Results of the Anaconda endovascular graft in abdominal aortic aneurysm with a severe angulated infrarenal neck

Objective: Proximal neck anatomy of an abdominal aortic aneurysm (AAA), especially a severe angulated neck of more than 60 degrees, predicts adverse outcome in endovascular aneurysm repair. In the present study, we evaluate the feasibility of the use of the Anaconda endovascular graft (Vascutec, Terumo, Inchinnan, Scotland) for treating infrarenal AAA with a severe angulated neck (>60 degrees) and report the midterm outcomes. Methods: In total, nine Dutch hospitals participated in this prospective cohort study. From December 2005 to January 2011, a total of 36 AAA patients, 30 men and six women, were included. Mean and median follow-up were both 40 months. Results: Mean infrarenal neck angulation was 82 degrees. Successful deployment was reached in 34 of 36 patients. Primary technical success was achieved in 30 of 36 patients (83%). There was no aneurysm-related death. Four-year primary clinical success was 69%. In the first year, eight clinical failures were reported including four leg occlusions which could be solved using standard procedures. After the first year, three patients with additional failures occurred; two of them were leg occlusions. Four patients needed conversion to open AAA exclusion. In six of 36 patients, one or more reinterventions were necessary. Three of them were performed for occlusion of one Anaconda leg and two were for occlusion of the body. Conclusions: The use of the Anaconda endovascular graft in AAA with a severe angulated infrarenal neck is feasible but has its side effects. Most clinical failures occur in the first year. Thereafter, few problems occur, and midterm results are acceptable. Summarizing the present experiences, we conclude that open AAA repair is still a preferable option in patients with challenging aortic neck anatomy and fit for open surgery

Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response

Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggregated Mtb relative to phagocytosis of non-aggregated single or multiple bacilli. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNFα signaling via the NFκB pathway. These pathways were significantly more upregulated relative to infection with single or multiple non-aggregated bacilli per cell. Phagocytosis of aggregates led to a decreased phagosome acidification on a per bacillus basis and increased phagocyte cell death, which was not observed when Mtb aggregates were heat killed prior to phagocytosis. Mtb aggregates, observed in a granuloma from a patient, were found surrounding a lesion cavity. These observations suggest that TB aggregation may be a mechanism for pathogenesis. They raise the possibility that aggregated Mtb, if spread from individual to individual, could facilitate increased inflammation, Mtb growth, and macrophage cell death, potentially leading to active disease, cell necrosis, and additional cycles of transmission

Clusters and networks as enablers of product and process innovation

One of the strategies adopted in the Philippines to facilitate a more consistent supply of good quality vegetables from smallholder farmers is the clustering approach, whereby a small group or cluster of smallholder farmers is organized to deliver a pre-determined amount of produce to a focal customer (CRS-Philippines, 2007). Developed from the CIAT Territorial Approach, the CRS Eight Step Clustering Approach for Agro-enterprise Development employs a participatory action learning process, where the cluster members proactively plan their production to meet the specifc quality and delivery requirements of their focal customer. The clustering approach is a strategy which allows smallholder farmers to access higher value chains. Evidence is provided to demonstrate how several of the clusters facilitated have utilised the skills and knowledge acquired in servicing their focal customer to develop new products for new markets, to adopt alternative low cost systems of production to reduce their reliance on external inputs, to reduce postharvest losses and product deterioration through improved packaging, to improve access to low cost community-based loans and to take advantage of local and national government grants that provide production inputs and support the development of community-based infrastructure projects

An amphitropic cAMP-binding protein in yeast mitochondria

ABSTRACT: We describe the first example of a mitochondrial protein with a covalently attached phos-phatidylinositol moiety acting as a membrane anchor. The protein can be metabolically labeled with both stearic acid and inositol. The stearic acid label is removed by phospholipase D whereupon the protein with the retained inositol label is released from the membrane. This protein is a cAMP receptor of the yeast Saccharomyces cereuisiae and tightly associated with the inner mitochondrial membrane. However, it is converted into a soluble form during incubation of isolated mitochondria with Ca2+ and phospholipid (or lipid derivatives). This transition requires the action of a proteinaceous, N-ethylmaleimide-sensitive component of the intermembrane space and is accompanied by a decrease in the lipophilicity of the cAMP receptor. We propose that the component of the intermembrane space triggers the amphitropic behavior of the mitochondrial lipid-modified CAMP-binding protein through a phospholipase activity. Only in recent years specific fatty acids have been recog-nized to play important roles in the association of proteins with membranes. Both noncovalent and covalent interactions be-tween fatty acids and proteins have been reported. Among the latter are GTP-binding proteins (Molenaar et al., 1988)

HIV status alters disease severity and immune cell responses in Beta variant SARS-CoV-2 infection wave

There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (Beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes

CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II

Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the recommended dose of neoadjuvant CPT-11 (three times weekly 90 mg m−2) concomitant to hyperfractionated accelerated radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cN+). Median age was 60 years (range 43–75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery with total mesorectal excision (TME) was performed within 1 week (range 2–15 days). The preoperative chemoradiotherapy was overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% (95% confidence interval 0.48–0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse remains a concern in this patient population