MagicTouch PTA Sirolimus-Coated Balloon for Femoropopliteal and Below-the-Knee Disease: 3-Year Outcomes of the XTOSI Trial.

BACKGROUND: Sirolimus-coated balloon (SCB) is a potential treatment option for peripheral arterial disease (PAD). There are currently no long-term clinical data for this novel treatment for PAD. We present the 3-year results of the first-in-human study of MagicTouch PTA SCB for treatment of PAD for both femoropopliteal and below-the-knee arteries. METHODS: The XTOSI pilot study is a prospective, single-arm, open-label, single-center trial evaluating MagicTouch PTA SCB for symptomatic PAD. Assessments through 3 years included freedom from clinically driven target lesion revascularization (CD-TLR), freedom from major amputation, amputation-free survival (AFS), overall survival, and ulcer-free status. RESULTS: At 3 years, the overall freedom from CD-TLR was 84.4%, freedom from major amputation was 86.1%, AFS was 63.3%, overall survival was 63.3%, and ulcer-free status in remaining survivors with intact limbs was 100%. For femoropopliteal lesions, at 3 years, the freedom from CD-TLR was 92.9%, freedom from major amputation was 93.3%, AFS was 70%, and overall survival was 70%. For below-the-knee lesions, at 3 years, the freedom from CD-TLR was 77.8%, freedom from major amputation was 81.0%, AFS was 58.6%, and overall survival was 58.6%. CONCLUSIONS: SCB in the XTOSI pilot study showed promising clinical results sustained to 3 years, and no long-term safety concerns were raised. Randomized trials are currently ongoing to investigate the safety and efficacy of SCB for treatment of PAD.

Contrast enhanced mammography in breast cancer surveillance.

PURPOSE: Mammography (MG) is the standard imaging in surveillance of women with a personal history of breast cancer or DCIS (PHBC), supplemented with ultrasound. Contrast Enhanced Mammography (CEM) has higher sensitivity than MG and US. We report the performance of CEM compared with MG ± US. METHODS: A retrospective study of patients undergoing their first surveillance CEM in an Australian hospital setting between June 2006 and October 2020. Cases where a patient was recalled for assessment were identified, recording radiology, pathology and treatment details. Blinded re-reading of recalled cases was performed to determine the contribution of contrast. Use of surveillance US across the board was assessed for the period. RESULTS: 73/1191 (6.1%) patients were recalled. 35 (48%) were true positives (TP), with 26 invasive cancers and 9 cases of DCIS, while 38 (52%) were false positive (FP) with a positive predictive value (PPV) 47.9%. 32/73 were recalled due to MG findings, while 41/73 were only recalled due to Contrast. 14/73 had 'minimal signs' with a lesion identifiable on MG with knowledge of the contrast finding, while 27/73 were visible only with contrast. 41% (17/41) recalled due to contrast were TP. Contrast-only TPs were found with low and high mammographic density (MD). Screening breast US reduced by 55% in the year after CEM was implemented. CONCLUSION: Compared to MG, CEM as a single surveillance modality for those with PHBC has higher sensitivity and comparable specificity, identifying additional malignant lesions that are clinically significant. Investigation of interval cancer and subsequent round outcomes is warranted.

Cleaner XT Rotational Thrombectomy: An Efficacious Endovascular Technique for Salvage of Thrombosed Arteriovenous Access and a 12 Month Outcome Analysis.

PURPOSE: This study aims to describe an efficacious method using Cleaner XT rotational thrombectomy with catheter-directed thrombolysis and drug-eluting balloon angioplasty for the salvage of thrombosed arteriovenous fistulae and grafts. MATERIALS AND METHODS: Retrospective analysis of all patients with thrombosed hemodialysis accesses who underwent endovascular salvage using the Cleaner XT rotational thrombectomy system at a single institution between June 2019 and September 2020 was performed. Patency was presented as Kaplan-Meier survival curves, and regression analysis was performed to examine predictors of postintervention primary patency and assisted primary patency based on Cox proportional-hazards model. RESULTS: Thirty-four patients with thrombosed accesses underwent Cleaner XT rotational thrombectomy between June 2019 and September 2020. Technical and clinical success were both 100%. Mean procedure time was 62 ± 20 minutes. Mean postintervention primary patency time was 152 ± 51 days; 30, 90, 180, and 365 day postintervention primary patency rates were 89%, 80%, 68%, and 56%, respectively. Mean postintervention-assisted primary patency time was 157 ± 59 days; 30, 90, 180, and 365 day postintervention-assisted primary patency rates were 91%, 82%, 71%, and 59%, and 180 and 365 day secondary patency rates were 97.2% and 94.4%, respectively. CONCLUSION: The Cleaner XT rotational thrombectomy device demonstrates excellent clinical and technical success rates, with good patency results at all time points up to 12 months postintervention.

