across groups post‐phenylephrine (P = 0.050), and post hoc testing indicated the difference was confined to the able‐bodied–obstructive sleep apnea group (P < 0.001). No other upper airway structures showed significant changes with phenylephrine administration. In conclusion, people with obstructive sleep apnea and quadriplegia do not have a structurally smaller airway than able‐bodied subjects. They did, however, have greater volumes of soft palate and lateral pharyngeal walls, possibly due to greater neck fat deposition. The acute response to upper airway topical vasoconstriction was not enhanced in those with obstructive sleep apnea and quadriplegia. Changes in upper airway anatomy likely contribute to the high incidence in obstructive sleep apnea in quadriplegic subjects.     

Hyperactivation of the hypothalamo‐pituitary‐adrenocortical axis in streptozotocin‐diabetic gerbils (Gerbillus gerbillus)

This study was designed to investigate the HPA‐axis impairment in the streptozotocin (STZ)‐diabetic gerbils (Gerbillus gerbillus). Twenty‐six male gerbils (body weight ~27 g) were divided into 3 groups: vehicle control (n = 10), 2 days of diabetes (n = 09) and 30 days of diabetes (n = 07). The latter 2 groups received an intraperitoneal injection of STZ (150 mg/kg of body weight). At 2 and 30 days of diabetes, streptozotocin‐diabetic gerbils underwent a retro‐orbital puncture for assessment of biochemical and hormonal parameters. Subsequently the animals were decapitated and the adrenal glands were removed, weighed and processed for light microscopy and stereology. Nondiabetic control gerbils that had been injected with citrate buffer were examined as a comparison. At 2 days of diabetes, STZ gerbils exhibited symptoms that are characteristic of human diabetes type 1. The adrenal gland showed significant increase in weight, associated with a larger cortex layer, hypertrophy of the fasciculate cells and a significant decrease in the nucleocytoplasmic index. These changes were associated with higher plasma ACTH and cortisol concentrations compared to nondiabetic controls. At 30 days postdiabetes, ACTH levels remained elevated, whereas cortisol levels decreased compared to the early stage of diabetes. Histological analysis revealed the existence of a band of connective tissue (collagen) that separates the cortical and medullary zones and is not present in humans or laboratory rodents, which represents a striking change seen throughout the disease. STZ‐induced diabetes mellitus in Gerbillus gerbillus resulted in hyperactivation of the HPA axis in the early stages of diabetes mellitus which did not persist into the final stages of the disease, suggesting a possible reduction in adrenocortical sensitivity over time.     

Toddler's self‐regulation strategies in a challenge context are nap‐dependent

Early childhood represents a time of developmental changes in both sleep and self‐regulation, a construct reflecting the ability to control one's behaviour, attention and emotions when challenged. Links between sleep and self‐regulation processes have been proposed, but experimental evidence with young children is lacking. In the current study, we tested the effects of acute sleep restriction (nap deprivation) on toddlers’ self‐regulation. Healthy children (n = 12; four males; aged 30–36 months (33.9 ± 1.7)) slept on a strict schedule (verified with actigraphy and sleep diaries) for 5 days before each of two afternoon assessments following a nap and a no‐nap condition (~11‐day protocol). Children were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive self‐regulation strategies were later coded. On average, children lost ~90 min of sleep on the no‐nap versus the nap day. Nap deprivation resulted in moderate‐to‐large effects on self‐regulation strategies, with decreases in scepticism (d = 0.77; 7% change), negative self‐appraisal (d = 0.92; 5% change) and increases in physical self‐soothing (d = 0.68; 10% change), focus on the puzzle piece that would not fit (perseveration; d = 0.50; 9% change) and insistence on completing the unsolvable puzzle (d = 0.91; 10% change). Results suggest that sleep serves an important role in the way that toddlers respond to challenging events in their daily lives. After losing daytime sleep, toddlers were less able to engage effectively in a difficult task and reverted to less mature self‐regulation strategies than when they were well rested. Over time, chronically missed sleep may impair young children's self‐regulation abilities, resulting in risk for social–emotional, behavioural and school problems.     

Procedural memory consolidation is associated with heart rate variability and sleep spindles

Sleep and memory studies often focus on overnight rather than long‐term memory changes, traditionally associating overnight memory change (OMC) with sleep architecture and sleep patterns such as spindles. In addition, (para‐)sympathetic innervation has been associated with OMC after a daytime nap using heart rate variability (HRV). In this study we investigated overnight and long‐term performance changes for procedural memory and evaluated associations with sleep architecture, spindle activity (SpA) and HRV measures (R‐R interval [RRI], standard deviation of R‐R intervals [SDNN], as well as spectral power for low [LF] and high frequencies [HF]). All participants (N = 20, M_age = 23.40 ± 2.78 years) were trained on a mirror‐tracing task and completed a control (normal vision) and learning (mirrored vision) condition. Performance was evaluated after training (R1), after a full‐night sleep (R2) and 7 days thereafter (R3). Overnight changes (R2‐R1) indicated significantly higher accuracy after sleep, whereas a significant long‐term (R3‐R2) improvement was only observed for tracing speed. Sleep architecture measures were not associated with OMC after correcting for multiple comparisons. However, individual SpA change from the control to the learning night indicated that only “SpA enhancers” exhibited overnight improvements for accuracy and long‐term improvements for speed. HRV analyses revealed that lower SDNN and LF power was associated with better OMC for the procedural speed measure. Altogether, this study indicates that overnight improvement for procedural memory is specific for spindle enhancers, and is associated with HRV during sleep following procedural learning.     

