Stage-dependent detection of CD14+ and CD16+ cells in the human heart after myocardial infarction

Monocytes are critically involved in cardiovascular wound healing processes. Human monocytes can be classified into two subsets based on the expression of CD14 and CD16. Here, we examined the temporal and spatial distribution of CD14⁺ and CD16⁺ cells after myocardial infarction (MI) in human heart and spleen tissue and correlated it with markers of cardiac repair. Heart samples obtained at autopsy were histologically classified into acute (AMI; n?=?11), subacute (SAMI; n?=?10) and old (OMI; n?=?16) MI, or control myocardium (CONTR; n?=?8). Histochemical analyses revealed marked fibrosis in OMI (p?<?0.001 vs. CONTR). The adhesion molecule CD56 was also strongly expressed in OMI (p?<?0.01 vs. CONTR) and found to correlate with fibrosis (p?<?0.001). The number of capillaries was reduced in OMI (p?<?0.01 vs. CONTR; p?<?0.05 vs. AMI), whereas the hypoxia indicator carbonic anhydrase IX was predominantly expressed in AMI (p?<?0.01 vs. OMI and CONTR) and SAMI (p?<?0.05 vs. OMI and CONTR). The monocyte chemoattractrant osteopontin was also more highly expressed in hearts of SAMI patients (p?<?0.01 vs. CONTR). Numbers of CD14⁺ monocytes were found to correlate with CD16⁺ cells (p?<?0.05) and inversely with fibrosis (p?<?0.05). Regarding a MI-associated release of monocytes from spleen reservoirs, a non-significant reduction of splenic CD14⁺ and CD16⁺ cells was detected in subjects with AMI. In conclusion, disease stage-specific alterations in CD14⁺ and CD16⁺ cells in human heart may contribute to cardiac repair processes following MI.     

Long-Term Outcomes Following Vocational Rehabilitation Treatments in Patients with Prolonged Fatigue

Background

Multi-component vocational rehabilitation (VR) provides positive short-term outcomes in patients with prolonged fatigue.

Purpose

The purpose of this study is to evaluate the long-term outcomes of Dutch multi-component VR up to 18 months after treatment.

Method

In a pre–post-study, measurements were taken before treatment (t0), after treatment (t1) and in long-term follow-ups at 6 (t2), 12 (t3) and 18 months (t4) after treatment. Primary outcomes (fatigue, work participation and workability) and secondary outcomes [physical and social functioning, mental health and heart rate variability (HRV)] were assessed over time using linear mixed models analyses. Post hoc long-term outcomes were compared with t0 and t1.

Results

Sixty patients with severe fatigue complaints participated. The primary outcomes significantly (p?<?0.001) improved at follow-ups compared with t0 and showed no relapse compared with t1. Moreover, fatigue decreased (p?<?0.002) whereas workability (p?<?0.001) and work participation (p?<?0.001) increased further after treatment (t1). The secondary outcomes, physical functioning, mental health, social functioning and HRV, improved significantly (p?<?0.001, p?<?0.001, p?<?0.001 and p?=?0.049, respectively) over the long term compared with t0. At 6-month follow-up (t2), mental health (p?<?0.003) and social functioning (p?=?0.003) further increased after the treatment was stopped.

Conclusion

Multi-component VR treatments seem to significantly and in a clinically relevant way decrease fatigue symptoms and improve individual functioning and work participation in patients with severe prolonged fatigue over the long term and without showing relapse.     

