Long-Term Outcome for Covered Endovascular Reconstruction of Aortic Bifurcation for Aortoiliac Disease: A Single-Center Experience.

PURPOSE: The gold standard for the treatment of complex (TASC II C and D) atherosclerotic aortoiliac lesions is still open surgical repair. Endovascular techniques have a lower mortality and morbidity rate but this comes at the cost of worse patency rates when compared with open repair. Improved short- and mid-term results have been reported using the covered endovascular reconstruction of aortic bifurcation (CERAB) technique. The aim of this study was to report our initial experience with the CERAB technique and report long-term patency rates. MATERIALS AND METHODS: All patients treated with the CERAB technique between 2012 and 2018 were prospectively registered in an institutional database and included in this study. Patient demographics, characteristics, symptoms, procedural, and follow-up details were collected and analyzed retrospectively. Perioperative complications and reinterventions were also identified. The Kaplan-Meier survival method was used to assess cumulative rates of patency. RESULTS: A total of 44 patients were treated with the CERAB technique and included in this study. The majority of the treated aortoiliac occlusions were classified as complex: TASC II C (n=7; 15.9%) or TASC II D (n=25; 56.8%). Primary patency rate at 60 months was 83.3%, assisted primary patency was 90.9% and secondary patency 95%. No significant differences were found in patency rates comparing noncomplex (TASC II A and B) and complex (TASC II C and D) aortoiliac lesions. Seven patients (15.9%) required at least one additional procedure to maintain either assisted primary patency or secondary patency during follow-up. The 30-day complication rate in this series was 20.5% (n=9), of which 55.6% (n=5) were minor complications. All major 30-day complications (n=4) occurred during or directly after the CERAB procedure. Thirty-day mortality was 0%. No limb occlusions occurred within 30 days of the procedure. CONCLUSION: Good long-term patency rates can be achieved with the CERAB technique to treat aortoiliac stenosis or occlusions while maintaining advantages associated with endovascular interventions. This remains true even when a CERAB is used to treat complex aortoiliac lesions. An endo-first approach to treat complex aortoiliac lesions seems viable.

Up to 10-year follow-up after EVAR with the Endurant stent graft system: a single-center experience.

BACKGROUND: Endovascular aneurysm repair (EVAR) has become the preferred treatment for infrarenal abdominal aortic aneurysms (AAA) over open surgical repair. The Endurant stent graft is widely used, and large registries report low rates of aneurysm-related mortality and reinterventions at midterm follow-up. Reports of long-term follow-up are limited. The aim of this study is to report our experiences and share our results, reintervention rate and mortality at long-term follow-up after using the Endurant stent graft. METHODS: All consecutive patients treated between 2009 and 2013 with the Medtronic Endurant I and II stent graft for an infrarenal AAA in an elective setting were included. Primary outcomes were overall and aneurysm-related survival and reintervention rates. RESULTS: One hundred sixty-five consecutive patients (median age 74; IQR: 68-79) with an aneurysm diameter of 62 mm (IQR: 58-70) and neck length of 29 mm (IQR: 21-40) were electively treated with the Endurant I or II stent graft. One hundred thirty-four patients (81.2%) were treated inside IFU (instructions for use) and 31 (18.8%) outside IFU. At median follow-up of 76 months (IQR: 50-97), 60 patients (36.4%) were deceased. Kaplan-Meier estimates at 10 years follow-up of overall survival and freedom from aneurysm-related mortality were respectively 48.5% (CI: 43.7-53.3%) and 97.3% (CI: 95.7-98.9%). Freedom from reintervention was 86.0% with an CI: 83.1-88.9% at 5 years follow-up and 75.6% with a CI: 70.2-81.0% at 10 years follow-up. A total of 25 (15.2%) patients had an EVAR-related reintervention; indications were endoleak (EL) type 1A (N.=11), EL type 1B (N.=3), EL type 2 (N.=6), EL type 3 (N.=1) and limb occlusion (N.=4). We found no significant differences in outcome between the inside and outside IFU groups. At 5 years follow-up 92.6% of patients had stable or decreased diameter, and 7.4% had an increased diameter. CONCLUSIONS: This large cohort single-center study demonstrates the effectiveness and safety of the Endurant stent graft system at long-term follow-up with low reintervention rates and aneurysm-related mortality.

Chilblains in COVID-19 Infection.

COVID-19 has quickly become a worldwide pandemic and is well-known for its pulmonary complications. Dermatologic manifestations such as chilblain-like lesions have been recently described, but it is unclear if they are truly secondary to the infection or not. Here we describe a young patient who developed chilblain-like eruptions on his toes, likely secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We discuss the literature that supports the hypothesis that these are in fact secondary to the infection, as well as provide insight into the pathology of these lesions.

The invertebrate pharmacology of insecticides acting at nicotinic acetylcholine receptors.

The nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel composed of 5 protein subunits arranged around a central cation selective pore. Several classes of natural and synthetic insecticides mediate their effect through interacting at nAChRs. This review examines the basic pharmacology of the neonicotinoids and related chemistry, with an emphasis on sap-feeding insects from the order Hemiptera, the principle pest target for such insecticides. Although the receptor subunit stoichiometry for endogenous invertebrate nAChRs is unknown, there is clear evidence for the existence of distinct neonicotinoid binding sites in native insect preparations, which reflects the predicted wide repertoire of nAChRs and differing pharmacology within this insecticide class. The spinosyns are principally used to control chewing pests such as Lepidoptera, whilst nereistoxin analogues are used on pests of rice and vegetables through contact and systemic action, the pharmacology of both these insecticides is unique and different to that of the neonicotinoids.

A review of treatment options for Graves' disease: why total thyroidectomy is a viable option in selected patients.

Graves' disease is the most common cause of hyperthyroidism. If left untreated, patients may have multiple systemic complications such as cardiac, reproductive, and skeletal disease. Thionamides, such as methimazole and propylthiouracil, and I(131) iodine ablation are the most commonly prescribed treatment for Graves' disease. Total thyroidectomy is often overlooked for treatment and is usually only offered if the other options have failed. In our case, we discuss a patient who was admitted to our medical center with symptomatic hyperthyroidism secondary to long-standing Graves' disease. She had a history of non-compliance with medications and medical clinic follow-up. The risks and benefits of total thyroidectomy were explained and she consented to surgery. A few months after the procedure, she was biochemically and clinically euthyroid on levothyroxine. She had no further emergency room visits or admissions for uncontrolled thyroid disease. Here we review the advantages and disadvantages of the more typically prescribed treatments, thionamides and I(131)iodine ablation. We also review the importance of shared decision making and the benefits of total thyroidectomy for the management of Graves' disease. Given the improvement in surgical techniques over the past decade and a significant reduction of complications, we suggest total thyroidectomy be recommended more often for patients with Graves' disease.

Overall Quality of Life in Adult Biliary Atresia Survivors with or without Liver Transplantation: Results from a National Cohort.

Background Biliary atresia (BA) is a rare cholestatic disease of infancy. Kasai portoenterostomy and liver transplantation (LT) are the two sequential treatment options. An increasing number of patients survive into adulthood. Little is known about their health-related quality of life (HRQOL). This study aims to compare HRQOL of transplanted and nontransplanted patients in a cohort of young adult BA survivors. Patients and Methods RAND-36 and Liver Disease Index Score (LDSI) questionnaires were sent to eligible adult patients with BA. Clinical characteristics were obtained from the NeSBAR (Netherlands Study group on Biliary Atresia Registry) and the national pediatric LT database. RAND-36 domain and summary scores were compared with those of an age-matched Dutch reference group. The correlations between several clinical variables and HRQOL were analyzed. Results Mean RAND-36 domain and summary scores of transplanted (n = 15) and nontransplanted (n = 25) patients with BA (response 74%) were similar to the reference scores, with the exception of a decreased general health perception in nontransplanted patients (63 ± 21 vs. 75 ± 17; [p < 0.001], particularly in females. RAND-36 domain and summary scores were not significantly correlated to age at LT, time since LT, serum bilirubin, aspartate amino transferase or albumin levels, but were moderately to strongly correlated to LDSI total scores (r values 0.35-0.77). Conclusions Overall, young adult patients with BA have a HRQOL similar to an age-matched reference group. However, general health perception of nontransplanted patients, particularly of females, was decreased. HRQOL is correlated to liver disease symptoms but not to liver biochemistry parameters. Nontransplanted females and patients suffering from liver disease-associated symptoms may be a target for tailored supportive interventions.

Achievement of developmental milestones in young adults after liver transplantation in childhood.

Little is known about the achievement of developmental milestones (i.e., COL) after pediatric liver transplantation. The aim of this study was to examine the COL of young adults who underwent a liver transplantation during childhood and to compare it to healthy peers. Furthermore, we studied factors possibly related to their COL. COL was assessed using the CLQ, which assesses the achievement of developmental milestones (autonomy, psychosexual, social, and antisocial development) and risk behavior (substance abuse and gambling). Sociodemographic characteristics and clinical data were collected using the prospective institutional liver transplantation database. A total of 39 young adults who underwent a liver transplantation at the UMCG in their childhood completed the CLQ. They achieved fewer milestones with regard to autonomy, psychosexual, and social development compared to healthy peers, and they reported less risk behavior. Neither age at the time of study nor age at the time of transplantation was significantly correlated with any of the COL subscales. Young adults show delay in reaching developmental milestones in every dimension after a liver transplantation during their childhood.

Liver fibrosis during the development of biliary atresia: Proof of principle in the murine model.

BACKGROUND: The murine model of biliary atresia (BA) is used for examining the pathogenesis of BA. The aim of the study was description of the morphological features and illustrating the detailed development of fibrosis using the Biliary Atresia Research Consortium (BARC) system. METHODS: Neonatal mice were injected intraperitoneally with rhesus rotavirus (RRV) strain (N=17). Healthy mice were the control group (N=29). All mice were sacrificed at 7 or 14days after birth. Two pathologists examined the morphological features using the BARC system; CK19, αSMA and collagen type I were assessed by immunohistochemistry. RESULTS: In RRV mice, portal fibrous expansion with focal bile duct proliferation and strong portal cellular infiltrate was found in contrast to healthy mice. In RRV mice, CK19 bile duct staining was significantly less or absent (p<0.01), with stronger portal staining of collagen type I (p=0.02). Expansion of staining for αSMA was more in RRV mice (p<0.01), but αSMA portal staining was stronger in healthy mice (p=0.02). CONCLUSIONS: The morphological features observed in the murine model of BA correspond with the BA characteristics according to the BARC criteria. Fibrosis is an important feature of the model. Therefore, this murine model is useful for investigating the pathogenesis of BA.

Health status and quality of life in adult biliary atresia patients surviving with their native livers.

INTRODUCTION: Gaining an insight into the quality of life (QOL) in long-term biliary atresia (BA) survivors is becoming more important. Identifying patients with limitations might make tailor made interventions possible. This is the first study investigating the health status (HS) and QOL in adults surviving BA with their native livers, and comparing them with healthy peers. METHODS: BA patients surviving with their native liver were identified in the Netherlands Study Group on Biliary Atresia Registry database. The RAND-36 and the World Health Organization Quality of Life assessment instrument-100 (WHOQOL-100) were used to measure HS and QOL, respectively. Correlation between the RAND-36 and WHOQOL-100 was also assessed. Hospital Anxiety and Depression Scale (HADS) and the Impact Event Scale (IES) were also completed. RESULTS: In total, 25 (83%) of the 30 eligible patients after Kasai portoenterostomy completed the questionnaires (median age 23.2 years). A lower perceived level of general health in HS was found as compared with the reference group and a higher score on the social domain was reported in QOL. Correlations between HS and QOL questionnaires were moderate to good. For the group, overall HADS and IES scores were good, though individual patients did score above the cutoff of both the questionnaires. CONCLUSION: Adult BA patients surviving with their native liver have similar HS and QOL as compared with their healthy peers. RAND-36 and WHOQOL-100 questionnaires are not interchangeable, but complementary to assess the patients' outcomes. The overall scores did not point to increased levels of anxiety and depression. However, on an individual level, three and six patients had a score above the cutoff of the HADS subscales demonstrating clinically relevant levels of anxiety and depression, respectively.

