pT3 colorectal cancer revisited: a multicentric study on the histological depth of invasion in more than 1000 pT3 carcinomas—proposal for a new pT3a/pT3b subclassification

BACKGROUND: Pathological TNM staging (pTNM) is the strongest prognosticator in colorectal carcinoma (CRC) and the foundation of its post-operative clinical management. Tumours that invade pericolic/perirectal adipose tissue generally fall into the pT3 category without further subdivision. METHODS: The histological depth of invasion into the pericolic/perirectal fat was digitally and conventionally measured in a training cohort of 950 CRCs (Munich). We biostatistically calculated the optimal cut-off to stratify pT3 CRCs into novel pT3a (≤3 mm)/pT3b (>3 mm) subgroups, which were then validated in two independent cohorts (447 CRCs, Bayreuth/542 CRCs, Mainz). RESULTS: Compared to pT3a tumours, pT3b CRCs showed significantly worse disease-specific survival, including in pN0 vs pN+ and colonic vs. rectal cancers (DSS: P < 0.001, respectively, pooled analysis of all cohorts). Furthermore, the pT3a/pT3b subclassification remained an independent predictor of survival in multivariate analyses (e.g. DSS: P < 0.001, hazard ratio: 4.41 for pT3b, pooled analysis of all cohorts). While pT2/pT3a CRCs showed similar survival characteristics, pT3b cancers remained a distinct subgroup with dismal survival. DISCUSSION: The delineation of pT3a/pT3b subcategories of CRC based on the histological depth of adipose tissue invasion adds valuable prognostic information to the current pT3 classification and implementation into current staging practices of CRC should be considered

Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype

HIV non-progression despite persistent viraemia is rare among antiretroviral therapy (ART)-naïve adults, but relatively common among ART-naïve children. Previous studies indicate that ART-naïve paediatric slow-progressors (PSPs) adopt immune evasion strategies similar to those described in the SIV natural hosts. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T-cells immediately prior to ATI was the main predictor of slow progression during ATI (r=0.77, p=0.002). PD-1+ CD8+ T-cell frequency was also negatively correlated with CCR5 (r=-0.74, p=0.005) and HLA-DR (r=-0.63, p=0.02) expression on CD4+ T-cells and predicted stronger HIV-specific T-lymphocyte responses. In the CD8+ T-cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas paediatric progressors and viraemic adults were populated with a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T-cells was associated with higher proliferative activity (r=0.41, p=0.03) and stronger Gag-specific effector functionality. These data prompt the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in early-ART-treated infants with a preserved and non-exhausted T-cell compartment

Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection

Female children and adults typically generate more efficacious immune responses to vaccines and infections than age-matched males, but also suffer greater immunopathology and autoimmune disease. We here describe, in a cohort of>170 in utero HIV-infected infants from KwaZulu-Natal, South Africa, fetal immune sex differences resulting in a 1.5-2-fold increased female susceptibility to intrauterine HIV infection. Viruses transmitted to females have lower replicative capacity (p=0.0005) and are more type I interferon-resistant (p=0.007) than those transmitted to males. Cord blood cells from females of HIV-uninfected sex-discordant twins are more activated (p=0.01) and more susceptible to HIV infection in vitro (p=0.03). Sex differences in outcome include superior maintenance of aviraemia among males (p=0.007) that is not explained by differential antiretroviral therapy adherence. These data demonstrate sex-specific innate immune selection of HIV associated with increased female susceptibility to in utero infection and enhanced functional cure potential among infected males. Sex differences in the immune response to vaccines and infections have been well described in children and adults. Here the authors describe, in a cohort of 177 HIV-infected infants, innate immune sex differences in fetal life that increase female susceptibility to intrauterine HIV infection and increase the chances of subsequent HIV remission in infected males

Slow progression of pediatric HIV associates with early CD8 + T cell PD-1 expression and a stem-like phenotype

HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ART-naive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8 + T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1 + CD8 + T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4 + T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8 + T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1 + PD-1 + memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1 + CD39 + population. TCF-1 + PD-1 + expression on CD8 + T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment

Participation of older newly-diagnosed cancer patients in an observational prospective pilot study: an example of recruitment and retention

<p>Abstract</p> <p>Background</p> <p>There have been few prospective observational studies which recruited older newly-diagnosed cancer patients, and of these only some have reported information on the number needed to screen to recruit their study sample, and the number and reasons for refusal and drop-out. This paper reports on strategies to recruit older newly-diagnosed cancer patients prior to treatment into an observational prospective pilot study and to retain them during a six-month period.</p> <p>Methods</p> <p>Medical charts of all patients in the Segal Cancer Centre aged 65 and over were screened and evaluated for inclusion. Several strategies to facilitate recruitment and retention were implemented. Reasons for exclusion, refusal and loss to follow-up were recorded. Descriptive statistics were used to report the reasons for refusal and loss to follow-up. A non-response analysis using chi-square tests and t-tests was conducted to compare respondents to those who refused to participate and to compare those who completed the study to those who were lost to follow-up. A feedback form with open-ended questions was administered following the last interview to obtain patient's opinions on the length of the interviews and conduct of this pilot study.</p> <p>Results</p> <p>3060 medical charts were screened and 156 eligible patients were identified. Of these 112 patients participated for a response rate of 72%. Reasons for refusal were: feeling too anxious (40%), not interested (25%), no time (12.5%), too sick (5%) or too healthy (5%) or other reasons (5%). Ninety-one patients participated in the six-month follow-up (retention 81.3%), seven patients refused follow-up (6.2%) and fourteen patients died (12.5%) during the course of the study. The median time to conduct the baseline interview was 45 minutes and 57% of baseline interviews were conducted at home. Most patients enjoyed participation and only five felt that the interviews were too long.</p> <p>Conclusion</p> <p>It was feasible to recruit newly-diagnosed cancer patients prior to treatment although it required considerable time and effort. Once patients were included, the retention rate was high despite the fact that most were undergoing active cancer treatment.</p