Haematological and acute-phase response of dogs with experimental skin <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> infection to treatment with antibiotic and parthenolide

Changes in white blood cells, leukogram patterns, the positive acute-phase protein (APP) fibrinogen and negative APPs (albumin and arylesterase) were monitored to evaluate their potential as sensitive indicators throughout the course of therapy in canine skin Pseudomonas aeruginosa infection. The study was performed on 15 male mixed-breed dogs, divided in three groups of 5 dogs each. Dogs from group A were injected subcutaneously with P. aeruginosa bacterial culture (1?×?10⁸ CFU/mL) at a dose of 0.3 mL/kg and treated with enrofloxacin (5 mg/kg, s.c.) on post infection hour 48 for 10 consecutive days. Dogs from group B were infected and treated with a combination of enrofloxacin (at above-mentioned dose and intervals) and parthenolide (feverfew extract 90 mg, 0.7 % parthenolide). The schedule consisted of daily oral intake of two capsules of feverfew beginning on post infection hour 4 and continued for 6 days. The control group C included healthy dogs, injected s.c. with 0.3 mL/kg physiological saline. The haematological indices and APPs were assayed before infection and on 4th, 24th, 48th and 72nd hours and on 7th, 10th and 14th days after infection. Infected and antibiotic-treated dogs responded with significant leukocytosis, left shift, eosinopaenia and lymphopaenia between hours 24 and 72. In this group, fibrinogen increased substantially by post infection hours 24 (p?<?0.01 vs 0 h; p?<?0.05 vs group C), 48 (p?<?0.001 vs 0 h; p?<?0.05 vs group C) and 72 (p?<?0.001 vs 0 h; p?<?0.01 vs group C) while albumin reduction was marked by hours 48 (p?<?0.05 vs 0 h) and 72 (p?<?0.05 vs 0 h; p?<?0.001 vs group C) and day 7 (p?<?0.01 vs 0 h; p?<?0.001 vs group C). The combination of enrofloxacin and parthenolide modified, at a significant extent, the deviations in studied parameters except for eosinophil percentage, which persisted low.     

Clinical and laboratory features of invasive community-onset methicillin-resistant Staphylococcus aureus infection: a prospective case–control study

Differences between the features of invasive community-onset methicillin-resistant Staphylococcus aureus (cMRSA) and methicillin-susceptible S. aureus (cMSSA) infections are incompletely understood. Fifty-seven patients with invasive cMRSA infection were prospectively identified at two teaching hospitals; for each cMRSA case, two cases of invasive cMSSA infection acted as controls. The primary outcome was 30-day all-cause mortality. Patients with invasive cMRSA infection were more likely to be Aboriginal (25% vs. 14%, age-adjusted odds ratio [OR] 2.5, p?=?0.037), reside in a long-term care facility and/or have been hospitalised in the previous year (51% vs. 34%, p?=?0.04) and less likely to have endocarditis (2% vs. 12%, p?=?0.02) or require admission to an intensive care unit or high-dependency area (7% vs. 21%, p?=?0.02). All-cause mortality at 30 days was similar in the cMRSA and cMSSA groups (9% vs. 7%, p?=?0.68). Panton–Valentine leukocidin (PVL) genes were detected in a similar proportion of cMRSA and cMSSA isolates (32% vs. 27%, p?=?0.49) and the presence of PVL genes was associated with younger age (35 years vs. 55 years, p?<?0.001), Aboriginal ethnicity (38% vs. 10%, p?<?0.001), skin and soft-tissue infection (54% vs. 19%, p?<?0.001), lower illness severity at presentation (SAPS II score 9 vs. 21, p?=?0.001) and shorter hospitalisation (9 days vs. 24 days, p?<?0.001). Patients with “PVL-positive” and “PVL-negative” S. aureus infection had similar 30-day all-cause mortality (4% vs. 9%, p?=?0.28). Few clinical features differentiated patients with invasive cMRSA infection from those with infection caused by cMSSA. Invasive “PVL-positive” S. aureus infection was associated with less morbidity but similar mortality to “PVL-negative” infection.     

Risk prediction in infective endocarditis by modified MELD-XI score

The suitability of the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score to predict adverse outcomes in infective endocarditis (IE) patients remains uncertain. This study was performed to explore the prognostic value of the MELD-XI score and modified MELD-XI score for patients with IE. A total of 858 patients with IE were consecutively enrolled and classified into two groups: MELD-XI ≤?10 (n?=?588) and MELD-XI >?10 (n?=?270). Multivariate analysis was performed to determine risk factors independent of MELD-XI score. Higher MELD-XI score was associated with higher in-hospital mortality (15.6 vs. 4.8%, p?<?0.001) and major adverse clinical events (33.3 vs. 18.4%, p?<?0.001). MELD-XI score was an independent predictor of in-hospital death (odds ratio [OR]?=?1.06, 95% CI, 1.02–1.10, p?=?0.005). Based on a multivariate analysis, NYHA class III or IV (3 points), C-reactive protein >?9.5 mg/L (4 points), and non-surgical treatment (6 points) were added to MELD-XI score. Modified MELD-XI score produced higher predictive power than previous (AUC 0.823 vs. 0.701, p?<?0.001). The cumulative incidence of long-term mortality (median 29 months) was significantly higher in patients with modified MELD-XI score >?13 than those without (log-rank?=?25.30, p?<?0.001). Modified MELD-XI score was independently associated with long-term mortality (hazard ratio?=?1.08, 95% CI, 1.04–1.12, p?<?0.001). MELD-XI score could be used as a risk assessment tool in IE. Furthermore, modified MELD-XI score remained simple and more effective in predicting poor prognosis.     

Respiration and heart rate complexity: Effects of age and gender assessed by band-limited transfer entropy

Aging and disease are accompanied with a reduction of complex variability in the temporal patterns of heart rate. This reduction has been attributed to a break down of the underlying regulatory feedback mechanisms that maintain a homeodynamic state. Previous work has established the utility of entropy as an index of disorder, for quantification of changes in heart rate complexity. However, questions remain regarding the origin of heart rate complexity and the mechanisms involved in its reduction with aging and disease. In this work we use a newly developed technique based on the concept of band-limited transfer entropy to assess the aging-related changes in contribution of respiration and blood pressure to entropy of heart rate at different frequency bands. Noninvasive measurements of heart beat interval, respiration, and systolic blood pressure were recorded from 20 young (21–34 years) and 20 older (68–85 years) healthy adults. Band-limited transfer entropy analysis revealed a reduction in high-frequency contribution of respiration to heart rate complexity (p < 0.001) with normal aging, particularly in men. These results have the potential for dissecting the relative contributions of respiration and blood pressure-related reflexes to heart rate complexity and their degeneration with normal aging.     

Cancer stem cell characteristics, ALDH1 expression in the invasive front of nasopharyngeal carcinoma

The invasive tumor front underlies the biological aggressiveness and epithelial–mesenchymal transition (EMT) in various human malignances. However, the molecular and biological characteristics of invasive tumor front in NPC have rarely been described. Additionally, the features of cancer stem cells (CSCs) in the invasive front of tumors and its correlation with EMT also remain elusive. Our study was to investigate the expression of CSCs marker aldehyde dehydrogenase 1 (ALDH1) in the invasive front of nasopharyngeal carcinoma (NPC) and its clinical significance. Immunohistochemistry was mainly used to detect ALDH1 expression in the invasive front of NPC. The relationship between ALDH1 expression and EMT-associated markers was also examined. ALDH1 expression in the invasive front correlated strongly with lymphatic invasion (p?<?0.001), T classification (p?=?0.001), M classification (p?<?0.001), clinical stage (p?<?0.001), and local recurrence (p?=?0.008). ALDH1 overexpression in the invasive front contributed to worse survival of NPC, particularly in patients with early stage (T1-T2 or N0-N1) (p?<?0.001 and p?=?0.002, respectively), though it was not an independent prognostic factor (p?=?0.196). Furthermore, in the invasive front of NPC, ALDH1 expression correlated significantly with EMT-related biomarkers E-cadherin (p?=?0.026), Vimentin (p?<?0.001), Periostin (p?<?0.001), and Snail (p?<?0.001), but not with β-catenin (p?=?0.143). Our findings demonstrate first that ALDH1 expression in the invasive front links closely with EMT characteristics and tumor aggressiveness, which might provide a useful prognostic marker for NPC patients.     