Chronic disease and lifestyle factors associated with change in sleep duration among older adults in the Singapore Chinese Health Study

Identifying risk factors for future change in sleep duration can clarify whether, and if so how, sleep and morbidity are bidirectionally related. To date, only limited longitudinal evidence exists characterizing changes to sleep duration among older adults. This study aimed to identify factors associated with change in sleep duration in a large sample of older adults (≥ 60 years) residing in Singapore (n = 10 335). These adults were monitored as part of the Singapore Chinese Health Study, which collected information regarding daily sleep duration at baseline (assessed in 1993–1998) and at a follow‐up wave conducted over a mean of 12.7 years later (assessed in 2006–2010). Among adults sleeping 6–8 h at baseline (n = 8265), most participants (55.6%) remained 6–8 h sleepers at follow‐up, while 8.4% became short (< 6 h) and 36.0% became long (> 8 h) sleepers. A history of stroke, diabetes, cancer, hip fracture and greater age all independently increased the odds of having long sleep duration at follow‐up, while greater educational attainment and weekly physical activity were both associated with reduced odds of becoming a long sleeper. Other than greater baseline age, the only factor related to higher odds of becoming a short sleeper was concurrent stomach/duodenal ulcer at follow‐up. Long sleep duration among older adults may therefore reflect longstanding disease processes, whereas the aetiology of short sleep may predominately involve factors other than those examined. Future research is needed to distinguish if/when long sleep duration serves the disease recovery process, and when long sleep duration complicates disease and requires sleep medicine interventions.     

Dual immune effect of iNKT cells considering human cutaneous and visceral leishmaniasis: An example of cell plasticity according to different disease scenarios

Although the semi‐invariant natural killer T cells (iNKT) are a small subpopulation of cells in the peripheral blood, they are presumed to play a role in early stages of infection against various pathogens, including protozoa. This work investigates the activation status and cytokine profile of iNKT cells during human Leishmania infantum and Leishmania braziliensis infection. We studied iNKT cells in patients with symptomatic active visceral leishmaniasis (AVL) (n = 8), patients with symptomatic active cutaneous leishmaniasis (ACL) (n = 13), negative endemic controls (NEC) (n = 6) and non‐endemic controls (NonEC) (n = 6), with and without total Leishmania antigen stimulus (TLA). The number of iNKT cells in the peripheral blood of patients with ACL and AVL unaltered in relation to control groups. Moreover, the iNKT cells from ACL showed a hyperactivation profile compared to patients with AVL. Additionally, TLA induced IFN‐gamma production in iNKT cells from patients with ACL, while in iNKT of patients with AVL, TLA induced a decrease in this cytokine. Higher IL‐17 and IL‐10 production by iNKT cells from patients with ACL were also observed compared to all other groups. There were no changes in iNKT IL‐10‐producing cells in AVL after TLA stimulation. However, TLA induced increase in IL‐10 in iNKT cells in patients with ACL. These findings suggest that, although iNKT cells showed distinct profiles in patients with ACL and AVL, they play a dual role in immune modulation in both Leishmania infections.     

Shiftworkers report worse sleep than day workers,even in retirement

The aim of this study was to explore how the level of shiftwork exposure during an individual's working life might be related to subjectively reported sleep quality and timing during retirement. Telephone interviews regarding past employment and sleep timing and quality (among other variables) were conducted using a pseudo‐random age‐targeted sampling process. Subjective sleep quality was assessed using a telephone version of the Pittsburgh Sleep Quality Index. Timing of reported habitual bedtimes and rise‐times were assessed using the Sleep Timing Questionnaire. Questions measuring morningness and subjective health were also given. Retired seniors (aged >65 years, n = 1113) were studied. Analysis was by analysis of variance, with shiftwork exposure in three bins [0 (n = 387), 1–15 (n = 371) and >15 years (n = 355)], gender (n = 634 male, 479 female) and former occupation [in two broad categories, ‘managerial’ (n = 437) versus ‘other’ (n = 676)] as factors. In retired shiftworkers, relative to retired day workers, past exposure to shiftwork was associated with higher (worse) PSQI scores by 1.0 units (1–15 years) and 0.6 units (>15 years) (main effect P = 0.005). There were also main effects of gender and former occupation (males and managerials reporting better sleep), but neither variable interacted with shiftwork exposure. The timing of current mean habitual bedtimes and rise‐times (and also the variance around them) were very similar for the three shiftwork exposure groups. The shiftwork exposure effect did not appear to be mediated by either morningness or current health. Prior exposure to shiftwork would appear to be related to currently reported sleep problems during retirement.     

Emerging psychiatric disorders in Kleine‐Levin syndrome

In Kleine‐Levin syndrome (KLS), episodes of hypersomnia and cognitive, psychiatric and behavioural disturbances alternate with asymptomatic periods in adolescents. We evaluated whether psychiatric disorders would emerge during asymptomatic periods in a naturalistic, uncontrolled clinical cohort. Patients with primary KLS underwent psychiatric interviews at diagnosis and every year for 1–10 years, leading to diagnosis of former and present comorbid psychiatric disorders. Among the 115 patients (65.2% male and aged 16.1 ± 4.8 years at KLS onset), 19 (16.5%) had a history of psychiatric disorder prior to KLS onset, which persisted afterwards in 10. Twenty‐five (21%) patients developed a new, comorbid psychiatric disorder 1–6 years after KLS onset, during ‘asymptomatic’ periods, including mood disorders (n = 14; including major depressive episodes, n = 8; recurrent depressive episodes, n = 2; bipolar I disorder, n = 1; dysthymic disorder, n = 1; adjustment disorder with depressive mood, n = 1; and mood disorder not otherwise specified, n = 1), anxiety disorders (n = 7), eating disorders (n = 2), psychotic disorders not otherwise specified (n = 2), schizoaffective disorder (n = 1) and cannabis dependence (n = 1). Six patients attempted suicide: two before and two after KLS onset, and two during episodes. Female sex, longer disease course, longer time incapacitated (356 ± 223 versus 155 ± 186 days) and more frequent psychiatric symptoms during episodes (but no family or personal history of psychiatric disorders) were associated with emerging psychiatric disorders. Contrary to the alleged benignity of KLS and normality between episodes, one KLS patient in five suffers from emerging psychiatric disorders. These disorders may depend on personal vulnerability and, most probably, on psychiatric symptoms during episodes.     

Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies

The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real‐time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture‐negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld‐positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld‐positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.     

Effects of lactoferrin on infectious diseases in Japanese summer: A randomized,double-blinded,placebo-controlled trial

PurposeTo investigate the effects of lactoferrin (LF) on infectious diseases in Japanese summer.MethodsAn intake of placebo, 200 mg, or 600 mg of LF were administered to healthy adults in Kyushu University of Health and Welfare for 12 weeks in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The primary endpoints were the prevalence and duration of infectious diseases and changes in immune parameters.ResultsThree hundred and ten subjects were randomized (placebo, n = 104; 200 mg, n = 103; 600 mg, n = 103). Twenty subjects were lost to the follow-up, leaving 290 for a full analysis set (n = 99; n = 95; n = 96). The duration (day) of total infectious diseases was shorter in the 200 mg group (2.0, p = 0.045) and 600 mg group (2.0, p = 0.010) than in the placebo group (3.0). The duration of summer colds was shorter in the 600 mg group (2.0, p = 0.036) than in the placebo group (3.0). No significant differences were observed in the prevalence of infectious diseases or changes in immune parameters. In exploratory investigations, changes in the neutrophil phagocytic capacity, cortisol concentrations, and T score of “Vigor/Activity” in the Profile of Mood States 2 were greater in the 600 mg group than in the placebo group, when analysis was done on the lower half groups at the baseline. Adverse events were similar in each group and none had a causal relationship with the intake of the test foods.ConclusionsIn summer, the intake of LF attenuates infectious diseases, including summer colds.     

Survival Improvements in Adolescents and Young Adults after Myeloablative Allogeneic Transplantation for Acute Lymphoblastic Leukemia

Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children.     

Systemic inflammatory response and local cytokine expression in porcine models of endocarditis

The knowledge of systemic inflammation and local cytokine expression in porcine endocarditis models is limited, though it could provide valuable information about the pathogenesis and comparability to human endocarditis. Analyses of bacteriology and hematology were performed on blood samples from pigs with non‐bacterial thrombotic endocarditis (NBTE, n = 11), Staphylococcus aureus infective endocarditis (IE, n = 2), animals with S. aureus sepsis without endocarditis (n = 2) and controls (n = 2). Furthermore, immunohistochemistry was used to examine the local expression of IL‐1β and IL‐8. Bacterial blood cultures were continuously positive in IE pigs from inoculation to euthanasia, and negative in all other pigs at all times. The total white blood cell counts and total neutrophil counts were massively elevated in pigs with IE. Local IL‐1β and IL‐8 expression in IE pigs were moderate to high, and high, respectively. In addition, slight local expression of IL‐1β and IL‐8 was present in some NBTE pigs. In the IE model, both the systemic inflammatory response and the high local expression of IL‐8 were comparable to the human disease. Furthermore, the results indicate IL‐1β and IL‐8 as important contributors in the endocarditis pathogenesis.