Behavioural avoidance and enhanced dispersal in neonicotinoid-resistant Myzus persicae (Sulzer).

BACKGROUND: The peach potato aphid Myzus persicae is a major agricultural pest capable of transmitting over 100 plant viruses to a wide range of crops. Control relies largely upon treatment with neonicotinoid insecticides such as thiamethoxam (TMX). In 2009, a strain denoted FRC, which exhibits between 255- and 1679-fold resistance to current neonicotinoids previously linked to metabolic and target site resistance, was discovered in France. Dispersal behaviour may potentially further enhance the resistance of this strain. This study investigated this possibility and is the first to compare the dispersal behaviour of aphid clones of the same species with differing levels of neonicotinoid resistance. RESULTS: Comparing the dispersal behaviour of the FRC strain with that of a clone of lower neonicotinoid resistance (5191A), and a susceptible clone (US1L) highlighted several differences. Most importantly, the FRC strain exhibited an increased ability to locate untreated areas when presented with an environment consisting of both TMX-treated and untreated plant tissue. CONCLUSION: The altered dispersal behaviour of the FRC may partially account for the high level of neonicotinoid resistance exhibited by this strain in the field. Since the dispersal of aphid vectors is key to the transmission of viruses across crop fields this has implications for current crop protection practice.

Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair.

Fetal wounds have been found to have increased levels of high-molecular-weight hyaluronan (HMW-HA) compared with those of adults. The primary enzyme responsible for producing HMW-HA is hyaluronic acid synthase-1 (HAS-1). We hypothesized that over-expression of HAS-1 in adult dermal wounds would decrease inflammation and promote regenerative healing. To test this hypothesis, the flanks of adult C57Bl/6 mice were treated with a lentiviral construct containing either HAS-1-GFP or GFP transgenes. After 48 h, a 4-mm excisional wound was made at the site of treatment. Wounds were harvested at days 3, 7, or 28 after wounding. Wound phenotype was assessed by histology to examine tissue architecture and immunohistochemistry for CD45. At 7 and 28 days, lenti-HAS-1-treated wounds demonstrated the restoration of the normal dermal elements and organized collagen fiber orientation. In contrast, the lenti-GFP-treated wounds lacked normal dermal architecture and demonstrated a disorganized collagen scar. At 3 and 7 days, wounds treated with lenti-HAS-1 exhibited a significant decrease in the number of inflammatory cells when compared with wounds treated with lenti-GFP. Thus, HAS-1 over-expression promotes dermal regeneration, in part by decreasing the inflammatory response and by recapitulation of fetal extracellular matrix HMW-HA content.

Impaired biomechanical properties of diabetic skin implications in pathogenesis of diabetic wound complications.

Diabetic skin is known to have deficient wound healing properties, but little is known of its intrinsic biomechanical properties. We hypothesize that diabetic skin possesses inferior biomechanical properties at baseline, rendering it more prone to injury. Skin from diabetic and nondiabetic mice and humans underwent biomechanical testing. Real-time PCR was performed for genes integral to collagen synthesis and degradation. MMP-2 and MMP-9, and TIMP-1 protein levels were assessed by ELISA and zymography. Collagen I and III content was assessed using Western blot analysis. At baseline, both murine and human diabetic skin was biomechanically inferior compared to nondiabetic skin, with decreased maximum stress and decreased modulus (P < 0.001 and < 0.05, respectively). Surprisingly, the expression of genes involved in collagen synthesis were significantly up-regulated, and genes involved in collagen degradation were significantly down-regulated in murine diabetic skin (P < 0.01). In addition, MMP-2 and MMP-9/TIMP-1 protein ratios were significantly lower in murine diabetic skin (P < 0.05). Collagen I levels and I:III ratios were lower in diabetic skin (P < 0.05). These findings suggest that the predisposition of diabetics to wounds may be the result of impaired tissue integrity at baseline, and are due, in part, to a defect in the regulation of collagen protein synthesis at the post-transcriptional level.