Use of Temporary Abdominal Closure in Non-Trauma Surgery: A Cohort Study.

BACKGROUND: Damage control surgery in trauma is widely used but the evidence for the use of laparostomy in non-trauma abdominal emergencies is limited. This study aimed to characterise outcomes in emergency abdominal surgery by comparing laparostomy to one-stage laparotomy for patients of similar illness severity. METHODS: A retrospective study of adult patients requiring emergency abdominal surgery and post-operative intensive care stay was performed between 2016 and 2020 at a major Australian metropolitan hospital. Case selection was from a prospectively maintained database, and case notes were reviewed. Patients having delayed abdominal closure were compared with those having one-stage abdominal closure. The primary outcome was odds of in-hospital mortality. The secondary outcomes included intensive care unit length of stay (LOS), overall hospital LOS, definitive stoma rate and discharge destination. Multivariable logistic regression analysis was performed to adjust for potentially confounding variables. RESULTS: Two hundred and eighteen patients met inclusion criteria (80 laparostomy and 138 non-laparostomy). The most common indications for laparostomy were bowel ischaemia (41.3%), sepsis (26.3%) and physiological instability (22.5%). There was no evidence of difference in odds of in-hospital mortality between groups (adjusted OR = 1.67, CI: 0.85-3.28; p = 0.138). Patients requiring laparostomy had a slightly longer median ICU LOS (4 vs. 3 days; p < 0.001), similar median hospital LOS (19 vs. 14 days, p = 0.245) and similar discharge destination. There was no difference in stoma rate (35.0% vs. 35.5%). CONCLUSION: Compared with standard one-stage laparotomy, laparostomy resulted in similar odds of in-hospital mortality in emergency abdominal surgery patients requiring intensive care.

Medium-Term Survival After Unrepaired Ruptured Abdominal Aortic Aneurysm.

PURPOSE: Ruptured abdominal aortic aneurysm (AAA) is almost always considered fatal without open surgical or endovascular repair. We report a case that has defied this norm and explore the possible factors involved in this exceedingly rare outcome. CASE REPORT: An 87 year old gentleman presented with an acute ruptured AAA with left retroperitoneal hematoma. He was counseled for emergent repair, but opted for conservative management instead. He has remained well at the time of writing, 13 months from the rupture, with clinical resolution of symptoms along with radiological resolution of the hematoma. CONCLUSION: Timely repair remains the mainstay of management for ruptured AAA, although this rare case highlights that it is possible for ruptured AAA to seal spontaneously with patient surviving up to 13 months. We have sought to hypothesize the factors in this case that may have contributed to prolonged survival following untreated ruptured AAA. CLINICAL IMPACT STATEMENT: While the overwhelming evidence is that a ruptured AAA left unrepaired is fatal, our case report illustrates a rare case that shows it is possible for ruptured AAA to seal spontaneously, with patient surviving up to 13 months. We seek to hypothesize the factors that may contribute to such prolonged survival.

MagicTouch PTA Sirolimus Coated Balloon for Femoropopliteal and Below the Knee Disease: Results From XTOSI Pilot Study Up To 12 Months.

INTRODUCTION: Sirolimus coated balloon (SCB) is a promising treatment option to prevent restenosis for peripheral arterial occlusive disease (PAOD). This is a pilot first-in-human study of MagicTouch percutaneous transluminal angioplasty (PTA) SCB for treatment of PAOD for both femoropopliteal and below the knee arteries (BTK). MATERIAL AND METHODS: Xtreme Touch-Neo [MagicTouch PTA] Sirolimus Coated Balloon (XTOSI) pilot study is a prospective, single-arm, open-label, single-center trial evaluating MagicTouch PTA SCB for symptomatic PAOD. Primary endpoint was defined as primary patency at 6 months (duplex ultrasound peak systolic velocity ratio ≤2.4). Secondary endpoints included clinically driven target lesion revascularization (CD-TLR), amputation free survival (AFS), all-cause mortality, and limb salvage success. RESULTS: Fifty patients were recruited. The mean age was 67 (n=31 [62%] males). SCB was applied to femoropopliteal in 20 patients (40%) and BTK in 30 patients (60%). Majority of treatments (94%) were performed for limb salvage indications (Rutherford scores 5 or 6). This was a high risk cohort, in which 90% had diabetes, 36% had coronary artery disease, 20% had end stage renal failure, and American Society of Anaesthesiologists (ASA) score was 3 or more in 80%. Mean lesion length treated was 227±81 mm, of which 36% were total occlusions. Technical and device success were both 100%. At 30 days, mortality was 2% and major limb amputation was also 2%. Six-month primary patency was 80% (88.2% for femoropopliteal; 74% for BTK). At 12 months, freedom from CD-TLR was 89.7% (94.1% for femoropopliteal; 86.3% for BTK), AFS was 81.6% (90.0% for femoropopliteal; 75.9% for BTK), all-cause mortality was 14.3% (10.0% for femoropopliteal; 17.2% for BTK), and limb salvage success was 92.9% (94.4% for femoropopliteal; 91.7% for BTK). There was a statistically significant increase between baseline and 6-month toe pressures for both femoropopliteal (57.3±23.3 mm Hg vs 82.5±37.8 mm Hg; p<.001) and BTK lesions (52.8±19.2 mm Hg vs 70.7±37 mm Hg; p<.037). At 12 months, wound healing rate was 33/39 (84.6%). CONCLUSIONS: MagicTouch PTA SCB in the XTOSI study showed promising 6-month primary patency and encouraging 12-month freedom from CD-TLR, AFS, and limb salvage rates. No early safety concerns were raised. Randomized trials are needed to investigate the safety and efficacy of SCB for treatment of PAOD.

Association between Dietary Diversity and Weight Status of Aboriginal Primary School Children in Negeri Sembilan, Malaysia.

Background: The purpose of this study is to determine the association between dietary diversity and weight status of aboriginal primary school children. Methods: Dietary diversity measures food intake diversity in food groups, whereas weight status indicates nutritional status. Dietary serving score (DSS) method was used to determine dietary diversity status, while weight status was assessed using BMI-for-Age (BAZ). Results: Results reported that 51.9% and 54.2% were male and 10 years old-12 years old children, respectively. A total of 36.4% of children consumed cereal/grains diversely while fruits were not diversely consumed by 96.4% of them. Approximately 60.8% of children were reported to have normal weight status, which was followed by overweight (17.7%), obese (16.7%) and thinness to severe-thinness (4.8%). There was an association between DSS of fruits, meat/fish/ eggs, legumes/lentils and milk/dairy products with age group, vegetables DSS with gender and BAZ with parental employment status (P < 0.05). The association between DSS of all food groups and total with BAZ were reported to be insignificant, indicating no association between both variables (0.00 < r < 0.30; P > 0.05). Conclusion: Children from this study were shown to practice a monotonous diet, although the majority of them were within normal weight status.

COVID-19 end-of-life care: symptoms and supportive therapy use in an Australian hospital.