Coagulase-negative staphylococci are associated to the mild inflammatory pattern of healthcare-associated meningitis: a retrospective study

The epidemiology of healthcare-associated meningitis (HAM) is dominated by commensal bacteria from the skin, as coagulase-negative staphylococci (CoNS). We hypothesized that the pauci-symptomatic and mild inflammatory patterns of HAM are related to the low pathogenic state of CoNS. Our aim was to describe clinical and biological features of CoNS HAM, compared to other HAM. All consecutive patients with HAM admitted in our hospital were retrospectively included from 2007 to 2014. HAM due to CoNS were compared to HAM caused by other bacteria (controls) for clinical and laboratory patterns. Seventy-one cases of HAM were included, comprising 18 CoNS and 53 controls. Patients were not different in terms of baseline characteristics. CoNS HAM occurred later after the last surgery than controls (17 vs. 12 days, p?=?0.029) and had higher Glasgow Coma Scale (GCS) score (14 vs. 13, p?=?0.038). Cerebrospinal fluid (CSF) analysis revealed a lower pleocytosis (25 vs. 1340/mm³, p?<?0.001), a higher glucose level (3.75 vs. 0.8 mmol/L, p?<?0.001), and a lower protein level (744 vs. 1751 mg/L, p?<?0.001) in the CoNS group than in the control group, respectively. HAM due to CoNS was significantly less symptomatic and less inflammatory than HAM due to other bacteria.     

Process and Outcome Evaluation of Vocational Rehabilitation Interventions in Patients with Prolonged Fatigue Complaints

Background

Prolonged fatigue can cause physical, mental and occupational disability. Fatigue often persists because of a combination of biopsychosocial factors.

Purpose

To evaluate the process and outcomes of three existing outpatient vocational rehabilitation interventions (VRI) in patients with prolonged fatigue complaints. The VRIs differ with regard to the content and treatment duration, enrolment procedure and financing.

Method

A pre-post design was used with repeated measurements before treatment, after treatment and 3 months after treatment. Primary outcomes (fatigue and work participation) and secondary outcomes (physical and social functioning, mental health and physiological indicators (heart rate variability)) were assessed over time using linear mixed models analysis. A process evaluation (i.e. patient reach, content completeness and patient satisfaction) was conducted as well.

Results

One hundred patients participated. Post-treatment, fatigue decreased (p?<?.001) and work participation (p?<?.010), physical functioning (p?<?.001) and mental health (p?<?.001) improved considerably in all three VRIs. Social functioning improved in one VRI (p?=?.022), but did not in the other two (p?=?.442, p?=?.196, respectively). Physiologically, heart rate variability improved in two VRIs (p?=?.044, p?=?.038, respectively). VRIs were administered according to the programme protocol. Almost all patients met their personal goals and the majority was satisfied with the outcomes of diminished constraints at work.

Conclusion

Three VRIs showed significant and clinically relevant outcomes over time regarding decreased fatigue and improved functioning and work participation in fatigued patients. The VRIs administered patient-tailored biopsychosocial interventions as planned and patients were satisfied with the interventions.     

Association of E-selectin Gene Polymorphism (S128R) with Ischemic Stroke and Stroke Subtypes

E-selectin is an important inflammatory cytokine involved in the pathogenesis of various diseases such as atherosclerosis and stroke. We investigated the association of E-selectin gene polymorphism (S128R) with ischemic stroke and its subtypes. We studied 610 patients with ischemic stroke and 610 age- and sex-matched healthy controls. The ischemic stroke was classified according to Trial of Org10172 in Acute Stroke Treatment (TOAST). E-selectin gene polymorphism (S128R) was determined by polymerase chain reaction–restriction fragment length polymorphism technique. We found statistically significant difference in the genotypic distribution between patients and controls (for AC vs. AA, χ ²?=?49.5; p?<?0.001, odds ratio?=?5.47(95 % CI, 3.25–9.21). A significant difference was observed in the frequency of C and A alleles in patients and controls (for C vs. A, χ ²?=?47.4; p?<?0.001, odds ratio?=?5.13 (95 % CI, 3.06–8.57). Multiple logistic regression analysis revealed that the most predictive risk factor for stroke was AC genotype (adjusted odds ratio?=?1.450 (95 % CI, 1.23–2.75) and p?=?0.001), hypertension, smoking, and diabetes (p?=?0.001 in each case). We also found a significant association of AC genotype with intracranial large artery atherosclerosis (p?<?0.01, odds ratio?=?9.37, (95 % CI, 5.31–16.5) and small artery occlusion (p?<?0.0001, odds ratio?=?9.81 (95 % CI, 4.94–19.4). Our results indicate that the individuals bearing AC genotype of E-selectin gene polymorphism (S128R) are more prone to stroke than AA genotype.     

