After registration of drugs, evidence about efficacy and safety is solely based on data of phase 2/3 clinical trial programs. A major drawback is the selection of patients following inclusion/exclusion criteria. There is a considerable time and knowledge gap between study and registry data that evaluate real-world evidence (RWE). To close this gap, prospective cohort data are helpful.

Soon after tildrakizumab, an interleukin 23p19-inhibitor, was registered for moderate-to-severe plaque psoriasis, a prospective single-center cohort study was established to evaluate efficacy and safety of tildrakizumab in daily practice.

Following approval of tildrakizumab, patients with moderate-to-severe plaque psoriasis eligible for systemic treatment were included into the Kiel Tildra Cohort (KTC) and followed using routine assessments of efficacy, psoriasis area and severity index (PASI), body surface area (BSA), dermatology life quality index (DLQI), itch (visual analog scale), and safety. Data of the KTC were compactice with tildrakizumab differed substantially from the phase 3 studies. Despite systemic pre-treatment and increased comorbidity, tildrakizumab showed comparable efficacy and safety in the KTC. Prospective cohort studies are a suitable tool to generate RWE before registry data become available.It has never been taken into account that the fetus itself, by being trapped within the iatrogenic openings in the amniotic membrane from a previous intervention, can tear her home to pieces. As early rupture of membranes within hours or days after percutaneous fetoscopic surgery for spina bifida occurs in less than 10% of our cases, I would attribute most ruptures later in gestation to this effect. Fetal fingers and toes fit all too easily and – with advanced gestational age (the mean age of PROM after my approach to fetoscopic spina bifida surgery occurs around 30 weeks of gestation) – the fetus becomes certainly strong enough to achieve this mischievous feat. Supporting this notion of the (trapped) fetus as a potential culprit, many expectant mothers report a period of stronger fetal movements shortly prior to the occurrence of PROM.

Breast cancer resistance protein (BCRP), or ABCG2 (ATP-binding cassette sub-family G member 2), is an ATP-binding cassette (ABC) transporter that mediates energy-dependent transport of substrate drugs out of the cell. Its overexpression may contribute to intrinsic drug resistance in vitro. However, the current literature has not yet clarified the clinical significance of BCRP/ABCG2 in invasive breast carcinoma.

The purpose of this study was to validate the expression of BCRP/ABCG2 in invasive breast carcinoma and its role in response to neoadjuvant chemotherapy.

In this study, a pretherapeutic core biopsy was performed in 222 patients. BCRP/ABCG2 expression in carcinoma tissue was measured by immunohistochemistry. BCRP/ABCG2 expression correlations with clinicopathological features, molecular subtypes, and therapy response after neoadjuvant chemotherapy were investigated.

The results showed that BCRP/ABCG2 was expressed in different molecular subtypes. The proportions of patients with high BCRP/ABCG2 expression were similar in luminal A and luminal B tumors (Luminal B, 80%; Luminal A, 78%), compared with other molecular subtypes (Triple-negative, 63%; HER-2+, 58%. P=0.05). BCRP/ABCG2 expression and the number of lymphatic metastases (Training of the innate immune system with orally ingested bacterial extracts was demonstrated to have beneficial effects on infection clearance and disease outcome. The aim of our study was to identify cellular and molecular processes responsible for these immunological benefits. We used a murine coronavirus (MCoV) A59 mouse model treated with the immune activating bacterial extract Broncho-Vaxom (BV) OM-85. Tissue samples were analysed with qPCR, RNA sequencing, histology, and flow cytometry. After BV OM-85 treatment, interstitial macrophages accumulated in lung tissue leading to a faster response of type I interferon (IFN) signalling after MCoV infection resulting in overall lung tissue protection. Moreover, RNA sequencing showed that lung tissue from mice receiving BV OM-85 resembled an intermediate stage between healthy and viral infected lung tissue at day 4, indicating a faster return to normal tissue homoeostasis. The pharmacologic effect was mimicked by adoptively transferring naive lung macrophages into lungs from recipient mice before virus infection. The beneficial effect of BV OM-85 was abolished when inhibiting initial type I IFN signalling. Overall, our data suggest that BV OM-85 enhances lung macrophages allowing for a faster IFN response towards a viral challenge as part of the oral-induced innate immune system training.

Little is known about the role of inflammation in the process of small vessel vascular dementia (VaD). Recently, the notion that small vessel VaD is caused solely by vascular pathology has been challenged by new evidence of concomitant breakdown of the blood-brain barrier and dysregulation of neuroinflammation in the white matter.

We examined selected inflammatory cytokines and chemokines in the plasma from patients with small vessel VaD (n = 41) and from age-matched controls (n = 131) using multiplex bead-based assays. Participants were recruited from a memory disorder clinic and from a hospital or community.

