Eighteen‐year experience with femoro‐femoral bypass

Background : The role of femoro‐femoral bypass in the management of aorto‐iliac occlusive disease has evolved during the past two decades. The aim of the present study was to evaluate the early and long‐term outcomes of femoro‐femoral bypass grafts performed at the University of Hong Kong Medical Centre during an 18‐year period. Methods : From 1981 to 1998, a retrospective analysis of 61 patients who underwent femoro‐femoral bypass at the University of Hong Kong Medical Centre was undertaken. Data on demographic features and results of surgical intervention were reviewed. Early outcomes (morbidity, mortality and improvement of clinical category) and long‐term outcomes (graft patency, patient survival and limb salvage rates) were analysed. Results : The postoperative morbidity and mortality rates were 16% and 7%, respectively. Clinical success was achieved in 48 patients (79%) after operation. The primary patency of femoro‐femoral bypass was 86%, 79% and 71% at 1, 3 and 5 years, respectively. The limb salvage rate was 85% at 3 years. The cumulative survival rate of the study population was 89%, 82% and 73% at 1, 3 and 5 years, respectively. Conclusions : Femoro‐femoral bypass was successful in relieving ischaemic pain and limb salvage in ~ 80% of patients. A 5‐year patency rate of 71% was achieved. Femoro‐femoral bypass remains a valuable surgical procedure for limb salvage in poor‐risk patients with unilateral iliac artery occlusion.     

Mindfulness‐based Coping with University Life: A Non‐randomized Wait‐list‐controlled Pilot Evaluation

The aim of this study was to explore the feasibility of implementing a new 8‐week mindfulness‐based programme, ‘Mindfulness‐Based Coping with University Life’ (MBCUL), specifically tailored to the needs and demand of students and to explore its impact in a pilot evaluation. Participants were drawn from the University of Northampton (MBCUL N = 10; control N = 6). A non‐randomized wait‐list‐controlled design was employed. Measures examined anxiety and depression, perceived stress, mindfulness and personally relevant change before and immediately after the programme. The diurnal profile of salivary cortisol and alpha‐amylase level was collected for two consecutive days. No significant intergroup differences were observed on any of the measures at either time point. However, significant change was observed for the MBCUL group in terms of perceived stress (d = 1.06; z = ?2.25, p = 0.03), anxiety (d = 1.04; z = ?2.14, p = 0.03), depression (d = 0.52; z = ?0.69, p = 0.5) and personally relevant change (d = 2.63; z = ?2.68, p = 0.01), along with an increase in mindfulness (d = 1.06; z = ?1.89, p = 0.06). In contrast, no significant change was found in the daily profiles of cortisol and alpha‐amylase. The data from this pilot tentatively suggest that MBCUL appears to be a promising programme that warrants further evaluation using a randomized study with a larger sample size. Copyright © 2011 John Wiley & Sons, Ltd.     

Low‐order multi‐rate linear time‐invariant decentralized trackers using the new observer‐based sub‐optimal method for unknown sampled‐data nonlinear time‐delay system with closed‐loop decoupling

This paper presents the low‐order multi‐rate linear time‐invariant decentralized trackers using the new observer‐based sub‐optimal method for a class of unknown sampled‐data nonlinear time‐delay system with closed‐loop decoupling. For the unknown sampled‐data nonlinear time‐delay system, we assume that the inner time delay is clearly known. Under this prerequisite, the appropriate (low‐) order decentralized linear observer for the unknown sampled‐data nonlinear system is determined by the off‐line observer/Kalman filter identification (OKID) method with artificial delay input and actual delay output. Then, the above observer has been further improved based on the proposed new observer‐based sub‐optimal approach. Sequentially, the decentralized tracker with the high gain property is proposed, so that the closed‐loop system has the decoupling property. The proposed approach constructs complete mathematics method including the concept of optimal control theory and state‐matching digital redesign technique and is quite useful for the complicated interconnected large‐scale sampled‐data nonlinear time‐delay system with unknown system equation. Copyright © 2010 John Wiley & Sons, Ltd.     

Thrombotic Micro‐Angiopathy with Sirolimus‐Based Immunosuppression: Potentiation of Calcineurin‐Inhibitor‐Induced Endothelial Damage?

Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration.     

Co‐circulation of Peste‐des‐Petits‐Ruminants Virus Asian lineage IV with Lineage II in Nigeria

Peste‐des‐petits‐ruminants (PPR), a major small ruminant transboundary animal disease, is endemic in Nigeria. Strains of the causal agent, peste‐des‐petits‐ruminants virus (PPRV), have been differentiated into four genetically distinct lineages based on the partial sequence of the virus nucleoprotein (N) or fusion (F) genes. Peste‐des‐petits‐ruminants virus strains that were identified initially in Africa were grouped into lineages I, II and III and viruses from Asia were classified as lineage IV and referred to as the Asian lineage. Many recent reports indicate that the Asian lineage is now also present in Africa. With this in mind, this study was conducted to reassess the epidemiology of PPRV in Nigeria. A total of 140 clinical samples from 16 sheep and 63 goats with symptoms suggestive of PPR were collected from different states of Nigeria during a four‐year period (2010–2013). They were analysed by the amplification of fragments of the N gene. Results for 33 (42%) animals were positive. The phylogenetic analysis of the N gene sequences with those available in GenBank showed that viruses that were detected belong to both lineage II and IV. Based on an analysis of the N gene sequences, the lineage IV isolates grouped into two clades, one being predominant in the north‐eastern part of the country and the other found primarily in the southern regions of the country. This study reports the presence of PPRV Asian lineage IV in Nigeria for the first time.     