Are hip hemiarthroplasty and total hip arthroplasty infections different entities? The importance of hip fractures

Hip hemiarthroplasty (HHA) and total hip arthroplasty (THA) infections are usually considered as one entity; however, they may show important differences. We analyze these differences, as well as predictors of treatment failure (TF) and poor functional status among patients with prosthetic hip infections (PHIs). A multicenter cohort study of consecutive patients with PHIs was performed. The main outcome variable was TF after the first surgical treatment performed to treat the infection. Multivariate analysis was used to identify predictors of TF. A total of 127 patients with PHI were included (43 HHA, 84 THA). Patients with HHA infections were more frequently women (88 % vs. 54 %; p?<?0.001), had comorbidities (86 % vs. 67 %, p?=?0.02), and were older (median age 79 vs. 65 years, p?<?0.001), and the reason for arthroplasty was more frequently a fracture (100 % vs. 18 %, p?<?0.001). Failure of initial treatment and crude mortality were more frequent among HHA patients (44 % vs. 23 %, p?=?0.01 and 28 % vs. 7 %, p?=?0.001, respectively). However, HHA was not associated with TF in the multivariate analysis when hip fracture was considered; thus, variables independently associated with TF were hip fracture, inadequate surgical management, prosthesis retention, and higher C-reactive protein level. Failure of the first surgical treatment was associated with poorer functional status. HHA and THA infections showed significant differences in epidemiology, clinical features, and outcome. Although patients with HHA infections had a higher risk of TF, this was related to the reason for hip implant: a hip fracture. Success of the initial management of infection is a predictor of better clinical and functional outcome.     

Local and systemic pro-inflammatory and anti-inflammatory cytokine patterns in patients with chronic subdural hematoma: a prospective study

Objective and design

Innate immune pro- and anti-inflammatory responses in patients with chronic subdural hematoma (CSDH) were investigated by measuring and comparing the systemic and subdural fluid levels of cytokines.

Materials and method

Cytokine values were analyzed in samples obtained during surgery of 56 adult patients who were operated on for unilateral CSDHs using a Multiplex antibody bead kit.

Results

There were significantly higher levels of the pro-inflammatory IL-2R (p?=?0.004), IL-5 (p?<?0.001), IL-6 (p?<?0.001), and IL-7 (p?<?0.001), and anti-inflammatory mediators IL-10 (p?<?0.001) and IL-13 (p?=?0.002) in CSDH fluid compared with systemic levels. The pro-inflammatory TNF-alpha (p?<?0.001), IL-1beta (p?<?0.001), IL-2 (p?=?0.007) and IL-4 (p?<?0.001) were significantly lower in hematoma fluid compared with systemic levels. The ratios between pro- versus anti-inflammatory cytokines were statistically significant higher in CSDH (7.8) compared with systemic levels (1.3).

Conclusions

The innate immune responses occur both locally at the site of CSDH, as well as systematically in patients with CSDH. The local hyper-inflammatory and low anti-inflammatory responses exist simultaneously. The findings suggest poorly coordinated innate immune responses at the site of CSDH that may lead to propagating of local inflammatory process and basically contribute to formation and progression of CSDH.     