What is the use of workplace health promotion? : An analysis of needs at the University of Applied Sciences Osnabrück

Hintergrund Betriebliche Gesundheitsförderung ist ein Instrument, um auf die gesamtgesellschaftlichen und strukturellen Veränderungen, die an Hochschulen gestellt werden, zu reagieren. Um betriebliche Gesundheitsförderung an der Fachhochschule Osnabrück zu etablieren, wurde zunächst der Bedarf analysiert. Methode Der Bedarf an betrieblicher Gesundheitsförderung wurde mittels Web-basierter, schriftlicher Mitarbeiter- und Studierendenbefragung erhoben und hinsichtlich der Statusgruppen differenziert ausgewertet. Ergebnisse Es bestehen signifikante Unterschiede sowohl im Gesundheitsverhalten als auch im Gesundheitszustand der Beschäftigten und Studierenden. Nackenschmerzen sind bei Mitarbeitern häufiger, wohingegen Studierende stärkere psychische Belastungen angaben. Auch die Erwartungen an BGF unterscheiden sich hinsichtlich der Statusgruppen. Schlussfolgerung Die Angehörigen der Fachhochschule Osnabrück weisen insgesamt einen relativ guten Gesundheitszustand auf, dennoch zeigte die Bedarfsanalyse die Notwendigkeit und auch das Potential für BGF-Maßnahmen auf.Background Universities could use workplace health promotion as one suitable instrument for dealing with social and structural changes. In order to implement health promotion, the University of Applied Sciences Osnabrück undertook a needs analysis. Method A web survey of students and staff members was conducted. The results were analysed for each group. Results Both the health-related behaviour and health status of staff members showed significant differences compared with students. Neck pain was a common problem for staff, whereas students reported more psychological stress. Also, the prospects of a health promotion project differed in these groups. Conclusion The members of the University of Applied Sciences Osnabrück showed good health overall; nevertheless, the study points out both the necessity and potential for health-promoting activities

Identification of barriers and facilitators of successful interprofessional education (IPE) – a scoping umbrella review / Identifizierung der Einflussfaktoren für die interprofessionelle Ausbildung (IPE) – ein Umbrella Scoping Review

The study aims to provide an overview of factors influencing interprofessional education (IPE)

Pneumocystis jirovecii pneumonia in paediatric acute lymphoblastic leukaemia: A report from the multi-international clinical trial AIEOP-BFM ALL 2009.

Pneumocystis jirovecii can cause life-threatening pneumonia (PjP), and patients with haematological malignancies are at high risk of this infection. Prophylactic measures have significantly decreased morbidity and mortality, but there is a paucity of contemporary data on the incidence and clinical course of PjP in well-defined and homogenous patient populations, such as children suffering from acute lymphoblastic leukaemia (ALL). In the multi-international trial AIEOP-BFM ALL2009, PjP was diagnosed in six children (incidence 1/1000) and was associated with insufficient prophylaxis in five of them. Although none of the patients died of PjP, the long-term impact of the infection is unclear

Long-Term Kinetics of Serum Galactomannan during Treatment of Complicated Invasive Pulmonary Aspergillosis

Several studies have evaluated the serum galactomannan (GM) antigen assay in pediatric patients, and there is convincing evidence for its usefulness as a diagnostic tool for invasive Aspergillus infections in patients with acute leukemias or post allogeneic hematopoietic cell transplantation (HCT). Less is known about the utility of the assay in monitoring responses to treatment in patients with established invasive aspergillosis (IA). Here, we present the long-term kinetics of serum galactomannan in two severely immunocompromised adolescents with invasive pulmonary aspergillosis (IPA) who were cured after complicated clinical courses. We also review the utility of the GM antigen assay in serum as a prognostic tool around the time of diagnosis of IA and as a biomarker to monitor disease activity in patients with established IA and assess responses to systemic antifungal therapy

Epidemiology, utilisation of healthcare resources and outcome of invasive fungal diseases following paediatric allogeneic haematopoietic stem cell transplantation

Summary Background Epidemiology and management practices of invasive fungal diseases (IFD) after allogeneic haematopoietic stem cell transplantation (HSCT) are a subject of constant change. We investigated the contemporary incidence, diagnostics, antifungal management and outcome at a major paediatric transplant centre in Germany. Methods The single‐centre retrospective observational study included all paediatric allogeneic HSCT patients (pts) transplanted between 2005 and 2015. Patient‐related data were assessed up to 365 days post‐transplant. The primary endpoint was the incidence of possible, probable and proven IFDs. Secondary endpoints included diagnostics and antifungal treatment; analysis of risk factors; and overall survival with the last follow‐up in January 2017. Results A total of 221 first (196), second (21) or third (4) procedures were performed in 200 pts (median age: 9 years, range, 0.5‐22) for leukaemia/lymphoma (149) and non‐malignant disorders (72). Prophylaxis was administered in 208 HSCT procedures (94%; fluconazole, 116, mould‐active agents, 92). At least one computed tomography scan of the chest was performed in 146, and at least one galactomannan antigen assay in 60 procedures. There were 15 cases of proven (candidemia, 4; aspergillosis, 4) or probable (aspergillosis, 7) IFDs, accounting for an incidence rate of 6.8%. Overall mortality at last follow‐up was 30%; the occurrence of proven/probable IFDs was associated with a reduced survival probability (P < .001). Conclusion Morbidity and mortality from IFDs at our institution were consistent with data reported from other centres. Utilisation of healthcare resources for prevention, diagnosis and management of IFDs was considerable