Cyclosporine‐mediated allograft fibrosis is associated with micro‐RNA‐21 through AKT signaling

Calcineurin inhibitors (CNIs) are potent immunosuppressants with associated long‐term nephrotoxicity mediated by tubular epithelial cell injury and arterial vasoconstriction. We hypothesized that CNI‐induced renal injury is regulated by specific microRNAs (miRNAs). In this study, we found that 46 miRNAs were significantly altered in human proximal tubular epithelial cells (HPTECs) following exposure to cyclosporine A (CsA), particularly miR‐21 (5.47 ± 0.47‐fold versus vehicle, P = 0.002). This increase was accompanied by alterations in epithelial–mesenchymal transformation (EMT) markers including vimentin (2.80 ± 0.28‐fold; P = 0.03), S100A4 (2.29 ± 0.29‐fold; P = 0.04), and α‐SMA (5.0 ± 0.31‐fold; P = 0.03). Notably, transfection of HPTECs with miR‐21 precursor also resulted in significant induction of EMT‐associated genes, which were inhibited by a single‐stranded nucleic acid inhibitor of miR‐21. miR‐21 induction resulted in a rapid increase of phosphorylated AKT and downregulation of PTEN. While CsA induces SMAD7 downregulation and TGF‐β1 upregulation in HPTECs, such changes were independent of miR‐21. Moreover, there was no effect on ERK phosphorylation. We confirmed these changes using a mouse model of CsA toxicity. Collectively, our results suggest that miR‐21 mediates CsA nephrotoxicity via PTEN/AKT signaling pathway. Further exploration into the epigenetic response to CsA exposure may provide new therapeutic targets to ameliorate CsA nephrotoxicity.     

Management of extremely hard‐to‐heal extremity wounds with severe life‐threatening complications

The introduction of neoadjuvant radiotherapy has allowed limb‐preserving surgical treatment in patients with extremity soft tissue sarcoma, and the overall prognosis of this approach is similar to that of limb amputation. The benefits of this treatment, however, are often accompanied with a higher risk of major complications and blood vessel damage because of radiation‐induced inflammation and necrosis of the vessel wall. In particular, it is associated with the rupture of large vessels like the femoral artery and more severe complications of wounds located in the proximal lower extremity. We present a series of four patients with soft tissue sarcoma of the thigh undergoing tumour removal and reconstruction of the defect after neoadjuvant radiotherapy. The post‐operative outcome depended on the total dose of radiation used as well as the closing technique of the resulting wound. Major wound complications occurred when the irradiated skin was closed directly over the resection cavity or when local skin flaps were used. In one case, severe radiation‐induced life‐threatening multiple bleeding events occurred, which led to multiple flap failures. Even if the skin cover is not a problem, we propose a combined interdisciplinary approach involving immediate plastic surgical transfer of healthy, well‐vascularised tissue into a defect resulting from oncological resection of sarcoma of the lower extremity following neoadjuvant radiotherapy in order to avoid secondary wound breakdown and severe bleeding complications.     

A case of SARS‐CoV‐2 pneumonia with successful antiviral therapy in a 77‐year‐old man with a heart transplant

The SARS‐CoV‐2 infection can be seen as a single disease, but it also affects patients with relevant comorbidities who may have an increased risk of a severe course of infection. In this report, we present a 77‐year‐old patient with a heart transplant receiving relevant immunosuppressive therapy who tested positive for SARS‐CoV‐2 after several days of dyspnea, dry cough, and light general symptoms. Computed tomography confirmed interstitial pneumonia. The patient received antiviral therapy with hydroxychloroquine and showed no further deterioration of the clinical state. After 12 days of hospitalization, the patient was released; he was SARS‐CoV‐2 negative and completely asymptomatic.     

Tumor‐derived syndecan‐1 mediates distal cross‐talk with bone that enhances osteoclastogenesis

Tumor‐stimulated bone resorption fuels tumor growth and marks a dramatic decline in the health and prognosis of breast cancer patients. Identifying mechanisms that mediate cross‐talk between tumor and bone remains a key challenge. We previously demonstrated that breast cancer cells expressing high levels of heparanase exhibit enhanced shedding of the syndecan‐1 proteoglycan. Moreover, when these heparanase‐high cells are implanted in the mammary fat pad, they elevate bone resorption. In this study, conditioned medium from breast cancer cells expressing high levels of heparanase was shown to significantly stimulate human osteoclastogenesis in vitro (p < .05). The osteoclastogenic activity in the medium of heparanase‐high cells was traced to the presence of syndecan‐1, intact heparan sulfate chains, and heat‐labile factor(s), including the chemokine interleukin 8 (IL‐8). The enhanced osteoclastogenesis promoted by the heparanase‐high cells results in a dramatic increase in bone resorption in vitro. In addition, the long bones of animals bearing heparanase‐high tumors in the mammary fat pad had significantly higher numbers of osteoclasts compared with animals bearing tumors expressing low levels of heparanase (p < .05). Together these data suggest that syndecan‐1 shed by tumor cells exerts biologic effects distal to the primary tumor and that it participates in driving osteoclastogenesis and the resulting bone destruction. © 2010 American Society for Bone and Mineral Research