Antimicrobial activity of prulifloxacin in comparison with other fluoroquinolones against community-acquired urinary and respiratory pathogens isolated in Greece

Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum fluoroquinolone rather recently introduced in certain European countries. We compared the antimicrobial potency of ulifloxacin with that of other fluoroquinolones against common urinary and respiratory bacterial pathogens. The microbial isolates were prospectively collected between January 2007 and May 2008 from patients with community-acquired infections in Greece. Minimum inhibitory concentrations (MICs) were determined for ciprofloxacin, levofloxacin, moxifloxacin (for respiratory isolates only), and ulifloxacin using the E-test method. The binary logarithms of the MICs [log₂(MICs)] were compared by using the Wilcoxon signed-ranks test. A total of 409 isolates were studied. Ulifloxacin had the lowest geometric mean MIC for the 161 Escherichia coli, 59 Proteus mirabilis, and 22 Staphylococcus saprophyticus urinary isolates, the second lowest geometric mean MIC for the 38 Streptococcus pyogenes respiratory isolates (after moxifloxacin), and the third lowest geometric mean MIC for the 114 Haemophilus influenzae and the 15 Moraxella catarrhalis respiratory isolates (after ciprofloxacin and moxifloxacin). Compared with levofloxacin, ulifloxacin had lower log₂(MICs) against E. coli (p?<?0.001), P. mirabilis (p?<?0.001), S. saprophyticus (p?<?0.001), and S. pyogenes (p?<?0.001). Compared with ciprofloxacin, ulifloxacin had lower log₂(MICs) against P. mirabilis (p?<?0.001), S. saprophyticus (p?=?0.008), and S. pyogenes (p?<?0.001), but higher log₂(MICs) against H. influenzae (p?<?0.001) and M. catarrhalis (p?=?0.001). In comparison with other clinically relevant fluoroquinolones, ulifloxacin had the most potent antimicrobial activity against the community-acquired urinary isolates studied and very good activity against the respiratory isolates.     

Leishmania donovani-specific 25- and 28-kDa urinary proteins activate macrophage effector functions, lymphocyte proliferation and Th1 cytokines production

Growing incidence of drug resistance against leishmaniasis in endemic areas and limited drug options necessitates the need for a vaccine. Notwithstanding significant leishmanial research in the past decades, a vaccine candidate is far from reality. In this study, we report the potential of two urinary leishmanial proteins to induce macrophage effector functions, inflammatory cytokines production and human lymphocytes proliferation. A total four proteins of molecular mass 25, 28, 54 and 60 kDa were identified in human urine samples. The 25 and 28 kDa proteins significantly induced NADPH oxidase (p?<?0.001), superoxide dismutase (p?<?0.001) and inducible nitric oxide synthase (p?<?0.001) activities in stimulated RAW264.7 macrophages. The release of nitric oxide, tumor necrosis factor-alpha and interleukin (IL)-12 was also significantly (p?<?0.001) higher in 25 and 28 kDa activated macrophages as compared with cells activated with other two proteins. These two proteins also induced significant (p?<?0.001) proliferation and release of IFN-γ and IL-12 in human peripheral blood mononuclear cells.     

COVID-19 and cardiovascular complications – preliminary results of the LATE-COVID study

IntroductionCoronavirus disease 2019 (COVID-19) may affect many organs and may be responsible for numerous complications including cardiovascular problems.MethodsWe analysed consecutive patients (n = 51) admitted to the cardiology department between 1^st October 2020 and 31^st January 2021 due to symptoms which might have reflected cardiovascular complications following COVID-19. We collected data concerning clinical characteristics, results of laboratory tests, echocardiography and 24-hour ambulatory ECG recording.ResultsThe post-COVID-19 complications appeared 1–4 months after disease recovery. Severe cardiovascular complications were observed in 27.5% of hospitalized patients. In comparison to those with mild complications, patients with severe complications had significantly higher prevalence of diabetes (36 vs. 8%; p = 0.01), decrease in ejection fraction (36% vs. 0%, p < 0.001), higher resting heart rate at admission (85 vs. 72 bpm; p < 0.001), and higher levels of C-reactive protein (p = 0.02) and troponin T (17.9 vs. 4.2 pg/ml; p = 0.01). Dyspnoea and exercise intolerance were also more frequent in patients with severe complications.ConclusionsDiabetes, elevated level of CRP and troponin, heart rate variability parameters and worsening of left ventricular ejection fraction are related to the severity of cardiovascular complications following COVID-19 infection.     

What is the clinical relevance of respiratory syncytial virus bronchiolitis?: findings from a multi-center, prospective study

Acute bronchiolitis (AB) is caused primarily by respiratory syncytial virus (RSV). Recent laboratory tools have implicated a variety of other pathogens; however, their clinical relevance has not been clearly defined. The purpose of this study was to determine whether the etiological agents of AB affect its course. A multicenter prospective study was performed in previously healthy children <24?months of age who presented with <4?days duration of AB. Subjects were divided into the following groups: “only RSV,” “also RSV,” “no RSV,” and “no pathogen.” The clinical severity score on admission as well as the overall severity of disease was assessed. RSV was the most common cause of AB (77.5?%). “Only RSV” or “also RSV” patients had a higher clinical score on admission compared to those with “no RSV,” p?<?0.001 and p?<?0.02, respectively. “Only RSV” and “also RSV” patients had a higher disease severity score when compared to patients with “no RSV,” 5.9?±?1.4 vs. 5.1?±?1.5, p?<?0.001, and 5.6?±?1.4 vs. 5.1?±?1.5, p?<?0.02, respectively. Disease severity did not vary as a function of transfer to the pediatric intensive care unit (PICU) or duration of supplemental oxygen, yet, “only RSV” was associated with a longer length of stay (LOS) than “no RSV,” p?<?0.02. “Only RSV”-related AB was associated with a more severe initial clinical presentation and a longer LOS. There appears to be little immediate clinical benefit to diagnosing RSV AB to the individual patient, but the application of these diagnostic methods may have significant cost-saving implications and, thus, deserves consideration by medical professionals and health policy analysts.     

High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer

Aneuploidy is a result of the abnormal expression of spindle assembly checkpoint (SAC) proteins and resulting abnormal spindle function during mitosis. High expression of cell division cycle 20 homolog (CDC20) and mitotic arrest defective protein 2 (MAD2), key components of the SAC, has been reported in various carcinomas. However, the clinicopathological significance of CDC20 and MAD2 expressions in urothelial carcinoma of the human bladder (UCB) is unknown. We therefore studied the expression of CDC20 and MAD2 in UCB specimens by immunohistochemistry. High expression of CDC20 and MAD2 was observed in 59.0 % (200/339) and 51.0 % (173/339) of UCB cases, respectively. Most high-grade tumor cells exhibited diffuse nuclear and/or cytoplasmic staining for CDC20 and MAD2, whereas most low-grade tumor cells and normal urothelial cells were not stained. CDC20 overexpression was associated with advanced age (p?=?0.010), high grade (p?<?0.001), advanced stage (p?<?0.001), non-papillary growth pattern (p?<?0.001), and distant metastasis (p?=?0.042). Similarly, high MAD2 expression correlated with high grade (p?<?0.001), advanced stage (p?<?0.001), and non-papillary growth pattern (p?<?0.001). In univariate survival analyses, high CDC20 expression correlated with shorter recurrence-free survival (RFS) (p?=?0.032) and poorer overall survival (OS) (p?=?0.007) in patients with UCB, whereas high MAD2 expression was associated with poorer OS (p?=?0.008). In multivariate analyses, high CDC20 expression correlated with shorter RFS of patients with Ta stage UCB (hazard ratio, 1.91; p?=?0.01). In conclusion, increased expression of CDC20 and MAD2 is related to poor prognosis of UCB.     

Aberrations of MET are associated with copy number gain of EGFR and loss of PTEN and predict poor outcome in patients with salivary gland cancer

Hepatocyte growth factor receptor (MET) is a key driver of oncogenic transformation. Copy number gain and amplification of MET positively enhance tumour growth, invasiveness and metastasis in different cancer types. In the present study, 266 carcinomas of the major and minor salivary glands were investigated for genomic MET status by fluorescence in situ hybridization and for protein expression by immunohistochemistry. Results were matched with clinicopathological parameters, long-term survival and the status of epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN). Low polysomy (n?=?42), high polysomy (n?=?27), amplification (n?=?2) and deletion (n?=?18) were found as aberrations of genomic MET in certain subtypes. MET aberrations were associated with increased patient age (>70 years, p?=?0.003), male gender (p?=?0.01), increased tumour size (p?=?0.002), lymph node metastases (p?<?0.001), high-grade malignancy (p?<?0.001) and unfavourable overall survival (p?<?0.001). Both copy number gain (p?<?0.001) and deletion (p?=?0.031) of MET correlated with copy number gain of EGFR. Tumours with genomic loss of PTEN (n?=?48) concurrently presented aberration of genomic MET (p?<?0.001). MET gene status significantly correlated with protein status (p?=?0.038). In conclusion, gain but also loss of genomic MET activity correlates with aggressive tumour growth, nodal metastasis and worse overall survival in salivary gland cancer. Moreover, aberrations of MET are associated with EGFR and PTEN signalling and might possess relevance for targeted therapies of salivary gland carcinomas in the future.     

The predictor of mortality outcome in adult patients with Ebola virus disease during the 2014–2015 outbreak in Guinea

The purpose of this study was to examine the association of any demographic and clinical factors with mortality outcome among adult patients with Ebola virus disease (EVD) in Guinea. This retrospective observational study analyzed medical records of laboratory confirmed EVD adult patients during the 2014–2015 EVD outbreak in Guinea. The associations between any demographic or clinical variables and mortality outcome of EVD were assessed using univariate and multivariate logistic regression analyses. Of 2,310 EVD adult patients included for analysis, the overall case fatality rate was 68.1%. Univariate analyses identified factors possibly associated with mortality outcome, including patient age (p?<?0.001), history of visiting or close contact with a suspected or confirmed EVD patient (p?=?0.035), and seven clinical symptoms on admission, i.e., fever (p?=?0.003), hiccups (p?<?0.001), vomiting (p?=?0.003), diarrhea (p?<?0.001), cough (p?=?0.001), sore throat (p?=?0.016), and unexplained bleeding (p?=?0.021). The multivariate analysis showed that patient age was independently associated with mortality outcome of EVD (OR?=?1.06; 95%CI?=?1.03–1.09; p?<?0.001), while none the of clinical symptoms on admission were significantly associated with the mortality outcome. Our analysis indicates that older age was the only independent factor associated with death among EVD adult patients in Guinea. This suggests that older EVD patients should receive intensive medical care and be carefully monitored.     

Pubertal timing,menstrual irregularity,and mental health: results of a population-based study

Reproductive events have a significant impact on women’s lives. The aim of this study was to analyze the effects of age at menarche and current menstrual irregularity on psychological well-being and psychopathology. Data were collected in the context of the Finnish population-based Health 2000 study with self-administered questionnaires, a home interview, and a clinical health examination. The Beck Depression Inventory (BDI-21), the General Health Questionnaire-12 (GHQ-12), and the Composite International Diagnostic Interview (M-CIDI) were used to assess psychopathology. The relationships between age at menarche and current menstrual flow irregularity vs. BDI-21 and GHQ-12 scores and M-CIDI diagnoses were studied among 4,391 women aged 30 years and over. Negative, nonsignificant associations were found between age at menarche and BDI-21 and GHQ-12 scores. Young age at menarche was associated with increased risks of any recent mental disorder (OR?=?0.894, p?<?0.01), major depressive episode (OR?=?0.900, p?<?0.05), major depressive disorder (OR?=?0.888; p?<?0.05), and anxiety disorder (OR?=?0.892; p?<?0.05). Menstrual irregularity was associated with BDI-21 (p?<?0.001) and GHQ-12 (p?<?0.05) scores, but not with any recent psychiatric diagnosis. Age at menarche and menstrual irregularity have an influence on mental health, particularly on mood and anxiety symptoms. Reproductive features (age at menarche and menstrual irregularity) should be paid attention to during psychiatric evaluations.