BACKGROUND: Descriptions of symptoms and medication use at end of life in COVID-19 are limited to small cross-sectional studies, with no Australian longitudinal data. AIMS: To describe end-of-life symptoms and care needs of people dying of COVID-19. METHODS: This retrospective cohort study included consecutive admitted patients who died at a Victorian tertiary referral hospital from 1 January to 30 September directly due to COVID-19. Clinical characteristics, symptoms and use of supportive therapies, including medications and non-pharmacological interventions in the last 3 days of life were extracted. RESULTS: The cohort comprised 58 patients (median age 87 years, interquartile range (IQR) 81-90) predominantly admitted from home (n = 30), who died after a median of 11 days (IQR 6-28) in the acute medical (n = 31) or aged care (n = 27) wards of the hospital. The median Charlson Comorbidity Score was 7 (IQR 5-8). Breathlessness (n = 42), agitation (n = 36) and pain (n = 33) were the most frequent clinician-reported symptoms in the final 3 days of life, with most requiring opioids (n = 52), midazolam (n = 40), with dose escalation commonly being required. While oxygen therapy was commonly used (n = 47), few (n = 13) required an anti-secretory agent. CONCLUSIONS: This study presents one of the first and largest Australian report of the end of life and symptom experience of people dying of COVID-19. This information should help clinicians to anticipate palliative care needs of these patients, for example, recognising that higher starting doses of opioids and sedatives may help reduce prevalence and severity of breathlessness and agitation near death.

Treatment of lower limb ischaemia in patients with diabetes.

Diabetic chronic limb-threatening ischaemia is a challenging clinical problem with patients at high risk of diabetic foot ulceration (DFU) and limb loss. Patients often remain asymptomatic even in the presence of severe pedal ischaemia until first presenting with tissue loss such as DFU or frank gangrene. Limb salvage units should have the facilities and expertise to provide multidisciplinary team-based holistic care through best medical therapy, rapid diagnosis, prompt revascularisation with endovascular or open surgical techniques and expert wound management. Endovascular revascularisation has become the first line strategy in contemporary clinical practice because of similar outcomes in wound healing and amputation rates in most patients when compared with open surgery. The primary goal is restoration of pulsatile in-line blood flow to the ankle or foot, with an angiosome-directed approach possibly achieving superior outcomes especially in diabetics with poor collaterals. A comprehensive overview of conventional endovascular techniques (such as antegrade true lumen and subintimal approaches), advanced techniques for complex disease (such as retrograde subintimal and pedal-plantar loop approaches or even deep venous arterialisation) and the various treatment options are described. Diabetic limb salvage rates can be excellent with suitable multidisciplinary expertise and care.

Experimental and Computational Studies on Regiodivergent Chiral Phosphoric Acid Catalyzed Cycloisomerization of Mupirocin Methyl Ester.

This article presents a new strategy for achieving regiocontrol over the endo versus exo modes of cycloisomerizations of epoxide-containing alcohols, which leads to the formation of five- or six-membered cyclic ethers. Unlike traditional methods relying on achiral reagents or enzymes, this approach utilizes chiral phosphoric acids to catalyze the regiodivergent selective formations of either tetrahydrofuran- or tetrahydropyran-containing products. By using methyl ester of epoxide-containing antibiotic mupirocin as the substrate, it is demonstrated that catalytic chiral phosphoric acids (R)-TCYP and (S)-TIPSY could be used to achieve the selective formation of either the six-membered endo product (95:5 r.r.) or the five-membered exo product (77:23 r.r.), correspondingly. This cyclization was found to be unselective under the standard conditions involving various achiral acids, bases, or buffers. The subsequent mechanistic studies using state-of-the-art quantum chemical solutions provided the description of the potential energy surface, which is fully consistent with the experimental observations. Based on these results, highly detailed reaction paths are obtained and a concerted and highly synchronous mechanism is proposed for the formation of both exo and endo products.

Regiodivergent Glycosylations of 6-Deoxy-erythronolide B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis.

This work describes the first example of using chiral catalysts to control site-selectivity for the glycosylations of complex polyols such as 6-deoxyerythronolide B and oleandomycin-derived macrolactones. The regiodivergent introduction of sugars at the C3, C5, and C11 positions of macrolactones was achieved by selecting appropriate chiral acids as catalysts or through introduction of stoichiometric boronic acid-based additives. BINOL-based chiral phosphoric acids (CPAs) were used to catalyze highly selective glycosylations at the C5 positions of macrolactones (up to 99:1 rr), whereas the use of SPINOL-based CPAs resulted in selectivity switch and glycosylation of the C3 alcohol (up to 91:9 rr). Additionally, the C11 position of macrolactones was selectively functionalized through traceless protection of the C3/C5 diol with boronic acids prior to glycosylation. Investigation of the reaction mechanism for the CPA-controlled glycosylations revealed the involvement of covalently linked anomeric phosphates rather than oxocarbenium ion pairs as the reactive intermediates.

Worker reproduction of the invasive yellow crazy ant Anoplolepis gracilipes.

BACKGROUND: Reproductive division of labor is one of the key features of social insects. Queens are adapted for reproduction while workers are adapted for foraging and colony maintenance. In many species, however, workers retain functional ovaries and can lay unfertilized male eggs or trophic eggs. Here we report for the first time on the occurrence of physogastric workers and apparent worker reproduction in the invasive yellow crazy ant Anoplolepis gracilipes (Fr. Smith). We further examined the reproductive potential and nutritional role of physogastric workers through multidisciplinary approaches including morphological characterization, laboratory manipulation, genetic analysis and behavioral observation. RESULTS: Egg production with two types of eggs, namely reproductive and trophic eggs, by physogastric workers was found. The reproductive egg was confirmed to be haploid and male-destined, suggesting that the workers produced males via arrhenotokous parthenogenesis as no spermatheca was discovered. Detailed observations suggested that larvae were mainly fed with trophic eggs. Along with consumption of trophic eggs by queens and other castes as part of their diet, the vital role of physogastric workers as "trophic specialist" is confirmed. CONCLUSION: We propose that adaptive advantages derived from worker reproduction for A. gracilipes may include 1) trophic eggs provisioned by physogastric workers likely assist colonies of A. gracilipes in overcoming unfavorable conditions such as paucity of food during critical founding stage; 2) worker-produced males are fertile and thus might offer an inclusive fitness advantage for the doomed orphaned colony.

Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice.

microRNAs (miRNAs) are dysregulated in a variety of disease states, suggesting that this newly discovered class of gene expression repressors may be viable therapeutic targets. A microarray of miRNA changes in ALS-model superoxide dismutase 1 (SOD1)(G93A) rodents identified 12 miRNAs as significantly changed. Six miRNAs tested in human ALS tissues were confirmed increased. Specifically, miR-155 was increased 5-fold in mice and 2-fold in human spinal cords. To test miRNA inhibition in the central nervous system (CNS) as a potential novel therapeutic, we developed oligonucleotide-based miRNA inhibitors (anti-miRs) that could inhibit miRNAs throughout the CNS and in the periphery. Anti-miR-155 caused global derepression of targets in peritoneal macrophages and, following intraventricular delivery, demonstrated widespread functional distribution in the brain and spinal cord. After treating SOD1(G93A) mice with anti-miR-155, we significantly extended survival by 10 days and disease duration by 15 days (38%) while a scrambled control anti-miR did not significantly improve survival or disease duration. Therefore, antisense oligonucleotides may be used to successfully inhibit miRNAs throughout the brain and spinal cord, and miR-155 is a promising new therapeutic target for human ALS.

Induced Disturbances Cause Monomorium pharaonis (Hymenoptera: Formicidae) Nest Relocation.

Budding and relocation of nests are important characteristics of the Pharaoh ant, Monomorium pharaonis (L.), an important pest of artificial structures. Pharaoh ant colony movements induced by several types of disturbances were evaluated in the laboratory. The percentages of workers and brood in the source and new nest sites were determined at Days 0, 1, 3, and 5 following physical disturbance (temporal removal of nestmates), chemical disturbance (application of pyrethroid insecticide), invasion by heterospecific ants, food depletion, and moisture depletion in the laboratory. All disturbances were performed in the source nest, which was connected to an empty new nest site. Almost all workers moved and carried the entire brood to the new nest site when subjected to physical disturbance, chemical disturbance, and ant invasion on Day 1, whereas only <5% of workers were present in the new nest site in the undisturbed control. After these disturbances, the brood was never relocated back to the original nest site in this 5-d study. When subjected to food depletion, ∼60% of the brood were found in the new nest site and ∼40% of the brood remained in the original nest on Day 5, resulting in a polydomous population. In contrast, moisture depletion did not show any significant effect on colony movement. These results provide useful information about the causes of Pharaoh ant colony budding and guidance about how to develop effective control and prevention strategies.

Influences of pyriproxyfen on fecundity and reproduction of the Pharaoh ant (Hymenoptera: Formicidae).

The effects of the juvenile hormone analog pyriproxyfen (at concentrations of 0.1, 0.5, and 1%) on egg production, number of ovarioles, and length of oocytes were examined in queens of the Pharaoh ant Monomorium pharaonis (L.). Pyriproxyfen significantly reduced egg production in queens from week 3 onwards. Queens that were exposed to 1% pyriproxyfen stopped producing eggs at week 8. After 8 wk, ovaries were dissected from all queens, and the number of ovarioles and the length of the largest oocytes were recorded. The ovaries of queens in treated colonies were smaller than those in untreated queens, and the number of ovarioles in the ovaries was significantly lower in all pyriproxyfen-treated queens. Queens treated with the highest concentrations of pyriproxyfen tended to have significantly shorter oocytes than untreated queens. Histological studies of the ovaries revealed that pyriproxyfen caused vacuolation in the ovarioles, thickening of the tunica propria, development of small eggs, and underdevelopment of nurse cells and the follicular epithelium. Exposure to pyriproxyfen reduced egg production and induced severe morphological changes in the ovaries of queens, and the effects increased with increased concentration of pyriproxyfen.

Catalytic asymmetric enyne addition to aldehdyes and Rh(I)-catalyzed stereoselective domino Pauson-Khand/[4 + 2] cycloaddition.

The 1,1'-bi-2-naphthol-ZnEt2-Ti(O(i)Pr)4-Cy2NH system is found to catalyze the 1,3-enyne addition to aliphatic aldehydes as well as other aldehydes at room temperature with 75-96% yield and 82-97% ee. This system is also broadly applicable for the highly enantioselective reaction of other alkyl-, aryl-, and silylalkynes with structurally diverse aldehydes. The propargylic alcohols prepared from the catalytic asymmetric enyne addition to aliphatic aldehydes are used to prepare a series of optically active trienynes. In the presence of a catalytic amount of [RhCl(CO)2]2 and 1 atm of CO, the optically active trienynes undergo highly stereoselective domino Pauson-Khand/[4 + 2] cycloaddition to generate optically active multicyclic products. The Rh(I) catalyst is also found to catalyze the coupling of a diyne with CO followed by [4 + 2] cycloaddition to generate an optically active multicyclic product. These transformations are potentially useful for the asymmetric synthesis of polyquinanes containing a quaternary chiral carbon center.

Larvicidal, oviposition, and ovicidal effects of Artemisia annua (Asterales: Asteraceae) against Aedes aegypti, Anopheles sinensis, and Culex quinquefasciatus (Diptera: Culicidae).

This study focuses on the larvicidal, oviposition, and ovicidal effects of a crude extract of Artemisia annua against Aedes aegypti, Anopheles sinensis, and Culex quinquefasciatus. Dried cells of Artemisia annua from cell suspension cultures were extracted using hexane. The extract showed moderate larvicidal effects against mosquitoes. At 24-h post treatment, the LC50 values for Anopheles sinensis, Aedes aegypti, and Culex quinquefasciatus were recorded as 244.55, 276.14, and 374.99 ppm, respectively. The percentage mortality of larvae was directly proportional to the tested concentration. Anopheles sinensis was found to be the most susceptible species, whereas Culex quinquefasciatus was the most tolerant to the Artemisia annua extract. The results indicated that the Artemisia annua extract showed concentration-dependent oviposition deterrent activity and had a strong deterrent effect. At 500 ppm, the percentage effective repellency was more than 85% compared with the control group for all the species, with oviposition activity index values of -0.94, -0.95, and -0.78 for Aedes aegypti, Anopheles sinensis, and Culex quinquefasciatus, respectively. In the ovicidal assay, the percentage hatchability of eggs after treatment with 500 ppm of Artemisia annua extract was significantly lower than the control, with values of 48.84 ± 4.08, 38.42 ± 3.67, and 79.35 ± 2.09% for Aedes aegypti, Anopheles sinensis, and Culex quinquefasciatus, respectively. Artemisia annua was found to be more effective against Aedes aegypti and Anopheles sinensis compared with Culex quinquefasciatus. This study indicated that crude extract of A. annua could be a potential alternative for use in vector management programs.