When compared to controls, patients with small vessel VaD had a highly significant increase in the plasma interferon-γ-inducible protein 10 (IP-10) level (p < 0.0001) and a highly significant decrease in plasma macrophage inflammatory protein 1-beta (MIP-1β) level (p < 0.0001). We also observed a significant increase in patients’ levels of interleukin-10 (IL-10) (p = 0.022) as well as decreathis disease.

Tumorigenesis is associated with deregulation of nutritional requirements, intermediary metabolites production, and microenvironment interactions. Unlike their normal cell counterparts, tumor cells rely on aerobic glycolysis, through the Warburg effect.

The pentose phosphate pathway (PPP) is a major glucose metabolic shunt that is upregulated in cancer cells. The PPP comprises an oxidative and a nonoxidative phase and is essential for nucleotide synthesis of rapidly dividing cells. The PPP also generates nicotinamide adenine dinucleotide phosphate, which is required for reductive metabolism and to counteract oxidative stress in tumor cells. This article reviews the regulation of the PPP and discusses inhibitors that target its main pathways. Key Message Exploiting the metabolic vulnerability of the PPP offers potential novel therapeutic opportunities and improves patients’ response to cancer therapy.

The pentose phosphate pathway (PPP) is a major glucose metabolic shunt that is upregulated in cancer cells. The PPP comprises an oxidative and a nonoxidative phase and is essential for nucleotide synthesis of rapidly dividing cells. The PPP also generates nicotinamide adenine dinucleotide phosphate, which is required for reductive metabolism and to counteract oxidative stress in tumor cells. This article reviews the regulation of the PPP and discusses inhibitors that target its main pathways. Key Message Exploiting the metabolic vulnerability of the PPP offers potential novel therapeutic opportunities and improves patients’ response to cancer therapy.

The impact of the length of the occluded vessel in acute large-vessel occlusion on successful reperfusion by mechanical thrombectomy remains unclear. This study evaluated whether diameter and length of the occluded vessel in acute middle cerebral artery (MCA) occlusion might relate to successful reperfusion following mechanical thrombectomy.

This retrospective study included patients with acute MCA occlusion who underwent intra-aortic injection of contrast medium to obtain maximum intensity projection (MIP) images acquired by flat-panel detector computed tomography (FD-CT) equipped with an angiographic system. All patients received mechanical thrombectomy and were divided into two groups those with successful reperfusion (Thrombolysis in Cerebral Infarction [TICI] 2b/3) and those without. We compared the diameter and length of the occluded vessel between the groups. In the sub-analysis of patients with stent retriever use, ratio of length of occluded vessel to length of the active zone was compared.

We enrolled 29 patients (median age 73, M1 occlusion 51%, stent retriever use 72%). Eighteen patients achieved TICI 2b/3 with significantly larger distal end diameter (1.7 [interquartile range 1.5-1.9] vs. 1.2 [1.2-1.5] mm, p = 0.007) and shorter length (7.1 [4.9-9.7] vs. 12.3 [7.2-15.8] mm, p = 0.043) of the occluded vessel. Sub-analysis of 21 patients showed that the cut-off value for TICI 2b/3 reperfusion was 0.32 as the ratio between the occluded vessel and stent retriever active zone (receiver operating characteristic area under the curve 0.90).

In acute MCA occlusion, larger diameter of the distal end and shorter length of the occluded vessel on FD-CT MIP images might indicate a higher possibility of achieving TICI 2b/3 following mechanical thrombectomy.

In acute MCA occlusion, larger diameter of the distal end and shorter length of the occluded vessel on FD-CT MIP images might indicate a higher possibility of achieving TICI 2b/3 following mechanical thrombectomy.

The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have demonstrated the additional value of foetal motor assessment and evaluation in a multidisciplinary team for the period 2007-2016. An applied care pathway was developed for foetuses presenting with joint contracture(s) in one anatomic region (e.g., talipes equinovarus [TEV]), more than one body part with non-progressive contractures and motility (AMC) and with deterioration over time (FADS).

The multidisciplinary team of Amsterdam University Medical Centre Expertise Centre FADS and AMC developed the care pathway. Additional tools are provided including a motor assessment by ultrasound examination and a post-mortem assessment form.

An eight-step care pathway is presented with a proposed timing for prenatal sonographic examination, genetic examinations, multidisciplinary meetings, prenatal and postnatal counselling of the parents by a specialist also treating after birth, and the follow-up of prenatal and postnatal findings with counselling for future pregnancies.

The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase the detection rate and diagnosis of isolated contracture(s), TEV with underlying genetic causes, and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams.

The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase the detection rate and diagnosis of isolated contracture(s), TEV with underlying genetic causes, and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams.